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From Medicineworld.org: Ovarian Cancer News Blog

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July 5, 2011, 8:17 PM CT

Biomechanics of ovarian cells

Biomechanics of ovarian cells
Masoud Agah directs Virginia Tech's Microelectromechanical Systems Laboratory or VT MEMS Lab. The lab resides within the Bradley Department of Electrical and Computer Engineering and is affiliated with the Department of Mechanical Engineering and the MicrON Research Group. Some of its recent work includes: the development of micro gas analyzers for environmental and health-care applications, and biochips for cancer diagnosis and cancer treatment monitoring.

Credit: Virginia Tech Photo


Using ovarian surface epithelial cells from mice, scientists from Virginia Tech have released findings from a study that they believe will help in cancer risk evaluation, cancer diagnosis, and therapy efficiency in a technical journal: Nanomedicine http://www.nanomedjournal.com/article/S1549-9634%2811%2900184-5/abstract.

By studying the viscoelastic properties of the ovarian cells of mice, they were able to identify differences between early stages of ovary cancer and more advanced and aggressive phenotypes.

Their studies showed a mouse's ovarian cells are stiffer and more viscous when they are benign. Increases in cell deformation "directly correlates with the progression from a non-tumor non-malignant cell to a cancerous one that can produce tumors and metastases in mice," said Masoud Agah, director of Virginia Tech's Microelectromechanical Systems (MEMS) Laboratory http://www.ece.vt.edu/mems/ and the lead investigator on the study.

Their findings are consistent with a University of California at Los Angeles study that reported lung, breast, and pancreatic metastatic cells are 70 percent softer than non-malignant cells. http://www.nature.com/nnano/journal/v2/n12/full/nnano.2007.388.html.

The findings also support Agah group's prior reports on elastic properties of breast cell lines. The digital object identifiers to find the studies on the web are: doi:10.1016/j.biomaterials.2010.05.023.........

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December 13, 2010, 6:49 AM CT

Biological diversity of ovarian cancer

Biological diversity of ovarian cancer
Cancer prevention experts have long been frustrated by the lack of a meaningful way to screen women for ovary cancer. It is a relatively rare disease that often progresses with few symptoms until it is too late for potentially curative therapys, and elevated values of the most usually used biomarker used in screening, CA125, are also correlation to other disorders.

Now, researchers at the Duke Cancer Institute say that incorporating the latest information about the biological diversity of ovary cancer appears to lessen the potential value of screening even further.

"I feel that what this and other studies are telling us is that we will have to do a whole lot more than screening to protect women from this terrible disease," said Laura Havrilesky, MD, an associate professor of gynecologic oncology at Duke and the main author of the study appearing in the journal CANCER "We need to work harder to find better approaches to screening and also consider the potential value of preventive strategies." .

Until recently, ovary cancer has been regarded as a single disease. But studies at Duke and elsewhere have shown that it has at least two distinct subtypes, a slow-growing, indolent form, which takes months to years to move into an advanced stage, and a more aggressive variety driven by key gene mutations that gallops through stages I and II in about half that time.........

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October 11, 2010, 7:41 AM CT

Investigational ovarian cancer drug shows promise

Investigational ovarian cancer drug shows promise
A drug being developed as a therapy for ovary cancer has shown single agent activity with durable disease control in some patients in a Phase-II clinical trial, an international research group has reported.

Dr Ursula Matulonis from Dana-Farber Cancer Institute in the USA reported the results of the single-agent trial of the drug, called MLN8237, in a poster at the 35th Congress of the European Society for Medical Oncology (ESMO).

MLN8237 selectively inhibits an enzyme known as Aurora A kinase, which is a member of a family of kinase enzymes involved in normal cell division. Scientists have observed that Aurora A kinase is over-expressed in some cancer cells, leading to growth of cancers.

"In epithelial ovary cancer, Aurora A kinase has been reported to be frequently upregulated or overexpressed, and linked to worse clinical outcome," Dr Matulonis said. "This is why an effective Aurora A Kinase inhibitor is a potential new treatment to be used alone or in combination with other standard agents such as paclitaxel".

In addition to ovary cancer, the Aurora A kinase gene is amplified or overexpressed, or both, in other cancers including colon, breast, pancreatic, and bladder cancers, as well as certain lymphomas, leukemias and myeloma.

Unlike other aurora kinase inhibitors currently being studied, MLN8237 selectively targets aurora A Kinase and can be administered orally, Dr Matulonis said.........

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September 20, 2010, 7:18 AM CT

New genetic links to ovarian cancer risk

New genetic links to ovarian cancer risk
An international consortium of researchers has discovered new genetic variants in five regions of the genome that affect the risk of ovary cancer in the general population, as per two separate studies published recently (Sunday), online in Nature Genetics

The consortium, including researchers from the U.S., Europe, Canada and Australia, based the new work on their earlier research comparing 10,283 women with ovary cancer to 13,185 women without the disease. That effort had found a stretch of DNA on chromosome 9 containing single DNA letter variations (SNPs) linked to ovary cancer risk.

The scientists have now found additional stretches of DNA on chromosomes 2, 3, 8, 17 and 19 after grouping patients as per the type of ovary cancer they had developed. Four out of five of the new DNA variations were more common in women who had developed the most common and aggressive form of disease, known as serous ovary cancer.

Andrew Berchuck, MD, professor of gynecologic oncology at Duke University Medical Center and head of the steering committee of the international Ovarian Cancer Association Consortium (OCAC), says the associations of these genetic variants with ovary cancer were discovered using genome-wide association studies (GWAS).

"Since the critical validation of these findings waccording toformed by a large consortium of researchers from around the world, we see this research as a triumph of science without borders for the benefit of women everywhere."........

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August 11, 2010, 7:35 PM CT

New Ovarian Cancer Tests Have High Accuracy

New Ovarian Cancer Tests Have High Accuracy
Researchers at the Georgia Institute of Technology have attained very promising results on their initial investigations of a new test for ovary cancer. Using a new technique involving mass spectrometry of a single drop of blood serum, the test correctly identified women with ovary cancer in 100 percent of the patients tested. The results can be found online in the journal Cancer Epidemiology, Biomarkers, & Prevention Research.

"Because ovary cancer is a disease of relatively low prevalence, it's essential that tests for it be extremely accurate. We believe we may have developed such a test," said John McDonald, chief research scientist at the Ovarian Cancer Institute (Atlanta) and professor of biology at Georgia Tech.

The measurement step in the test, developed by the research group of Facundo Fernandez, associate professor in the School of Chemistry and Biochemistry at Tech, uses a single drop of blood serum, which is vaporized by hot helium plasma. As the molecules from the serum become electrically charged, a mass spectrometer is used to measure their relative abundance. The test looks at the small molecules involved in metabolism that are in the serum, known as metabolites. Machine learning techniques developed by Alex Gray, assistant professor in the College of Computing and the Center for the Study of Systems Biology, were then used to sort the sets of metabolites that were found in malignant plasma from the ones found in healthy samples. Then, McDonald's lab mapped the results between the metabolites found in both sets of tissue to discover the biological meaning of these metabolic changes.........

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July 6, 2010, 7:08 AM CT

Advances in chemotherapy of ovarian patients

Advances in chemotherapy of ovarian patients
Investigators at the Translational Genomics Research Institute (TGen) have discovered a way that may help ovary cancer patients who no longer respond to conventional chemotherapy.

A scientific paper that would be reported in the recent issue of the journal Gynecologic Oncology describes how the inhibition of a protein, CHEK1, appears to be an effective element to incorporate into therapies for women with ovary cancer.

The research led by TGen's Dr. David Azorsa, a Senior Investigator, and Dr. Shilpi Arora, a Staff Scientist, observed that inhibiting CHEK1 by a small molecule known as PD 407824, enabled ovary cancer cells to be attacked again by cisplatin, a widely used platinum-based chemotherapy drug for women with ovary cancer.

"PD 407824 is only available for laboratory research, but other drugs inhibiting CHEK1 are already used to treat patients in the clinic," said Dr. Raoul Tibes, one of the paper's senior a co-authors and an Associate Investigator in TGen's Clinical Translational Research Division.

The prognosis remains poor for patients with ovary cancer, which kills nearly 14,600 women in the U.S. annually. The standard therapy for cancer of the ovaries, which produce human egg cells, is surgical removal of the cancer, followed by chemotherapy.........

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June 17, 2010, 7:23 AM CT

Early detection of ovarian cancer

Early detection of ovarian cancer
Joshua LaBaer
Despite a number of research advances, ovary cancer remains lethal in a majority of cases, due to late diagnosis of the disease. In a newly released study, Dr. Joshua LaBaer of the Biodesign Institute at Arizona State University, along with Arturo Ramirez and Paul Lampe, scientists at the Fred Hutchinson Cancer Research Center in Seattle, used a novel method for identifying biomarkers-proteins in blood that can identify ovary cancer before symptoms appear.

The work, which appeared recently in the journal Molecular and Cellular Proteomics, holds the potential for significant improvements in patient survival rate. The research is part of the Early Detection Research Network program of the National Cancer Institute.

As LaBaer notes, ovary cancer is an attractive target for biomarker study. "This is a disease for which an early diagnostic test would make an enormous difference in the health of women." Highly treatable in its early stage, ovary cancer is typically not identified until it has progressed to stage 3 or beyond. Often, it is detected accidentally, in the course of some other test or procedure, for example, during an oophorectomy. "By the time it's caught," LaBaer says, "it has commonly speckled the abdomen with advanced tumors".

At present, only one reliable biomarker for ovary cancer exists. Known as CA 125, this protein is produced on the surface of cells and released into the bloodstream. Elevated levels of CA 125 are indicative of ovary cancer, but testing for CA 125 alone is not adequate. Such tests can produce both false positive and false negative results. Further, the level of CA 125 tends to go up in proportion to tumor growth, sometimes providing good evidence only after the disease has reached its later, terminal stages.........

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June 9, 2010, 11:22 PM CT

Chemotherapy of Late-stage ovarian cancer

Chemotherapy of Late-stage ovarian cancer
The combination of decitabine and carboplatin appears to improve the outcome of women who have late-stage ovary cancer. In an upcoming issue of the journal Cancer (online today), Indiana University scientists report four of 10 patients who participated in a phase I clinical trial had no disease progression after six months of therapy. One patient experienced complete resolution of tumor tissue for a period of time.

Advanced ovary cancer is often diagnosed too late for therapy to be effective. Patients are often told they have virtually no chance of recovery and only months to live.

Women participating in the study were between 51 and 71, and had previously exhausted all approved therapys for ovary cancer. They enrolled in an Indiana University Melvin and Bren Simon Cancer Center clinical trial designed to increase their sensitivity to the usually prescribed ovary cancer drug, platinum-based carboplatin.

Women with ovary cancer commonly survive less than one year after they become resistant to carboplatin and their cancer recurs, said co-principal investigator Daniela Matei, M.D., an associate professor of medicine at the Indiana University School of Medicine. Matei led the clinical portion of the trial.

"Carboplatin is the most efficient drug treatment for ovary cancer," Matei said. "Unfortunately, patients with recurrent disease become resistant to the drug after one or two rounds."........

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June 6, 2010, 8:40 PM CT

New treatment regimen for ovarian cancer

New treatment regimen for ovarian cancer
Newly reported results from a major clinical trial show that adding bevacizumab (Avastin) to standard frontline chemotherapy for women with advanced ovary cancer and then continuing one of the majortenance dose of the drug afterwards significantly extends progression-free survival. Women receiving the new therapy regimen saw no worsening of their disease for 14.1 months, in comparison to 10.3 months for women receiving standard treatment.

The international, multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial was conducted by a network of scientists known as the Gynecologic Oncology Group (GOG) and sponsored by the U.S. National Cancer Institute. The trial results were presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO).

The trial marked the first time a molecularly targeted agent has been part of a validated strategy for treating advanced ovary cancer. It was also the first time one of the majortenance dosing approach involving any treatment has been outlined for the disease. Additionally, ongoing analysis of the trial data may offer insights into genetically defined subgroups of patients who benefited more than others, pointing to the possibility of more personalized, even more effective therapy for ovary cancer in the future.........

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May 21, 2010, 6:46 AM CT

CA-125 change over time as screening tool for ovarian cancer

CA-125 change over time as screening tool for ovarian cancer
Karen Lu, M.D., is a professor in MD Anderson's Department of Gynecologic Oncology and Robert Bast, M.D., is vice president for translational research at MD Anderson.

Credit: MD Anderson

Evaluating its change over time, CA-125, the protein long-recognized for predicting ovary cancer recurrence, now shows promise as a screening tool for early-stage disease, as per scientists at The University of Texas MD Anderson Cancer Center.

The findings were presented today by Karen Lu, M.D., professor in MD Anderson's Department of Gynecologic Oncology, in advance of the American Society of Clinical Oncology (ASCO) annual meeting. If a larger study shows survival benefit, the simple blood test could offer a much-needed screening tool to detect ovary cancer in it early stages - even in the most aggressive forms - in post-menopausal women at average risk for the disease.

MD Anderson has a long history in the research of the important biomarker. In the 1980s, Robert Bast, M.D., vice president for translational research at MD Anderson and co-investigator on the ASCO study, discovered CA-125 and its predictive value of ovary cancer recurrence. Since then, scientists at MD Anderson and beyond have been trying to determine its role in early disease detection. The marker, however, can become elevated for reasons other than ovary cancer, leading to false positives in early screening.

"Over the last ten years, there's been a lot of excitement over new markers and technologies in ovary cancer," said Lu, the trial's principal investigator. "I and other researchers in the gynecologic oncology community thought we would ultimately find a better marker than CA-125 for the early detection of the disease. After looking at new markers and testing them head-to-head in strong, scientific studies, we found no marker better than CA125".........

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March 10, 2010, 8:21 AM CT

Elective removal of ovaries during hysterectomy

Elective removal of ovaries during hysterectomy
Removal of the ovaries (bilateral oophorectomy) while performing a hysterectomy is common practice to prevent the subsequent development of ovary cancer. This prophylactic procedure is performed in 55% of all U.S. women having a hysterectomy, or approximately 300,000 times each year. An article in the March/recent issue of The Journal of Minimally Invasive Gynecology suggests that this procedure may do more harm than good.

William H. Parker, MD, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, provides a comprehensive analysis of the medical literature relating to the benefit of oophorectomy at the time of hysterectomy. His investigation includes studies of post-hysterectomy cancer incidence, all cause mortality, cardiovascular disease, osteoporosis and hip fractures, coronary artery disease, and many other conditions. He concludes that, on balance, removal of the ovaries is not generally warranted for all women undergoing hysterectomy. In women not at high risk for development of ovarian or breast cancer, removing the ovaries at the time of hysterectomy should be approached with caution.

Dr. Parker states, "Presently, findings based on observation suggest that bilateral oophorectomy may do more harm than good. Given that 300 000 U.S. women a year undergo elective oophorectomy, the findings of increased long-term risks have important public health implicationsPrudence suggests that a detailed informed consent process covering the risks and benefits of oophorectomy and ovarian conservation should be conducted with women faced with this important decision."........

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February 2, 2010, 9:21 AM CT

Fat tissue in women with Polycystic Ovary Syndrome

Fat tissue in women with Polycystic Ovary Syndrome
Fat tissue in women with Polycystic Ovary Syndrome produces an inadequate amount of the hormone that regulates how fats and glucose are processed, promoting increased insulin resistance and inflammation, glucose intolerance, and greater risk of diabetes and heart disease, as per a research studyconducted at the Center for Androgen-Related Research and Discovery at Cedars-Sinai Medical Center.

Polycystic Ovary Syndrome, or PCOS, is the most common hormonal disorder of women of childbearing age, affecting approximately 10 percent of women. It is the most common cause of infertility, and an important risk factor for early diabetes in women.

"We're beginning to find that fat tissue behaves very differently in patients with PCOS than in other women," said Ricardo Azziz, M.D.,M.P.H., director of the Center for Androgen-Related Research and Discovery, and principal investigator on the study. "Identifying the unusual behavior of this fat-produced hormone is an important step to better understanding the causes underlying the disorder, and appears to be helpful in developing therapys that will protect patients against developing heart disease and insulin resistance".

Fat tissue is the body's largest hormone-producing organ, secreting a large number of hormones that affect appetite, bowel function, brain function, and fat and sugar metabolism. One of these hormones is adiponectin, which in sufficient quantities encourages the proper action of insulin on fats and sugars and reduces inflammation. Women with PCOS produce a smaller amount of adiponectin than women who do not have the disease, in response to other fat-produced hormones, as per the research to be reported in the recent issue of Journal of Clinical Endocrinology and Metabolism (Published online ahead of print and available at http://jcem.endojournals.org/cgi/rapidpdf/jc.2009-1158v1.).........

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July 29, 2009, 11:15 PM CT

Chemo directly to ovarian cancer cells

Chemo directly to ovarian cancer cells
Anil K. Sood, M.D. is a professor and in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson.
With a novel therapeutic delivery system, a research team led by researchers at The University of Texas M. D. Anderson Cancer Center has successfully targeted a protein that is over-expressed in ovary cancer cells. Using the EphA2 protein as a molecular homing mechanism, chemotherapy was delivered in a highly selective manner in preclinical models of ovary cancer, the scientists report in the July 29 issue of the Journal of the National Cancer Institute

EphA2 is attractive for such molecularly targeted treatment because it has increased expression in ovarian and other cancers, including breast, colon, prostate and non-small cell lung cancers and in aggressive melanomas, and its expression has been linked to a poor prognosis.

"One of our goals has been to develop more specific ways to deliver chemotherapeutic drugs," said senior author Anil K. Sood, M.D., professor and in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson. "Over the last several years we have shown that EphA2 is a target that is present quite frequently in ovarian and other cancers, but is either present in low levels or is virtually absent from most normal adult tissues. EphA2's preferential presence on tumor cells makes it an attractive therapeutic target".

The scientists used a carrier system to deliver chemotherapy directly to ovary cancer cells. The immunoconjugate contains an anti-EphA2 monoclonal antibody associated with the chemotherapy drug monomethyl auristatin phenylalanine (MMAF) through the non-cleavable linker maleimidocaproyl. Research has shown that auristatins induce cell cycle arrest at the G - M border, disrupt microtubules and induce apoptosis (programmed cell death) in cancer cells.........

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April 22, 2009, 5:11 AM CT

New chemo combination against recurrent gynecologic cancers

New chemo combination against recurrent gynecologic cancers
Recurrent and metastatic endometrial and ovary cancers can be notoriously difficult to treat: They have spread to other organs and typically have developed resistance to chemotherapy; and patients already heavily treated with chemotherapy may not be able to endure more chemo. Now, physicians at Albert Einstein College of Medicine of Yeshiva University have shown that a combination of two chemotherapy drugs not only produced clinical benefit for such patients but were also well tolerated. The findings are published online in the journal Gynecologic Oncology

"Women with recurrent gynecologic cancers have often had multiple rounds of chemotherapy, which can cause tumor cells to develop resistance to these drugs," says Mark H. Einstein, M.D., associate professor of obstetrics & gynecology and women's health at Einstein, who headed the study. "This resistance can make it difficult for doctors to devise a therapy protocol that will impact the cancers while avoiding the often-severe side effects that certain chemotherapy drugs can cause, especially when patients have already been heavily pretreated with other anti-cancer drugs".

In prior clinical studies, the chemotherapy drugs topotecan and docetaxel showed effectiveness when used separately against recurrent gynecologic cancers. The phase 2 trial conducted by Dr. Einstein and colleagues─the first to evaluate the combination of the drugs for this purpose─involved 24 women with recurrent uterine, ovarian, fallopian or peritoneal cancers. The women were given the topotecan-docetaxel combination on Day 1 of the trial and then weekly for three weeks; after a one-week rest, the women received another three-week therapy cycle, ultimately undergoing six such therapy cycles.........

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April 2, 2009, 5:00 AM CT

Ovarian cancer screening

Ovarian cancer screening
The only available screening tests for ovary cancer fail to catch early signs of the disease and often result in unnecessary surgery, said scientists at the University of Alabama at Birmingham (UAB) Comprehensive Cancer Center.

The newly released study looked at a screening regimen that combines ultrasound and a blood test for CA-125, a marker for women's cancer.

Results showed the combo screening caught 70 percent of the ovary cancers in their late stages, when effective therapy options are limited.

Knowing this screening limitation means the search has intensified for a better way to detect ovary cancer, often called the "silent killer," said Edward Partridge, M.D., director of the UAB Comprehensive Cancer Center and the lead study author.

"We still have some comparison data to review, but right now it looks like the positive predictive value of these tests is pretty low," Partridge said.

The study puts the positivity value for both tests at around 1.6 percent per 100 positive screening results, a remarkably low positivity rate that led to a number of false positives, he said. False positives are erroneous signals of cancer where there is none.

The UAB results are published April 1 in the journal Obstetrics & Genecology.........

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February 6, 2009, 6:02 AM CT

No increased risk of ovarian cancer from fertility drugs

No increased risk of ovarian cancer from fertility drugs
The use of fertility drugs does not increase a woman's risk of developing ovary cancer, finds a large study from Danish scientists published on bmj.com today.

During the past three decades there has been considerable debate as to whether use of fertility drugs increases a woman's risk of developing ovary cancer. Prior studies have given conflicting results and concerns remain, especially for women who undergo several cycles of therapy or who never succeed in becoming pregnant.

So Allan Jensen and his colleagues at the Danish Cancer Society examined the effects of fertility drugs on ovary cancer risk by using data from the largest cohort of infertile women to date.

The study involved 54,362 women with infertility problems referred to all Danish fertility clinics between 1963 and 1998. 156 of these women had ovary cancer. After adjusting for several risk factors, the scientists assessed the effects of four groups of fertility drugs over an average period of 16 years.

They found no overall increased risk for ovary cancer after use of any fertility drug. They also found no increased risk among women who had undergone 10 or more cycles of therapy or among those who did not become pregnant.

Eventhough the authors did observe a statistically significant increase in risk of the most common serious type of ovary cancer among women who had used the drug clomiphene, they stress that this was probably a chance association.........

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February 3, 2009, 6:17 AM CT

Genes associated with ovarian cancer survival

Genes associated with ovarian cancer survival
A newly released study published this week in the open-access journal PLoS Medicine identifies molecular pathways linked to outcomes in ovary cancer. Currently, outcomes following diagnosis of ovary cancer are very poor, with up to 65-70% of women dying within five years of diagnosis.

Anne Crijns and her colleagues from the University of Groningen in the Netherlands aimed to find out whether the expression levels of particular genes were linked to overall survival in ovary cancer. The scientists initially studied a series of tissue samples, obtained during surgery to remove malignant tissue from 157 consecutive patients seen at the University Medical Center Groningen. Analysis of the samples identified 86 genes which correlated with overall survival in the women. The scientists were then able to confirm, for 57 of the 86 genes, that these were also correlated with survival in a second, entirely separate dataset. Specific genes, and pathways, were identified which provide specific targets around which scientists might be able to design potential therapies in future.

For example, Crijns and his colleagues find high expression of a gene encoding a FK506 binding protein, FKBP7, is linked to poor prognosis. This protein can be targeted with existing drugs, the mTOR inhibitors. Another implication of the work discussed by the scientists is the use of this expression signature to identify women who are at greater risk of relapse, and thus potentially personalize therapy. However, as the authors acknowledge, such implications are still some way off. It would be important to carry out prospective studies in order to show that the signature performs effectively in a clinical setting.........

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September 15, 2008, 9:46 PM CT

Ovarian cancer drug: promising new treatment

Ovarian cancer drug: promising new treatment
Irvine, Calif. Women with recurrent ovary cancer can be helped by an experimental treatment using a drug already touted for its ability to fight other cancers, a finding that provides hope for improved therapy of this deadly disease.

Dr. Bradley Monk, a UC Irvine gynecologic oncologist who led the worldwide phase III clinical trial, said trabectedin is the most recent addition to a short list of active drug therapies for recurrent ovary cancer. He presents study results Sept. 15 at the 33rd Congress of the European Society for Medical Oncology in Stockholm.

"These are exciting results because positive trials in recurrent ovary cancer are rare and have almost always led to federally approved therapys," said Monk, an associate professor who studies and treats ovary cancers at the Chao Family Comprehensive Cancer Center at UC Irvine. "This therapy undoubtedly will be reviewed carefully by the U.S. Food and Drug Administration and, if approved, will give women with ovary cancer another much needed option".

Phase III studies are multicenter trials on large patient groups designed to be the definitive assessment of a drug's effectiveness. Such a study is often the last step before a drug is evaluated by a regulatory agency like the FDA for approval as a safe, effective therapy.........

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April 17, 2008, 8:09 PM CT

Ovarian cancer stem cells identified

Ovarian cancer stem cells identified
Scientists at Yale School of Medicine have identified, characterized and cloned ovary cancer stem cells and have shown that these stem cells may be the source of ovary cancers recurrence and its resistance to chemotherapy.

These results bring us closer to more effective and targeted therapy for epithelial ovary cancer, one of the most lethal forms of cancer, said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.

Mor presented his findings recently at the annual meeting of the American Association for Cancer Research (AACR) Meeting in San Diego, California.

Malignant tumors are made up of cells that are both malignant and non-malignant. Within malignant cells, there is a further subclass referred to as cancer stem cells, which can replicate indefinitely.

Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal, said Mor, who is also a member of the Yale Cancer Center. Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities.

Mor and his colleagues isolated cells from 80 human samples of either peritoneal fluid or solid tumors. The cancer stem cells that were identified were positive for traditional cancer stem cell markers including CD44 and MyD88. These cells also showed a high capacity for repair and self-renewal.........

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April 17, 2008, 7:47 PM CT

Drug compound leads to death of ovarian cancer cells

Drug compound leads to death of ovarian cancer cells
In a discovery that may be useful for maintaining remission in chemo-resistant ovary cancer, Yale researchers report that pre-clinical studies have shown the drug compound NV-128 can induce the death of ovary cancer cells by halting the activation of a protein pathway called mTOR.

Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine, and associate research scientist Ayesha Alvero, M.D. presented the data April 15 during an oral presentation at the annual meeting of the American Association for Cancer Research.

In cancer cells, mTOR signals enhance tumor growth and may be linked to resistance to conventional therapies. Inhibition of mTOR could shut down a number of of these survival pathways, including proteins that protect the mitochondria of cancer cells.

NV-128, developed by Novogen Limited, holds promise as a more targeted treatment for ovary cancer because it works differently from traditional therapies that are dependent on enzymes known as caspases to trigger cell death. Therapies using caspases to kill cancer cells can be ineffective in chemo-resistant cancer cells due to mutations that short-circuit signals that trigger cancer cell death.

We consider that the capacity of NV-128 to trigger caspase-independent cell death, in otherwise chemoresistant ovary cancer cells, opens new possibilities for the use of NV-128 as a potential addition to conventional chemotherapy targeting ovary cancer cells, said Mor.........

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March 13, 2008, 9:10 PM CT

Preventing spread of ovarian cancer

Preventing spread of ovarian cancer
A drug that blocks production of an enzyme that enables ovary cancer to gain a foothold in a new site can slow the spread of the disease and prolong survival in mice, as per a research studyby scientists from the University of Chicago Medical Center, but only if the drug is given early in the disease process.

In the recent issue of the Journal of Clinical Investigation, the scientists show that an enzyme known as MMP-2 is necessary for ovary cancer to attach itself to the sites where it tends to spread. Several drugs known as MMP inhibitors (for example, marimastat or prinomastat) inhibit the enzyme, dramatically reducing the tumor's ability to establish itself at sites beyond the ovary. But such MMP inhibitors, which were abandoned after they failed to extend survival in earlier clinical trials, have to be given before the cancer has spread.

"Our study suggests that MMP-2 inhibitors could have a significant impact on ovary cancer but only if administered quite early, before the cancer has advanced beyond the ovary," said Ernst Lengyel, assistant professor of obstetrics and gynecology at the University of Chicago.

This approach could help women who receive surgical therapy while the disease is still limited to the ovary as well as those who have successful surgery to remove all evidence of local spread of the disease. In the earlier trial, marimastat was given to women with late-stage disease that had already spread.........

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March 11, 2008, 5:42 AM CT

Recurrent low-grade carcinoma of the ovary less responsive to chemo

Recurrent low-grade carcinoma of the ovary less responsive to chemo
Recurrent low-grade serous carcinoma, a rare type of ovary cancer, is less sensitive to chemotherapy and therefore more difficult to treat than more common high-grade ovary cancers, as per scientists from The University of Texas M. D. Anderson Cancer Center. The findings were reported at the Society of Gynecologic Oncologists 39th Annual Meeting on Women's Cancers.

The retrospective study is the first to analyze how women with low-grade tumors respond to chemotherapy in recurrent setting and confirms clinical impressions that the tumors are chemoresistant, said lead author David M. Gershenson, M.D., professor and chair of the Department of Gynecologic Oncology at M. D. Anderson. Prior studies have shown similar tumor resistance in newly diagnosed patients, and there is currently no standard of care for women facing the disease.

The results support a growing body of research that shows low-grade ovarian tumors behave differently than their high-grade counterparts, genetically and clinically. "In order to make meaningful advances in therapy, women with low-grade ovarian tumors must not be grouped together with those with more common ovarian tumors. They require unique consideration and more targeted therapy options for a better chance of survival," Gershenson said.........

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February 12, 2008, 9:41 PM CT

Test detects early stage ovarian cancer with 99 percent accuracy

Test detects early stage ovarian cancer with 99 percent accuracy
Dr. Gil Mor at Yale Department of Obstetrics, Gynecology & Reproductive Sciences.

Credit: Yale University
Scientists at Yale School of Medicine have developed a blood test with enough sensitivity and specificity to detect early stage ovary cancer with 99 percent accuracy.

Results of this new study are reported in the February 15 issue of the journal Clinical Cancer Research. The results build on work done by the same Yale group in 2005 showing 95 percent effectiveness of a blood test using four proteins.

The ability to recognize almost 100 percent of new tumors will have a major impact on the high death rates of this cancer, said Mor. We hope this test will become the standard of care for women having routine examinations.

Epithelial ovary cancer is the leading cause of gynecologic cancer deaths in the United States and three times more lethal than breast cancer. It is commonly not diagnosed until its advanced stages and has come to be known as the silent killer.

This new phase II clinical trial led by Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale, included 500 patients; 350 healthy controls and 150 ovary cancer patients. Mor and his colleagues validated the prior research and used a new platform called multiplex technology to simplify the test into one single reaction using very small amounts of serum from the blood. The new platform uses six protein biomarkers instead of four, increasing the specificity of the test from 95 to 99.4 percent. The team looked for the presence of specific proteins and quantified the concentration of those proteins in the blood.........

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February 10, 2008, 9:47 PM CT

Why certain ovarian cancers develop resistance

Why certain ovarian cancers develop resistance
A team of scientists led by Fred Hutchinson Cancer Research Center has identified a new mechanism that explains why some recurrent ovarian tumors become resistant to therapy with usually used platinum-based chemotherapy drugs such as cisplatin and carboplatin. They describe their research online Feb. 10 in the journal Nature.

While these findings are based on the study of ovarian-cancer cells from women with inherited mutations in the BRCA2 gene, they also may help explain the mechanics of cisplatin resistance in ovarian-cancer patients with BRCA1-gene mutations. Together such genetic mistakes are thought to cause about 10 percent of ovary cancers, as per senior author Toshiyasu (Toshi) Taniguchi, M.D., Ph.D.

Because BRCA1 and BRCA2 have similar functions in terms of DNA repair, we may be able to generalize these findings for women with either mutation, said Taniguchi, an assistant member of the Hutchinson Centers Human Biology and Public Health Sciences divisions.

BRCA2 works to repair damaged DNA; inherited mutations in this gene disrupt that ability, which increases the risk of ovarian and breast cancer. At the same time, such mutations also make cancer cells more vulnerable to DNA-damaging agents such as cisplatin and carboplatin. While ovarian tumors initially respond very well to platinum-based chemotherapy, eventually between 70 percent and 80 percent of advanced-stage ovarian-cancer patients develop a resistance to these drugs.........

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Did you know?
newly identified gene expression profile could help predict how patients with advanced ovary cancer will respond to chemotherapy treatment. Described in a study in the November 1, 2005 issue of The Journal of Clinical Oncology (JCO), the new findings further establish an important role for microarray gene profiling as a predictor of clinical outcome in ovary cancer, and could eventually provide physicians with insights into the mechanisms of drug resistance.

Medicineworld.org: Ovarian Cancer News Blog

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