Radhika Gogoi

Bio: Radhika Gogoi is an academic researcher from Geisinger Medical Center. The author has contributed to research in topics: Medicine & Ovarian cancer. The author has an hindex of 10, co-authored 30 publications receiving 361 citations. Previous affiliations of Radhika Gogoi include New York University & Lankenau Medical Center.

Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells.

Abstract: // Venkata Ramesh Dasari 1 , Virginia Mazack 1 , Wen Feng 2 , John Nash 1 , David J. Carey 1 , Radhika Gogoi 1 1 Weis Center for Research, Geisinger Medical Center, Danville, PA, USA 2 Henry Hood Center for Health Research, Geisinger Medical Center, Danville, PA, USA Correspondence to: Radhika Gogoi, email: rpgogoi@geisinger.edu Keywords: endometrial carcinoma, hippo pathway, verteporfin, YAP, organoids Received: October 07, 2016 Accepted: January 24, 2017 Published: February 22, 2017 ABSTRACT Endometrial Carcinoma (EMCA) is the most common gynecologic malignancy and the fourth most common malignancy in women in the United States. Yes-associated protein (YAP) is a potent transcription coactivator acting via binding to the TEAD transcription factor, and plays a critical role in organ size regulation. Verteporfin (VP), a benzoporphyrin derivative, was identified as an inhibitor of YAP-TEAD interaction. We investigated the therapeutic efficacy and mechanism of VP in EMCA. The efficacy of VP on cell viability, cytotoxicity and invasion was assayed in EMCA cell lines. An organoid model system was also developed to test the effect of VP on apoptotic markers in an in vitro model system. Treatment with VP resulted in a decrease in cell viability, invasion and an increase in cytotoxicity of EMCA cells. These effects occurred as early as 15 minutes following treatment. Similarly, VP treatment versus vehicle control increased apoptosis in human organoid model systems. Quantitative RT-PCR, cDNA based RTPCR array analysis and western blotting were performed to investigate the mechanism of VP action. The cytotoxic and anti-proliferative effects appeared to be independent of its effect on YAP. Our results suggest that VP is a promising chemotherapeutic agent for the treatment of endometrial cancer.

The tumor microenvironment: key to early detection.

Abstract: The tumor microenvironment plays an important role equal to the tumor cell population in the progression of cancer. Consisting of stromal fibroblasts, inflammatory cells, components of the vasculature, normal epithelia, and extracellular matrix, the surrounding environment interacts or “cross-talks” with tumor cells through the release of growth factors, cytokines, proteases, and other bioactive molecules. Tumor growth, formation of new vascular networks, evasion of the host immune system, and invasion and metastasis are processes that co-evolve and become finely optimized and regulated within the tumor microenvironment. However, relatively recent reports on three areas of study have come together to add new levels of complexity to the tumor microenvironment. These include ectodomain shedding of proteins, shedding of membrane-derived vesicles, and novel roles for phospholipids. These dynamic changes that take place in the tumor microenvironment provide new avenues for study and for the early detection of ...

Yes-associated protein (YAP) modulates oncogenic features and radiation sensitivity in endometrial cancer.

Abstract: Background Yes-associated protein (YAP) is a transcriptional co-activator and regulates cell proliferation and apoptosis. We investigated the clinical and biological significance of YAP in endometrial cancer (EMCA). Methods YAP expression in 150 primary tumor tissues from patients with EMCA was evaluated by immunohistochemistry and its association with clinicopathological data was assessed. The biological functions of YAP were determined in EMCA cell lines through knockdown/overexpression of YAP. The role of YAP in modulating radiation sensitivity was also investigated in EMCA cells. Results Increased nuclear YAP expression was significantly associated with higher grade, stage, lympho-vascular space invasion, postoperative recurrence/metastasis and overall survival in estrogen mediated EMCA, called type 1 cancer (p = 0.019, = 0.028, = 0.0008, = 0.046 and = 0.015, respectively). In multivariate analysis, nuclear YAP expression was confirmed as an independent prognostic factor for overall survival in type 1 EMCA. YAP knockdown by siRNA resulted in a significant decrease in cell proliferation (p<0.05), anchorage-dependent growth (p = 0.015) and migration/invasion (p<0.05), and a significant increase in the number of cells in G0/G1 phase (p = 0.002). Conversely, YAP overexpression promoted cell proliferation. Clonogenic assay demonstrated enhanced radiosensitivity by approximately 36% in YAP inhibited cells. Conclusions Since YAP functions as a transcriptional co-activator, its differential localization in the nucleus of cancer cells and subsequent impact on cell proliferation could have important consequences with respect to its role as an oncogene in EMCA. Nuclear YAP expression could be useful as a prognostic indicator or therapeutic target and predict radiation sensitivity in patients with EMCA.

Randomized Trial of Exercise on Quality of Life in Women With Ovarian Cancer: Women's Activity and Lifestyle Study in Connecticut (WALC).

Abstract: Background Ovarian cancer survivors experience a wide range of treatment side effects that can negatively affect health-related quality of life (HRQOL) Physical activity has been shown to improve HRQOL and cancer-related fatigue (CRF) for other cancer survivors; however, no large randomized controlled trial (RCT) has been conducted for ovarian cancer Methods This study examined the impact of a six-month RCT of exercise vs attention control on change in HRQOL (Short Form Health Survey-36) and CRF (Functional Assessment of Cancer Therapy-Fatigue Scale) in ovarian cancer survivors Women (n = 144) were randomly assigned to study arms between May 1, 2010, and March 20, 2014 All statistical tests were two-sided Results A total of 74 women were randomly assigned to exercise and 70 to attention control A total of 113 (785%) of the participants completed the six-month assessment Adherence to the exercise intervention was excellent (1660±661 minutes/week in the exercise arm) At six months, women in the exercise arm had improved physical HRQOL (SF-36 Physical Component Summary Score) compared with the control arm, 18 (SD = 11) vs -20 (SD = 12) , respectively (group difference = 37, SD = 12, 95% confidence interval [CI] = 07 to 68, P = 02) No group differences were seen for change in mental HRQOL There was a statistically significant improvement in the fatigue score (Functional Assessment of Cancer Therapy-Fatigue) for exercisers (40, SD = 11, 95% CI = 18 to 62, P < 001) but not for controls (12, SD = 12, 95% CI = -11 to 35, P = 31), with a between-group difference of 28 (SD = 15, 95% CI = -02 to 57, P = 06) Conclusions We found a six-month home-based, telephone-delivered exercise intervention of primarily brisk walking to be associated with improved physical HRQOL in women with ovarian cancer Given that higher HRQOL and exercise have both been associated with overall survival in women diagnosed with ovarian cancer, oncologists and primary care providers should recommend and refer women diagnosed with ovarian cancer to clinic- or community-based exercise programs

Inflammation: gearing the journey to cancer.

Abstract: Chronic inflammation plays a multifaceted role in carcinogenesis. Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. The possible mechanisms by which inflammation can contribute to carcinogenesis include induction of genomic instability, alterations in epigenetic events and subsequent inappropriate gene expression, enhanced proliferation of initiated cells, resistance to apoptosis, aggressive tumor neovascularization, invasion through tumor-associated basement membrane and metastasis, etc. Inflammation-induced reactive oxygen and nitrogen species cause damage to important cellular components (e.g., DNA, proteins and lipids), which can directly or indirectly contribute to malignant cell transformation. Overexpression, elevated secretion, or abnormal activation of proinflammatory mediators, such as cytokines, chemokines, cyclooxygenase-2, prostaglandins, inducible nitric oxide synthase, and nitric oxide, and a distinct network of intracellular signaling molecules including upstream kinases and transcription factors facilitate tumor promotion and progression. While inflammation promotes development of cancer, components of the tumor microenvironment, such as tumor cells, stromal cells in surrounding tissue and infiltrated inflammatory/immune cells generate an intratumoral inflammatory state by aberrant expression or activation of some proinflammatory molecules. Many of proinflammatory mediators, especially cytokines, chemokines and prostaglandins, turn on the angiogenic switches mainly controlled by vascular endothelial growth factor, thereby inducing inflammatory angiogenesis and tumor cell-stroma communication. This will end up with tumor angiogenesis, metastasis and invasion. Moreover, cellular microRNAs are emerging as a potential link between inflammation and cancer. The present article highlights the role of various proinflammatory mediators in carcinogenesis and their promise as potential targets for chemoprevention of inflammation-associated carcinogenesis.

A Phase III Trial of Surgery With or Without Adjunctive External Pelvic Radiation Therapy in Intermediate-Risk Endometrial Adenocarcinoma: A Gynecologic Oncology Group Study

Abstract: Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received fall-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatrnent. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.

Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine

Abstract: The Hippo pathway is an evolutionarily conserved signalling pathway with key roles in organ development, epithelial homeostasis, tissue regeneration, wound healing and immune modulation Many of these roles are mediated by the transcriptional effectors YAP and TAZ, which direct gene expression via control of the TEAD family of transcription factors Dysregulated Hippo pathway and YAP/TAZ–TEAD activity is associated with various diseases, most notably cancer, making this pathway an attractive target for therapeutic intervention This Review highlights the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discusses new strategies and therapeutic implications of targeting this pathway In this Review, Dey and colleagues discuss the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discuss new strategies and therapeutic implications of targeting this pathway

What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)

Abstract: What constitutes "optimal" cytoreduction for women operated on for ovarian cancer remains uncertain. A majority of studies have employed a cutoff of 1-2 cm to define optimal cytoreduction. Recent studies suggest that removing all gross disease promotes disease-free survival compared to the current Gynecologic Oncology Group threshold of 1 cm or less of residual disease. This prospective database analysis reviewed the records of 465 patients with stage IIIC epithelial ovarian carcinoma (EOC) who had cytoreductive surgery in the years 1989-2003. All participants had bulky abdominal tumor, and maximal cytoreduction was attempted if technically possible. The patients, whose median age was 60 years, were followed up for a median of 38 months. Nearly all the patients received at least 6 cycles of platinum-based systemic chemotherapy. Univariate analysis showed age at the time of surgery and the preoperative platelet count to be significant continuous variables. Categorical variables with prognostic significance included the presence of ascites, the site of the largest tumor mass, extensive upper abdominal cytoreduction, and the extent of residual disease. Multivariate analysis confirmed age, the presence or absence of ascites, and the diameter of residual disease as being significant factors. Median survival was 106 months when there was no gross residual disease, and declined steadily as the amount of residual disease increased. Median survival was 34 months when patients were left with more than 2 cm of residual disease. The major distinctions with regard to survival rate were between no gross residual disease, 1 cm or less of gross disease, and more than 1 cm of residual disease. A trend toward improved survival was noted in patients left with 0.5 cm or less of residual disease compared with those retaining 0.6-1 cm of disease (Fig. 1). The investigators conclude from these findings that removing all evidence of gross stage IIIC EOC prolongs survival and is an appropriate goal of primary cytoreductive surgery. If complete gross resection is not feasible, as little residual tumor as possible should be left behind. An incremental decrease in residual disease below 1 cm can incrementally enhance overall survival.