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duminică, 5 august 2012

Teen Survival Expectations Predict Later Risk-Taking Behavior

Some young people's expectations that they will not live long, healthy lives may actually foreshadow such outcomes.

New research published in the open access journal PLOS ONE reports that, for American teens, the expectation of death before the age of 35 predicted increased risk behaviors including substance abuse and suicide attempts later in life and a doubling to tripling of mortality rates in young adulthood.

The researchers, led by Quynh Nguyen of Northeastern University in Boston, found that one in seven participants in grades 7 to 12 reported perceiving a 50-50 chance or less of surviving to age 35. Upon follow-up interviews over a decade later, the researchers found that low expectations of longevity at young ages predicted increased suicide attempts and suicidal thoughts as well as heavy drinking, smoking, and use of illicit substances later in life relative to their peers who were almost certain they would live to age 35. "The association between early survival expectations and detrimental outcomes suggests that monitoring survival expectations may be useful for identifying at-risk youth," the authors state.

The study compared data collected from 19,000 adolescents in 1994-1995 to follow-up data collected from the same respondents 13-14 years later. The cohort was part of the National Longitudinal Study of Adolescent Health (Add Health), conducted by the Carolina Population Center and funded by the National Institutes of Health and 23 other federal agencies and foundations.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our mental health section for the latest news on this subject. Citation: Nguyen QC, Villaveces A, Marshall SW, Hussey JM, Halpern CT, et al. (2012) Adolescent Expectations of Early Death Predict Adult Risk Behaviors. PLoS ONE 7(8): e41905. doi:10.1371/journal.pone.0041905
Financial Disclosure: The authors have no support or funding to report.
Competing Interest Statement: The authors have declared that no competing interests exist.
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vineri, 9 decembrie 2011

Proteins Do Not Predict Outcome Of Herceptin Treatment In HER2-Positive Breast Cancer

Main Category: Breast Cancer
Article Date: 09 Dec 2011 - 2:00 PST

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Precisely quantifying the amount of three different HER growth proteins, along with several other proteins believed linked to breast cancer, did not predict a patient's outcome after treatment for HER2-Positive Breast Cancer with Herceptin, say Mayo Clinic researchers. HER2-positive breast cancer gets its name from a protein called human epidermal growth factor receptor 2 that promotes cancer cell growth.

The finding, presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, represents a disappointment to oncologists who had hoped to find distinct biomarkers beyond standard HER2 testing that could help them gauge how well Herceptin will work for patients.

"This study debunks the hopeful notion, strongly felt in the breast cancer community, that measuring levels of a number of different proteins in the HER2 family could help oncologists better tailor their use of Herceptin," says the study's senior investigator, Edith Perez, M.D., director of Mayo Clinic's Breast Program in Florida.

"Improving our ability to predict the benefit of Herceptin treatment beyond testing for HER2 protein and genes remains an important goal, but we are not there yet," she says.

Currently, patients are considered eligible for Herceptin if a pathologist estimates that at least 10 percent of their tumor samples test positive for HER2 growth proteins. However, the test is relatively subjective, based on a HER2 stain on a slide of tumor tissue. While the test can predict the outcome of Herceptin treatment, which shuts down the HER2 growth receptor for some patients, it cannot do so for all patients, Dr. Perez says.

Researchers used a tool that precisely measures the amount of a protein expressed in a cancer sample. According to Dr. Perez, this study was the first to meticulously measure protein levels, including HER2, HER3, HER4, EGFR (epidermal growth factor receptor), ER (estrogen receptor), and PTEN (a tumor suppressor gene) in almost 1,400 tumor biopsies.

Many researchers thought that analysis of the HER3 protein might be a good predictive marker because HER2 and HER3 interact together to promote cancer growth, Dr. Perez says.

"A biopsy could have 80 percent HER3 protein, and it wouldn't be any different in terms of a patient's outcome from Herceptin use than a tumor that had 5 percent HER3 protein," she says.

The next step to finding predictive biomarkers showing a benefit to Herceptin use will be to look at multi-gene profiles, not single biomarkers, Dr. Perez says.

The study was led by Dr. Perez and her team at Mayo Clinic with the collaboration of David Rimm, M.D., Ph.D., at Yale School of Medicine, and investigators who enrolled patients in the N9831 trial throughout the United States. The work was funded by the National Institutes of Health and the Breast Cancer Research Foundation. The original N9831 patient study was partially supported by the National Cancer Institute and Genentech.

Article adapted by Medical News Today from original press release. Source: Elsevier
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joi, 8 decembrie 2011

How To Better Predict Success In HIV Prevention Clinical Trials

Main Category: HIV / AIDS
Also Included In: Preventive Medicine; Clinical Trials / Drug Trials
Article Date: 08 Dec 2011 - 3:00 PST

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New research from the University of North Carolina at Chapel Hill schools of medicine and pharmacy may help explain the failure of some recent clinical trials of prevention of HIV infection, compared to the success of others that used the same drugs.

The study published online December 7, 2011 in the journal Science Translational Medicine, also suggests how to improve the chances for success, even before the research begins. These suggestions are reinforced in an editorial by several of the UNC authors writing in The Lancet, also published online December 7, 2011.

Over the past two years, results from several clinical trials involving pre-exposure prophylaxis (PrEP) for HIV infection have been a mixed bag of successful prevention and futility. Reports described varying degrees of successful HIV infection prevention in four trials and failure in two others. In all the PrEP trials, the drugs used were tenofovir (TFV) and emtricitabine (FTC) in daily oral and/or gel combinations.

These drugs have been shown to be protective against HIV infection in animal PrEP studies and are now being used clinically, and tenofovir is considered the backbone of HIV therapy, both used orally and topically.

The new UNC study looked at drug concentrations in the mucus membrane tissues that are most susceptible to HIV infection: the tissue lining the vagina, cervix and rectum.

The study was led by Angela D.M. Kashuba, PharmD, professor in the UNC Eshelman School of Pharmacy and director of the UNC Center for AIDS Research Clinical Pharmacology and Analytic Chemistry Core. She also is a member of the UNC Institute for Global Health & Infectious Diseases.

"We did this study to understand how much drug got into these tissues and how long they lasted over two weeks," Kashuba said. And after giving normal, healthy volunteers a single pill combination of TFV/FTC, "What we found over the next 14 days was somewhat surprising. When a person takes a drug, it doesn't end up in the same concentration in different tissues."

Indeed, concentrations of tenofovir were 100 times higher in rectal tissue than in vaginal or cervical tissue. "And FTC achieved concentrations 10 to 15 times higher in vaginal and cervical tissue than they were in rectal tissue," Kashuba said.

"And this raised some questions: because of these discrepancies can the two drugs be used equally well in both populations women at risk for HIV infection and men at risk for HIV infection? And are the concentrations achieved even after a single dose high enough to prevent HIV infections?"

According to Kashuba, it's clear from the recent clinical studies that drug concentration in tissue may make a difference in effectiveness. For example, in one of the placebo-controlled PrEP clinical trials involving men who have sex with men, the combination of these drugs provided about 44 percent effectiveness overall.

But the half the men given the active form of the drugs had no detectable drug in their system when they were sampled during the study and, therefore, were not taking it consistently every day. Thus, the high tenofovir concentrations in rectal tissue could explain the relatively high efficacy of 44 percent.

Results of a PrEP clinical trial (VOICE) conducted in heterosexual women in Uganda, South Africa and Zimbabwe, also paralleled the UNC findings. The daily tenofovir arm was stopped because no protection was seen for the drug taken daily. "If these women did not take the drug every single day, we think our study supports the fact there would not be good efficacy because tenofovir drug concentrations in the vagina and cervix are so much lower than what we see in rectal tissue, Kashuba said."

The authors of the study and the editorial say adherence to taking the drug as prescribed is crucial. They lament that the only prospective means of measuring adherence now available is what the patient reports. "And so if you ask someone did you take all your doses, most will say yes," Kashuba said "People want to be considered good study participants, and sometimes they just can't remember how many doses they took last week, or in the last month, be it almost all of the doses or half of them."

The UNC researcher points to lessons learned: "Before delving into a clinical trial, we need to keep in mind that when someone takes a pill, you can't assume that the drug gets in all places at the same amount. And before we can select the drugs and the right doses for a clinical trial, we need to know what concentrations in tissue prevent HIV infection. They could be different."

And along with the above, the authors emphasize the need to develop ways to objectively measure drug-taking behavior in clinical studies so that the research can be designed and interpreted correctly.

The study was funded in part from the National Institutes of Health, the UNC Center for AIDS Research, the UNC TraCS Clinical Translational Research Center, and the Gilead Sciences Investigator Initiated Research Program.

Article adapted by Medical News Today from original press release. Source: University of North Carolina
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In Early Vs. Late Hormone Receptor-Positive Breast Cancer, Molecular Differences May Be Used To Predict Breast Cancer Recurrence

Main Category: Breast Cancer
Also Included In: Genetics
Article Date: 08 Dec 2011 - 0:00 PST

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Researchers may have discovered a series of genes that will help predict whether or not a woman with hormone receptor-positive invasive breast cancer will experience early, late or no recurrence of her disease.

Minetta C. Liu, M.D., associate professor of medicine and oncology and director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center, presented the findings at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

"There are clear biological differences within the supposedly unified group of hormone receptor (HR)-positive breast cancers, and these differences distinguish subtypes relative to the time at which they recur," Liu said. "Understanding what drives these distinctions will allow us to tailor treatment and improve patient outcomes."

Women with HR-positive breast cancer are frequently treated with tamoxifen, which is credited with saving the lives of hundreds of thousands of women. Although tamoxifen prevents or delays cancer recurrence in many women, some will recur 10 years or more from their original diagnosis. Until now, the molecular basis for this recurrence pattern was unknown.

Liu and colleagues, in collaboration with investigators from the University of Edinburgh, evaluated high-quality frozen tumor samples obtained at the time of breast cancer diagnosis. These tissue samples were linked to data on treatment and clinical outcomes, allowing researchers to analyze gene expression patterns present before the initiation of any systemic therapy.

Together with engineers at Virginia Polytechnic Institute, Liu and colleagues identified significant gene expression patterns among the tumor samples. These patterns correlated strongly with the development of distant metastatic disease.

"We confirmed what many have already suspected," said Liu. "There are biological drivers that define - at the time of tumor development - whether or not breast cancer will recur early, late or not at all. Now we need to validate these findings and take our knowledge to the next step."

Liu hopes that this research can be used to help personalize treatment in day-to-day clinical practice. "Endocrine therapy and chemotherapy are not without toxicity," she said. "The ability to predict which patients will recur early in their treatment course can lead to more appropriate recommendations for adjuvant chemotherapy. It might also identify those women who would benefit most from studies using investigational agents to enhance the effects of tamoxifen or aromatase inhibitors."

She added: "At the other extreme are those patients with HR-positive tumors who recur long after completing five years of endocrine therapy. These are the patients for whom extended endocrine therapy and its related side effects are really worth it."

The team's next step is to validate their predictive model for the timing of recurrences on tamoxifen so that physicians and patients can make more informed decisions about the potential added benefits of adjuvant chemotherapy, extended endocrine therapy and involvement in clinical trials. They will also investigate combinations of molecular targets with the ultimate goal of delaying or preventing the development of metastatic breast cancer, Liu said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

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American Association for Cancer Research. "In Early Vs. Late Hormone Receptor-Positive Breast Cancer, Molecular Differences May Be Used To Predict Breast Cancer Recurrence." Medical News Today. MediLexicon, Intl., 8 Dec. 2011. Web.
8 Dec. 2011. APA
American Association for Cancer Research. (2011, December 8). "In Early Vs. Late Hormone Receptor-Positive Breast Cancer, Molecular Differences May Be Used To Predict Breast Cancer Recurrence." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/238755.php.

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