Poly(ADP-Ribose) Polymerase Inhibition Synergizes with 5-Fluorodeoxyuridine but not 5-Fluorouracil in Ovarian Cancer Cells-abstract

"5-Fluorouracil (5-FU) and 5-fluorodeoxyuridine (FdUrd, floxuridine) have activity in multiple tumors, and both agents undergo intracellular processing to active metabolites that disrupt RNA and DNA metabolism." "These findings underscore differences in the cytotoxic mechanisms of 5-FU and FdUrd and suggest that combining FdUrd and PARP inhibitors may be an innovative therapeutic strategy for ovarian tumors."

MGH (blood) test for cancer gets backing - The Boston Globe

"Boston researchers plan to announce today that they are partnering with pharmaceutical giant Johnson & Johnson to develop and bring to market a sophisticated, noninvasive test that can detect tiny traces of cancer cells in a blood sample......."

health media: BRCA1 Breast Cancer Risk Linked To Other Genes

"...People who carry certain mutations of the BRCA1 gene are known to have a higher risk of developing breast cancer.

Couch told the media that their findings should be "useful in helping determine individual risk for breast cancer in BRCA1 carriers".

"It also provides insights into hormone-receptor-negative breast cancer in the general population," he added.

For the study, Couch and colleagues conducted four phases of genome-wide association studies (GWAS) that altogether involved 20 research centers in 10 North American and European countries and Israel.

For the first phase, to identify candidate gene variants, they scanned the genomes of 1,193 carriers of BRCA1 mutations who were under 40 and had invasive breast cancer and compared them to scans of about the same number of controls: BRCA1 carriers of similar age who did not have breast cancer.

In comparing the genomes from the two populations the researchers examined over half a million genetic alterations. They found 96 pieces of DNA called SNPs, or "snips", short for single nucleotide polymorphisms, that they thought would be likely candidates because they differed between the two populations...."cont'd

Genetic Instability Influences Drug Response in Cancer Cells (abstract)

Abstract

One of the main reasons why most patients with advanced cancer are not curable with the therapies available is the broad heterogeneity of cancer cells, inherently related to their genomic instability that reflects defects of cell cycle checkpoints and DNA mismatch repair (MMR). The present paper reviews Today's knowledge of MMR. Microsatellite (DNA repetitive sequences) instability (MSI) used as a surrogate marker of MMR defects was associated with a predisposition to somatic mutations of several genes including those involved in the neoplastic transformation and tumor progression. Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by germ line mutation in genes involved in MMR such as hMLH1 or hMLH2, or less frequently hMLH6 or hPMS2; it is associated with a high risk of intestinal cancer (CRC) and other tumors including endometrial, stomach, kidney and brain (AND ovarian cancer). There is ample preclinical evidence that cells deficient in MMR are resistant to methylating agents and to some antimetabolites, including 5FU, which is the drug used most for the CRC, whereas they are equally sensitive to oxaliplatin and possibly more sensitive to irinotecan. More studies are needed on the importance of MMR for sensitivity to different anticancer regimens and drugs, so this knowledge can guide rational therapy according to the tumor MMR status.

abstract: DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma (research/pathology)

Note: in research

CONCLUSIONS: This study provides the first high resolution, genome-wide view of DNA copy number alterations in ovarian CCC. The findings provide a genomic landscape for future studies aimed at elucidating the pathogenesis and developing new target-based therapies for CCCs.


Abstract

PURPOSE: Advanced ovarian clear cell carcinoma (CCC) is one of the most aggressive ovarian malignancies, in part because it tends to be resistant to platinum-based chemotherapy. At present, little is known about the molecular genetic alterations in CCCs except that there are frequent activating mutations in PIK3CA. The purpose of this study is to comprehensively define the genomic changes in CCC based on DNA copy number alterations.

EXPERIMENTAL DESIGN: We performed 250K high-density single nucleotide polymorphism array analysis in 12 affinity-purified CCCs and 10 CCC cell lines. Discrete regions of amplification and deletion were also analyzed in additional 21 affinity-purified CCCs using quantitative real-time PCR.

RESULTS: The level of chromosomal instability in CCC as defined by the extent of DNA copy number changes is similar to those previously reported in low-grade ovarian serous carcinoma but much less than those in high-grade serous carcinoma. The most remarkable region with DNA copy number gain is at chr20, which harbors a potential oncogene, ZNF217. This discrete amplicon is observed in 36% of CCCs but rarely detected in serous carcinomas regardless of grade. In addition, homozygous deletions are detected at the CDKN2A/2B and LZTS1 loci. Interestingly, the DNA copy number changes observed in fresh CCC tissues are rarely detected in the established CCC cell lines.

CONCLUSIONS: This study provides the first high resolution, genome-wide view of DNA copy number alterations in ovarian CCC. The findings provide a genomic landscape for future studies aimed at elucidating the pathogenesis and developing new target-based therapies for CCCs.

abstract : Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening : British Journal of Cancer

Conclusion:

Our proof-of-principle study strengthens the hypothesis that neoplastic diseases generate characteristic miRNA fingerprints in blood cells. Still, the obtained OvCA-associated miRNA pattern is not yet sensitive and specific enough to permit the monitoring of disease progression or even preventive screening. Microarray-based miRNA profiling from peripheral blood could thus be combined with other markers to improve the notoriously difficult but important screening for OvCA.

Chronix Biomedical to Launch Cancer Detection and Monitoring Service at ASCO to Advance Clinical Research Using Its Apoptotic DNA Blood Test | Business Wire

Note: in research "Chronix Biomedical to Launch Cancer Detection and Monitoring Service at ASCO to Advance Clinical Research Using Its Apoptotic DNA Blood Test —ASCO Data Show Chronix’s Apoptotic DNA Blood Test Detects Early-Stage Cancer with Excellent Sensitivity and Specificity— —“For Investigational Use Only” Clinical Trial Service Is Designed to Provide Early Data on Patient Response and Disease Progression"