ovarian cancer

NEW HAVEN, Conn., Dec. 7, 2011 /PRNewswire/ – Mira Dx® today notes the publication of breakthrough research showing that the KRAS-variant acts as a biomarker of poor survival and worse response to treatment for patients with ovarian cancer(1). Ovarian cancer patients with the KRAS-variant are twice as likely to die of their ovarian cancer, and three times more resistant to standard platinum chemotherapy compared to ovarian cancer patients who do not carry the variant. The KRAS-variant is found in up to 25% of newly diagnosed ovarian cancer patients. Studies are being actively pursued to identify which chemotherapeutic agents work best for these patients.

The KRAS-variant is a germ-line mutated version of the KRAS oncogene, which plays a fundamental role in cancer biology in numerous cancer types. The variant was previously shown to predict an increased risk of developing several cancers, and most strongly ovarian cancer for women from families with histories of breast and ovarian cancers. The variant has also been associated with poor outcome in several cancer types and altered response to therapy in studies looking at Cetuximab.

“We are very excited with this finding as it underscores the importance of the KRAS-variant for all ovarian cancer patients, and more broadly supports the role of microRNA genetics in tumor biology. We look forward to completing additional clinical studies to add [click to continue…]

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Yale Cancer Center researchers have shown that a tiny genetic variation predicts chances of survival and response to treatment for patients with ovarian cancer.

The findings, published in the journal Oncogene, provide new insights into the biology of a new class of cancer marker and suggest a genetic test may help guide the treatment of women with ovarian cancer.

“This gives us a way to identify which women are at highest risk for resistance to platinum chemotherapy, the standard treatment for ovarian cancer, and helps identify ovarian cancer patients with [click to continue…]

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Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies.

This study is focused on identifying the differential expression of regulatory microRNAs (miRNAs) between cis-platin sensitive (A2780), and cis-platin resistant (A2780/CP70) cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin.

Differential expression pattern analysis  reveales changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and [click to continue…]

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Dr. Preethi Gunaratne Wins Key Grants to Unleash Body’s Natural Cancer-fighting Agents

December 21, 2010 – Houston – Ovarian cancer is the fifth deadliest cancer among women, with about 15,000 deaths annually in the United States. The day when an ovarian cancer patient can treat her tumor with a single, painless pill instead of a toxic drug cocktail is the ultimate goal of the pioneering research of a University of Houston (UH) scientist.
Preethi Gunaratne, assistant professor in the department of biology and biochemistry, is studying a class of tiny genetic molecules known as microRNAs and pinpointing those that could unleash the body’s natural cancer-fighting agents and make chemotherapy a thing of the past. She discovered that miR-31 can specifically target and kill cancer cells that are deficient in p53, a crucial gene that guards the integrity of the genome and prevents cancer. More than half of all cancers and 90 percent of papillary serous tumors – the most common type of malignant ovarian cancer – are p53-deficient.

Additionally, she is developing a novel method to effectively deliver this treatment to the targeted cells by using an unusual carrier – nanoparticles of gold – through the work of Lalithya Jayarathne, a postdoctoral researcher in Gunaratne’s lab.  In lab tests, gold nanoparticles containing miR-31 penetrated 90 percent of targeted cells within 20 minutes, killing cancer cells three times faster than microRNAs delivered through lentiviruses, which are traditionally used in carrying gene-based treatments to diseased cells.

(read the entire release… )

Selected Publications

  • Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, Olokpa E, Zariff A, Gunaratne PH, Matzuk MM, Anderson ML. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Cancer Res 70(5), 1906-15. [abstract]
  • Greene SB, Gunaratne PH, Hammond SM, Rosen JM. (2010) A putative role for microRNA-205 in mammary epithelial cell progenitors. J Cell Sci 123(Pt 4), 606-18. [abstract]
  • Gu P, Reid JG, Gao X, Shaw CA, Creighton C, Tran PL, Zhou X, Drabek RB, Steffen DL, Hoang DM, Weiss MK, Naghavi AO, El-daye J, Khan MF, Legge GB, Wheeler DA, Gibbs RA, Miller JN, Cooney AJ, Gunaratne PH. (2008) Novel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cellsPLoS ONE 3(7), e2548.  [abstract]

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The miR-200 family is a particularly nasty group of microRNAs. Changes in miR-200 family levels have been associated with enhanced tumorigenesis and significantly correlated with decreased survival. 

miR-200 family members are associated with resistance to several chemotherapy drugs: docetaxel  in non-small cell cancer cells1, cisplatin in breast cancer cells2, and gemcitabine in cholangiocarcinoma cells.

It has been shown that many microRNAs play an important role in regulating metastasis, the ultimate cause of death of most cancer patients, and in particular, miR-200 is responsible for direct enhancement of distant metastases of breast cancer3.

Additionally miR-200 family members are significantly over-expressed in human ovarian cancer4 and likewise are a factor in the etiology of endometriosis5.

  1. Rui W, Bing F, Hai-Zhu S, Wei D, Long-Bang C.  (2009)  Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1).  J Cell Mol Med [Epub ahead of print]  [abstract]
  2. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer [Epub ahead of print] [abstract]
  3. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J.  (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastasesPLoS One 4(9), e7181.  [abstract]
  4. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM. (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18), 8699-707. [abstract]
  5. Filigheddu N, Gregnanin I, Porporato PE, Surico D, Perego B, Galli L, Patrignani C, Graziani A, Surico N. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol 2010:369549. [abstract]

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