Minnesota Ovarian Cancer Alliance (MOCA) Awards $375,000 For Ovarian Cancer Research in Minnesota in 2008

Thanks to the generous support of our members/donors, Minnesota Ovarian Cancer Alliance (MOCA) has awarded $375,000 in grants for the following research projects on ovarian cancer in 2008.

MOCA’s research program began in 2001 with $91,000 in funding and has grown each year. The addition of $375,000 in grants for 2008 brings the total awards given by MOCA, in just eight years, to more than $2 million.

Grants are awarded for ovarian cancer research projects conducted in the state of Minnesota that support better treatment, diagnosis and a cure. Findings from MOCA funded grants have been published in peer review journals and presented at conferences throughout the country.

“MOCA plays a special role in supporting ovarian cancer research in Minnesota,” said Executive Director Kathleen Gavin, “We bring together survivors, families and other supporters with researchers and research institutions to stimulate research in the state and to ensure that researchers and institutions are responsive to the needs of survivors.”

Recommendations for funding are made by a national panel of three experts in gynecologic oncology, three at-large MOCA members and one board member.. The recommended awards are then voted on by MOCA’s Board of Directors.

The grant recipients for the six research projects as follows:

Carol Lange

Published reports suggest that the naturally-occurring hormone, progesterone, may inhibit tumor growth and foster tumor cell death in most women, but is inhibited by other elements in women who develop ovarian cancer. There has been much work on the gene expression of the nuclear progesterone receptor (n-PR). Researchers in Japan recently cloned a new progesterone receptor (mb-PR), making it possible for Dr. Lange to investigate the pathways through which progesterone might work in tumor suppression and cell death. If her work is successful, this would open the door to the development of new treatments that might make ovarian cancer cells more sensitive to standard chemotherapy, thus decreasing toxicity and improving clinical outcomes.

The study’s aims are:
1. To define the expression and regulation of the two progesterone receptors in ovarian cancer cell lines and tissues.
2. To define the pathways activated in response to mb-PR.
3. To define the mechanism and biology of mb-PR’s signaling for tumor cell death.

Amy Skubitz

Dr. Skubitz continues her search for novel biomarkers in women with ovarian cancer. If successful, these biomarkers could be used for early detection of ovarian cancer, the most important factor in successful clinical outcomes. Using proteomics, this lab has discovered several proteins which are more abundant in the blood of women with ovarian cancer. The current study is the “next step” in her search.

The study’s aims are:
1. We will grow ovarian cancer cell lines and normal ovarian surface epithelial cell lines in serum-free media and collect the spent media, which will contain the proteins secreted by the cells.
2. We will isolate the “low abundance” proteins from ovarian cancer ascites fluid samples and “non-ovarian cancer” ascites fluid samples by affinity chromatography on a ProteomeLab IgY12 HPLC column, followed by a GenWay SuperMix HPLC column.
3. We will identify new biomarkers for ovarian cancer by Differential In Gel Electrophoresis, in which two-dimensional gel electrophoresis will be used to simultaneously analyze proteins from ovarian cancer and non-ovarian cancer samples (from aims 1 and 2) in order to identify proteins that are different between the sample sets. Proteins will then be identified by mass spectrometry.
4. We will confirm and/or expand upon the differentially expressed biomarkers of aim 3 by iTRAQ methodology in which liquid chromatography coupled with mass spectrometry will be used to simultaneously analyze proteins from aims 1 and 2.

Jeremy Chien

Ovarian cancer is thought to be a multi-genetic disorder that develops as a result of changes in gene functions in certain women. Taking advantage of Mayo’s latest software, Dr. Chien proposes to examine up to 3 billion gene sequences (transcripts) in tumors obtained from women with either early- or late-stage ovarian cancer as well as normal tissues. In this way he hopes to address both ends of the spectrum, seeking to identify altered gene sequences and pathways associated with early-stage onset of ovarian cancer and late-stage chemoresistance.

The study’s aims are to:
1. Characterize transcripts in serous ovarian tumors by high-throughput sequencing.
2. Identify transcripts associated with early-stage ovarian tumors.
3. Identify transcripts associated with chemoresistant tumors.

William Cliby

This study proposes to evaluate the Mullerian inhibiting substance type II receptor (MISRII), with the eventual aim of using it as a target for therapy and imaging in ovarian cancer. Using a previous MOCA grant, Dr. Cliby demonstrated that MISRII is expressed in the majority of epithelial ovarian cancers. The general hypothesis to be tested is that MISRII is a receptor that is specific to the surface of ovaries and that it is linked to a signaling pathway that results in either inhibition of ovarian tumors or death of ovarian cancer cells. If either is supported, two separate therapeutic strategies are suggested: a) target the MISRII directly to take advantage of its possible signaling pathway for cell death and b) target the MISRII to deliver specific therapy or to improve imaging.

The study’s aims are:
1. Assess the ability to target MISRII expressing ovarian cancer cells in vitro.
2. Demonstrate effective and specific targeting of MISRII-expressing human ovarian cancer xenografts in the mouse model.

Viji Shridhar

Dr. Shridhar continues her work on chemoresistance. She has discovered that one gene, HSulf-1, is greatly decreased in 75% of ovarian cancers and is undetectable in clear cell ovarian cancer. Downregulation of the HSulf-1 pathway appears to be a mechanism by which ovarian cancer cells grow and inhibit ovarian cancer cell death. The naturally-occurring vHNF protein may reverse the effect of this downregulation.

The study’s aims are to:
1. Validate HSulf-1 as a vHNF target gene.
2. Determine if downregulation of vHNF contributes to cisplatin-induced cytotoxicity.
3. Determine whether HSulf-1 expression correlates with loss of vHNF in patients’ ovarian cancer tumors and correlate with clinical behavior of ovarian cancer.

Grant award recipients discussed their research projects at MOCA’s Annual Meeting on May 13 at the Southdale Library in Edina.