Genomic complexity and AKT dependence in serous ovarian cancer.

Unlabelled: Effective oncoprotein-targeted therapies have not yet been developed for ovarian cancer. To explore the role of PI3 kinase/AKT signaling in this disease, we performed a genetic and functional analysis of ovarian cancer cell lines and tumors. PI3K pathway alterations were common in both, but the spectrum of mutational changes differed.

RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis.

Previous studies described functional roles for Rho GDP dissociation inhibitor 2 (RhoGDI2) in bladder, gastric and breast cancers. However, only limited expression and no functional analyses have been done for RhoGDI2 in ovarian cancer. We determined RhoGDI2 protein expression and function in ovarian cancer.

Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth.

Although the potent antitumor activity of nitric oxide (NO) supports its promise as an antineoplastic agent, effective and selective delivery and action on tumor and not normal cells remains a limiting factor. Nanoparticle-based delivery of NO has been considered as one approach to overcome these limitations. Therefore, we determined the utility of NO delivery using silica nanoparticles and evaluated their antitumor efficacy against human ovarian tumor and nontumor cells.

Hyperphosphorylation of RNA polymerase II in response to topoisomerase I cleavage complexes and its association with transcription- and BRCA1-dependent degradation of topoisomerase I.

The progression of RNA polymerase II can be blocked by lesions on the DNA template. In this study, we focused on the modifications of the largest subunit of RNA polymerase II, Rpb1, in response to stabilized topoisomerase I (Top1)-DNA cleavage complexes. In addition to DNA modifications (base damages and strand breaks), Top1 cleavage complexes can be trapped by camptothecin (CPT) and its derivatives used in cancer treatment.

Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers.

Molecular profiling of markers involved in the activity of chemotherapeutic agents can shed light on the successes and failures of treatment in patients and can also provide a basis for individualization of therapy. Toward those ends, we have used reverse-phase protein lysate microarrays to evaluate expression of protein components of the nucleotide excision repair (NER) pathways. Those pathways strongly influence the anticancer activities of numerous drugs, including those that are the focus here, cisplatin and ecteinascidin 743 (Et-743; Yondelis, Trabectedin).

Expression of xeroderma pigmentosum A protein predicts improved outcome in metastatic ovarian carcinoma.

Background: The nucleotide excision repair (NER) proteins repair DNA adducts due to xenobiotics and cancer chemotherapy. The authors hypothesized that expression of the NER protein xeroderma pigmentosum A (XPA) would be reduced in a clinically significant fashion in metastatic ovarian carcinoma.

Methods: Malignant effusion specimens were studied so that there was a uniform metastatic ovarian carcinoma population for study.

Topoisomerase I-DNA complexes contribute to arsenic trioxide-induced apoptosis.

Topoisomerase I is an essential enzyme that relaxes DNA supercoiling by forming covalent DNA cleavage complexes, which are normally transient. Topoisomerase I-DNA complexes can be trapped by anticancer drugs (camptothecins) as well as by endogenous and exogenous DNA lesions. We show here that arsenic trioxide (a potent inducer of apoptosis that induces the intracellular accumulation of reactive oxygen species and targets mitochondria) induces cellular topoisomerase I cleavage complexes.