Robin Farias-Eisner

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (8)34.46 Total impact

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    ABSTRACT: Cystathionine β-synthase (CBS) is an enzyme in the transulfuration pathway that can catalyze the condensation of homocysteine (Hcy) and cysteine (Cys) to hydrogen sulfide (H2S) and cystathionine (CTH). CBS-derived H2S is important in angiogenesis and drug resistance in colon and ovarian cancers respectively. However, the mechanisms by which cancer cell- derived H2S is utilized by cancer cells as a protective agent against host derived activated macrophages are not yet investigated. This study investigated the mechanistic role of CBS derived H2S in the protection of human breast cancer (HBC) cells against activated macrophages. HBC patient derived tissue arrays and immunoblot analysis of HBC cells exhibited significantly increased levels of CBS when compared with their normal counterparts. This was associated with increased levels of H2S and CTH. Silencing of CBS in HBC cells caused a significant decrease in the levels of H2S and CTH but did not affect the growth of these cells per se, in in-vitro cultures. However CBS silenced cells exhibited significantly reduced growth in the presence of activated macrophages and in xenograft models. This was associated with an increase in the steady state levels of reactive aldehyde derived protein adducts. Exogenous addition of H2S countered, the effects of CBS silencing in the presence of macrophages. Conversely overexpression of CBS in human breast epithelial (HBE) cells (which do not naturally express CBS) protected them from activated macrophages, which were otherwise susceptible to the latter. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Jun 2015 · Free Radical Biology and Medicine
  • Sivakumar Ramadoss · Suvajit Sen · Gautam Chaudhuri · Robin Farias-Eisner

    No preview · Article · Oct 2014 · Cancer Research
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    Joshua G Cohen · Matthew White · Ana Cruz · Robin Farias-Eisner
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    ABSTRACT: Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years with the five-year overall survival remaining between 20% and 40% for stage III and IV disease. In contrast patients with stage I disease have a greater than 90% five-year overall survival. Detection of ovarian cancer at an early stage would likely have significant impact on mortality rate. Screening biomarkers discovered at the bench have not translated to success in clinical trials. Existing screening modalities have not demonstrated survival benefit in completed prospective trials. Advances in high throughput screening are making it possible to evaluate the development of ovarian cancer in ways never before imagined. Data in the form of human "-omes" including the proteome, genome, metabolome, and transcriptome are now available in various packaged forms. With the correct pooling of resources including prospective collection of patient specimens, integration of high throughput screening, and use of molecular heterogeneity in biomarker discovery, we are poised to make progress in ovarian cancer screening. This review will summarize current biomarkers, imaging, and multimodality screening strategies in the context of emerging technologies.
    Preview · Article · Aug 2014
  • Elena Diaz · Robert E Burky Iii · Charles S Hummel · Robin Farias-Eisner
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    ABSTRACT: Ovarian cancer is usually diagnosed after reaching an advanced stage, in part because of the nonspecific nature of the presenting symptoms. A method of early detection is urgently needed because of the stark difference in long-term survival between early- and late-stage disease. A useful screening test must be easy to perform, low cost, safe and have high positive-predictive value in order to reduce the number of unnecessary invasive procedures performed. A variety of modalities – from pelvic examination to transvaginal ultrasound to cancer antigen 125 to serum biomarker panels and proteomic and other novel approaches – have been explored as possible tests to detect early disease. To date, an effective screening approach has yet to be introduced to clinical practice. Here, the authors evaluate the approaches and highlight promising areas of new research aimed at improving early detection of ovarian cancer.
    No preview · Article · Jan 2014 · Expert Review of Obstetrics & Gynecology
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    ABSTRACT: It is established that high concentrations of nitric oxide (NO·), as released from activated macrophages, induce apoptosis in breast cancer cells. In this study, we assessed the potential of a light-activated NO· donor [(Me2bpb)Ru(NO)(Resf)], a recently reported apoptototic agent, in suppressing the anchorage independent growth potentials of an aggressive human breast cancer cell line. Our results demonstrated the down regulation of anchorage independent growth by light activated NO· treatment in the aggressive human breast cancer cell line MDA-MB-231 and afforded insight into the associated mechanism(s). The investigation revealed an up-regulation of the bioactivity of catalase with an accompanied reduction in the endogenous levels of H2O2, a direct substrate of catalase and a recently identified endogenous growth modulator in breast cancer cells. An earlier publication reported that endogenous superoxide (O2(.-)) in human breast cancer cells constitutively inhibits catalase bioactivity (at the level of its protein), resulting in increased H2O2 levels. Interestingly in this study, O2(.-) was also found to be down- regulated following NO treatment providing a basis for the observed increase in catalase bioactivity. Cells silenced for the catalase gene exhibited compromised reduction in anchorage independent growth upon light activated NO· treatment. Collectively this study detailed a mechanistic cross talk between exogenous NO· and endogenous ROS in attenuating anchorage independent growth.
    No preview · Article · Oct 2013 · Archives of Biochemistry and Biophysics
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    ABSTRACT: We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDLR(-/-) mice fed a Western Diet (WD). Here we demonstrate that WD increases unsaturated (but not saturated) LPA levels in small intestine of LDLR(-/-) mice and causes changes in small intestine gene expression. Confirmation of microarray analysis by RT-qPCR showed that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F) to WD prevented many WD-mediated small intestine changes in gene expression. If instead of feeding WD, unsaturated LPA was added to chow and fed to the mice, i) levels of LPA in small intestine were similar to those induced by feeding WD; ii) gene expression changes in small intestine mimicked WD-mediated changes; and iii) changes in plasma serum amyloid A (SAA), total cholesterol, triglycerides, HDL-cholesterol levels, and FPLC lipoprotein profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to LPA-supplemented chow prevented the LPA-induced changes. We conclude that i) WD-mediated systemic inflammation and dyslipidemia may be in part due to WD-induced increases in small intestine LPA levels; ii) Tg6F reduces WD-mediated systemic inflammation and dyslipidemia by preventing WD-induced increases in LPA levels in small intestine.
    Full-text · Article · Oct 2013 · The Journal of Lipid Research
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    ABSTRACT: To achieve malignancy, cancer cells convert numerous signaling pathways, with evasion from cell death being a characteristic hallmark. The cell death machinery represents an anti-cancer target demanding constant identification of tumor-specific signaling molecules. Control of mitochondrial radical formation, particularly superoxide interconnects cell death signals with appropriate mechanistic execution. Superoxide is potentially damaging, but also triggers mitochondrial cytochrome c release. While paraoxonase (PON) enzymes are known to protect against cardiovascular diseases, recent data revealed that PON2 attenuated mitochondrial radical formation and execution of cell death. Another family member, PON3, is poorly investigated. Using various cell culture systems and knockout mice, here we addressed its potential role in cancer. PON3 is found overexpressed in various human tumors and diminishes mitochondrial superoxide formation. It directly interacts with coenzyme Q10 and presumably acts by sequestering ubisemiquinone, leading to enhanced cell death resistance. Localized to the endoplasmic reticulum (ER) and mitochondria, PON3 abrogates apoptosis in response to DNA damage or intrinsic but not extrinsic stimulation. Moreover, PON3 impaired ER stress-induced apoptotic MAPK signaling and CHOP induction. Therefore, our study reveals the mechanism underlying PON3's anti-oxidative effect and demonstrates a previously unanticipated function in tumor cell development. We suggest PONs represent a novel class of enzymes crucially controlling mitochondrial radical generation and cell death.
    Full-text · Article · Mar 2012 · Cell death and differentiation
  • V. Nossov · F. Su · S. T. Reddy · R. Farias-Eisner

    No preview · Article · Nov 2007 · Gynecologic Oncology