A blood test to help physicians distinguish ovarian tumors from benign pelvic masses has won approval from the FDA.

Trade-named OVA1, the test is intended for use in women who would otherwise undergo exploratory surgery to diagnose pelvic masses visible on imaging.

The test was developed by Vermillion and will be available later this year exclusively from Quest Diagnostics.

It sums results from immunoassays for five known biomarkers of ovarian cancer: transthyretin, apolipoprotein A1, β2-microglobulin, transferrin, and the CA-125 II cancer antigen. A proprietary algorithm converts the immunoassay results into a single score indicating the risk that the mass is malignant.

In a pivotal clinical study, the test showed sensitivity of 85% to 96% depending on the type of malignancy, with higher sensitivity seen for epithelial tumors. Specificity was 50%.

Because the false-negative rate is relatively low, the test could spare many women from unnecessary surgeries, Quest suggested.

“The OVA1 test is an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy,” according to Quest.

“Physicians often do not know if a woman’s pelvic mass is malignant or benign until she undergoes surgery. The OVA1 Test is the first FDA-cleared blood test to help clinicians determine whether to refer a woman to a gynecologic oncologist or have a gynecologic oncologist present at the time of surgery,” the Quest statement said.

Quest was careful not to bill the test as suitable for screening purposes.

“The test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1 Test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis,” the company cautioned.

Another multimarker test for ovarian cancer, trade-named OvaSure, was marketed briefly last year as a screening test for women at high risk for ovarian cancer. Its seller, Laboratory Corporation of America, had not sought FDA approval for the test, claiming it was a “home brew” exempt from the agency’s premarket approval requirements.

LabCorp pulled the test last October after the FDA sent the firm a stern letter saying it was indeed a regulated product. (See FDA Says Ovarian Cancer Test is Marketed Illegally)

Related Article(s):

• FDA Says Ovarian Cancer Test is Marketed Illegally

While Fanconi anemia (FA) is a rare and dangerous disease, new laboratory research at The University of Texas M. D. Anderson Cancer Center shows it may lead researchers toward clues in more common diseases, including highly hereditary types of breast cancer.

In a study published in the Sept. 11 issue of the journal Molecular Cell, scientists report that recruitment of proteins to DNA damage sites is controlled by replication in both FA and BRCA cancer proteins.

Lei Li, Ph.D, professor in Experimental Radiation Oncology at M. D. Anderson, and corresponding author of the study, has spent much of his 15-year career studying how the body repairs DNA damage. He says DNA crosslinks are the most severe type of DNA damage; they’re actually turned against cancer in certain drugs, including cisplatin.

Answers have been elusive

People with FA, a hereditary disease, are extremely sensitive to DNA crosslinks and at a very high risk for cancer. How the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks has remained unclear despite extensive research.

“Our lab has been working for almost 10 years on why FA cells are so sensitive to crosslinking,” Li said. “We’ve known it must have something to do with how they deal with DNA crosslinks, but this is the first time we’ve been able to pinpoint a reason for some of them.”

FA involves 13 genes; a mutation in any one of them can cause the disease. Three of the FA genes recently were found to be identical to breast cancer susceptibility genes BRCA2, BACH1 and PALB2.

“This led us to begin to examine breast cancer genes, since we thought they might have something to do with the repair of DNA crosslinkers,” Li said.

Researchers developed a novel genetic technique, eChIP, a chromatin-IP-based strategy, to examine FA proteins with DNA crosslinks.

“The model scientists have been following for many years is that all 13 genes must work together to deal with DNA crosslinks, that there must be some kind of cascade or chain reaction,” Li said. “We developed a new genetic technique to look specifically at what proteins are present at the crosslinks.”

New method yields answers

Using this new tool, researchers found that all the FA genes are present in the site of a crosslink. This is the first time FA proteins have been linked directly with DNA crosslinking damage at the molecular level.

“The surprise is that the breast cancer proteins, although they are present at crosslinks, must have DNA replication at the crosslinks,” Li said. “If there is a DNA lesion on the genome but no DNA replication, the canonical FA proteins are used to deal with the damage. The breast cancer-related FA proteins are taking care of the DNA lesion that stops DNA replication.”

Li said this leads to a new paradigm that there must be two separate subgroups or subpathways within the 13 FA genes.

“The major implication of this study is that now we have a new working model,” Li said. “This provides a new direction for future research of breast cancer proteins and DNA damage response in general.

“Our next step is to continue to look at how FA proteins and the subgroup of breast cancer-related proteins help protect cells from DNA crosslink damage. And, in a more general sense, how these cellular mechanisms eventually may help us minimize mutations that ultimately lead to cancer.”

This research was supported by grants from the National Institutes of Health.

Co-authors include Xi Shen, Ph.D., Huong Do, and Woo-Hyun Chung, Ph.D. at M. D. Anderson; Yongjiang Li, Ph.D., and Weidong Wang, Ph.D., at the National Institute on Aging; Maria Tomasz, Ph.D., at City University of New York; Johan P. de Winter, Ph.D., at VU Medical Center in The Netherlands; Bing Xia, B.D., UMDNJ-Robert Wood Johnson Medical School; Stephen J. Elledge, Ph.D., at Harvard Medical School.

Source
M. D. Anderson

The American Society of Clinical Oncology (ASCO) along with The Chicago Convention and Tourism Bureau (CCTB) announced that ASCO will hold its Annual Meeting at Chicago’s McCormick Place for the next 10 years. The contract will begin when ASCO holds its 46th Annual Meeting on June 4-8, 2010 and runs through 2019 (with an out clause for 2016 should Chicago be awarded the 2016 summer Olympics.) Chicago was the home of the 2008 meeting. The 2009 meeting was held in Orlando, Florida.

As ASCO’s Annual Meeting continues to grow - more than 29,000 attendees attended this year - the Society’s leadership has worked to identify the most appropriate host city that can not only accommodate what is one of the world’s largest medical association meetings, but also provide the convenience and atmosphere ASCO attendees desire.

“We are very glad to be entering this partnership with the City of Chicago,” said Allen S. Lichter, M.D., CEO of ASCO. “Chicago is a terrific town for ASCO for so many reasons - the convention center, the hotel space, the cultural offerings, the restaurants. We are so pleased that our Annual Meeting has found such a welcoming and hospitable home for the next decade.”
In a survey of meeting attendees conducted this year by Alan Newman Research, 70 percent of all attendees to the 2008 Annual meeting in Chicago rated their “overall experience” in Chicago as “very good” or “excellent.”

Chicago offers a central location for attendees to meet from around the United States and is easily accessible for a large number of ASCO’s international attendees. There are 75 major hotels within an easy commute to one of the largest and most modern convention facilities in the United States. This, along with the city’s wealth of restaurants, world class cultural attractions, and friendly hospitality made Chicago a very attractive choice.

“This long-term agreement is a true partnership with ASCO and further solidifies that Chicago continues to be a preferred meetings destination, particularly among the medical industry,” said Tim Roby, CCTB President and CEO. “We look forward to welcoming ASCO back to showcase the depth and breadth of resources available within the city, state and Midwest region.”

Source
American Society of Clinical Oncology

Why are some pediatric cancers able to spontaneously regress? Prof. Michael Fainzilber and his team in the Weizmann Institute’s Biological Chemistry Department seem to have unexpectedly found part of the answer. Further research toward a better understanding of the mechanism of action might hopefully lead, in the future, to the development of drugs that will be able to induce regression of certain tumors.

TrkA is a particular cell receptor well known for its “pro-life advocacies”: when nerve growth factor proteins bind to TrkA receptors, it activates the receptors into promoting the growth and survival of neurons.

So when Fainzilber, together with Ph.D. student Liraz Harel, postdoctoral student Dr. Barbara Costa, technician Zehava Levy, and former Ph.D. student Dr. Marianna Tcherpakov carried out screening tests to identify other molecules involved in this signaling cascade, it took them by surprise to learn that TrkA may not be who it seems. They found that if TrkA teams up with another molecule called CCM2 the newly identified player in this signaling cascade they become “partners in crime,” with TrkA turning into a cell killer.

However, though paradoxical, this atypical behavior may actually be rooting for life after all. This idea comes from findings concerning pediatric tumors of neural origin; specifically, medulloblastoma the most common malignant brain tumor and the second most common malignancy among children less than 20 years of age, and neuroblastoma the most common extracranial solid cancer in childhood.

Neuroblastoma displays unusual behavior, being one of the few human malignancies known to demonstrate spontaneous regression in some cases, but nobody knows how or why. Studies have shown that the tumors with positive prognosis usually express TrkA, while aggressive forms of the tumor do not. However, how TrkA induces tumor regression is yet unknown and the mechanism was an enigma.

What if CCM2 was the missing piece to the tumor regression puzzle? Together with a group of scientists in Germany who were conducting a large-scale gene expression study in tumors from neuroblastoma patients, they checked the expression levels of CCM2 and TrkA from the patient samples collected. The results were clear- cut: TrkA and CCM2 were always expressed together in certain tumors those that showed the highest incidences of regression and patient survival.

The scientists confirmed their results by blocking the expression of either TrkA or CCM2 in some cells, which resulted in cell survival. On the other hand, by introducing CCM2 to cells lacking it, cell death was induced if TrkA was also present, suggesting that this mechanism could lead to tumor regression.

This research, recently published in Neuron, is one of the first to elucidate this paradoxical “pro-cell death” behavior of TrkA and the first to identify CCM2 as a crucial accessory in this particular pathway, as well as describing in detail just how these two molecules interact.

Prof. Michael Fainzilber’s research is supported by the M.D. Moross Institute for Cancer Research; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the Helen and Martin Kimmel Institute for Stem Cell Research; the Irving B. Harris Foundation; and Mr. and Mrs. Michael Salzberg, Bethesda, MD. Prof. Fainzilber is the incumbent of the Chaya Professorial Chair for Molecular Neuroscience.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.

Source: Weizmann Institute of Science

The American Society of Clinical Oncology (ASCO) has earned CEO Cancer Gold Standard™ accreditation from the CEO Roundtable on Cancer, recognizing its commitment to reducing the cancer risk of its employees and their families through screenings, early detection, and healthy changes in lifestyle and in the workplace.

“We are very proud to gain this designation. It demonstrates an unwavering commitment to the health and well-being of our employees,” said Allen S. Lichter, MD, CEO of ASCO. “As additional organizations become certified, we can make great strides in reducing cancer incidence and improving cancer treatment.”

To earn CEO Cancer Gold Standard™ accreditation, an organization must take extensive actions in five key areas of health and wellness (tobacco use, diet and nutrition, physical activity, prevention and screening, and access to quality treatment and clinical trials) to prevent and treat cancer in the workplace. ASCO has met these challenges by:

- Establishing a tobacco-free worksite policy, in addition to offering tobacco cessation workplace initiatives and coverage of cessation counseling, therapies and medications in its employee health plans.

- Creating a wellness program that includes employee events (informational sessions, screenings, and demonstrations), a collection of information on wellness topics, local resources and discounts to nutritional counseling in its employee health plans.

- Providing a well-equipped, onsite fitness center for employees to use before and after work and during their lunch breaks, as well as a discount membership to a larger, local health club.

- Offering employee health benefit plans that eliminate cost as barrier to accessing preventive/screening tests and fostering an organizational culture that encourages age and gender-specific cancer screenings.

- Ensuring that its health benefit plans offer access to clinical trial participation and care at cancer centers approved by the Commission on Cancer or the National Cancer Institute (NCI).

“As the world’s leading professional organization representing physicians who care for people with cancer, it is fitting that our Gold Standard certification demonstrates that ASCO also cares for its employees and their family members and supports efforts to reduce their cancer risk,” said William C. Weldon, Chairman of the CEO Roundtable on Cancer and CEO of Johnson & Johnson.

The CEO Roundtable on Cancer was founded in 2001 when former President George H.W. Bush challenged a group of executives to “do something bold and venturesome about cancer within your own corporate families.” The Roundtable responded by establishing the CEO Cancer Gold Standard™ in 2006. The most recent President’s Cancer Panel report cites the Gold Standard as an example of the diverse efforts being used to address access and organizations problems in the health care system.

Source
ASCO

The American Brain Tumor Association has launched a new Special Projects Discovery Grant program to support fresh and creative research ideas for solving the challenges of brain tumor diagnosis and treatment.

“While there have been some significant scientific breakthroughs over the past decade resulting in better treatments and longer lives for many patients, a brain tumor remains a devastating diagnosis,” said American Brain Tumor Association Executive Director Elizabeth Wilson.

“Through this program, we hope to stimulate and invigorate greater engagement in brain tumor research across and beyond traditional medical and scientific research disciplines and specialties and bring new perspectives, ideas and dreams to the foreground,” said Wilson.

Each year, approximately 60,000 Americans are diagnosed with a primary brain tumor and more than 150,000 have cancer that spreads to, or “metastasizes,” to the brain.

The American Brain Tumor Association Special Project Discovery Grant pilot program one of four grant programs offered through ABTA’s Research Awards Program - will offer one-year, $50,000 grants for high-risk, high-impact projects deemed to have the potential to change current diagnostic or treatment paradigms for adult and/or pediatric brain tumors.

Investigators from sciences outside traditional biology fields are encouraged to apply. Proposed studies should be at the hypothesis-driven level. Priority will be given to proposals that address underfunded areas of brain tumor research. Of particular interest for this first round of funding are proposals pertaining to meningioma or oligodendroglioma, however, other research topics are also invited.

Eligible researchers include advanced post-doctoral trainees, junior faculty, and principal investigators who have not received funding at the equivalent of NIH RO1, or higher level.

Projects will be pre-screened by letter of intent, due October 15th, 2009. Select individuals will be invited to submit proposals.

The American Brain Tumor Association Research Awards Program will again offer Basic Research Fellowship and Translational Research Grant awards for 2009-2010. Basic Research Fellowships are two-year, $80,000 training awards that support young researchers entering the field of brain tumor research. One year, $75,000 Translational Grants help scientists to further develop research that is on the cusp of moving from the laboratory into patient testing.

Basic Research Fellowship and Translational grant applications will post at the ABTA web site, in the Research Progress section, by October( )15th.. Applications for these awards are due no later than January 8, 2010.

Founded in Chicago in 1973, the American Brain Tumor Association was the first national nonprofit organization dedicated solely to brain tumors. Today, ABTA is a recognized leader in brain tumor research and patient information, education and support services.

Source: American Brain Tumor Association

Every moment, millions of a body’s cells flawlessly divvy up their genes and pinch perfectly in half to form two identical progeny for the replenishment of tissues and organs - even as they collide, get stuck, and squeeze through infinitesimally small spaces that distort their shapes.

Now Johns Hopkins scientists, working with the simplest of organisms, have discovered the molecular sensor that lets cells not only “feel” changes to their neat shapes, but also to remodel themselves back into ready-to-split symmetry. In a study published September 15 in Current Biology, the researchers show that two force-sensitive proteins accumulate at the sites of cell-shape disturbances and cooperate first to sense the changes and then to resculpt the cells. The proteins - myosin II and cortexillin I - monitor and correct shape changes in order to ensure smooth division.

“What we found is an exquisitely tuned mechanosensory system that keeps the cells shipshape so they can divide properly,” says Douglas N. Robinson, Ph.D., an associate professor of Cell Biology, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine.

Faulty cell division can put organisms, including people, on the pathway to diseases such as stress on their shapes could present new targets for both diagnosing and treating such diseases.

Working with hardy, single-celled protozoa that move and divide similarly to human cells, the scientists watched through microscopes while they deformed the cells’ shapes with a tiny instrument that, like a soda straw, sucks in on the cell surface and creates distorted shapes.

“This particular method, based on a very old principle that dates back to Archimedes, enables us to deform cells without killing them, much in the same way that natural processes in the body constantly assault them, Robinson says.”

Once the cells were warped, the scientists monitored the movements of fluorescent-tagged myosin II and cortexillin I. Myosin, which normally accumulates in the middles of cells during division to help power that process, collected instead at the sites of disturbances made by the micropipette. Also amassing with myosin was cortexillin I, a so-called actin-crosslinking protein that, like glue, holds the toothpick-like filaments of a cell’s housing together.

In the experiments, as soon as the two proteins accumulated to a certain level, the cells contracted, escaping the pipettes and assuming their original shapes. After the cells righted themselves, the proteins realigned along the cells’ midlines and pinched to divide symmetrically into two daughter cells.

The researchers repeated the experiment using cells engineered to lack myosin II and then again with cells lacking cortexillin I. They discovered that cortexillin I responded to deformations except when myosin II was removed, and myosin II responded to deformations except when cortexillin I was removed.

“It’s clear that the two need each other to operate as a cellular mechanosensor,” Robinson says.

The research was funded by grants from the National Institutes of Health, the American Cancer Society and the National Science Foundation.

In addition to Robinson, authors of the paper are Yixin Ren, Janet C. Effler, Pablo A. Iglesias and Tianzhi Luo, all of Johns Hopkins; Melanie Norstrom and Ronald S. Rock, both of the University of Chicago; and Richard A. Firtel, University of California San Diego.

Source:
Maryalice Yakutchik

Johns Hopkins Medical Institutions

• Explain to patients that depression may modestly increase cancer patients’ risk of dying, but not the risk that the disease itself will progress.
• The findings were based on a retrospective statistical analysis, which does not prove that depression increases the risk of cancer death and does not indicate that treatment of depression will necessarily improve mortality.

Cancer patients have a modest but statistically significant increase in risk of death if they are clinically depressed, according to a meta-analysis.

Depressive symptoms increased the mortality risk by as much as 25%, and patients with a diagnosis of major or minor depression had almost a 40% greater risk of dying.

However, neither depressive symptoms nor a depression diagnosis increased the risk of cancer progression, authors reported online in Cancer.

“This meta-analysis presented reasonable evidence that depression predicts mortality, but not progression, in cancer patients,” Jillian R. Satin, of the University of British Columbia in Vancouver, and colleagues concluded.

“The associated risk was statistically significant but relatively small. The effect of depression remains after adjustment for clinical prognosticators, suggesting that depression may play a causal role.”

Studies have shown that most cancer patients and oncologists believe that psychological variables affect the likelihood of disease progression.

The current study focused on depressive symptoms and clinical diagnosis of depression because depression has been the most commonly studied psychological variable with respect to cancer progression and mortality, the authors said.

Moreover, depression is the only psychological condition found more often in cancer patients than in the general population, they continued.

Further rationale for studying depression has come from the existence of a plausible model to link depression and cancer outcome. Specifically, chronic activation of the hypothalamopituitary-adrenal axis has been implicated as a possible mediator of depression’s effect on cancer.

The authors queried multiple databases to identify studies that prospectively evaluated the association between depression and the risk of cancer progression or mortality. They found five studies that examined the association between depression and cancer progression in a total of 2,097 patients, and 27 studies that evaluated depression and cancer mortality in 9,417 patients.

The studies of cancer progression consisted of three that examined the effect of depressive symptoms and two that assessed the impact of a clinical diagnosis of depression, as determined by Diagnostic and Statistical Manual criteria.

The adjusted relative risk of cancer progression did not reach statistical significance for depressive symptoms (RR 1.23, P=0.275) or clinical depression (RR 1.179 to 1.26, P=0.633 to P=0.764).

Studies that examined depression and cancer mortality yielded an unadjusted risk ratio of 1.25 (95% CI 1.12-1.40, P<0.001) for depressive symptoms and a relative risk of 1.39 for a diagnosis of minor or major depression (95% CI 1.10 to 1.89, P=0.03).

“Our meta-analysis provides an empirical justification for systematic screening of psychological distress and subsequent treatments,” the authors concluded.

“Although psychological treatment should be available to distressed cancer patients … an impressive improvement in survival is unlikely unless a subgroup is identified that could benefit more than others,” they added.

They also cautioned that their analysis “does not support a need for patients and their families to feel responsible for their disease outcome if they experience depression.”