By Will Boggs, MD
NEW YORK (Reuters Health) - An enlarged prostate due to benign prostatic hyperplasia, or BPH, can be safely and effectively removed using a type of minimally invasive single-keyhole surgery, researchers report.
The procedure, known as single-port transvesical enucleation of the prostate, or STEP, is "indicated in patients with large (greater than 80 to 100 grams) prostate glands that require surgery, in lieu of open surgery," Dr. Mihir M. Desai from the Cleveland Clinic, Ohio told Reuters Health.
"Our preliminary data suggest that it is effective and the postoperative pain is minimal and most patients are discharged the next day," Desai said, and "there should be minimal to no effect on erectile dysfunction with our approach."
In the medical journal Urology, Desai and colleagues report their initial experience with STEP performed through a single incision in three patients suffering from bothersome BPH symptoms, which may include frequent and sometimes painful urination.
In two patients, the prostatic mass was successfully removed in less than 2.5 hours. In the other patient, the operation took 6 hours because of an inadvertent injury to the bowel that required traditional open surgery to repair.
The catheter used for draining urine from the bladder was removed within eight days in all three patients, and none of them had trouble urinating or suffered from incontinence.
The two patients without complications were sent home after only one day in the hospital, whereas the patient with the bowel injury was discharged after three days in the hospital.
SOURCE: Urology, November 2008.
Saturday, March 14, 2009
Weiva Sieh: Searching for Genetic Cancer Markers in the Real World
project: A studying of brain function in rats
What led to the project: Weiva Sieh's parents—immigrants to New York City from China—made an early bet, in real estate, that their children would both be top science students. In the 1970s, years before their children would be old enough to attend, "they bought their house so we could walk to The Bronx High School of Science," the selective school known for producing several Nobel Prize winners over the years, Sieh says.
Of course, getting into the Bronx school meant an exam, not living in a neighborhood. Fortunately, Sieh and her brother both gained admission. Her sophomore year, Sieh entered the school's extracurricular research program, and began working in the lab of Lucy Brown, a professor of neurology and neuroscience at the Albert Einstein College of Medicine in Manhattan. The work involved treating rats with naltrexone, a drug that blocks the effects of narcotics and is marketed as Revia and Vivitrol. They then studied images of the rats' brains to see how naltrexone affected brain activity. Sieh entered her part of the project in the 1988 Westinghouse Science Talent Search and placed sixth overall.
The effect on her career: "That was my first real experience with practicing science," Sieh says, and it whetted her appetite for more. She went to Harvard University to study biology, and then went to McGill University in Montreal for medical school.
For awhile she thought she might both practice medicine and do research. After doing a genetic epidemiology research project at McGill, looking at whether family members of head and neck cancer patients had an increased risk of the disease (and finding the topic fascinating), she went to the University of Washington (U.W.) in Seattle to earn a master's degree in epidemiology. She fully intended to do a residency afterward and spend a big part of her life treating patients. Then she fell in love with graduate school and immediately switched into the PhD program. "It wasn't that I didn't like medicine," she says. But "I was so engaged and stimulated by the research that I pretty much never had a chance to go back to do a clinical residency—I was always too interested in what I was doing."
In particular, she became fascinated by the complexities of epidemiology, which is less straightforward than doing experiments on rats as she did as a high schooler. "Studying people is always going to be harder," she says, because there is limited ability to control or measure their environments. "You're not even trying to draw conclusions about causes—only attempting to find associations or correlations." Even then, it takes several studies for a consensus to emerge. But Sieh enjoys these complications and the real-world nature of the field "because I'm interested in people," she says. "If you want to understand what causes human disease, it's not like there are better options."
Her dissertation looked at whether variants in the PSA gene—that is, the gene that codes for the PSA (prostate specific antigen)protein doctors use as a screen for the existence or recurrence of prostate cancer—had any influence on developing the cancer. (Later she did a postdoc at U.W., focusing on statistical genetics; she also met her husband there, a fellow MD/PhD, although his career took the opposite turn—he's now a practicing family
What led to the project: Weiva Sieh's parents—immigrants to New York City from China—made an early bet, in real estate, that their children would both be top science students. In the 1970s, years before their children would be old enough to attend, "they bought their house so we could walk to The Bronx High School of Science," the selective school known for producing several Nobel Prize winners over the years, Sieh says.
Of course, getting into the Bronx school meant an exam, not living in a neighborhood. Fortunately, Sieh and her brother both gained admission. Her sophomore year, Sieh entered the school's extracurricular research program, and began working in the lab of Lucy Brown, a professor of neurology and neuroscience at the Albert Einstein College of Medicine in Manhattan. The work involved treating rats with naltrexone, a drug that blocks the effects of narcotics and is marketed as Revia and Vivitrol. They then studied images of the rats' brains to see how naltrexone affected brain activity. Sieh entered her part of the project in the 1988 Westinghouse Science Talent Search and placed sixth overall.
The effect on her career: "That was my first real experience with practicing science," Sieh says, and it whetted her appetite for more. She went to Harvard University to study biology, and then went to McGill University in Montreal for medical school.
For awhile she thought she might both practice medicine and do research. After doing a genetic epidemiology research project at McGill, looking at whether family members of head and neck cancer patients had an increased risk of the disease (and finding the topic fascinating), she went to the University of Washington (U.W.) in Seattle to earn a master's degree in epidemiology. She fully intended to do a residency afterward and spend a big part of her life treating patients. Then she fell in love with graduate school and immediately switched into the PhD program. "It wasn't that I didn't like medicine," she says. But "I was so engaged and stimulated by the research that I pretty much never had a chance to go back to do a clinical residency—I was always too interested in what I was doing."
In particular, she became fascinated by the complexities of epidemiology, which is less straightforward than doing experiments on rats as she did as a high schooler. "Studying people is always going to be harder," she says, because there is limited ability to control or measure their environments. "You're not even trying to draw conclusions about causes—only attempting to find associations or correlations." Even then, it takes several studies for a consensus to emerge. But Sieh enjoys these complications and the real-world nature of the field "because I'm interested in people," she says. "If you want to understand what causes human disease, it's not like there are better options."
Her dissertation looked at whether variants in the PSA gene—that is, the gene that codes for the PSA (prostate specific antigen)protein doctors use as a screen for the existence or recurrence of prostate cancer—had any influence on developing the cancer. (Later she did a postdoc at U.W., focusing on statistical genetics; she also met her husband there, a fellow MD/PhD, although his career took the opposite turn—he's now a practicing family
Bisphenol A: What you need to know
Bisphenol A, or BPA, is a hormone-like chemical used in many plastics and lined cans so commonly used by consumers that nearly every American has been exposed.
The chemical is at the heart of worldwide scientific investigation and a debate over whether it is harmful to the very young.
U.S. government:
• The Food and Drug Administration does not recommend discontinuing use of products that contain BPA.
ON THE WEB: FDA Overview
• The journal Environmental Health Perspectives published a research article on urinary analysis from the National Center for Environmental Health and CDC that BPA can be detected in an estimated 95% of Americans.
FIND MORE STORIES IN: Congress | Food and Drug Administration | Human Services | Commerce | House Committee | Energy | Environmental Working Group | Rep. Edward Markey | Policy Center | National Toxicology Program | Tips | Environmental Health Perspectives | National Center for Environmental Health | Bisphenol A | Baby Bottles | Invention
• The National Toxicology Program of the U.S. Department of Health and Human Services released a report (pdf) in September 2008 concluding that there was cause for "some concern for effects on the brain, behavior and prostate gland in fetuses, infants and children at current human exposures."
• In Congress, Rep. Edward Markey introduced a bill that would ban BPA in food and beverage containers. It was most recently referred to the House Committee on Energy and Commerce June 10.
Risk assessment:
•Environmental Health Perspectives published commentary (pdf) analyzing how standards related to "Good Laboratory Practices" vary and how that affects the risk assessment of BPA.
• In the international community, the advocacy group Friends of Earth Europe published "Blissfully unaware of Bisphenol A" (pdf) in June, reviewing the science on the chemical and also urging a revisal of the risk assessment process.
Consumer info:
The non-profit Environmental Working Group has issued a number of reports and advice on BPA, including:
•Tips to Avoid BPA Exposure, with information similar to our recycling code guide at left.
•Timeline: BPA from Invention to Phase-Out, explaining the widespread use and the most recent government decisions and health reports to date.
•Survey of Bisphenol A in Canned Foods, reporting that BPA levels are unsafe in 1 in 10 servings of canned foods and 1 in 3 servings of infant formula.
•Guide to Infant Formla and Baby Bottles, comparing brands and summarizing the group's findings on BPA.
Environment California Research & Policy Center also issued a report (pdf) on toxic leaching chemicals in clear plastic baby bottles.
The chemical is at the heart of worldwide scientific investigation and a debate over whether it is harmful to the very young.
U.S. government:
• The Food and Drug Administration does not recommend discontinuing use of products that contain BPA.
ON THE WEB: FDA Overview
• The journal Environmental Health Perspectives published a research article on urinary analysis from the National Center for Environmental Health and CDC that BPA can be detected in an estimated 95% of Americans.
FIND MORE STORIES IN: Congress | Food and Drug Administration | Human Services | Commerce | House Committee | Energy | Environmental Working Group | Rep. Edward Markey | Policy Center | National Toxicology Program | Tips | Environmental Health Perspectives | National Center for Environmental Health | Bisphenol A | Baby Bottles | Invention
• The National Toxicology Program of the U.S. Department of Health and Human Services released a report (pdf) in September 2008 concluding that there was cause for "some concern for effects on the brain, behavior and prostate gland in fetuses, infants and children at current human exposures."
• In Congress, Rep. Edward Markey introduced a bill that would ban BPA in food and beverage containers. It was most recently referred to the House Committee on Energy and Commerce June 10.
Risk assessment:
•Environmental Health Perspectives published commentary (pdf) analyzing how standards related to "Good Laboratory Practices" vary and how that affects the risk assessment of BPA.
• In the international community, the advocacy group Friends of Earth Europe published "Blissfully unaware of Bisphenol A" (pdf) in June, reviewing the science on the chemical and also urging a revisal of the risk assessment process.
Consumer info:
The non-profit Environmental Working Group has issued a number of reports and advice on BPA, including:
•Tips to Avoid BPA Exposure, with information similar to our recycling code guide at left.
•Timeline: BPA from Invention to Phase-Out, explaining the widespread use and the most recent government decisions and health reports to date.
•Survey of Bisphenol A in Canned Foods, reporting that BPA levels are unsafe in 1 in 10 servings of canned foods and 1 in 3 servings of infant formula.
•Guide to Infant Formla and Baby Bottles, comparing brands and summarizing the group's findings on BPA.
Environment California Research & Policy Center also issued a report (pdf) on toxic leaching chemicals in clear plastic baby bottles.
Ft. Chip cancer rate high
Unexpectedly high cancer rates uncovered in Fort Chipewyan are no cause for alarm but demand further study, say researchers.
A government study of the town downstream from the tarsands released yesterday found 30% more cancer cases than predicted by the Alberta Cancer Board.
The higher rate is cause for concern, but not panic, said Dr. Tony Fields, vice-president of the Cancer Corridor, Alberta Health Services - and not a carte blanche to lay blame on the tarsands.
'NO CAUSE FOR ALARM'
"The overall findings show there's no cause for alarm, but they do warrant further investigation," Fields said after unveiling the numbers. "This is 51 cases of cancer over 12 years. It's not huge."
He warned that the high rate could be a product of statistical oddity, not concrete causes.
"This is based on a small number of cases. It could be chance. Had we seen something more significant ... then we'd have your black and white answer."
But Fields said the study calls for ongoing observation of the community. Cancer in the community should be tracked over the next several years to see if more definitive trends emerge.
"You don't forget (about these numbers). You don't sweep them away," said Fields.
The study was intended to count cases, not assess causes of cancer. The report said further investigation is required to see if residents are at risk from other causes, including seemingly obvious environmental causes flowing downstream from the tarsands.
The study did not support local worries about cholangiocarcinoma cancer, which infects bile ducts between the liver, gallbladder and small intestine.
A local physician, Dr. John O'Connor, went public in 2006 with five alleged cholangiocarcinoma deaths in the town of 1,200 since 2000. He believed the normal rate was nine cases per 100,000 people, according to the report. He also reported concerning numbers of common cancers, too.
That move prompted the study, said Fields. "I think the community should be reassured the numbers are not as high as reported," he said.
BILE DUCT CANCER
Only two cases of the rare bile duct cancer were proven - still higher than the 0.4 cases predicted.
The 51 cases, including all kinds of cancer, ranged on the high end of what researchers guessed were possible case counts between 1995 and 2006.
Rates also ranked higher than neighbouring Fort McMurray, the Northern Lights Health Region and Alberta in general - given a wide margin of error due to the small case count.
Expected numbers were lowered to reflect that aboriginal Canadians, who make up a large part of the town's population, have lower cancer rates, said Fields.
A government study of the town downstream from the tarsands released yesterday found 30% more cancer cases than predicted by the Alberta Cancer Board.
The higher rate is cause for concern, but not panic, said Dr. Tony Fields, vice-president of the Cancer Corridor, Alberta Health Services - and not a carte blanche to lay blame on the tarsands.
'NO CAUSE FOR ALARM'
"The overall findings show there's no cause for alarm, but they do warrant further investigation," Fields said after unveiling the numbers. "This is 51 cases of cancer over 12 years. It's not huge."
He warned that the high rate could be a product of statistical oddity, not concrete causes.
"This is based on a small number of cases. It could be chance. Had we seen something more significant ... then we'd have your black and white answer."
But Fields said the study calls for ongoing observation of the community. Cancer in the community should be tracked over the next several years to see if more definitive trends emerge.
"You don't forget (about these numbers). You don't sweep them away," said Fields.
The study was intended to count cases, not assess causes of cancer. The report said further investigation is required to see if residents are at risk from other causes, including seemingly obvious environmental causes flowing downstream from the tarsands.
The study did not support local worries about cholangiocarcinoma cancer, which infects bile ducts between the liver, gallbladder and small intestine.
A local physician, Dr. John O'Connor, went public in 2006 with five alleged cholangiocarcinoma deaths in the town of 1,200 since 2000. He believed the normal rate was nine cases per 100,000 people, according to the report. He also reported concerning numbers of common cancers, too.
That move prompted the study, said Fields. "I think the community should be reassured the numbers are not as high as reported," he said.
BILE DUCT CANCER
Only two cases of the rare bile duct cancer were proven - still higher than the 0.4 cases predicted.
The 51 cases, including all kinds of cancer, ranged on the high end of what researchers guessed were possible case counts between 1995 and 2006.
Rates also ranked higher than neighbouring Fort McMurray, the Northern Lights Health Region and Alberta in general - given a wide margin of error due to the small case count.
Expected numbers were lowered to reflect that aboriginal Canadians, who make up a large part of the town's population, have lower cancer rates, said Fields.
Prostate cancer patient: Don’t procrastinate
For six years it was on John Jackson’s to-do list.
It’s called a prostate specific antigen test and by the time he got around to it, cancer had inundated his body.
Just before Christmas, Jackson, 60, a Cody real estate agent with two grown daughters, was diagnosed with prostate cancer.
“I didn’t get one (a PSA test) done for six years,” Jackson says. “Time just got away from me, like it does everyone.”
He didn’t think he needed to worry about cancer �“ after all there’s no family history and he felt healthy. But prostate cancer doesn’t necessarily follow family history.
The disease occurs when cells of the prostate, a gland in the male reproductive system, mutate and multiply out of control. These cells then spread to other parts of the body, typically to the bones and lymph nodes.
The normal range for a PSA test, which measures an enzyme produced by the prostate, is 1-4.
“By the time I had mine tested, my level was at 258,” Jackson says. “That was extremely high and I was told I probably had cancer.”
A biopsy and bone scan would later verify that he not only had prostate cancer, but that it had started to spread to his bones.
“The prognosis wasn’t good,” he said.
He immediately began treatment. Rather than chemotherapy or radiation treatment as is done with most cancers, Jackson is on Lupron, a hormone blocker that essentially starves the cancer cells.
Since starting treatment Jackson says he is doing better, and some days are better than others.
In an effort to help more men realize the importance of prostate cancer screening, Jackson says he has made it his mission to spread the word to men about the important of testing.
“As inexpensive as it is, anybody who doesn’t do it is stupid,” Jackson says. “The earlier it’s detected the greater the lifespan. It’s really much more treatable than other cancers.”
One in six men will get prostate cancer but with early detection only one in 35 will die from the disease. It’s recommended that men get a baseline PSA at age 40 and annual tests starting at age 50. Men at high risk are encouraged to start regular screening earlier.
For more information on prostate cancer screening contact West Park Hospital Health Check, 899-0693 or healthcheck@wphcody.org.
“It’s one little blood test that could save your life,” Jackson says. “Early detection is the key.”
PSA screenings
PSA blood draws are conducted 7-9:30 a.m.
Tuesdays and Thursdays at the rec center. Cost is $25.
Benefit for Jackson on Friday
A Mardi Gras benefit for John Jackson will be 6-9 p.m. Friday at the Silver Dollar Bar.
The event will feature a crawfish boil and silent auctions. Cost is $15 at the door and all funds will go to assist Jackson, who was recently diagnosed with advanced prostate cancer.
“The support from my friends and the community has been wonderful,” Jackson says. “I’m amazed and humbled by the number of people who are willing to help a complete stranger.”
For more information about the event call Laurie Parker, 527-6757 or 272-8766.
It’s called a prostate specific antigen test and by the time he got around to it, cancer had inundated his body.
Just before Christmas, Jackson, 60, a Cody real estate agent with two grown daughters, was diagnosed with prostate cancer.
“I didn’t get one (a PSA test) done for six years,” Jackson says. “Time just got away from me, like it does everyone.”
He didn’t think he needed to worry about cancer �“ after all there’s no family history and he felt healthy. But prostate cancer doesn’t necessarily follow family history.
The disease occurs when cells of the prostate, a gland in the male reproductive system, mutate and multiply out of control. These cells then spread to other parts of the body, typically to the bones and lymph nodes.
The normal range for a PSA test, which measures an enzyme produced by the prostate, is 1-4.
“By the time I had mine tested, my level was at 258,” Jackson says. “That was extremely high and I was told I probably had cancer.”
A biopsy and bone scan would later verify that he not only had prostate cancer, but that it had started to spread to his bones.
“The prognosis wasn’t good,” he said.
He immediately began treatment. Rather than chemotherapy or radiation treatment as is done with most cancers, Jackson is on Lupron, a hormone blocker that essentially starves the cancer cells.
Since starting treatment Jackson says he is doing better, and some days are better than others.
In an effort to help more men realize the importance of prostate cancer screening, Jackson says he has made it his mission to spread the word to men about the important of testing.
“As inexpensive as it is, anybody who doesn’t do it is stupid,” Jackson says. “The earlier it’s detected the greater the lifespan. It’s really much more treatable than other cancers.”
One in six men will get prostate cancer but with early detection only one in 35 will die from the disease. It’s recommended that men get a baseline PSA at age 40 and annual tests starting at age 50. Men at high risk are encouraged to start regular screening earlier.
For more information on prostate cancer screening contact West Park Hospital Health Check, 899-0693 or healthcheck@wphcody.org.
“It’s one little blood test that could save your life,” Jackson says. “Early detection is the key.”
PSA screenings
PSA blood draws are conducted 7-9:30 a.m.
Tuesdays and Thursdays at the rec center. Cost is $25.
Benefit for Jackson on Friday
A Mardi Gras benefit for John Jackson will be 6-9 p.m. Friday at the Silver Dollar Bar.
The event will feature a crawfish boil and silent auctions. Cost is $15 at the door and all funds will go to assist Jackson, who was recently diagnosed with advanced prostate cancer.
“The support from my friends and the community has been wonderful,” Jackson says. “I’m amazed and humbled by the number of people who are willing to help a complete stranger.”
For more information about the event call Laurie Parker, 527-6757 or 272-8766.
New Treatment Hope For Prostate Cancer
Melbourne's Burnet Institute have developed a potential new treatment for patients with prostate cancer. An article, which described the invention, has recently been published in The Journal of Clinical Investigation.Head of the Burnet Institute's Cancer Immunotherapy Laboratory, Associate Professor Pei Xiang Xing said his group has produced a monoclonal antibody to a unique tumour marker for the treatment of prostate cancer. The monoclonal antibody is directed at cancer-producing cells carrying the specific molecule known as PIM-1, which is responsible for cell survival, proliferation and differentiation. Over-expression of PIM-1 plays a critical role in the development, progression and metastasis of prostate cancer and other cancers such as leukaemia. The monoclonal antibody significantly inhibited cancer cell growth when used in laboratory models of prostate cancer.
Professor Xing's group demonstrated that the monoclonal antibody binds to PIM-1 present in cancer cells and creates a chain of events leading to the death of the cells. In particular, the therapeutic effect was improved by combination of the antibody with other drugs currently used to treat prostate cancer.
Prostate cancer is one of the most frequently diagnosed invasive cancers and the third leading cause of death in men worldwide. More than 3,000 men die each year from prostate cancer, equal to the number of women who die from breast cancer; and more than 18,000 new cases are diagnosed in Australia each year. A new strategy to treat prostate cancer is urgently needed as there is no efficient method to treat advanced prostate cancer.
Director of the Burnet Institute, Professor Brendan Crabb said that while the therapy was still in its early days this was the first time that researchers had found a treatment that targeted prostate cancer cells with a specific antibody to PIM-1 and which resulted in the death of the malignant cells and a reduction in tumour size.
"This is an exciting step in the development of new treatments for patients with prostate cancer with very promising laboratory-test results," Professor Crabb said.
While further laboratory research is still required to refine the treatment, it is expected that clinical trials of the new therapy will commence in the near future.
Professor Xing's group demonstrated that the monoclonal antibody binds to PIM-1 present in cancer cells and creates a chain of events leading to the death of the cells. In particular, the therapeutic effect was improved by combination of the antibody with other drugs currently used to treat prostate cancer.
Prostate cancer is one of the most frequently diagnosed invasive cancers and the third leading cause of death in men worldwide. More than 3,000 men die each year from prostate cancer, equal to the number of women who die from breast cancer; and more than 18,000 new cases are diagnosed in Australia each year. A new strategy to treat prostate cancer is urgently needed as there is no efficient method to treat advanced prostate cancer.
Director of the Burnet Institute, Professor Brendan Crabb said that while the therapy was still in its early days this was the first time that researchers had found a treatment that targeted prostate cancer cells with a specific antibody to PIM-1 and which resulted in the death of the malignant cells and a reduction in tumour size.
"This is an exciting step in the development of new treatments for patients with prostate cancer with very promising laboratory-test results," Professor Crabb said.
While further laboratory research is still required to refine the treatment, it is expected that clinical trials of the new therapy will commence in the near future.
NEW - Prostate cancer – from a patient’s perspective
As many Australian men die of prostate cancer each year as women do of breast cancer.
Image
The thought of a prostate exam may be daunting for men, but early detection is vital. As one doctor said, “I’ve never seen a patient too early, but I’ve seen plenty too late.”
A national survey conducted by the Prostate Cancer Foundation of Australia in 2002, however, shows only half of all men feel well informed about the condition, as opposed to almost 80 per cent of women feeling well informed about breast cancer.
Every day, over 30 men on average will be told they have prostate cancer, and sadly, one will die every three hours.
Yet the subject of prostate cancer affects a person’s manhood, and so it is largely taboo in comparison to other cancers.
So when a man agrees to discuss the condition, it is all the more important his story is heard.
“It is often said that men are not conscious of their health,” says Jack*, of Kadina. “This is not entirely true, most of my friends know which doctor they are staying away from.
“It’s a bloke thing, a ‘gung ho, she’ll be right’ attitude that works on the premise men only visit the doctor when they are standing at death’s door. And so it was with me.”
Jack was diagnosed with prostate cancer last year, after a relative’s passing caused him to start taking PSA tests on a regular basis.
His doctor told him recently if he hadn’t taken the tests, the two would not have been speaking in 12 months.
“I considered I was fit and healthy, had never been in hospital, was not taking any medication, I hadn’t increased my weight for 40 years and played sport twice a week,” said Jack, who often bragged he had taken only three sick days off of work in 35 years.
“But then a close relative on my wife’s side died of prostate cancer after a relatively short time, and my wife exhorted me to have the blood test, to check the possibility of prostate cancer.”
Testing
“Reluctantly, I visited my doctor, who thought it was a good idea at my age, and after a digital rectal examination, I had a blood test to measure my levels of PSA.”
PSA (Prostate-Specific Antigen) is a protein produced by the prostate, low levels of which can be found in the bloodstream. However, when the normal structure of the prostate tissue is disrupted, most notably by cancer, higher levels can be detected, making it the leading test for prostate cancer.
“The results of my test showed no cause for alarm,” said Jack.
“However, I agreed to have a PSA test done on a regular basis, and did so over a period of three years with none of them sinister, so it was disconcerting to receive a call from my doctor following the latest test, requesting me to see him.”
Jack’s doctor explained his PSA levels had risen from their formerly level plateau, so much so he referred Jack to an urologist specialising in prostate disorders.
“After undergoing several tests with the urologist, I was not unduly concerned when he prescribed a month-long course of medication, which he thought would do the job.
“After all, I was feeling well, having no trouble passing urine and only requiring the toilet once a night.”
Unfortunately, after two months of treatment, Jack’s next blood test showed his PSA levels had more than doubled.
“For the first time I began to realise the fallacy of my perceived invincibility,” he said.
Following the unexpected result, Jack’s urologist arranged for a Prostate Ultrasound Biopsy procedure, which entailed an ultrasound probe being inserted into the rectum, guiding an instrument that snips out 12 sections of tissue from the prostate gland.
Diagnosis
The results became available less than a fortnight later, at which point Jack was diagnosed with cancer.
“The results were not a complete surprise,” he said.
“After the failure of the first treatment, the possibility of cancer loomed even larger, so I was half expecting the verdict, but in truth, my first reaction was surprisingly one of relief.
“Relief, to the extent it had happened to me at this stage of my life, I am in my 70s, my children have grown up and are successful in their chosen careers, and no longer dependent on me. I also have the knowledge my wife will be financially secure in future years, no matter what happens.”
If he had been diagnosed 30 years earlier, the news would have been devastating.
Jack informed his wife, knowing the condition can often put strain on a relationship, though he believes the couple have only grown closer since.
He decided not to tell his children until he knew more about the condition, including the big question — had the cancer spread?
“My urologist explained the next step would be to ascertain if the cancer has spread outside the prostate gland, and so doctors took a radionuclide bone scan involving radioactive material being injected into my bloodstream.”
The test showed Jack’s cancer had not spread outside the prostate gland, at which point he informed his children, something he says he could not imagine having to do at an age his children were still dependent on him.
Treatment
Jack’s urologist referred him onto a number of specialists, who had a combined meeting to discuss how to treat his cancer, in regard to how it was defined.
Prostate cancers are defined on a Tumor/Nodes/Metastases (TNM) scale of one to four, one being the least aggressive stage, or using a Gleason Scale, which ranks the cancer from two to 10 based on abnormalities.
Jack’s TNM score was two, raising his chances of surgery being successful.
The panel of specialists discussed which treatment option would be the most viable, from a Radical Prostatectomy (physical surgery), to external beam radiation therapy or Brachytherapy, a procedure in which small radioactive seeds are implanted directly into the prostate.
“The next meeting the panel advised me I had met the criteria for Brachytherapy, and suggested this be done as soon as possible,” said Jack.
Surgery
“The urologist on the panel decided because of my latest urine test flow, a procedure known as Cystoscopy and Bladder Neck Incision be done before the implant, to allow for a greater amount of waste and blood to be passed following the operation.”
A Cystoscopy is an Endoscopy of the urinary bladder, in which the doctor uses a cystoscope to see inside the urethra and bladder to detect any problems.
A Bladder Neck Incision was then done, essentially cutting the bladder neck, allowing for easier passage of waste and blood after the Brachytherapy.
“This operation was done five days later, but even though I was only hospitalised for two days, it set the seed implant back weeks, to allow the bladder to heal,” said Jack.
“The seed implant operation began at 8am. The radioactive seeds, each the size of a grain of rice, had arrived from the Canberra Lucas Heights depository overnight, and in my case, 78 seeds were implanted directly into the prostate gland.”
The seeds required vary from person to person, and are placed into the prostate through hollow needles. The radioactivity within each seed lasts 12 months.
Recovery
“I awoke from the operation at 4pm, and after the doctor removed the catheter, a cat scan showed all the seeds were in place,” he said.
“I experienced no pain, and the bleeding stopped after a few days, at which point I was back to my morning walks.
“For the first four days, I was required to filter my urine through a sieved funnel in case any seeds were passed, as they had to be placed in a lead lined container and returned to the hospital due to their radioactivity, but I passed none.
“I was also issued a Radiation Exposure Card, which I have to present at airports as the seeds can activate security alarms.”
As Jack now looks to the future, neither he nor the panel know the prognosis.
Regular blood tests must be maintained, with PSA levels projected to rise and fall, in what is known as “the bounce”.
After two years a trend of either up or down will become apparent, and until that time, Jack simply plans to live his life to the fullest.
“What I have learned from all of this, is that without exception, all the doctors to whom I’ve spoken agree on one thing — early intervention is the key to successful treatment,” he said.
“One of the urologists on my team remarked, ‘I’ve never seen a patient too early, but I’ve seen plenty too late’.”
* Name changed upon request to protect identity.
The chances you have of being diagnosed with prostate cancer:
A man in his 40s - one in 1,000
A man in his 50s - 12 in 1,000
A man in his 60s - 45 in 1,000
A man in his 70s - 81 in 1,000
Image
The thought of a prostate exam may be daunting for men, but early detection is vital. As one doctor said, “I’ve never seen a patient too early, but I’ve seen plenty too late.”
A national survey conducted by the Prostate Cancer Foundation of Australia in 2002, however, shows only half of all men feel well informed about the condition, as opposed to almost 80 per cent of women feeling well informed about breast cancer.
Every day, over 30 men on average will be told they have prostate cancer, and sadly, one will die every three hours.
Yet the subject of prostate cancer affects a person’s manhood, and so it is largely taboo in comparison to other cancers.
So when a man agrees to discuss the condition, it is all the more important his story is heard.
“It is often said that men are not conscious of their health,” says Jack*, of Kadina. “This is not entirely true, most of my friends know which doctor they are staying away from.
“It’s a bloke thing, a ‘gung ho, she’ll be right’ attitude that works on the premise men only visit the doctor when they are standing at death’s door. And so it was with me.”
Jack was diagnosed with prostate cancer last year, after a relative’s passing caused him to start taking PSA tests on a regular basis.
His doctor told him recently if he hadn’t taken the tests, the two would not have been speaking in 12 months.
“I considered I was fit and healthy, had never been in hospital, was not taking any medication, I hadn’t increased my weight for 40 years and played sport twice a week,” said Jack, who often bragged he had taken only three sick days off of work in 35 years.
“But then a close relative on my wife’s side died of prostate cancer after a relatively short time, and my wife exhorted me to have the blood test, to check the possibility of prostate cancer.”
Testing
“Reluctantly, I visited my doctor, who thought it was a good idea at my age, and after a digital rectal examination, I had a blood test to measure my levels of PSA.”
PSA (Prostate-Specific Antigen) is a protein produced by the prostate, low levels of which can be found in the bloodstream. However, when the normal structure of the prostate tissue is disrupted, most notably by cancer, higher levels can be detected, making it the leading test for prostate cancer.
“The results of my test showed no cause for alarm,” said Jack.
“However, I agreed to have a PSA test done on a regular basis, and did so over a period of three years with none of them sinister, so it was disconcerting to receive a call from my doctor following the latest test, requesting me to see him.”
Jack’s doctor explained his PSA levels had risen from their formerly level plateau, so much so he referred Jack to an urologist specialising in prostate disorders.
“After undergoing several tests with the urologist, I was not unduly concerned when he prescribed a month-long course of medication, which he thought would do the job.
“After all, I was feeling well, having no trouble passing urine and only requiring the toilet once a night.”
Unfortunately, after two months of treatment, Jack’s next blood test showed his PSA levels had more than doubled.
“For the first time I began to realise the fallacy of my perceived invincibility,” he said.
Following the unexpected result, Jack’s urologist arranged for a Prostate Ultrasound Biopsy procedure, which entailed an ultrasound probe being inserted into the rectum, guiding an instrument that snips out 12 sections of tissue from the prostate gland.
Diagnosis
The results became available less than a fortnight later, at which point Jack was diagnosed with cancer.
“The results were not a complete surprise,” he said.
“After the failure of the first treatment, the possibility of cancer loomed even larger, so I was half expecting the verdict, but in truth, my first reaction was surprisingly one of relief.
“Relief, to the extent it had happened to me at this stage of my life, I am in my 70s, my children have grown up and are successful in their chosen careers, and no longer dependent on me. I also have the knowledge my wife will be financially secure in future years, no matter what happens.”
If he had been diagnosed 30 years earlier, the news would have been devastating.
Jack informed his wife, knowing the condition can often put strain on a relationship, though he believes the couple have only grown closer since.
He decided not to tell his children until he knew more about the condition, including the big question — had the cancer spread?
“My urologist explained the next step would be to ascertain if the cancer has spread outside the prostate gland, and so doctors took a radionuclide bone scan involving radioactive material being injected into my bloodstream.”
The test showed Jack’s cancer had not spread outside the prostate gland, at which point he informed his children, something he says he could not imagine having to do at an age his children were still dependent on him.
Treatment
Jack’s urologist referred him onto a number of specialists, who had a combined meeting to discuss how to treat his cancer, in regard to how it was defined.
Prostate cancers are defined on a Tumor/Nodes/Metastases (TNM) scale of one to four, one being the least aggressive stage, or using a Gleason Scale, which ranks the cancer from two to 10 based on abnormalities.
Jack’s TNM score was two, raising his chances of surgery being successful.
The panel of specialists discussed which treatment option would be the most viable, from a Radical Prostatectomy (physical surgery), to external beam radiation therapy or Brachytherapy, a procedure in which small radioactive seeds are implanted directly into the prostate.
“The next meeting the panel advised me I had met the criteria for Brachytherapy, and suggested this be done as soon as possible,” said Jack.
Surgery
“The urologist on the panel decided because of my latest urine test flow, a procedure known as Cystoscopy and Bladder Neck Incision be done before the implant, to allow for a greater amount of waste and blood to be passed following the operation.”
A Cystoscopy is an Endoscopy of the urinary bladder, in which the doctor uses a cystoscope to see inside the urethra and bladder to detect any problems.
A Bladder Neck Incision was then done, essentially cutting the bladder neck, allowing for easier passage of waste and blood after the Brachytherapy.
“This operation was done five days later, but even though I was only hospitalised for two days, it set the seed implant back weeks, to allow the bladder to heal,” said Jack.
“The seed implant operation began at 8am. The radioactive seeds, each the size of a grain of rice, had arrived from the Canberra Lucas Heights depository overnight, and in my case, 78 seeds were implanted directly into the prostate gland.”
The seeds required vary from person to person, and are placed into the prostate through hollow needles. The radioactivity within each seed lasts 12 months.
Recovery
“I awoke from the operation at 4pm, and after the doctor removed the catheter, a cat scan showed all the seeds were in place,” he said.
“I experienced no pain, and the bleeding stopped after a few days, at which point I was back to my morning walks.
“For the first four days, I was required to filter my urine through a sieved funnel in case any seeds were passed, as they had to be placed in a lead lined container and returned to the hospital due to their radioactivity, but I passed none.
“I was also issued a Radiation Exposure Card, which I have to present at airports as the seeds can activate security alarms.”
As Jack now looks to the future, neither he nor the panel know the prognosis.
Regular blood tests must be maintained, with PSA levels projected to rise and fall, in what is known as “the bounce”.
After two years a trend of either up or down will become apparent, and until that time, Jack simply plans to live his life to the fullest.
“What I have learned from all of this, is that without exception, all the doctors to whom I’ve spoken agree on one thing — early intervention is the key to successful treatment,” he said.
“One of the urologists on my team remarked, ‘I’ve never seen a patient too early, but I’ve seen plenty too late’.”
* Name changed upon request to protect identity.
The chances you have of being diagnosed with prostate cancer:
A man in his 40s - one in 1,000
A man in his 50s - 12 in 1,000
A man in his 60s - 45 in 1,000
A man in his 70s - 81 in 1,000
Sex can protect against cancer and fight colds and flu
SEX is good for you. In fact, it can cure cold, prevent heart attacks, stave off cancer increase longevity and stop mood swings.
Researchers at Nottingham University in the UK have already found that mean who keep up a regular sex life into their 50s have a much lower risk in developing prostate cancer.
There was one disclaimer: that too much sexual activity, more than 20 times a month, could increase the risk.
As for regular sexual activity, doctors agree that it is as good as exercise.
“In fitness terms, it's equivalent is going for a mile-long walk or climbing up and down two flights of stairs,” cardiologist Dr Graham Jackson from Guy's & St Thomas' Hospital and president of the Sexual Dysfunction Association.
A study at Queens University in Belfast found that having sex three times a week could actually halve the risk of heart attack or stroke, the Daily Mail reports.
As for protecting the skeleton and bone density in general, Dr Sarah Brewer said: “Testosterone levels have been found to increase during and after sex.
“This may provide some protection against male osteoporosis.”
And mood - as well as the immune system - is given a boost during and after sex.
“During lovemaking and orgasm, a cocktail of endorphins (the body's natural mood-lifting opiates), neurotransmitters and hormones are released,” says Professor Nadir Farid, consultant endocrinologist and founder of the London Endocrine Clinic.
“Oxytocin, in particular, is a hormone released during and after sex that has been shown to make people more generous towards their partners and can also help induce calm and sleep.”
While the immune system is fortified is a person has sex once or twice a week thanks to the body producing higher levels of immunoglobulin A – a substance that helps fight colds and flu.
However, there are downsides to sex.
Unbridled sexual activity – particularly with a new partner without protection comes with risks – particularly sexually transmitted diseases.
Since Viraga was released 10 years ago the rate of STIs I nthe over 45s group has doubled.
"This is a generation that didn't have the open sex education that young people get today," says Professor Janice Rymer, professor of obstetrics and gynaecology at St Thomas' Hospital London.
"Today's 50-somethings probably know less about sexual protection than many of today's teenagers."
Researchers at Nottingham University in the UK have already found that mean who keep up a regular sex life into their 50s have a much lower risk in developing prostate cancer.
There was one disclaimer: that too much sexual activity, more than 20 times a month, could increase the risk.
As for regular sexual activity, doctors agree that it is as good as exercise.
“In fitness terms, it's equivalent is going for a mile-long walk or climbing up and down two flights of stairs,” cardiologist Dr Graham Jackson from Guy's & St Thomas' Hospital and president of the Sexual Dysfunction Association.
A study at Queens University in Belfast found that having sex three times a week could actually halve the risk of heart attack or stroke, the Daily Mail reports.
As for protecting the skeleton and bone density in general, Dr Sarah Brewer said: “Testosterone levels have been found to increase during and after sex.
“This may provide some protection against male osteoporosis.”
And mood - as well as the immune system - is given a boost during and after sex.
“During lovemaking and orgasm, a cocktail of endorphins (the body's natural mood-lifting opiates), neurotransmitters and hormones are released,” says Professor Nadir Farid, consultant endocrinologist and founder of the London Endocrine Clinic.
“Oxytocin, in particular, is a hormone released during and after sex that has been shown to make people more generous towards their partners and can also help induce calm and sleep.”
While the immune system is fortified is a person has sex once or twice a week thanks to the body producing higher levels of immunoglobulin A – a substance that helps fight colds and flu.
However, there are downsides to sex.
Unbridled sexual activity – particularly with a new partner without protection comes with risks – particularly sexually transmitted diseases.
Since Viraga was released 10 years ago the rate of STIs I nthe over 45s group has doubled.
"This is a generation that didn't have the open sex education that young people get today," says Professor Janice Rymer, professor of obstetrics and gynaecology at St Thomas' Hospital London.
"Today's 50-somethings probably know less about sexual protection than many of today's teenagers."
First Genome-wide Expression Analysis Yields Better Understanding Of How Leukemia Develops
study published Feb. 9, 2009, in the Proceedings of the National Academy of Sciences (PNAS), scientists performed a genome-wide expression analysis comparing highly enriched normal blood stem cells and leukemic stem cells, and identified several new pathways that have a key role in cancer development.Many scientists believe the best way to eradicate cancer is to find therapies that target cancer's stem cells, the cells thought to be responsible for maintaining the disease. Most cancer treatments today fail to attack cancer at its root, which is why the disease can recur despite aggressive therapy.
Before the development of cancer stem cell therapies can take place, however, scientists must improve our understanding of the similarities and differences between biological networks active in leukemic stem cells and their normal cell counterparts
The PNAS paper showed that by using modern microarray technology, scientists could reveal a swath of stem-cell pathways – some of which were already well known and others not previously implicated in leukemia and other cancers. In fact, researchers identified 3,005 differentially expressed genes. Among them, a ribosome and T-cell receptor signaling pathway emerged as new players in the regulation of cancer stem cells.
The direct comparison of leukemic stems cells (obtained by consent from patients) to normal blood stem cells, also provides critical insight into the differences found in malignancy that may be used to develop targeted therapy, said Michael W. Becker, M.D., an assistant professor at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Becker was a co-first author.
Before the development of cancer stem cell therapies can take place, however, scientists must improve our understanding of the similarities and differences between biological networks active in leukemic stem cells and their normal cell counterparts
The PNAS paper showed that by using modern microarray technology, scientists could reveal a swath of stem-cell pathways – some of which were already well known and others not previously implicated in leukemia and other cancers. In fact, researchers identified 3,005 differentially expressed genes. Among them, a ribosome and T-cell receptor signaling pathway emerged as new players in the regulation of cancer stem cells.
The direct comparison of leukemic stems cells (obtained by consent from patients) to normal blood stem cells, also provides critical insight into the differences found in malignancy that may be used to develop targeted therapy, said Michael W. Becker, M.D., an assistant professor at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Becker was a co-first author.
Looking for a sign of deadly prostate cancer
It may soon be possible to distinguish aggressive prostate tumors requiring immediate treatment from those that grow slowly and can be safely ignored, a problem that has vexed oncologists and patients for decades.
Looking at the complete profiles of chemicals produced by prostate tumors, researchers found that levels of sarcosine -- a simple derivative of the amino acid glycine -- are substantially higher in patients with aggressive tumors, they reported Wednesday in the journal Nature.Levels of sarcosine in the blood could be easily and cheaply identified with a simple test that could replace or complement the prostate-specific antigen, or PSA, test now widely used in prostate cancer patients. The PSA is very useful for identifying the presence of tumors, but says little about their ultimate prognosis.
Perhaps equally important as the metabolic findings, tests in laboratory dishes showed that adding sarcosine to benign tumors dramatically increased their aggressiveness, while blocking sarcosine production in aggressive tumors rendered them much less potent.
The findings may eventually lead to new ways of preventing the spread of the tumors, said Dr. Arul M. Chinnaiyan, a pathologist at the University of Michigan Medical School and senior author of the Nature paper.
Prostate cancer is the most common form of cancer in American men, with an estimated 186,320 cases diagnosed last year, according to the American Cancer Society. About 28,660 men died of the disease in 2008. And 80% of men over the age of 80 develop it.
The conundrum for clinicians is that while many of the tumors can be highly aggressive and immediately life-threatening, others are so slow-growing that they can be safely ignored, a concept known as watchful waiting. But there has not been any good way to distinguish between the two forms.
If physicians could distinguish between the forms, they could minimize unnecessary treatment of patients who are likely to die of other causes before their prostate tumors progress, Chinnaiyan said. That treatment is expensive and can lead to side effects such as impotence and incontinence.
To address the problem, the Michigan group used the new science of metabolomics, in which researchers look at all the metabolites -- chemicals produced during metabolism -- associated with an organ. They studied 1,126 metabolites in 262 samples of healthy prostate tissue, localized prostate tumors and aggressive or metastatic prostate cancer.
The researchers identified 10 chemicals whose levels increased during prostate cancer progression. The most dramatic results were with sarcosine: Levels were elevated sharply in 79% of metastatic cancer patients and less sharply in 42% of early stage patients. The chemical was not found at all in cancer-free samples.
The chemical was also readily detected in the urine of prostate cancer patients, suggesting that it may be possible to develop a simple, noninvasive test for the tumor. Their overall findings have to be validated in larger studies, Chinnaiyan said, but a urine test could be available in three to five years.
To the researchers' surprise, they also found that manipulating sarcosine levels in the test tube could alter the course of tumor growth, suggesting that the chemical plays an as-yet-unknown role in metastasis. If that proves to be the case, chemicals that block its production could serve as new cancer drugs.
The team is now taking a closer look at the other chemicals whose concentrations change with tumor progression. Using a panel of chemicals rather than just one would provide a more accurate diagnosis, Chinnaiyan said.
Analyzing metabolites is "particularly attractive" because it could provide an accurate assessment of tumors' cellular physiology and biochemical activity, wrote Dr. Cory Abate-Shen and Dr. Michael M. Shen in an editorial accompanying the paper. The Michigan team's is the first application of metabolomics to tumors, and the researchers speculate that further studies could produce diagnostic markers for a broad variety of cancers.
Looking at the complete profiles of chemicals produced by prostate tumors, researchers found that levels of sarcosine -- a simple derivative of the amino acid glycine -- are substantially higher in patients with aggressive tumors, they reported Wednesday in the journal Nature.Levels of sarcosine in the blood could be easily and cheaply identified with a simple test that could replace or complement the prostate-specific antigen, or PSA, test now widely used in prostate cancer patients. The PSA is very useful for identifying the presence of tumors, but says little about their ultimate prognosis.
Perhaps equally important as the metabolic findings, tests in laboratory dishes showed that adding sarcosine to benign tumors dramatically increased their aggressiveness, while blocking sarcosine production in aggressive tumors rendered them much less potent.
The findings may eventually lead to new ways of preventing the spread of the tumors, said Dr. Arul M. Chinnaiyan, a pathologist at the University of Michigan Medical School and senior author of the Nature paper.
Prostate cancer is the most common form of cancer in American men, with an estimated 186,320 cases diagnosed last year, according to the American Cancer Society. About 28,660 men died of the disease in 2008. And 80% of men over the age of 80 develop it.
The conundrum for clinicians is that while many of the tumors can be highly aggressive and immediately life-threatening, others are so slow-growing that they can be safely ignored, a concept known as watchful waiting. But there has not been any good way to distinguish between the two forms.
If physicians could distinguish between the forms, they could minimize unnecessary treatment of patients who are likely to die of other causes before their prostate tumors progress, Chinnaiyan said. That treatment is expensive and can lead to side effects such as impotence and incontinence.
To address the problem, the Michigan group used the new science of metabolomics, in which researchers look at all the metabolites -- chemicals produced during metabolism -- associated with an organ. They studied 1,126 metabolites in 262 samples of healthy prostate tissue, localized prostate tumors and aggressive or metastatic prostate cancer.
The researchers identified 10 chemicals whose levels increased during prostate cancer progression. The most dramatic results were with sarcosine: Levels were elevated sharply in 79% of metastatic cancer patients and less sharply in 42% of early stage patients. The chemical was not found at all in cancer-free samples.
The chemical was also readily detected in the urine of prostate cancer patients, suggesting that it may be possible to develop a simple, noninvasive test for the tumor. Their overall findings have to be validated in larger studies, Chinnaiyan said, but a urine test could be available in three to five years.
To the researchers' surprise, they also found that manipulating sarcosine levels in the test tube could alter the course of tumor growth, suggesting that the chemical plays an as-yet-unknown role in metastasis. If that proves to be the case, chemicals that block its production could serve as new cancer drugs.
The team is now taking a closer look at the other chemicals whose concentrations change with tumor progression. Using a panel of chemicals rather than just one would provide a more accurate diagnosis, Chinnaiyan said.
Analyzing metabolites is "particularly attractive" because it could provide an accurate assessment of tumors' cellular physiology and biochemical activity, wrote Dr. Cory Abate-Shen and Dr. Michael M. Shen in an editorial accompanying the paper. The Michigan team's is the first application of metabolomics to tumors, and the researchers speculate that further studies could produce diagnostic markers for a broad variety of cancers.
Engineers create intelligent molecules that seek-and-destroy diseased cells
Current treatments for diseases like cancer typically destroy nasty malignant cells, while also hammering the healthy ones. Using new advances in synthetic biology, researchers are designing molecules intelligent enough to recognize diseased cells, leaving the healthy cells alone.
"We basically design molecules that actually go into the cell and do an analysis of the cellular state before delivering the therapeutic punch," said Christina Smolke, assistant professor of bioengineering who joined Stanford University in January.
"When you look at a diseased cell (e.g. a cancer cell) and compare it to a normal cell, you can identify biomarkers—changes in the abundance of proteins or other biomolecule levels—in the diseased cell," Smolke said. Her research team has designed molecules that trigger cell death only in the presence of such markers. "A lot of the trick with developing effective therapeutics is the ability to target and localize the therapeutic effect, while minimizing nonspecific side effects," she said.
Smolke will present the latest applications of her lab's work at the American Association for the Advancement of Science (AAAS) meeting in Chicago on Friday, Feb. 13.
These designer molecules are created through RNA-based technologies that Smolke's lab developed at the California Institute of Technology. A recent example of these systems, developed with postdoctoral researcher Maung Nyan Win (who joined Smolke in her move to Stanford), was described in a paper published in the Oct. 17, 2008, issue of Science.
"We do our design on the computer and pick out sequences that are predicted to behave the way we like," Smolke said. When researchers generate these sequences inside the operating system of a cell, they reprogram the cell and change its function. "Building these molecules out of RNA gives us a very programmable and therefore powerful design substrate," she said.
Smolke's team focuses on well-researched model systems in breast, prostate and brain cancers, including immunotherapy applications based on reprogramming human immune response to different diseases. The researchers work directly with clinicians at the City of Hope Cancer Center (a National Cancer Institute designated Comprehensive Cancer Center in Duarte, Calif.) that have ongoing immunotherapy trials for treating glioma, a severe type of brain cancer.
"Our goal is to make more effective therapies by taking advantage of the natural capabilities of our immune system and introducing slight modifications in cases where it is not doing what we would like it to do," Smolke said. She hopes to translate her technologies into intelligent cellular therapeutics for glioma patients in the next five years. "That's a very optimistic view," she said. "But so far things have been moving quickly."
The broader implications for using intelligent molecules in immunotherapy and gene therapy seem limitless. Researchers and doctors can use this approach by targeting a specific cellular function or behavior they want to control in a particular disease. Then they can identify signals indicative of viral infection, host immune response, or drugs the clinician is administering and engineer the molecules to change the cell function in response to those signals.
"In a lot of therapies, you have nonspecific side effects or you're balancing the desired effect of the therapy on diseased cells or infection with its undesired effects on the entire host," Smolke said. Current chemotherapy treatments for cancer, and even many gene therapies, have drastic and debilitating consequences for patients. The designer molecules provide a whole new targeting accuracy that should mitigate these side effects.
"This is all very front-end work," Smolke said. "We've just started to move these foundational technologies into these sorts of downstream medical applications, and so there is a lot to learn … which makes it that much more exciting."
Smolke's work is funded by the National Institutes of Health, National Science Foundation, Department of Defense and the Beckman Foundation.
At the AAAS meeting, Smolke will present her work alongside Drew Endy, assistant professor of bioengineering at Stanford University, as part of the Synthetic Life symposium.
Endy, who joined Stanford last fall, will discuss the societal and safety implications of molecular synthesis technology. This includes the consequences of researchers moving toward building registries for standard biological parts and the education aspects of iGEM—an international forum where student teams compete to design and assemble engineered machines using advanced genetic components and technologies—which has led to the training of a new generation of scientists and bioengineers. Stanford will be hosting its first iGEM team this year. Endy will also discuss his efforts, along with colleagues, to start fabrication facilities focused on churning out libraries of open-access biological parts and the resulting implications for biological engineering.
"We basically design molecules that actually go into the cell and do an analysis of the cellular state before delivering the therapeutic punch," said Christina Smolke, assistant professor of bioengineering who joined Stanford University in January.
"When you look at a diseased cell (e.g. a cancer cell) and compare it to a normal cell, you can identify biomarkers—changes in the abundance of proteins or other biomolecule levels—in the diseased cell," Smolke said. Her research team has designed molecules that trigger cell death only in the presence of such markers. "A lot of the trick with developing effective therapeutics is the ability to target and localize the therapeutic effect, while minimizing nonspecific side effects," she said.
Smolke will present the latest applications of her lab's work at the American Association for the Advancement of Science (AAAS) meeting in Chicago on Friday, Feb. 13.
These designer molecules are created through RNA-based technologies that Smolke's lab developed at the California Institute of Technology. A recent example of these systems, developed with postdoctoral researcher Maung Nyan Win (who joined Smolke in her move to Stanford), was described in a paper published in the Oct. 17, 2008, issue of Science.
"We do our design on the computer and pick out sequences that are predicted to behave the way we like," Smolke said. When researchers generate these sequences inside the operating system of a cell, they reprogram the cell and change its function. "Building these molecules out of RNA gives us a very programmable and therefore powerful design substrate," she said.
Smolke's team focuses on well-researched model systems in breast, prostate and brain cancers, including immunotherapy applications based on reprogramming human immune response to different diseases. The researchers work directly with clinicians at the City of Hope Cancer Center (a National Cancer Institute designated Comprehensive Cancer Center in Duarte, Calif.) that have ongoing immunotherapy trials for treating glioma, a severe type of brain cancer.
"Our goal is to make more effective therapies by taking advantage of the natural capabilities of our immune system and introducing slight modifications in cases where it is not doing what we would like it to do," Smolke said. She hopes to translate her technologies into intelligent cellular therapeutics for glioma patients in the next five years. "That's a very optimistic view," she said. "But so far things have been moving quickly."
The broader implications for using intelligent molecules in immunotherapy and gene therapy seem limitless. Researchers and doctors can use this approach by targeting a specific cellular function or behavior they want to control in a particular disease. Then they can identify signals indicative of viral infection, host immune response, or drugs the clinician is administering and engineer the molecules to change the cell function in response to those signals.
"In a lot of therapies, you have nonspecific side effects or you're balancing the desired effect of the therapy on diseased cells or infection with its undesired effects on the entire host," Smolke said. Current chemotherapy treatments for cancer, and even many gene therapies, have drastic and debilitating consequences for patients. The designer molecules provide a whole new targeting accuracy that should mitigate these side effects.
"This is all very front-end work," Smolke said. "We've just started to move these foundational technologies into these sorts of downstream medical applications, and so there is a lot to learn … which makes it that much more exciting."
Smolke's work is funded by the National Institutes of Health, National Science Foundation, Department of Defense and the Beckman Foundation.
At the AAAS meeting, Smolke will present her work alongside Drew Endy, assistant professor of bioengineering at Stanford University, as part of the Synthetic Life symposium.
Endy, who joined Stanford last fall, will discuss the societal and safety implications of molecular synthesis technology. This includes the consequences of researchers moving toward building registries for standard biological parts and the education aspects of iGEM—an international forum where student teams compete to design and assemble engineered machines using advanced genetic components and technologies—which has led to the training of a new generation of scientists and bioengineers. Stanford will be hosting its first iGEM team this year. Endy will also discuss his efforts, along with colleagues, to start fabrication facilities focused on churning out libraries of open-access biological parts and the resulting implications for biological engineering.
New cancer treatment gives quick, precise doses
Each weekday morning, Don Libby, 75, leaves his boat docked on the Oakland shores and drives to Berkeley's Alta Bates Summit Medical Center for a quick shot of radiation."The valet doesn't even park my car anymore," Libby said one recent morning after his daily stop, which lasted about eight minutes. "He just leaves it at the curb. He knows I'm not in there long."
Libby is one of the first in the Bay Area to undergo a new kind of quick but frequent radiation treatment for prostate cancer that is reportedly leaving patients with fewer side effects than they experience with traditional radiation treatments.
Instead of zapping Libby's midsection with a few beams of high-dosage radiation every few days to eradicate his walnut-size tumor, software called RapidArc helps target it and, while spinning 360 degrees around Libby's body, uses several rays to precisely pinpoint the cancerous cells while limiting exposure to the surrounding healthy tissue and organs.
Dr. Patrick Swift, the director of radiation oncology services at the hospital's Comprehensive Cancer Center, said that for years physicians and physicists have been trying to improve the accuracy and dosage amounts of radiation treatment, hoping to limit the side effects of nausea, rectal bleeding and damage to the bladder and rectum experienced by some patients. While other companies make software that can shorten radiation treatment for prostate cancer to just a few days, Palo Alto's Varian Medical Systems, the maker of RapidArc, extends the overall length of treatment - Libby will go every weekday from late January until mid-March - but limits the time spent on the doctor's table from about 40 minutes per session to less than 10.
According to Varian, the treatment costs about $30,000 and is covered by Medicare in California.
Swift added that the time saved with each patient also has the potential to save hospital costs in the long run because he's able to see more patients in a workday, from about 30 patients before to as many as 45.
"We want to get to the point one day where we can treat it (with such precision) in under a week," Swift said. (Swift said he does not receive any compensation from Varian Medical Systems.)
After Libby was diagnosed late last year, the former boat racer said he considered more aggressive dosages that would have treated his cancer within a week or two. But he decided on the smaller, daily dose spread over time to diminish the effect on the quality of his daily life. He said he preferred to view his cancer treatment as a quick daily errand, more like a stop to pick up coffee.
"By 10 a.m., I'm off and doing the things I need to do for the rest of my day," Libby said. "I don't even feel like I'm sick."
That's the point, said Swift. "If we don't have a cure, my second priority as a physician is to minimize the risk of injury during treatment and improve the safety of the radiation delivery. My patients are reporting they're comfortable."
Though RapidArc was cleared for use by the FDA in January 2008, there are no published peer-reviewed clinical studies that measure the outcomes for patients with prostate cancer. But there are studies that show that RapidArc delivers the radiation treatment faster than previous delivery systems. And because patients are on the table for a shorter period, there's less chance that the prostate will move and less chance that the radiation will strike surrounding healthy tissue.
Dr. Jonathan Simons, an oncologist and president of the Prostate Cancer Foundation in Santa Monica, said that although the published data on RapidArc is limited but promising, he viewed the technology as an "incremental improvement" on treating prostate cancer.
Simons added that reduced time in the hospital alone could have a positive emotional impact on patients, but has not yet been studied.
"The more you're reminded you're sick, maybe the more sick you feel," Simons said. "There's an emotional side effect of not being in a hospital all day."
Dr. Kamal Patel, a radiation oncologist at the Cancer Treatment Centers of America in Zion, Ill., said the RapidArc treatment is part of a broader push in radiation treatment called "dose painting" - where highly advanced software allows the beams to precisely target cancer cells, even while accounting for the slightest movement of the prostate (up to 2 millimeters) while the patient is lying on the table.
"We've learned in the last 10, 20 years that we're able to survive cancer," Patel said. "So now the quality of life during and after treatment needs to improve. Reducing the toxicity to the surrounding tissues and organs allows us to do that."
The advances in technology also have implications for treating breast, neck and brain cancers, Swift said. Delicate areas where doctors once resisted aiming radiation for fear of damaging nearby organs are becoming new target zones.
Libby said he was happy to be part of a new treatment, even if it meant rescheduling his daily regimen.
"Considering the alternative, going in every day for a few minutes isn't bad at all."
Facts about prostate cancer
In 2008, 24,380 new cases of prostate cancer were diagnosed in California, according to the National Prostate Cancer Coalition.
-- The disease is the most common cancer among American men.
-- One in 6 American men is at lifetime risk of contracting prostate cancer.
-- An estimated 28,660 American men died from the disease in 2008, up 3 percent from 2007.
-- More than 90 percent of prostate cancer cases are found while the cancer is still either local or regional, and nearly 100 percent of these men are still alive five years after being diagnosed.
-- According to the Mayo Clinic, men can "help avoid prostate cancer by exercising and eating a low-fat diet rich in fruits, vegetables and fish. Maintaining a healthy weight can also help reduce your risk."
-- It is recommended that men older than 50 be screened for prostate cancer every two years, with either a digital rectal examination or an ultrasound. Experts also suggest that men older than 50 get a prostate-specific antigen test every two years. If the results indicate that there might be a problem, doctors may recommend a biopsy, which is considered the definitive test for prostate cancer.
Libby is one of the first in the Bay Area to undergo a new kind of quick but frequent radiation treatment for prostate cancer that is reportedly leaving patients with fewer side effects than they experience with traditional radiation treatments.
Instead of zapping Libby's midsection with a few beams of high-dosage radiation every few days to eradicate his walnut-size tumor, software called RapidArc helps target it and, while spinning 360 degrees around Libby's body, uses several rays to precisely pinpoint the cancerous cells while limiting exposure to the surrounding healthy tissue and organs.
Dr. Patrick Swift, the director of radiation oncology services at the hospital's Comprehensive Cancer Center, said that for years physicians and physicists have been trying to improve the accuracy and dosage amounts of radiation treatment, hoping to limit the side effects of nausea, rectal bleeding and damage to the bladder and rectum experienced by some patients. While other companies make software that can shorten radiation treatment for prostate cancer to just a few days, Palo Alto's Varian Medical Systems, the maker of RapidArc, extends the overall length of treatment - Libby will go every weekday from late January until mid-March - but limits the time spent on the doctor's table from about 40 minutes per session to less than 10.
According to Varian, the treatment costs about $30,000 and is covered by Medicare in California.
Swift added that the time saved with each patient also has the potential to save hospital costs in the long run because he's able to see more patients in a workday, from about 30 patients before to as many as 45.
"We want to get to the point one day where we can treat it (with such precision) in under a week," Swift said. (Swift said he does not receive any compensation from Varian Medical Systems.)
After Libby was diagnosed late last year, the former boat racer said he considered more aggressive dosages that would have treated his cancer within a week or two. But he decided on the smaller, daily dose spread over time to diminish the effect on the quality of his daily life. He said he preferred to view his cancer treatment as a quick daily errand, more like a stop to pick up coffee.
"By 10 a.m., I'm off and doing the things I need to do for the rest of my day," Libby said. "I don't even feel like I'm sick."
That's the point, said Swift. "If we don't have a cure, my second priority as a physician is to minimize the risk of injury during treatment and improve the safety of the radiation delivery. My patients are reporting they're comfortable."
Though RapidArc was cleared for use by the FDA in January 2008, there are no published peer-reviewed clinical studies that measure the outcomes for patients with prostate cancer. But there are studies that show that RapidArc delivers the radiation treatment faster than previous delivery systems. And because patients are on the table for a shorter period, there's less chance that the prostate will move and less chance that the radiation will strike surrounding healthy tissue.
Dr. Jonathan Simons, an oncologist and president of the Prostate Cancer Foundation in Santa Monica, said that although the published data on RapidArc is limited but promising, he viewed the technology as an "incremental improvement" on treating prostate cancer.
Simons added that reduced time in the hospital alone could have a positive emotional impact on patients, but has not yet been studied.
"The more you're reminded you're sick, maybe the more sick you feel," Simons said. "There's an emotional side effect of not being in a hospital all day."
Dr. Kamal Patel, a radiation oncologist at the Cancer Treatment Centers of America in Zion, Ill., said the RapidArc treatment is part of a broader push in radiation treatment called "dose painting" - where highly advanced software allows the beams to precisely target cancer cells, even while accounting for the slightest movement of the prostate (up to 2 millimeters) while the patient is lying on the table.
"We've learned in the last 10, 20 years that we're able to survive cancer," Patel said. "So now the quality of life during and after treatment needs to improve. Reducing the toxicity to the surrounding tissues and organs allows us to do that."
The advances in technology also have implications for treating breast, neck and brain cancers, Swift said. Delicate areas where doctors once resisted aiming radiation for fear of damaging nearby organs are becoming new target zones.
Libby said he was happy to be part of a new treatment, even if it meant rescheduling his daily regimen.
"Considering the alternative, going in every day for a few minutes isn't bad at all."
Facts about prostate cancer
In 2008, 24,380 new cases of prostate cancer were diagnosed in California, according to the National Prostate Cancer Coalition.
-- The disease is the most common cancer among American men.
-- One in 6 American men is at lifetime risk of contracting prostate cancer.
-- An estimated 28,660 American men died from the disease in 2008, up 3 percent from 2007.
-- More than 90 percent of prostate cancer cases are found while the cancer is still either local or regional, and nearly 100 percent of these men are still alive five years after being diagnosed.
-- According to the Mayo Clinic, men can "help avoid prostate cancer by exercising and eating a low-fat diet rich in fruits, vegetables and fish. Maintaining a healthy weight can also help reduce your risk."
-- It is recommended that men older than 50 be screened for prostate cancer every two years, with either a digital rectal examination or an ultrasound. Experts also suggest that men older than 50 get a prostate-specific antigen test every two years. If the results indicate that there might be a problem, doctors may recommend a biopsy, which is considered the definitive test for prostate cancer.
Gene Linked To Aggressive Progression Of Liver Cancer Identified
Commonwealth University researchers have identified a gene that plays a key role in regulating liver cancer progression, a discovery that could one day lead to new targeted therapeutic strategies to fight the highly aggressive disease.Hepatocellular carcinoma, HCC, or liver cancer, is the fifth most common cancer and the third leading cause of cancer deaths in the world. Treatment options for HCC include chemotherapy, chemoembolization, ablation and proton-beam therapy. Liver transplantation offers the best chance for a cure in patients with small tumors and significant associated liver disease.
In the study, published online in the February issue of the Journal of Clinical Investigation, researchers reported that the astrocyte elevated gene-1, AEG-1, plays a key role in regulating HCC in series of cellular models. By examining human liver tumor cells of patients with HCC, the team found that the expression of AEG-1 gradually increases as the tumor becomes more and more aggressive. Using microarray technology, they analyzed cDNA from the tumor cells and determined that AEG-1 modulates expression of genes relevant to the progression of HCC, including invasion, metastasis, resistance to chemotherapy, the formation of new blood vessels, and senescence. cDNAs are complementary DNAs that are generated from mRNAs to analyze gene expression profiles.
“AEG-1 also activates multiple intracellular signaling pathways that are known to be involved in HCC progression. So, strategies to inhibit AEG-1 that could lead to the shutdown of these pathways, either by small molecules or by siRNAs, might be an important therapeutic modality for HCC patients,” said principal investigator Devanand Sarkar, Ph.D., MBBS, assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine, and Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center.
siRNAs are small inhibitory RNAs that can specifically inhibit targeted mRNA and protein production. siRNAs may be used in the future for targeted inhibition of AEG-1 in patients, Sarkar said.
According to Sarkar, the team found a significantly higher expression of AEG-1 protein in more than 90 percent of tumor samples from HCC patients compared to normal human liver cells.
“The expression of AEG-1 protein gradually increases as the disease becomes more aggressive. No other genes have been shown to be upregulated in such a high percentage of HCC patients,” said Sarkar.
Further, he said that findings from a separate pool of 132 HCC patients revealed significant overexpression of AEG-1 mRNA compared to normal liver. In a subset of these patients, the team detected an increased number of copies of the AEG-1 gene.
“We observed an increase in AEG-1 DNA, mRNA and protein in HCC patients, which indicates a significant involvement of AEG-1 in HCC progression. Stable overexpression of AEG-1 converts non-tumorigenic human HCC cells into highly aggressive vascular tumors and inhibition of AEG-1 abrogates tumorigenesis by aggressive HCC cells,” he said.
Previous studies suggest that the expression of AEG-1 is very low in normal cells or tissues such as breast, prostate and brain. However, in cancers of the same organs, expression of AEG-1 is significantly increased.
The team will conduct studies to further understand the molecular mechanisms by which AEG-1 works and identify other proteins with which it interacts.
This work was supported by grants from The Goldhirsh Foundation, the National Institutes of Health, the Spanish National Health Institute, and the Samuel Waxman Cancer Research Foundation.
Sarkar worked with a team that included VCU School of Medicine researchers, Byoung Kwon Yoo, Ph.D., Zao-zhong Su, Ph.D., Nitai D. Mukhopadhyay, Ph.D., Alan Scott Mills, M.D., Robert A. Fisher, M.D., and Paul B. Fisher, M.Ph., Ph.D.; Luni Emdad Ph.D., Augusto Villanueva, Ph.D., Samuel Waxman, M.D., Josep M. Llovet, M.D., all from the Mount Sinai School of Medicine in New York; and Derek Y Chiang, Ph.D., with the Broad Institute of Harvard and MIT. Sarkar and Paul B. Fisher are the founding members of the VCU Institute of Molecular Medicine, which also provided support in conducting these studies.
In the study, published online in the February issue of the Journal of Clinical Investigation, researchers reported that the astrocyte elevated gene-1, AEG-1, plays a key role in regulating HCC in series of cellular models. By examining human liver tumor cells of patients with HCC, the team found that the expression of AEG-1 gradually increases as the tumor becomes more and more aggressive. Using microarray technology, they analyzed cDNA from the tumor cells and determined that AEG-1 modulates expression of genes relevant to the progression of HCC, including invasion, metastasis, resistance to chemotherapy, the formation of new blood vessels, and senescence. cDNAs are complementary DNAs that are generated from mRNAs to analyze gene expression profiles.
“AEG-1 also activates multiple intracellular signaling pathways that are known to be involved in HCC progression. So, strategies to inhibit AEG-1 that could lead to the shutdown of these pathways, either by small molecules or by siRNAs, might be an important therapeutic modality for HCC patients,” said principal investigator Devanand Sarkar, Ph.D., MBBS, assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine, and Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center.
siRNAs are small inhibitory RNAs that can specifically inhibit targeted mRNA and protein production. siRNAs may be used in the future for targeted inhibition of AEG-1 in patients, Sarkar said.
According to Sarkar, the team found a significantly higher expression of AEG-1 protein in more than 90 percent of tumor samples from HCC patients compared to normal human liver cells.
“The expression of AEG-1 protein gradually increases as the disease becomes more aggressive. No other genes have been shown to be upregulated in such a high percentage of HCC patients,” said Sarkar.
Further, he said that findings from a separate pool of 132 HCC patients revealed significant overexpression of AEG-1 mRNA compared to normal liver. In a subset of these patients, the team detected an increased number of copies of the AEG-1 gene.
“We observed an increase in AEG-1 DNA, mRNA and protein in HCC patients, which indicates a significant involvement of AEG-1 in HCC progression. Stable overexpression of AEG-1 converts non-tumorigenic human HCC cells into highly aggressive vascular tumors and inhibition of AEG-1 abrogates tumorigenesis by aggressive HCC cells,” he said.
Previous studies suggest that the expression of AEG-1 is very low in normal cells or tissues such as breast, prostate and brain. However, in cancers of the same organs, expression of AEG-1 is significantly increased.
The team will conduct studies to further understand the molecular mechanisms by which AEG-1 works and identify other proteins with which it interacts.
This work was supported by grants from The Goldhirsh Foundation, the National Institutes of Health, the Spanish National Health Institute, and the Samuel Waxman Cancer Research Foundation.
Sarkar worked with a team that included VCU School of Medicine researchers, Byoung Kwon Yoo, Ph.D., Zao-zhong Su, Ph.D., Nitai D. Mukhopadhyay, Ph.D., Alan Scott Mills, M.D., Robert A. Fisher, M.D., and Paul B. Fisher, M.Ph., Ph.D.; Luni Emdad Ph.D., Augusto Villanueva, Ph.D., Samuel Waxman, M.D., Josep M. Llovet, M.D., all from the Mount Sinai School of Medicine in New York; and Derek Y Chiang, Ph.D., with the Broad Institute of Harvard and MIT. Sarkar and Paul B. Fisher are the founding members of the VCU Institute of Molecular Medicine, which also provided support in conducting these studies.
Innovative Method To Starve Tumors
The development of cancerous tumours is highly dependent on the nutrients the tumours receive through the blood. The team of Dr. Janusz Rak, of the Research Institute of the McGill University Health Centre (MUHC) at the Montreal Children's Hospital, including Dr. Khalid Al-Nedawi and Brian Meehan, has just discovered a new mechanism that tumours use to stimulate the growth of the blood vessels that feed them. The researchers have also proposed a new way to control this process, which may translate into future therapies.These findings were published the week of February 9 in the Proceedings of the National Academy of Sciences (PNAS).
An innovative method…
According to the researchers, tumour cells can release "bubbles" called microvesicles, which allow the tumours to communicate with the endothelial cells of blood vessels and stimulate changes in their behaviour. The microvesicles are armed with specific cancer proteins as they leave the tumour. When they are taken up by endothelial cells, the specific cancer proteins that they carry can trigger mechanisms that promote the abnormal formation of new blood vessels. The vessels then grow towards the tumour and supply it with the nutrients it requires to grow.
"We had already demonstrated the existence of these vesicles as well as their importance in the communication process between cancer cells and their environment. But this new discovery is much more targeted and represents a new direction in terms of therapy," said a delighted Dr. Rak.
… to starve tumors
In fact, a family of molecules derived from annexin V seems to effectively fight this process and ultimately may help "starve" the tumour. "The molecule we used is effective both in vitro and in vivo. It prevents the formation of new blood vessels in mice with cancer and therefore strongly inhibits tumour growth," explained Dr. Rak.
Called Diannexin, this molecule acts to block the in vitro fusion of vesicles and endothelial cells. In mice with cancer, Diannexin works to slow blood vessel growth towards the tumour, resulting in anti-cancer effects. This finding is particularly important considering the treatment was applied in isolation without additional chemotherapy. If combined with other agents, this new way of treating cancer may be even more potent.
Diannexin is currently being developed as an antithrombotic medication. It would therefore be possible to use it safely for different types of pathologies.
This project was funded through a grant from the Canadian Cancer Society Research Institute and the Fonds de la recherche en santé du Québec.
This project was carried out in partnership with Dr. R.S. Kerbel of the Sunnybrook Health Sciences Centre, University of Toronto, and Dr. A.C. Allison of Alavita Pharmaceuticals Inc.
An innovative method…
According to the researchers, tumour cells can release "bubbles" called microvesicles, which allow the tumours to communicate with the endothelial cells of blood vessels and stimulate changes in their behaviour. The microvesicles are armed with specific cancer proteins as they leave the tumour. When they are taken up by endothelial cells, the specific cancer proteins that they carry can trigger mechanisms that promote the abnormal formation of new blood vessels. The vessels then grow towards the tumour and supply it with the nutrients it requires to grow.
"We had already demonstrated the existence of these vesicles as well as their importance in the communication process between cancer cells and their environment. But this new discovery is much more targeted and represents a new direction in terms of therapy," said a delighted Dr. Rak.
… to starve tumors
In fact, a family of molecules derived from annexin V seems to effectively fight this process and ultimately may help "starve" the tumour. "The molecule we used is effective both in vitro and in vivo. It prevents the formation of new blood vessels in mice with cancer and therefore strongly inhibits tumour growth," explained Dr. Rak.
Called Diannexin, this molecule acts to block the in vitro fusion of vesicles and endothelial cells. In mice with cancer, Diannexin works to slow blood vessel growth towards the tumour, resulting in anti-cancer effects. This finding is particularly important considering the treatment was applied in isolation without additional chemotherapy. If combined with other agents, this new way of treating cancer may be even more potent.
Diannexin is currently being developed as an antithrombotic medication. It would therefore be possible to use it safely for different types of pathologies.
This project was funded through a grant from the Canadian Cancer Society Research Institute and the Fonds de la recherche en santé du Québec.
This project was carried out in partnership with Dr. R.S. Kerbel of the Sunnybrook Health Sciences Centre, University of Toronto, and Dr. A.C. Allison of Alavita Pharmaceuticals Inc.
Patient calls for a screening test for prostate cancer for all men in Wales
A PROSTATE cancer patient is hoping to offer all men over 50 in Wales a PSA test in a bid to detect the disease.
Reg Williams, who founded the South Wales-based Prostate Screening Trust, is exploring the possibility of using a mobile PSA testing machine which can give a result in just 20 minutes.
He hopes to be able to offer the test throughout Wales in the absence of a national screening programme.
The new technology uses a finger-prick blood sample to test levels of the prostate specific antigen. Raised levels can be an indication of prostate cancer and other benign conditions.
Mr Williams, 59, a council job advisor, said: “A lot of men, particularly in parts of the valleys, want to have a PSA test but are told to come back when they have symptoms.
“But that can be too late. I’d never had any symptoms, but I have an aggressive prostate cancer.”
A PSA test checks the level of prostate specific antigen – a natural chemical produced by the prostate gland – in the blood. Any condition that irritates or damages the prostate gland can cause leakage of PSA into the blood.
The test is the only prostate cancer test available, but as it is unable to distinguish between cancer and other prostate conditions it is not routinely available. It is also unable to distinguish between the less aggressive and the life-threatening forms of the disease.
Two large studies are currently assessing the viability of using the PSA test to screen for cancer.
Mr Williams, who lives near Chepstow, was diagnosed with an aggressive form of prostate cancer in 2005 and was given five years to live.
The cancer, which has spread outside his prostate, is currently under control.
Mr Williams hopes to be able to offer men over 50 a PSA test, using this new technology, providing they fit certain criteria.
And he says if the PSA test is positive it will give men the option to seek medical help for any prostate problems.
Mr Williams said: “So many men I have spoken to about the disease have been picked up because they were able to have a PSA test after asking for it or because they have private medical care.
“Men are not being routinely tested in the way that women are for cancer. Men should be given the option to have the test.”
The Prostate Screening Trust hopes to unveil the technology in a presentation to politicians at the Senedd next month.
Anna Jewell, head of policy and campaigns at the Prostate Cancer Charity, said: “The Prostate Cancer Charity understands the strong views held by many people that a PSA-based screening programme should be introduced.
“The charity does not currently support a PSA-based national screening programme for prostate cancer because the test is not a reliable screening tool and, as yet, there is no scientific evidence that such a programme would save lives.
“The introduction of a national screening programme for prostate cancer using the PSA test, at this stage, would suggest to men that screening for prostate cancer would be of benefit to the majority of men in the UK and that it would save lives.
“This would not necessarily be the case, as a screening programme for prostate cancer using the PSA test could cause more harm than good to some men.
“This is because some healthy men would be diagnosed with a cancer, through the screening programme, and go on to receive treatment – and experience the associated side effects – for a harmless cancer that would otherwise have gone undetected during their lifetime.
“Furthermore, the evidence currently available does not clearly show that a screening programme, using the PSA test, would save lives.”
Reg Williams, who founded the South Wales-based Prostate Screening Trust, is exploring the possibility of using a mobile PSA testing machine which can give a result in just 20 minutes.
He hopes to be able to offer the test throughout Wales in the absence of a national screening programme.
The new technology uses a finger-prick blood sample to test levels of the prostate specific antigen. Raised levels can be an indication of prostate cancer and other benign conditions.
Mr Williams, 59, a council job advisor, said: “A lot of men, particularly in parts of the valleys, want to have a PSA test but are told to come back when they have symptoms.
“But that can be too late. I’d never had any symptoms, but I have an aggressive prostate cancer.”
A PSA test checks the level of prostate specific antigen – a natural chemical produced by the prostate gland – in the blood. Any condition that irritates or damages the prostate gland can cause leakage of PSA into the blood.
The test is the only prostate cancer test available, but as it is unable to distinguish between cancer and other prostate conditions it is not routinely available. It is also unable to distinguish between the less aggressive and the life-threatening forms of the disease.
Two large studies are currently assessing the viability of using the PSA test to screen for cancer.
Mr Williams, who lives near Chepstow, was diagnosed with an aggressive form of prostate cancer in 2005 and was given five years to live.
The cancer, which has spread outside his prostate, is currently under control.
Mr Williams hopes to be able to offer men over 50 a PSA test, using this new technology, providing they fit certain criteria.
And he says if the PSA test is positive it will give men the option to seek medical help for any prostate problems.
Mr Williams said: “So many men I have spoken to about the disease have been picked up because they were able to have a PSA test after asking for it or because they have private medical care.
“Men are not being routinely tested in the way that women are for cancer. Men should be given the option to have the test.”
The Prostate Screening Trust hopes to unveil the technology in a presentation to politicians at the Senedd next month.
Anna Jewell, head of policy and campaigns at the Prostate Cancer Charity, said: “The Prostate Cancer Charity understands the strong views held by many people that a PSA-based screening programme should be introduced.
“The charity does not currently support a PSA-based national screening programme for prostate cancer because the test is not a reliable screening tool and, as yet, there is no scientific evidence that such a programme would save lives.
“The introduction of a national screening programme for prostate cancer using the PSA test, at this stage, would suggest to men that screening for prostate cancer would be of benefit to the majority of men in the UK and that it would save lives.
“This would not necessarily be the case, as a screening programme for prostate cancer using the PSA test could cause more harm than good to some men.
“This is because some healthy men would be diagnosed with a cancer, through the screening programme, and go on to receive treatment – and experience the associated side effects – for a harmless cancer that would otherwise have gone undetected during their lifetime.
“Furthermore, the evidence currently available does not clearly show that a screening programme, using the PSA test, would save lives.”
Depression risk increased among cancer patients
NEW YORK (Reuters Health) - People who have been diagnosed with cancer are at greater risk of being hospitalized with depression, new research from Denmark shows.
While the risk was greatest in the year following a person's diagnosis, the likelihood of being hospitalized for depression among survivors of certain types of cancer remained high for several years, Dr. Susanne O. Dalton of the Danish Cancer Society in Copenhagen and her colleagues found.
There's some evidence that cancer patients are more likely to be depressed than people in the general population, the researchers note. Estimates of depression prevalence among these patients range from 0 percent to 38 percent.
Despite this variability, which is likely due to differences in how depression is diagnosed and the type of cancer patients have, as well as how advanced their disease is and whether or not they are hospitalized, "depression has typically been underdiagnosed and undertreated in the oncology setting," Dalton and her team write in the Journal of Clinical Oncology.
To better understand the short- and long-term depression risk of cancer patients, the researchers looked at 608,591 Danish men and women who were diagnosed with cancer and were followed for up to 31 years. The average follow-up after diagnosis was 4.2 years.
Within the first year of being diagnosed with cancer, the researchers found, men and women with cancer were about twice as likely to be hospitalized for depression as were men and women in the general population. Over the next decade, the relative risk of hospitalization for depression was increased 21 percent for men and 5 percent for women.
Depression risk varied by cancer type. For both sexes, the risk remained high for up to 10 years after being diagnosed with a hormone-related cancer, such as breast cancer or prostate cancer. The risk also stayed high for a decade among women with smoking-related cancers and men with virus- and immune-related cancers.
In the first year after diagnosis, increased risk ranged from 1.16-fold for women with colorectal cancer to 3.08-fold for men with brain cancer.
Given that more and more people are living longer after being diagnosed with cancer, the researchers note, taking care of cancer survivors with depression will be increasingly important. "Early recognition and effective treatment of depression, both in the cancer setting and beyond, would have the potential to prevent admission for depression and thus reduce patient suffering and enhance the quality of life for cancer survivors," they conclude.
SOURCE: Journal of Clinical Oncology, online February 17, 2009.
Reuters Health
Copyright © 2009 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
While the risk was greatest in the year following a person's diagnosis, the likelihood of being hospitalized for depression among survivors of certain types of cancer remained high for several years, Dr. Susanne O. Dalton of the Danish Cancer Society in Copenhagen and her colleagues found.
There's some evidence that cancer patients are more likely to be depressed than people in the general population, the researchers note. Estimates of depression prevalence among these patients range from 0 percent to 38 percent.
Despite this variability, which is likely due to differences in how depression is diagnosed and the type of cancer patients have, as well as how advanced their disease is and whether or not they are hospitalized, "depression has typically been underdiagnosed and undertreated in the oncology setting," Dalton and her team write in the Journal of Clinical Oncology.
To better understand the short- and long-term depression risk of cancer patients, the researchers looked at 608,591 Danish men and women who were diagnosed with cancer and were followed for up to 31 years. The average follow-up after diagnosis was 4.2 years.
Within the first year of being diagnosed with cancer, the researchers found, men and women with cancer were about twice as likely to be hospitalized for depression as were men and women in the general population. Over the next decade, the relative risk of hospitalization for depression was increased 21 percent for men and 5 percent for women.
Depression risk varied by cancer type. For both sexes, the risk remained high for up to 10 years after being diagnosed with a hormone-related cancer, such as breast cancer or prostate cancer. The risk also stayed high for a decade among women with smoking-related cancers and men with virus- and immune-related cancers.
In the first year after diagnosis, increased risk ranged from 1.16-fold for women with colorectal cancer to 3.08-fold for men with brain cancer.
Given that more and more people are living longer after being diagnosed with cancer, the researchers note, taking care of cancer survivors with depression will be increasingly important. "Early recognition and effective treatment of depression, both in the cancer setting and beyond, would have the potential to prevent admission for depression and thus reduce patient suffering and enhance the quality of life for cancer survivors," they conclude.
SOURCE: Journal of Clinical Oncology, online February 17, 2009.
Reuters Health
Copyright © 2009 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
Suppressing Cancer With A Master Control Gene
tiny fruit fly and then moving into mice and humans, researchers at VIB and K. U. Leuven show that expression of the same gene suppresses cancer in all three organisms. Reciprocally, switching off the gene – called Ato in flies and ATOH1 in mammals – leads to cancer. The authors show there is a good chance that the gene can be switched on again with a drug. All of us begin our lives as a single cell (made when an egg and sperm fuse) which repeatedly divides into the few billion cells that constitute an adult human. During these divisions cells become increasingly differentiated from each other, until in an adult almost all cells are highly specialized to perform a specific function – skin cells, liver cells, eye lens cells, nerve cells, etc. Cancer is a collection of cells without a function, which grow when normal genetic controls of cell division are interrupted. Cancer cells are less differentiated than normal cells – leading to the hypothesis that the final steps of differentiation prevent cells from becoming cancerous.
New work conducted by Wouter Bossuyt, Bassem Hassan, and colleagues at VIB and K. U. Leuven has tested this theory. They demonstrate that in the fruit fly, master control genes steering the specialization step inhibit tumor formation.
In collaboration with colleagues from the United States, they show that loss of one of those genes, Atonal homolog 1 (ATOH1), causes colon cancer in mice. The gene regulates the last step in the specialization to epithelial cells of the colon. Humans with colon cancer frequently have an inactivated ATOH1 gene, the researchers show.
The researchers could reactivate the gene in human colon cancer cells grown in culture. This caused the tumor cells to stop growing and commit suicide. This exciting, but preliminary, result suggests that it may be possible to switch the gene back on in living patients to target their cancers. Taking this work in the test tube and using it to develop a therapy is an exciting but complicated challenge. Therefore, more work will be required to further understand the role of ATOH1 in suppressing cancer formation.
New work conducted by Wouter Bossuyt, Bassem Hassan, and colleagues at VIB and K. U. Leuven has tested this theory. They demonstrate that in the fruit fly, master control genes steering the specialization step inhibit tumor formation.
In collaboration with colleagues from the United States, they show that loss of one of those genes, Atonal homolog 1 (ATOH1), causes colon cancer in mice. The gene regulates the last step in the specialization to epithelial cells of the colon. Humans with colon cancer frequently have an inactivated ATOH1 gene, the researchers show.
The researchers could reactivate the gene in human colon cancer cells grown in culture. This caused the tumor cells to stop growing and commit suicide. This exciting, but preliminary, result suggests that it may be possible to switch the gene back on in living patients to target their cancers. Taking this work in the test tube and using it to develop a therapy is an exciting but complicated challenge. Therefore, more work will be required to further understand the role of ATOH1 in suppressing cancer formation.
Diet rich in calcium tied to lower cancer rate
CHICAGO - A study in nearly half a million older men and women bolsters evidence that diets rich in calcium may help protect against some cancers.
The benefits were mostly associated with foods high in calcium, rather than calcium tablets.
Previous studies have produced conflicting results. The new research involved food questionnaires from participants and a follow-up check of records for cancer cases during the subsequent seven years. This research method is less rigorous than some previous but smaller studies.
The benefits were mostly associated with foods high in calcium, rather than calcium tablets.
Previous studies have produced conflicting results. The new research involved food questionnaires from participants and a follow-up check of records for cancer cases during the subsequent seven years. This research method is less rigorous than some previous but smaller studies.
Mathematician Contends Earlier Study Overstated Validity Of Findings On Risks Of Bisphenol A
published in this week's Journal of the American Medical Association (JAMA), Dr. S. Stanley Young, Assistant Director of Bioinformatics at the National Institute of Statistical Sciences, and Ming Yu, University of British Columbia, highlight the statistical limitations of a study claiming that bisphenol A is associated with cardiovascular diagnoses, diabetes and abnormal blood level liver enzyme levels.The earlier study, published in JAMA (September 16, 2008) by Dr. Ian A. Lang and colleagues, did not adequately address the potential for multiple testing to result in a false positive result.
Young and Yu note that the CDC National Health and Nutrition Examination Survey [2003-2004] that was used in Lang et al's study measured 275 environmental chemicals and a wide range of health outcomes.
Although the Lang et al study focused on one chemical and 16 health outcomes, Young and Yu note that it is important to focus on how many questions were at issue. They point out that with 32 possible health outcomes, including combinations, potentially associated with any of the 275 chemicals, along with multiple confounders and statistical models, there could be as many as approximately 9 million statistical models available to analyze the data.
Given the number of questions at issue and possible modeling variations in the CDC design, Young and Yu conclude that the findings reported by the authors could well be the result of chance rather than representing real health concerns.
Young and Yu note that the CDC National Health and Nutrition Examination Survey [2003-2004] that was used in Lang et al's study measured 275 environmental chemicals and a wide range of health outcomes.
Although the Lang et al study focused on one chemical and 16 health outcomes, Young and Yu note that it is important to focus on how many questions were at issue. They point out that with 32 possible health outcomes, including combinations, potentially associated with any of the 275 chemicals, along with multiple confounders and statistical models, there could be as many as approximately 9 million statistical models available to analyze the data.
Given the number of questions at issue and possible modeling variations in the CDC design, Young and Yu conclude that the findings reported by the authors could well be the result of chance rather than representing real health concerns.
Indicator Found That Warns Leukemia Is Progressing To More Dangerous Form
Moores Cancer Center at the University of California, San Diego, Stanford University School of Medicine and other centers have identified a mechanism by which a chronic form of leukemia can progress into a deadlier stage of the disease. The findings may provide physicians with an indicator of when this type of cancer – chronic myeloid leukemia (CML) – is progressing, enabling them to make more accurate prognoses for the disease and improved treatment choices."If we can predict when a patient is moving from the chronic phase in CML to the blast crisis stage, then we can hopefully intervene before it's too late," said Catriona H.M. Jamieson, MD, PhD, assistant professor of medicine at the UC San Diego School of Medicine and Director for Stem Cell Research at the Moores UCSD Cancer Center.
The findings, reported online during the week of February 16, 2009 in the Proceedings of the National Academy of Sciences, also shed light on the development of potentially treatment-resistant leukemia stem cells and provide insights for new strategies against CML and other cancers.
Led by Jamieson and Irving Weissman, MD, director of the Stem Cell Biology and Regenerative Medicine Institute at the Stanford University School of Medicine, the researchers discovered that when a molecular off-switch called glycogen synthase kinase (GSK) 3 beta becomes faulty in chronic stage CML cells, it fails to turn off another protein, beta-catenin. This in turn enables pre-leukemia stem cells to develop into leukemia stem cells and expand their numbers, leading to progression to the more dangerous "blast crisis" stage of CML. This errant off-switch is a potential therapeutic target, Jamieson explained.
"This paper further underscores the importance of the cell type and specific context of molecular events in the evolution of leukemia," Jamieson said. "It also highlights the malignant consequences of GSK 3 beta deregulation."
"This knowledge may enable us to design and develop more effective, personalized therapies for these patients," said staff research associate and co-first author Annelie Abrahamsson.
In CML, an enzyme called ABL goes in overdrive because of a chromosomal mix-up that occurs during blood cell development. The genes ABL and BCR fuse and produce a hybrid BCR-ABL enzyme that drives the excessive proliferation of white blood cells. CML progresses from a chronic stage in hematopoietic stem cells that carry BCR-ABL to the blast crisis stage. This stage is characterized by the over-production of beta-catenin in white blood cells called granulocyte macrophage progenitors (GMP) – in effect, leukemia stem cells.
According to Jamieson, a major roadblock in predicting and stopping the conversion of chronic CML to blast crisis stage was the failure to understand what turned on beta-catenin. The team showed that by injecting blast crisis CML progenitor cells – GMP – into mice lacking working immune systems, they could "transplant" leukemia into the animals. When they did this, they discovered that GSK 3 beta levels dropped. Looking more closely, they found an aberrant "misspliced" form of GSK 3 beta that was unable to turn off beta-catenin, suggesting a potential mechanism behind the change to blast crisis stage.
The scientists also showed that the mice that had received the cells with the bad form of GSK 3 beta developed granulocytic sarcomas, tumors that are seen in patients with the most advanced form of CML.
"Many investigators have questioned the usefulness of finding and purifying leukemia and cancer stem cells," said Weissman. "This paper shows why. The damage to the enzyme GSK 3 beta that prevents beta-catenin activation of cell proliferation occurs only in the GMP leukemia stem cells, which are only about 1 in 20 bone marrow cells. Trying to analyze the missplicing of GSK in the whole leukemia would not have worked.
"These kinds of changes in gene expression, which are not mutations, need pure cells to find them. The final proof of the cancer stem cell hypothesis will be to show whether a treatment specific for the changed gene expression eliminates the cancer in the patient."
"Downregulating beta-catenin and GSK deregulation may have other implications in many cancers," Jamieson said. "By studying CML, we can understand the molecular evolution of disease and the stepwise progression to cancer. It becomes a useful paradigm for understanding how cancers evolve and the pathways that are essential to escape the normal control mechanisms."
Other authors include: Ifat Geron, Kim-Hien Dao, DO, PhD, Charlene Barroga, PhD, Isabel Newton, MD, PhD, UCSD; Jason Gotlib, MD, Remi Creusot, PhD, Mobin Karimi, PhD, Carol Jones, PhD, James Zehnder, MD, PhD, Robert Negrin, MD, Institute of Stem Cell Biology and Regenerative Medicine, Stanford; Francis Giles, MD, University of Texas Health Science Center, San Antonio; Jeffrey Durocher, PhD, Transgenomic Inc., Gaithersberg, MD; and Armand Keating, MD, Princess Margaret Hospital, Toronto. Much of the work received funding from the National Institutes of Health, the California Institute of Regenerative Medicine and the Moores UCSD Cancer Center.
The Moores UCSD Cancer Center is one of the nation's 41 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.
The findings, reported online during the week of February 16, 2009 in the Proceedings of the National Academy of Sciences, also shed light on the development of potentially treatment-resistant leukemia stem cells and provide insights for new strategies against CML and other cancers.
Led by Jamieson and Irving Weissman, MD, director of the Stem Cell Biology and Regenerative Medicine Institute at the Stanford University School of Medicine, the researchers discovered that when a molecular off-switch called glycogen synthase kinase (GSK) 3 beta becomes faulty in chronic stage CML cells, it fails to turn off another protein, beta-catenin. This in turn enables pre-leukemia stem cells to develop into leukemia stem cells and expand their numbers, leading to progression to the more dangerous "blast crisis" stage of CML. This errant off-switch is a potential therapeutic target, Jamieson explained.
"This paper further underscores the importance of the cell type and specific context of molecular events in the evolution of leukemia," Jamieson said. "It also highlights the malignant consequences of GSK 3 beta deregulation."
"This knowledge may enable us to design and develop more effective, personalized therapies for these patients," said staff research associate and co-first author Annelie Abrahamsson.
In CML, an enzyme called ABL goes in overdrive because of a chromosomal mix-up that occurs during blood cell development. The genes ABL and BCR fuse and produce a hybrid BCR-ABL enzyme that drives the excessive proliferation of white blood cells. CML progresses from a chronic stage in hematopoietic stem cells that carry BCR-ABL to the blast crisis stage. This stage is characterized by the over-production of beta-catenin in white blood cells called granulocyte macrophage progenitors (GMP) – in effect, leukemia stem cells.
According to Jamieson, a major roadblock in predicting and stopping the conversion of chronic CML to blast crisis stage was the failure to understand what turned on beta-catenin. The team showed that by injecting blast crisis CML progenitor cells – GMP – into mice lacking working immune systems, they could "transplant" leukemia into the animals. When they did this, they discovered that GSK 3 beta levels dropped. Looking more closely, they found an aberrant "misspliced" form of GSK 3 beta that was unable to turn off beta-catenin, suggesting a potential mechanism behind the change to blast crisis stage.
The scientists also showed that the mice that had received the cells with the bad form of GSK 3 beta developed granulocytic sarcomas, tumors that are seen in patients with the most advanced form of CML.
"Many investigators have questioned the usefulness of finding and purifying leukemia and cancer stem cells," said Weissman. "This paper shows why. The damage to the enzyme GSK 3 beta that prevents beta-catenin activation of cell proliferation occurs only in the GMP leukemia stem cells, which are only about 1 in 20 bone marrow cells. Trying to analyze the missplicing of GSK in the whole leukemia would not have worked.
"These kinds of changes in gene expression, which are not mutations, need pure cells to find them. The final proof of the cancer stem cell hypothesis will be to show whether a treatment specific for the changed gene expression eliminates the cancer in the patient."
"Downregulating beta-catenin and GSK deregulation may have other implications in many cancers," Jamieson said. "By studying CML, we can understand the molecular evolution of disease and the stepwise progression to cancer. It becomes a useful paradigm for understanding how cancers evolve and the pathways that are essential to escape the normal control mechanisms."
Other authors include: Ifat Geron, Kim-Hien Dao, DO, PhD, Charlene Barroga, PhD, Isabel Newton, MD, PhD, UCSD; Jason Gotlib, MD, Remi Creusot, PhD, Mobin Karimi, PhD, Carol Jones, PhD, James Zehnder, MD, PhD, Robert Negrin, MD, Institute of Stem Cell Biology and Regenerative Medicine, Stanford; Francis Giles, MD, University of Texas Health Science Center, San Antonio; Jeffrey Durocher, PhD, Transgenomic Inc., Gaithersberg, MD; and Armand Keating, MD, Princess Margaret Hospital, Toronto. Much of the work received funding from the National Institutes of Health, the California Institute of Regenerative Medicine and the Moores UCSD Cancer Center.
The Moores UCSD Cancer Center is one of the nation's 41 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.
Drug recommended to prevent prostate cancer in some older men
Healthy men over 55 who are concerned enough about the risk of prostate cancer to undergo annual PSA screening should consider taking the drug finasteride daily to reduce their risk of developing the disease, according to a new prevention guideline released Tuesday.
"If a man is interested enough in being screened, then at least he ought to have the benefits of a discussion" with his doctor about taking the drug, Dr. Barnett S. Kramer of the National Institutes of Health said at a news conference revealing the guideline.Kramer was co-chairman of the panel that developed the recommendation for the American Society of Clinical Oncology and the American Urological Assn. It will be published in the March issues of the Journal of Clinical Oncology and the Journal of Urology.
The most likely initial candidates to take the drug would be men who are African American or who have a father or brother with the disease, factors which sharply increase risk, said Dr. Jack Jacoub, a medical oncologist at Orange Coast Memorial Medical Center in Fountain Valley, who was not a member of the panel. Many physicians have already been prescribing it for their patients at the highest risk, he said.
The recommendation targets men with a normal reading on the prostate-specific antigen or PSA, test, which is considered the best indicator of the presence of a tumor, because clinical trials of the drug covered only such men.
The panel stopped short of recommending that all men take the drug because clinical trials have not yet shown that it reduces deaths.
Prostate cancer is the second-leading cause of cancer deaths among men, behind lung cancer, with 186,000 new cases diagnosed and 28,660 deaths each year.
Finasteride is used in low doses under the brand name Propecia as an anti-balding drug and in higher doses under the name Proscar for shrinking enlarged prostate glands. The dose recommended for cancer prevention is the same dosage used in Proscar.
The drug interferes with the production of male hormones, starving the tumors of fuel they need to grow.
A major clinical trial reported in 2003 showed that finasteride reduced the risk of prostate cancer by about 25% in men who took it, preventing about 15 cases in every 1,000 men. That means 71 men would have to take the drug for seven years to prevent one case, Kramer said.
Another drug in the same family, called dutasteride, or Avodart, is thought to be even more potent and is undergoing clinical trials for prevention. It is also recommended in the guideline.
The medical groups did not issue new recommendations after the completion of the 2003 trial because it appeared that finasteride might have been promoting the growth of more aggressive tumors at the expense of those that are more benign.
"Now we know this is not the case," Jacoub said. Subsequent studies have shown that shrinkage of the prostate caused by finasteride simply made the aggressive tumors more easily discovered.
The drug does have side effects in some men, however, including reduced potency and loss of sexual desire. Those effects can go away after a couple of months. On the other hand, the drug can result in reduced incontinence and fewer urinary problems.
Cost can also be a problem. The pills cost $2 to $3 a day, or about $1,000 per year, and most insurers do not cover them for cancer prevention.
Speaking at the news conference, panel member Dr. Howard Sandler of Cedars-Sinai Medical Center said: "If I tried the medication for a month or two and I got some side effects, then for me personally the benefit wouldn't be worth the risk." But if there were no side effects, he added, "I might sleep better at night."
"If a man is interested enough in being screened, then at least he ought to have the benefits of a discussion" with his doctor about taking the drug, Dr. Barnett S. Kramer of the National Institutes of Health said at a news conference revealing the guideline.Kramer was co-chairman of the panel that developed the recommendation for the American Society of Clinical Oncology and the American Urological Assn. It will be published in the March issues of the Journal of Clinical Oncology and the Journal of Urology.
The most likely initial candidates to take the drug would be men who are African American or who have a father or brother with the disease, factors which sharply increase risk, said Dr. Jack Jacoub, a medical oncologist at Orange Coast Memorial Medical Center in Fountain Valley, who was not a member of the panel. Many physicians have already been prescribing it for their patients at the highest risk, he said.
The recommendation targets men with a normal reading on the prostate-specific antigen or PSA, test, which is considered the best indicator of the presence of a tumor, because clinical trials of the drug covered only such men.
The panel stopped short of recommending that all men take the drug because clinical trials have not yet shown that it reduces deaths.
Prostate cancer is the second-leading cause of cancer deaths among men, behind lung cancer, with 186,000 new cases diagnosed and 28,660 deaths each year.
Finasteride is used in low doses under the brand name Propecia as an anti-balding drug and in higher doses under the name Proscar for shrinking enlarged prostate glands. The dose recommended for cancer prevention is the same dosage used in Proscar.
The drug interferes with the production of male hormones, starving the tumors of fuel they need to grow.
A major clinical trial reported in 2003 showed that finasteride reduced the risk of prostate cancer by about 25% in men who took it, preventing about 15 cases in every 1,000 men. That means 71 men would have to take the drug for seven years to prevent one case, Kramer said.
Another drug in the same family, called dutasteride, or Avodart, is thought to be even more potent and is undergoing clinical trials for prevention. It is also recommended in the guideline.
The medical groups did not issue new recommendations after the completion of the 2003 trial because it appeared that finasteride might have been promoting the growth of more aggressive tumors at the expense of those that are more benign.
"Now we know this is not the case," Jacoub said. Subsequent studies have shown that shrinkage of the prostate caused by finasteride simply made the aggressive tumors more easily discovered.
The drug does have side effects in some men, however, including reduced potency and loss of sexual desire. Those effects can go away after a couple of months. On the other hand, the drug can result in reduced incontinence and fewer urinary problems.
Cost can also be a problem. The pills cost $2 to $3 a day, or about $1,000 per year, and most insurers do not cover them for cancer prevention.
Speaking at the news conference, panel member Dr. Howard Sandler of Cedars-Sinai Medical Center said: "If I tried the medication for a month or two and I got some side effects, then for me personally the benefit wouldn't be worth the risk." But if there were no side effects, he added, "I might sleep better at night."
Vitamin D delivers multiple benefits
It may help lower risk of cancer, kidney disease
By VIKKI CONWELL
The Atlanta Journal-Constitution
Wednesday, February 25, 2009
Vitamin D may not just be good for you, it may help save your life.
Recent research from Johns Hopkins University suggests that higher amounts of vitamin D in your diet decreases your likelihood of dying. Studies found that a vitamin D deficiency increases your risk of death by 26 percent, and vitamin D decreases the mortality rate from almost every type of cancer including breast, colon and prostate. Research also suggests that vitamin D helps prevent diabetes, kidney disease and cardiovascular disease.
Surprising news for some, but not for Atlanta physician Reginald Fowler.
The doctor of internal medicine found that 80 percent of his patients lacked the crucial vitamin that maintains normal blood levels of calcium and phosphorus in the body.
“It’s nothing new, but if we can do something about it, we will decrease the incidence of disease significantly,” said Fowler, who regularly screens for vitamin D during exams. A simple blood test can check for levels that should remain at 30 (nanograms per milliliter) or above.
People who are deficient in vitamin D may experience muscle pain or a feeling of achiness. Severe and long-term deficiency of vitamin D leads to rickets, a softening or weakening of the bones.
The sun helps the body produce vitamin D, but too much time in direct sunlight can increase the risk of skin cancer. So food and supplements are generally deemed the best sources.
The U.S. Department of Agriculture recommends an intake value of 200 International Units per day for people up to age 50, but Fowler and other health officials recommend at least double that amount.
To increase your intake, eat more vitamin D-rich foods such as salmon and tuna, fortified cereals, nuts, orange juice and dairy products. An 8-ounce glass of fortified milk contains about 100 IUs of vitamin D. You can also take a vitamin D-3 supplement such as cholecalciferol.
“This is not something to play around with,” Fowler said. “These are little changes that can make a huge impact.”
A SUNNIER DIET
Foods that are rich in vitamin D include dairy products (make sure they are made from vitamin D-fortified milk), fortified cereals, salmon, tuna, mackerel, orange juice and nuts such as walnuts and almonds. Some examples:
• Cod liver oil, 1 tablespoon: 1,360 International Units
• Salmon, cooked, 3 1/2 ounces: 360 IUs
• Mackerel, cooked, 3 1/2 ounces: 345 IUs
• Sardines, canned in oil, drained, 3 1/2 ounces: 270 IUs
• Milk (nonfat, reduced fat and whole) vitamin D-fortified, 1 cup: 98 IUs
• Margarine, fortified, 1 tablespoon: 60 IUs
• Pudding, 1/2 cup prepared from mix and made with vitamin D-fortified milk: 50 IUs
• Dry cereal, vitamin D-fortified, 3/4 cup: 40-50 IUs
• Liver, beef, cooked, 3 1/2 ounces: 30 IUs
• 1 egg (vitamin D is present in the yolk): 25 IUs
By VIKKI CONWELL
The Atlanta Journal-Constitution
Wednesday, February 25, 2009
Vitamin D may not just be good for you, it may help save your life.
Recent research from Johns Hopkins University suggests that higher amounts of vitamin D in your diet decreases your likelihood of dying. Studies found that a vitamin D deficiency increases your risk of death by 26 percent, and vitamin D decreases the mortality rate from almost every type of cancer including breast, colon and prostate. Research also suggests that vitamin D helps prevent diabetes, kidney disease and cardiovascular disease.
Surprising news for some, but not for Atlanta physician Reginald Fowler.
The doctor of internal medicine found that 80 percent of his patients lacked the crucial vitamin that maintains normal blood levels of calcium and phosphorus in the body.
“It’s nothing new, but if we can do something about it, we will decrease the incidence of disease significantly,” said Fowler, who regularly screens for vitamin D during exams. A simple blood test can check for levels that should remain at 30 (nanograms per milliliter) or above.
People who are deficient in vitamin D may experience muscle pain or a feeling of achiness. Severe and long-term deficiency of vitamin D leads to rickets, a softening or weakening of the bones.
The sun helps the body produce vitamin D, but too much time in direct sunlight can increase the risk of skin cancer. So food and supplements are generally deemed the best sources.
The U.S. Department of Agriculture recommends an intake value of 200 International Units per day for people up to age 50, but Fowler and other health officials recommend at least double that amount.
To increase your intake, eat more vitamin D-rich foods such as salmon and tuna, fortified cereals, nuts, orange juice and dairy products. An 8-ounce glass of fortified milk contains about 100 IUs of vitamin D. You can also take a vitamin D-3 supplement such as cholecalciferol.
“This is not something to play around with,” Fowler said. “These are little changes that can make a huge impact.”
A SUNNIER DIET
Foods that are rich in vitamin D include dairy products (make sure they are made from vitamin D-fortified milk), fortified cereals, salmon, tuna, mackerel, orange juice and nuts such as walnuts and almonds. Some examples:
• Cod liver oil, 1 tablespoon: 1,360 International Units
• Salmon, cooked, 3 1/2 ounces: 360 IUs
• Mackerel, cooked, 3 1/2 ounces: 345 IUs
• Sardines, canned in oil, drained, 3 1/2 ounces: 270 IUs
• Milk (nonfat, reduced fat and whole) vitamin D-fortified, 1 cup: 98 IUs
• Margarine, fortified, 1 tablespoon: 60 IUs
• Pudding, 1/2 cup prepared from mix and made with vitamin D-fortified milk: 50 IUs
• Dry cereal, vitamin D-fortified, 3/4 cup: 40-50 IUs
• Liver, beef, cooked, 3 1/2 ounces: 30 IUs
• 1 egg (vitamin D is present in the yolk): 25 IUs
Vitamin C Production: Molecular Gatekeeper In Enzyme Discovered
Wageningen University, along with colleagues from the University of Groningen and the University of Pavia (Italy), have unravelled the mechanism that plays a role in the natural production of vitamin C. In this process, a molecular gatekeeper blocks the entrance to the reaction centre of a crucial enzyme.The biological production of vitamin C in plants, fungi and many animals is a complicated process that involves enzymes. A large group of these catalysts need oxygen to function well. In plants, a chemical, cytochrome C, replaces the function of oxygen. Cytochrome C or oxygen ensures that the co-factor flavin in the enzyme's action centre is brought back to its original state after reaction. Because of this restoration, the enzyme is ready for a new reaction.
The research team wondered why the one group of enzymes reacted with oxygen and the other, closely related group did not. How does the oxygen reach the centre of the enzyme, which consists of about 500 hundred linked building blocks (amino acids) of different sizes and forms. This string of building blocks is, as it were, bunched up into a little lump with 'holes, caverns and tunnels' in between. Oxygen has to seep through this little lump or clear a path through the tangle of amino acids in order to penetrate the hidden flavin in the centre.
Imagine, the researchers said, that in some enzymes oxygen can reach the enzyme's centre through tunnels and holes. You should then be able to discover the route using the structure. Unfortunately, there was no crystalline structure of the enzyme in question on hand. There was, however, one other possibility. By laying side by side all of the individual building blocks of the enzymes that react with oxygen and those that do not, the differences should become clear.
Comparing both analyses brought a subtle difference to light. Only one building block, number 113, at the end of a possible route turned out to be a bit different. This difference relates to the amino acid alanine. When alanine was replaced by the smaller building block glycine at that position, it turned out that the enzyme was suddenly oxygen permeable. And not just a little bit. The difference is so large it's as if a dam has burst: a factor of 400.
How is it possible that one building block in a construction of 500 blocks can have so much effect? The researchers support the tunnel theory: the building block alanine has four different protrusions, while glycine has only three. Alanine's extra protrusion, a methyl group, blocks the tunnel and prevents oxygen from penetrating the centre. At this site, alanine works as a gatekeeper and it keeps the door tightly shut.
But, why isn't the gate just simply open? Evidently, having a strict gatekeeper has its advantages. It turns out that the aggressive substance hydrogen peroxide ('domestic bleach') forms in the reaction with oxygen. Hydrogen peroxide accelerates the ageing of cells and a plant, which makes a lot of vitamin C, does not like this.
The way is now open to prepare vitamin C in a natural way. However, the chemical route already exists, is cheap and yields an identical product. The deciphered mechanism is, however, also applicable to similar biochemical reactions, for example, the preparation of vanilla. Additionally, the deciphered process can mean a step forward in synthetic biology in which products that do not occur or hardly occur in nature can be produced in a natural way.
The article in which the team reports its finding has been declared Paper of the Week by the Journal of Biological Chemistry, an honour given to only one in every hundred articles.
The research team wondered why the one group of enzymes reacted with oxygen and the other, closely related group did not. How does the oxygen reach the centre of the enzyme, which consists of about 500 hundred linked building blocks (amino acids) of different sizes and forms. This string of building blocks is, as it were, bunched up into a little lump with 'holes, caverns and tunnels' in between. Oxygen has to seep through this little lump or clear a path through the tangle of amino acids in order to penetrate the hidden flavin in the centre.
Imagine, the researchers said, that in some enzymes oxygen can reach the enzyme's centre through tunnels and holes. You should then be able to discover the route using the structure. Unfortunately, there was no crystalline structure of the enzyme in question on hand. There was, however, one other possibility. By laying side by side all of the individual building blocks of the enzymes that react with oxygen and those that do not, the differences should become clear.
Comparing both analyses brought a subtle difference to light. Only one building block, number 113, at the end of a possible route turned out to be a bit different. This difference relates to the amino acid alanine. When alanine was replaced by the smaller building block glycine at that position, it turned out that the enzyme was suddenly oxygen permeable. And not just a little bit. The difference is so large it's as if a dam has burst: a factor of 400.
How is it possible that one building block in a construction of 500 blocks can have so much effect? The researchers support the tunnel theory: the building block alanine has four different protrusions, while glycine has only three. Alanine's extra protrusion, a methyl group, blocks the tunnel and prevents oxygen from penetrating the centre. At this site, alanine works as a gatekeeper and it keeps the door tightly shut.
But, why isn't the gate just simply open? Evidently, having a strict gatekeeper has its advantages. It turns out that the aggressive substance hydrogen peroxide ('domestic bleach') forms in the reaction with oxygen. Hydrogen peroxide accelerates the ageing of cells and a plant, which makes a lot of vitamin C, does not like this.
The way is now open to prepare vitamin C in a natural way. However, the chemical route already exists, is cheap and yields an identical product. The deciphered mechanism is, however, also applicable to similar biochemical reactions, for example, the preparation of vanilla. Additionally, the deciphered process can mean a step forward in synthetic biology in which products that do not occur or hardly occur in nature can be produced in a natural way.
The article in which the team reports its finding has been declared Paper of the Week by the Journal of Biological Chemistry, an honour given to only one in every hundred articles.
Excessive Dietary Fat Caused 300 Percent Increase in Metastasizing Tumor Cells In Animal Models
Purdue University have precisely measured the impact of a high-fat diet on the spread of cancer, finding that excessive dietary fat caused a 300 percent increase in metastasizing tumor cells in laboratory animals.The researchers used an imaging technique to document how increasing fat content causes cancer cells to undergo changes essential to metastasis. Then they used another technique to count the number of cancer cells in the bloodstream of mice fed a high-fat diet compared to animals fed a lean diet.
The findings suggest that the combined tools represent a possible new diagnostic technique to determine whether a patient's cancer is spreading, said Ji-Xin Cheng, an assistant professor in Purdue's Weldon School of Biomedical Engineering and Department of Chemistry.
"It is generally accepted that diet and obesity are accountable for 30 percent of preventable causes of cancer, but nobody really knows why," Cheng said. "These findings demonstrate that an increase in lipids leads directly to a rise in cancer metastasis."
Researchers have theorized that tumor cells need more lipids than ordinary tissues to provide energy and material for tumor growth and metastasis.
"Before this work, however, most of the evidence was anecdotal, but here we present a mechanistic study," said Thuc T. Le, a National Institutes of Health postdoctoral fellow at Purdue who is working with Cheng.
Findings were detailed in a paper published on Jan. 30 in the journal BMC Cancer. The paper was written by Le; Terry B. Huff, a graduate research assistant in Purdue's Department of Chemistry; and Cheng. The research is supported by the Purdue Cancer Center.
The researchers implanted a cancerous lung tumor under the skin in each of the mice studied, and the animals were separated into two groups: one fed a high-fat diet and the other a lean diet.
The researchers then used an imaging method called coherent anti-Stokes Raman scattering, or CARS, to document how increasing lipids from fat intake induces changes to cancer cell membranes. Those changes, including processes called membrane phase separation and membrane rounding, enhance cancer metastasis.
"If the cancer cells don't have excess lipids they stick together and form very tight junctions in tumors, but increasing lipids causes them to take on a rounded shape and separate from each other," Le said.
The change in shape is critical to the ability of cancer cells to separate and spread throughout the body via the bloodstream.
The researchers then used another technique, called intravital flow cytometry, to count the number of cancer cells in the bloodstream of the mice. The technique works by shining a laser though the skin and into blood vessels, where the dyed cancer cells are visible.
Results showed the increase in lipids had no impact on the original tumors implanted in the mice. However, the rate of metastasis rose a dramatic 300 percent in the mice fed a high-fat diet.
The researchers later also examined the animals' lungs and counted the number of cancer cells that had migrated to the lungs as a result of metastasis. Those findings supported the other results showing increased metastasis in animals fed a high-fat diet.
The researches used the imaging and cell-counting tools to document that linoleic acid, which is predominant in polyunsaturated fats, caused increasing membrane phase separation, whereas oleic acid, found in monounsaturated fats, did not. Increased membrane phase separation could improve the opportunity of circulating tumor cells to adhere to blood vessel walls and escape to organs far from the original tumor site. The new findings support earlier evidence from other research that consuming high amounts of polyunsaturated fat may increase the risk of cancer spreading.
The findings suggest that combining CARS and intravital flow cytometry represents a possible new diagnostic tool to screen patients for cancer. The tool can be used to count lipid-rich tumor cells circulating in a patient's blood by shining a laser through the skin and into blood vessels. Because lipids can be detected without the need for dyes, the technique might be developed into a convenient method to diagnose whether a patient's cancer is spreading aggressively, Cheng said.
"These findings open the possibility of an entirely new, relatively simple method for diagnosing whether cancer is metastasizing," he said.
Future work will focus on not only how obesity increases metastasis but also how it might play a direct role in initiating the development of cancers.
The research has been funded by the National Institutes of Health.
Clean living way to beat cancer
Over 40% of breast and bowel cancer cases in rich countries are preventable through diet, physical activity and weight control alone, experts say.
Simple measures like cycling to work and swapping fatty foods for fruit can make all the difference for these and many other cancers, they say.
Globally, each year there are millions of these preventable cancer cases, the World Cancer Research Fund estimates.
Its report makes recommendations for "clean living" policies. According to the report, about a third of the 12 most common cancers in high-income countries and about a quarter in lower income countries could be prevented through diet, exercise and weight control.
This include cancers of the throat, lung and bowel.
See figures on cancers that could be prevented
The figures do not take into account the impact of smoking, which alone accounts for about a third of cancers.
The panel of 23 experts who compiled the report say urgent action is needed to avert a crisis, with cancer rates set to increase.
Not inevitable
Professor Martin Wiseman, project director, said: "We are expecting a substantial increase in cancer rates with the ageing population, obesity rates soaring, and with people becoming less active and increasingly consuming highly processed and energy dense foods and drinks. The good news is that this is not inevitable."
FROM THE BBC WORLD SERVICE
More from BBC World Service
Panel chair Professor Sir Michael Marmot said: "This report shows that by making relatively straightforward changes, we could significantly reduce the number of cancer cases around the world."
The report says all sections of society "from governments to households" should make public health, and cancer prevention in particular, a higher priority.
Among the 48 recommendations is the advice for schools and workplaces to actively encourage physical activity and ban unhealthy food.
Governments should require widespread walking and cycling routes to encourage physical activity.
And the people who do the weekly food shopping for their family should check food labels to make sure the food they buy is healthy.
Professor Mike Richards, National Clinical Director for Cancer, said: "The evidence linking diet, physical activity, obesity and cancer has become stronger over the last decade and this report can play a part in people adopting healthier lifestyles.
"After not smoking, it is clear that diet, physical activity and weight are the most important things people can do to reduce their cancer risk."
Major step forward
Dr Francesco Branca, Head of Nutrition at the World Health Organization, called the report a major step forward in understanding how policies and actions can help prevent cancer and other chronic diseases.
He said: "The recommendations will inspire policy-makers and decision-takers to act in a way that will play an important role in the fight against cancer."
Richard Davidson, of the charity Cancer Research UK said around 13,000 cancer cases in the UK were linked to being overweight or obese, and even more were linked to poor diet, drinking too much alcohol and not doing enough exercise.
He said: "Doing nothing could be disastrous.
"There is no magic bullet, no one single fix to the problem. If we are to tackle the situation we need individuals, business and government to work together to encourage healthy lifestyles by promoting things like cycle lanes and food labelling."
Estimated percentage of cancers that could be prevented
US UK Brazil China
Mouth, pharynx & larynx 63 67 63 44
Oesophagus 69 75 60 44
Lung 36 33 36 38
Stomach 47 45 41 33
Pancreas 39 41 34 14
Gallbladder 21 16 10 6
Bowel 45 43 37 17
Liver 15 17 6 6
Breast 38 42 28 20
Endometrium (womb) 70 56 52 34
Prostate 11 20 n/a n/a
Kidney 24 19 13 8
12 cancers combined 34 39 30 27
All cancers 24 26 19 20
World Cancer Research Fund
Simple measures like cycling to work and swapping fatty foods for fruit can make all the difference for these and many other cancers, they say.
Globally, each year there are millions of these preventable cancer cases, the World Cancer Research Fund estimates.
Its report makes recommendations for "clean living" policies. According to the report, about a third of the 12 most common cancers in high-income countries and about a quarter in lower income countries could be prevented through diet, exercise and weight control.
This include cancers of the throat, lung and bowel.
See figures on cancers that could be prevented
The figures do not take into account the impact of smoking, which alone accounts for about a third of cancers.
The panel of 23 experts who compiled the report say urgent action is needed to avert a crisis, with cancer rates set to increase.
Not inevitable
Professor Martin Wiseman, project director, said: "We are expecting a substantial increase in cancer rates with the ageing population, obesity rates soaring, and with people becoming less active and increasingly consuming highly processed and energy dense foods and drinks. The good news is that this is not inevitable."
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Panel chair Professor Sir Michael Marmot said: "This report shows that by making relatively straightforward changes, we could significantly reduce the number of cancer cases around the world."
The report says all sections of society "from governments to households" should make public health, and cancer prevention in particular, a higher priority.
Among the 48 recommendations is the advice for schools and workplaces to actively encourage physical activity and ban unhealthy food.
Governments should require widespread walking and cycling routes to encourage physical activity.
And the people who do the weekly food shopping for their family should check food labels to make sure the food they buy is healthy.
Professor Mike Richards, National Clinical Director for Cancer, said: "The evidence linking diet, physical activity, obesity and cancer has become stronger over the last decade and this report can play a part in people adopting healthier lifestyles.
"After not smoking, it is clear that diet, physical activity and weight are the most important things people can do to reduce their cancer risk."
Major step forward
Dr Francesco Branca, Head of Nutrition at the World Health Organization, called the report a major step forward in understanding how policies and actions can help prevent cancer and other chronic diseases.
He said: "The recommendations will inspire policy-makers and decision-takers to act in a way that will play an important role in the fight against cancer."
Richard Davidson, of the charity Cancer Research UK said around 13,000 cancer cases in the UK were linked to being overweight or obese, and even more were linked to poor diet, drinking too much alcohol and not doing enough exercise.
He said: "Doing nothing could be disastrous.
"There is no magic bullet, no one single fix to the problem. If we are to tackle the situation we need individuals, business and government to work together to encourage healthy lifestyles by promoting things like cycle lanes and food labelling."
Estimated percentage of cancers that could be prevented
US UK Brazil China
Mouth, pharynx & larynx 63 67 63 44
Oesophagus 69 75 60 44
Lung 36 33 36 38
Stomach 47 45 41 33
Pancreas 39 41 34 14
Gallbladder 21 16 10 6
Bowel 45 43 37 17
Liver 15 17 6 6
Breast 38 42 28 20
Endometrium (womb) 70 56 52 34
Prostate 11 20 n/a n/a
Kidney 24 19 13 8
12 cancers combined 34 39 30 27
All cancers 24 26 19 20
World Cancer Research Fund
Medicines From The Sea
Norwegian scientists have managed to produce completely new antibiotics from bacteria found in the sea. The eleven species of bacteria that create substances that kill cancerous cells and three other bacteria that produce new antibiotics were discovered by scientists at NTNU and SINTEF.In collaboration with research groups in Moscow and the University of Bergen, they have made breakthroughs in the field of biotechnology. Never before have Norwegian scientists carried out the entire process from gathering bacteria from the fjords to presenting completely new interesting substances in bottles.
Behind their success lies a long and painstaking process of screening, cultivation, isolation and testing. However, it will still take some time before they can be sure that the process will continue to the phases of commercialisation and medicine production.
A network is built up
The NTNU and SINTEF researchers have been bioprospecting for five or six years, searching for interesting substances that are produced by marine bacteria. The wide range of expertise of this research group makes it unique, as it brings together competence in physiology and genetics, and has access to modern screening and fermentation laboratories.
The pace of the process has risen during the past few months, since the recruitment of Professor Stein Ove Døskeland’s group at the University of Bergen. The scientists have also had bacterial fractions tested in Russia.
Ninety percent are of no interest
Many of the bacteria that have been brought up from the Trondheim Fjord have antibiotic functions, but most of these are already known, and are therefore of no interest. New compounds that can be patented are most interesting.
“Substances with a new chemical structure and, we hope, with a different mechanism of action than we already know of, could be extremely valuable, for example in fighting cancer. This is why we need more candidate structures. Not all of them can be developed into new medicines, but if we are successful with one or two of them, we will be quite happy,” says NTNU professor Sergey Zotchev.
Recent focus on a few selected bacteria has led to these exciting findings. In Bergen and Moscow, the 11 anti-cancer substances have been tested against leukemias and stomach, colon and prostate cancers.
“We have found that cancerous cells have been killed, while normal cells survive, and that individual extracts act on different types of cancer cells,” says senior scientist Håvard Sletta of SINTEF. “However, we still have not identified the active substances in the compounds produced by the bacteria”.
Much work still to be done
Meticulous laboratory experiments have enable the scientists to identify the chemical structure of one of the three substances that can be used as antibiotics, and which they now know act against multiresistant bacteria. Towards the end of January, this substance was due to be tested on animals in Moscow. If the results turn out to be positive, the way will be clear for a patent application.
“If it turns out that this substance does not work in animals, the worst that can happen is that there will be a pause in our efforts. However, in many cases, all that is needed to take us further is a chemical modification of the molecule, but that requires a lot of work, and we could be stopped for lack on funding,” says Sergey Zotchev.
“We need to remember that bacteria from the sea produce antibiotics in order to deal with their own natural competitors, rather than to act against infections in the human body”.
Behind their success lies a long and painstaking process of screening, cultivation, isolation and testing. However, it will still take some time before they can be sure that the process will continue to the phases of commercialisation and medicine production.
A network is built up
The NTNU and SINTEF researchers have been bioprospecting for five or six years, searching for interesting substances that are produced by marine bacteria. The wide range of expertise of this research group makes it unique, as it brings together competence in physiology and genetics, and has access to modern screening and fermentation laboratories.
The pace of the process has risen during the past few months, since the recruitment of Professor Stein Ove Døskeland’s group at the University of Bergen. The scientists have also had bacterial fractions tested in Russia.
Ninety percent are of no interest
Many of the bacteria that have been brought up from the Trondheim Fjord have antibiotic functions, but most of these are already known, and are therefore of no interest. New compounds that can be patented are most interesting.
“Substances with a new chemical structure and, we hope, with a different mechanism of action than we already know of, could be extremely valuable, for example in fighting cancer. This is why we need more candidate structures. Not all of them can be developed into new medicines, but if we are successful with one or two of them, we will be quite happy,” says NTNU professor Sergey Zotchev.
Recent focus on a few selected bacteria has led to these exciting findings. In Bergen and Moscow, the 11 anti-cancer substances have been tested against leukemias and stomach, colon and prostate cancers.
“We have found that cancerous cells have been killed, while normal cells survive, and that individual extracts act on different types of cancer cells,” says senior scientist Håvard Sletta of SINTEF. “However, we still have not identified the active substances in the compounds produced by the bacteria”.
Much work still to be done
Meticulous laboratory experiments have enable the scientists to identify the chemical structure of one of the three substances that can be used as antibiotics, and which they now know act against multiresistant bacteria. Towards the end of January, this substance was due to be tested on animals in Moscow. If the results turn out to be positive, the way will be clear for a patent application.
“If it turns out that this substance does not work in animals, the worst that can happen is that there will be a pause in our efforts. However, in many cases, all that is needed to take us further is a chemical modification of the molecule, but that requires a lot of work, and we could be stopped for lack on funding,” says Sergey Zotchev.
“We need to remember that bacteria from the sea produce antibiotics in order to deal with their own natural competitors, rather than to act against infections in the human body”.
Researchers identify potential therapeutic target in osteosarcoma
HOUSTON-A receptor known to be active in bone metastases, but previously unexplored in primary bone tumors, is a potential therapeutic target in osteosarcoma, investigators from The University of Texas M. D. Anderson Cancer Center report in the March 1 issue of Cancer Research.
The researchers found that the protein - interleukin-11 receptor alpha (IL-11Ra) - is highly expressed in primary osteosarcoma and in lung metastases from these tumors. Their research suggests the possibility of delivering therapeutic agents directly to osteosarcoma cells by targeting the receptor with circulating particles that display a peptide mimic of the natural ligand that binds IL-11Ra.
Osteosarcoma is the most common primary malignant tumor of bone. "Existing treatment has not changed the prognosis for osteosarcoma for the last 20 to 30 years," said lead investigator Valerae O. Lewis, M.D., associate professor and chief of Orthopedic Oncology at M. D. Anderson. "About 30 percent of patients still relapse and die of their disease. New therapeutic strategies and agents are needed."
The effectiveness of the current chemotherapy regimens for osteosarcoma is limited by toxic side effects, including damage to the heart and nerves, kidney failure and hearing loss, Lewis noted. Identification of a target specific for osteosarcoma cells opens the door for the development of therapies that can shut down the tumor cells without inflicting the collateral damage caused by conventional osteosarcoma treatments.
IL-11Ra is a target in bone metastasis; far less is known about its attributes, if any, in primary tumors of bone. To address IL-11R? as a potential molecular target in osteosarcoma, the authors confirmed the protein expression and localization of IL-11Ra in several mouse and human osteosarcoma cell lines.
In an orthotopic mouse model of human osteosarcoma, the investigators found that the IL-11Ra not only was markedly present in the primary osteosarcoma and in its metastases but was absent from normal bone marrow and lungs.
To evaluate the accessibility of IL-11Ra as a target, the researchers intravenously administered small, virus-like particles called phages equipped with a peptide that mimics IL-11, the receptor's natural ligand. After 24 hours in circulation, the ligand-directed particles were taken up in the tumors but showed little or no accumulation in several control organs.
"Connecting therapeutic agents to this ligand-directed system might result in improved, targeted drugs," said co-senior author Renata Pasqualini, Ph.D., Professor of Medicine and Cancer Biology in the David H. Koch Center at M. D. Anderson.
"It is conceptually unexpected that a receptor would be over-expressed not only in metastatic tumors to bone but also in primary bone tumors; this is quite important because human osteosarcoma is a malignant tumor with very few targets at the protein level," said co-senior author Wadih Arap, M.D, Ph.D., also Professor of Medicine and Cancer Biology in the David H. Koch Center.
Immunohistochemical staining analysis of IL-11Ra expression in primary and metastatic human osteosarcoma samples provided further evidence of the potential value of IL-11Ra as a therapeutic target. All primary human osteosarcoma samples exhibited moderate-to high-intensity staining of tumor cells. More than half of tumor blood vessels also showed moderate-to-high-intensity staining. All pulmonary metastases were positive for IL-11Ra expression, while normal, control lung tissue was negative.
"This indicates that therapeutic targeting of IL-11Ra may yield anti-tumor, anti-metastasis and anti-angiogenesis effects in osteosarcoma," Lewis said.
Phase I trial of IL-11R for bone metastasis
The U.S. Food and Drug Administration recently issued "safe to proceed" status for an M. D. Anderson-sponsored investigational new drug based on a cell-death-inducing therapy directed at IL-11R. The drug is defined as BMTP-11 (Bone Metastasis Targeting Peptide 11). The first clinical trial, in which BMTP-11 will be evaluated in prostate cancer patients, will soon be activated.
Lewis noted that the research group has initiated pre-clinical studies to measure potential anti-tumor effects of BMTP-11 in osteosarcoma models. If successful, such efforts may lead to a rapid evolution of BMTP-11 toward the management of osteosarcoma.
###
Research was funded by an M. D. Anderson Institutional Research Grant and a Robert Wood Johnson Foundation grant to Lewis and grants from the National Institutes of Health, the U.S. Department of Defense, the Gillson-Longenbaugh Foundation, and the Marcus Foundation, to Arap and Pasqualini.
Co-authors with Lewis, Arap and Pasqualini are Michael G. Ozawa, in the David H. Koch Center M. D. Anderson and an M.D./Ph.D. student in the Graduate School of Biomedical Sciences, operated jointly by The University of Texas Health Science Center at Houston and M. D. Anderson; Guiyang Wang, of the Department of Orthopedic Oncology; Michael T. Deavers, M.D. of M. D. Anderson's Department of Pathology; and Tamaki Shintani, D.D.S., Ph.D., of M. D. Anderson's Department of Radiation Oncology.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For six of the past nine years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.
The researchers found that the protein - interleukin-11 receptor alpha (IL-11Ra) - is highly expressed in primary osteosarcoma and in lung metastases from these tumors. Their research suggests the possibility of delivering therapeutic agents directly to osteosarcoma cells by targeting the receptor with circulating particles that display a peptide mimic of the natural ligand that binds IL-11Ra.
Osteosarcoma is the most common primary malignant tumor of bone. "Existing treatment has not changed the prognosis for osteosarcoma for the last 20 to 30 years," said lead investigator Valerae O. Lewis, M.D., associate professor and chief of Orthopedic Oncology at M. D. Anderson. "About 30 percent of patients still relapse and die of their disease. New therapeutic strategies and agents are needed."
The effectiveness of the current chemotherapy regimens for osteosarcoma is limited by toxic side effects, including damage to the heart and nerves, kidney failure and hearing loss, Lewis noted. Identification of a target specific for osteosarcoma cells opens the door for the development of therapies that can shut down the tumor cells without inflicting the collateral damage caused by conventional osteosarcoma treatments.
IL-11Ra is a target in bone metastasis; far less is known about its attributes, if any, in primary tumors of bone. To address IL-11R? as a potential molecular target in osteosarcoma, the authors confirmed the protein expression and localization of IL-11Ra in several mouse and human osteosarcoma cell lines.
In an orthotopic mouse model of human osteosarcoma, the investigators found that the IL-11Ra not only was markedly present in the primary osteosarcoma and in its metastases but was absent from normal bone marrow and lungs.
To evaluate the accessibility of IL-11Ra as a target, the researchers intravenously administered small, virus-like particles called phages equipped with a peptide that mimics IL-11, the receptor's natural ligand. After 24 hours in circulation, the ligand-directed particles were taken up in the tumors but showed little or no accumulation in several control organs.
"Connecting therapeutic agents to this ligand-directed system might result in improved, targeted drugs," said co-senior author Renata Pasqualini, Ph.D., Professor of Medicine and Cancer Biology in the David H. Koch Center at M. D. Anderson.
"It is conceptually unexpected that a receptor would be over-expressed not only in metastatic tumors to bone but also in primary bone tumors; this is quite important because human osteosarcoma is a malignant tumor with very few targets at the protein level," said co-senior author Wadih Arap, M.D, Ph.D., also Professor of Medicine and Cancer Biology in the David H. Koch Center.
Immunohistochemical staining analysis of IL-11Ra expression in primary and metastatic human osteosarcoma samples provided further evidence of the potential value of IL-11Ra as a therapeutic target. All primary human osteosarcoma samples exhibited moderate-to high-intensity staining of tumor cells. More than half of tumor blood vessels also showed moderate-to-high-intensity staining. All pulmonary metastases were positive for IL-11Ra expression, while normal, control lung tissue was negative.
"This indicates that therapeutic targeting of IL-11Ra may yield anti-tumor, anti-metastasis and anti-angiogenesis effects in osteosarcoma," Lewis said.
Phase I trial of IL-11R for bone metastasis
The U.S. Food and Drug Administration recently issued "safe to proceed" status for an M. D. Anderson-sponsored investigational new drug based on a cell-death-inducing therapy directed at IL-11R. The drug is defined as BMTP-11 (Bone Metastasis Targeting Peptide 11). The first clinical trial, in which BMTP-11 will be evaluated in prostate cancer patients, will soon be activated.
Lewis noted that the research group has initiated pre-clinical studies to measure potential anti-tumor effects of BMTP-11 in osteosarcoma models. If successful, such efforts may lead to a rapid evolution of BMTP-11 toward the management of osteosarcoma.
###
Research was funded by an M. D. Anderson Institutional Research Grant and a Robert Wood Johnson Foundation grant to Lewis and grants from the National Institutes of Health, the U.S. Department of Defense, the Gillson-Longenbaugh Foundation, and the Marcus Foundation, to Arap and Pasqualini.
Co-authors with Lewis, Arap and Pasqualini are Michael G. Ozawa, in the David H. Koch Center M. D. Anderson and an M.D./Ph.D. student in the Graduate School of Biomedical Sciences, operated jointly by The University of Texas Health Science Center at Houston and M. D. Anderson; Guiyang Wang, of the Department of Orthopedic Oncology; Michael T. Deavers, M.D. of M. D. Anderson's Department of Pathology; and Tamaki Shintani, D.D.S., Ph.D., of M. D. Anderson's Department of Radiation Oncology.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For six of the past nine years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.
Rehberg bill gets funds to vets exposed to weapons tests
WASHINGTON — Veterans unknowingly subjected to biological and chemical weapons tests decades ago would get medical coverage for their resulting cancers and other diseases under a bill introduced Thursday by Reps. Denny Rehberg, R-Mont., and Mike Thompson, D-Calif.
“It’s really frustrating to those of us who find it appalling that our own government chooses to have done the tests, but then shirks its responsibility as we start seeing some of the illnesses cropping up,” Rehberg said.
Angered by years of resistance from the departments of Defense and Veterans Affairs to help the affected veterans, the duo vowed to push the bill through the House quickly.
Due to a lack of cooperation and effort, the departments do not even know how many veterans would be affected by the legislation. The two congressmen estimated about 6,000, but said the Vietnam Veterans of America thinks the number is much higher.
The bill comes in the wake of a February report by the Government Accountability Office concluding that the Defense Department and VA need to improve efforts to identify and notify people who may have been exposed during the chemical and biological tests.
The tests were known as Project 112, which included the Shipboard Hazard and Defense project, or SHAD.
*
The Defense Department and other federal agencies conducted Project 112 between 1963 and 1973. Weapons with chemical and biological agents such as VX and Sarin nerve gases and E. coli were tested on unknowing military personnel.
In 2003, the Defense Department had identified 5,842 service members and estimated that about 350 civilians were potentially exposed and said it would stop looking for more, the report said. But the GAO found shortcomings in the department’s efforts and noted that other sources, including the Institute of Medicine, have found at least 600 more people.
Even of those identified by the department, many have not been notified, the report said.
The issue affects some in Montana, including John Olsen of Billings. He has had skin cancer, prostate cancer and an adrenal tumor the size of his fist. He believes that his health problems are linked to the chemical and biological agents to which he was exposed on an Army tugboat in the Pacific Ocean during the tests.
Thompson said the crews stayed below while airplanes flew over barges and sprayed caged animals on the decks. The crews later cleaned the decks using harsh solvents. The military first said the spray was simulated chemical and biological agents, Thompson said, but eventually admitted they were real.
Olsen has said the paper filters designed to prevent the materials from getting through air ducts often deteriorated when they got wet in rough seas.
The Defense Department long denied the existence of the tests, despite questions from lawmakers and reports that many participating veterans had developed highly unusual diseases. The department now admits that the tests took place, but the VA will not provide the veterans with health benefits and compensation for their diseases.
The legislation would require the VA to assume that toxins in the weapons tests caused their health conditions, making them eligible for medical benefits or compensation.
Veterans must provide proof of the connection between their service and health condition. The bill would provide the veterans of Project 112 a “presumption of service connection,” so that dates and location of service — the fact that they were part of the project — would be sufficient to be eligible for health care.
Veterans exposed to Agent Orange during the Vietnam War are given such a status. Rehberg said the bill was loosely crafted after similar legislation on Agent Orange.
The bill would also instruct the VA within 180 days to notify all veterans who were potentially exposed to the biological or chemical weapons used in Project 112 and Project SHAD.
Rehberg said some of the information on the tests is still considered classified, but added, “By God, take care of these veterans.”
Some of the affected veterans died of their health conditions long ago. The bill does not address survivor’s benefits.
The chairman of the House Veterans’ Affairs Committee wants to hold a hearing on the bill quickly and move it to the House floor, Thompson said.
The two congressmen passed similar legislation through the House last year, but the Senate never acted on it. Rehberg said he has not yet worked directly with either of Montana’s senators on moving the bill through that chamber.
The bill has been endorsed by the Vietnam Veterans of America.
Rehberg got involved in the issue shortly after taking office in 2001, when he met with Olsen. The two congressmen have worked on the issue together for years, introducing bills and pushing the Defense Department to provide information and health benefits.
“It’s really frustrating to those of us who find it appalling that our own government chooses to have done the tests, but then shirks its responsibility as we start seeing some of the illnesses cropping up,” Rehberg said.
Angered by years of resistance from the departments of Defense and Veterans Affairs to help the affected veterans, the duo vowed to push the bill through the House quickly.
Due to a lack of cooperation and effort, the departments do not even know how many veterans would be affected by the legislation. The two congressmen estimated about 6,000, but said the Vietnam Veterans of America thinks the number is much higher.
The bill comes in the wake of a February report by the Government Accountability Office concluding that the Defense Department and VA need to improve efforts to identify and notify people who may have been exposed during the chemical and biological tests.
The tests were known as Project 112, which included the Shipboard Hazard and Defense project, or SHAD.
*
The Defense Department and other federal agencies conducted Project 112 between 1963 and 1973. Weapons with chemical and biological agents such as VX and Sarin nerve gases and E. coli were tested on unknowing military personnel.
In 2003, the Defense Department had identified 5,842 service members and estimated that about 350 civilians were potentially exposed and said it would stop looking for more, the report said. But the GAO found shortcomings in the department’s efforts and noted that other sources, including the Institute of Medicine, have found at least 600 more people.
Even of those identified by the department, many have not been notified, the report said.
The issue affects some in Montana, including John Olsen of Billings. He has had skin cancer, prostate cancer and an adrenal tumor the size of his fist. He believes that his health problems are linked to the chemical and biological agents to which he was exposed on an Army tugboat in the Pacific Ocean during the tests.
Thompson said the crews stayed below while airplanes flew over barges and sprayed caged animals on the decks. The crews later cleaned the decks using harsh solvents. The military first said the spray was simulated chemical and biological agents, Thompson said, but eventually admitted they were real.
Olsen has said the paper filters designed to prevent the materials from getting through air ducts often deteriorated when they got wet in rough seas.
The Defense Department long denied the existence of the tests, despite questions from lawmakers and reports that many participating veterans had developed highly unusual diseases. The department now admits that the tests took place, but the VA will not provide the veterans with health benefits and compensation for their diseases.
The legislation would require the VA to assume that toxins in the weapons tests caused their health conditions, making them eligible for medical benefits or compensation.
Veterans must provide proof of the connection between their service and health condition. The bill would provide the veterans of Project 112 a “presumption of service connection,” so that dates and location of service — the fact that they were part of the project — would be sufficient to be eligible for health care.
Veterans exposed to Agent Orange during the Vietnam War are given such a status. Rehberg said the bill was loosely crafted after similar legislation on Agent Orange.
The bill would also instruct the VA within 180 days to notify all veterans who were potentially exposed to the biological or chemical weapons used in Project 112 and Project SHAD.
Rehberg said some of the information on the tests is still considered classified, but added, “By God, take care of these veterans.”
Some of the affected veterans died of their health conditions long ago. The bill does not address survivor’s benefits.
The chairman of the House Veterans’ Affairs Committee wants to hold a hearing on the bill quickly and move it to the House floor, Thompson said.
The two congressmen passed similar legislation through the House last year, but the Senate never acted on it. Rehberg said he has not yet worked directly with either of Montana’s senators on moving the bill through that chamber.
The bill has been endorsed by the Vietnam Veterans of America.
Rehberg got involved in the issue shortly after taking office in 2001, when he met with Olsen. The two congressmen have worked on the issue together for years, introducing bills and pushing the Defense Department to provide information and health benefits.
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