June 4, 2006, 8:51 AM CT

New Drug Combo For Kidney Cancers

By using a new combination of two anticancer drugs, scientists at Duke University Medical Center have dramatically improved response rates of patients with metastatic kidney cancer, which is now generally considered incurable.

The results suggest that combining the two drugs may slow the disease's progression in significant numbers of patients, eventhough the drug combination is not a cure, said the researchers.

In the study, 40 percent of patients who received the newly approved drug sorafenib together with the established drug interferon-alpha experienced "major shrinkage" of their kidney tumors and tumors that had metastasized, or spread elsewhere. A "major" response is generally is defined as 30 percent or greater shrinkage of all tumors in the body.

In comparison, only 5 percent of patients who receive sorafenib alone show a major response, recent studies have shown. Similarly, just 10 percent to 15 percent of patients who receive only interferon alpha, considered the standard therapy for kidney cancer, show a major response.

"By combining the drugs, we are seeing more major responses in greater numbers of patients, but we don't yet know how long the responses will last," said Jared Gollob, M.D., associate professor of medicine and immunology at Duke. "There are great new drugs on the market with relatively low toxicity, but the question physicians now face is how to make them work better for patients."........

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June 4, 2006, 8:38 AM CT

Gene Therapy Protects Mice From Radiation

University of Pittsburgh School of Medicine scientists have successfully protected mice against the damaging effects that radiation can have on bone marrow using gene treatment. Based on these results, the scientists believe this approach may be able to protect first responders in the event of a radiological accident or the detonation of a crude radiological weapon, or "dirty bomb." The findings are being presented at the American Society of Gene Therapy annual meeting in Baltimore, May 31 to June 4.

Since the events of Sept.11, there has been growing concern that terrorists may use a dirty bomb--a conventional explosive wrapped in radiological material--or attack a nuclear power facility to disperse high-dose radiation across a populated area. Experts believe a significant number of the population would die within 30 days of exposure to a high dose of radiation from such an event, which has prompted the federal government to fund efforts to develop medical interventions against radiological and nuclear threats.

In this study, Pitt scientists used gene treatment to deliver the compound manganese superoxide dismutase-plasmid liposome (MnSOD-PL) to the cells of female mice. Twenty-four hours later, groups of mice that received the therapy and control mice that did not were exposed to varying doses of whole body radiation. Following irradiation, the mice were weighed daily and observed for signs of irradiation-induced damage to their bone marrow. Control mice irradiated at the higher doses lost weight and died fairly rapidly due to bone marrow damage. In contrast, mice treated with the MnSOD-PL gene treatment showed no changes in body weight, had little bone-marrow damage, and lived longer compared to the control irradiated mice.........

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June 4, 2006, 8:35 AM CT

Gene Therapy For Ovarian Cancer

University of Pittsburgh School of Medicine scientists have used gene treatment to either completely abolish or significantly inhibit tumor progression in a mouse model of ovary cancer. The scientists believe these findings, which are being presented at the American Society of Gene Therapy annual meeting in Baltimore, May 31 to June 4, may significantly improve the prognosis for ovary cancer patients.

Ovary cancer is diagnosed in more than 25,000 women in the United States each year, and about 16,000 American women die from the disease annually. Despite aggressive surgery and chemotherapy approaches, the prognosis for ovary cancer is poor, and most women have a life expectancy of only three to four years after their diagnoses.

In this study, the Pitt researchers inoculated mice with an ovary cancer cell line. They treated some of the mice immediately with a genetically engineered vaccinia virus containing a gene coding cytosine deaminase, a suicide gene, and delayed therapy of other mice for 30 or 60 days. Control mice were inoculated with ovary cancer cells but were not given the gene treatment.

The scientists found complete inhibition of tumor growth in the mice that were treated immediately with gene treatment and significant tumor inhibition in the 30- and 60-day delayed therapy mice. In contrast, all non-gene-therapy treated mice either died or were euthanized due to overwhelming buildup of fluid in the peritoneal cavity by 94 days following tumor inoculation.........

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June 4, 2006, 8:30 AM CT

Switch From Tamoxifen To Aromasin

New data from the Intergroup Exemestane Study (IES) showed for the first time today that hormone sensitive postmenopausal early breast cancer patients who switched to Aromasin after 2 to 3 years of tamoxifen were 17% more likely to be alive and were 25% less likely to have their cancer return than patients who continued on tamoxifen for a full 5 years of therapy.

"Exemestane is the only anti-hormonal therapy that has been shown to demonstrate improved overall survival over tamoxifen alone," said Lead Investigator Professor Charles Coombes, director of cancer medicine, Imperial College, London. These significant survival benefits were seen in patients who are considered hormone sensitive, which represents 97% of the study population. Although not statistically significant in the intent to treat population, 15% of patients taking Aromasin were more likely to be alive versus those that continued on tamoxifen. These new findings were based on nearly 5 years of follow-up after randomization in the IES trial. IES was a large randomized double blind multinational trial of postmenopausal women with early breast cancer which was designed to compare the clinical benefits of switching 2352 patients to Aromasin after 2 to 3 years of tamoxifen versus continuing 2372 patients on tamoxifen for a full 5 years of therapy. The 5 year follow-up time includes a period of observation lasting over 2 years after completion of all treatment. ........

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June 4, 2006, 8:26 AM CT

Three-drug Combo In Head And Neck Cancers

The addition of docetaxel (Taxotere) to an initial chemotherapy regimen for inoperable head and neck cancers reduced mortality by nearly 30 percent over three years following therapy compared to the standard two-drug combination, scientists from Dana-Farber Cancer Institute in Boston will report at the American Society of Clinical Oncology's annual meeting in Atlanta.

The survival advantage emerged from an international clinical trial of more than 500 patients with squamous cell carcinoma of the head and neck treated with a sequential regimen that included induction chemotherapy and chemoradiotherapy, explains Marshall R. Posner, MD, director of head and neck oncology at Dana-Farber.

"This changes the standard of care for chemotherapy and radiation for head and neck cancer in this country," says Posner, who will present the data at a scientific special session on head and neck cancers on Sunday, June 4, 1 p.m., Building C, Level 1, Hall C4.

In recent years, Posner and his colleagues at Dana-Farber have developed a multi-modality treatment for inoperable, locally advanced head and neck cancers that can reduce the need to remove critical organs while giving the patient good odds of survival. The first phase is induction chemotherapy with a combination of drugs followed by simultaneous fractionated radiation treatment and weekly therapy with carboplatin chemotherapy. Patients then have surgery if needed.........

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June 1, 2006, 7:16 PM CT

Cancer Worries Continue

The doctor may give the cancer patient a clean bill of health, but worries about recurrences, lingering effects from therapy, a second cancer and a shortened life plague the thoughts of approximately one-third of long-term, older-adult cancer survivors, as per scientists from Case Western Reserve University's Cancer Survivor Research Project. This is one of the first studies to look at the worries experienced by long-term survivors.

It may be that these long-term survivors of five or more years after the end of their therapys may be worriers in general, said Gary Deimling, Case professor of sociology and lead investigator on the "Cancer-Related Health Worries and Psychology Distress among Older Adult, Long-Term Cancer Survivor" article in the journal, Psycho-Oncology.

But he adds that it raises concerns that cancer continues to impact survivors' lives.

Overall most survivors are not letting these worries compromise the quality of their lives either physically or psychologically, report Deimling and co-researchers Karen Bowman, Samantha Stern, Louis Wagner from Case's sociology department and Boaz Kahana from Cleveland State University, but these worries are linked to both depression and anxiety.

The researchers' concerns led to the study of 321 long-term survivors of breast, colorectal or prostate cancer in National Cancer Institute-funded Cancer Survivors Research Project at Case.........

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June 1, 2006, 7:04 AM CT

Novel Treatment Strategy For Sarcoma

Using molecular and cell-based models, scientists at Georgetown University Medical Center have refined the picture of how a cancer-promoting protein associated with Ewing's sarcoma functions. And in the process, they have hit upon a possible strategy for therapy of the cancer, which is a rare and highly cancerous cancer that most often strikes teens and young adults.

In the June 1st issue of the journal Cancer Research, published by the American Association for Cancer Research, the scientists report that the oncoprotein, EWS-FLI1, teams up with a helicase protein that bends the shape of RNA, and together they work to promote or repress transcription of various other proteins, leading to cancer development.

But because it is not possible to directly shut down helicase proteins, given their vital general role in protein transcription, and given that no one has figured out how to clinically inactivate EWS-FLI1 alone, the scientists propose driving a wedge-like drug between the two proteins that would eliminate their interaction.

"Proteins are three-dimensional structures, and the space between EWS-FLI1 and the helicase might be targetable by a small molecule that keeps the proteins apart," says the study's lead author Jeffrey Toretsky, M.D., an associate professor in the departments of Oncology and Pediatrics at the Lombardi Comprehensive Cancer Center. "It could render EWS-FLI1 harmless while not affecting its partnering helicase protein."........

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June 1, 2006, 6:59 AM CT

Environmental Estrogens Increases Prostate Cancer Risk

A study in the June 1 issue of Cancer Research presents the first evidence that exposure to low doses of environmental estrogens during development of the prostate gland in the male fetus may result in a predisposition to prostate cancer during the later part of life.

The study, done in an animal model, also demonstrates how the predisposition may arise, and a way to identify those at risk.

Man-made compounds that can mimic the hormone action of estrogens (xenoestrogens) are widespread in the environment. One of these agents is bisphenol A (BPA), used in the manufacture of plastics and epoxy resins. The United States alone produces over 1.6 million pounds of BPA annually. BPA, which can also leach from plastics when heated, turns up in human blood and in placental and fetal tissues in even higher concentrations.

In this study, a research team led by Dr. Gail Prins of the University of Illinois at Chicago and Dr. Shuk-Mei Ho of the University of Cincinnati exposed rats to low doses of estradiol, a natural estrogen, or to BPA during the developmental period corresponding to the second and third trimester of human pregnancy. They found that this early exposure predisposed male rats to premalignant lesions of the prostate in old age.

"Most remarkably, early BPA exposure sensitized the prostate to premalignant lesions brought on by exposure of the adult animal to elevated estradiol," said Prins, professor of urology at UIC and senior author of the study. "This is highly relevant to people, because relative estradiol levels increase in aging men as a result of their increased body fat and declining testosterone levels."........

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June 1, 2006, 6:55 AM CT

Promising Results For Advanced Lung Cancer

An early phase study pairing an experimental targeted treatment with a common anti-inflammatory produced promising results in patients with advanced lung cancer, scientists at UCLA's Jonsson Cancer Center reported.

Pairing the targeted treatment Tarceva with the anti-inflammatory drug Celebrex increased response rates in lung cancer patients by about three-fold, said Dr. Karen Reckamp, an assistant professor of hematology/oncology and lead author of the study. The research appears in the June 1 issue of Clinical Cancer Research, the peer-reviewed journal of the American Association of Cancer Research.

Prior laboratory studies at UCLA showed that a cell signaling pathway known as COX-2 may be linked to resistance to drugs like Tarceva, which block tumor cell growth by targeting the protein EGFR, or epidermal growth factor receptor. Scientists theorized that giving Tarceva with Celebrex, a COX-2 inhibitor, would help battle resistance and prove to be an affective combination against lung cancer.

Typically, about 10 percent of lung cancer patients respond to Tarceva. In Reckamp's study of the combination treatment, about 33 percent of patients responded.

"Tarceva alone is a great drug and has a lot of clinical benefits, but for a small proportion of patients," Reckamp said. "With this drug combination, we saw an increase in response rates, indicating we are overcoming some resistance. We also may be beginning to understand the mechanisms of that resistance."........

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May 31, 2006, 9:29 PM CT

Anti-epileptic Drug Could Help Beat Cancer

A new combination of two drugs, including one usually used in the therapy of epilepsy, has proved effective at killing cancer cells, as per research reported in the British Journal of Cancer* today.

The results, from the Section of Thoracic Oncology, Surgery Branch, of the National Cancer Institute's Center for Cancer Research in the United States, raise the prospect of a new form of chemotherapy to treat a number of types of cancer. The advantage of this combination is that the anti-epileptic, called valproic acid, is a NICE-approved drug, and the second compound, called UCN-01, has been used in clinical trials. Scientists therefore already know a lot about the effects of these molecules on the human body.

If successful, this combined treatment would be another example of medical compounds in use for other conditions later being developed for treating and preventing cancer. In recent years, for example, the household painkiller aspirin has shown promising anticancer properties in clinical trials. Valproic acid has a weak anticancer effect on its own but in this new combination it becomes highly effective against cancer cells.

Principal investigator Dr Dao Nguyen said: "We are very encouraged by these latest results, and strongly think that drug combinations including valproic acid will, in time, reach the clinic and help cancer patients".........

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