A5062471254- Ovarian cancer diagnosis and treatment
- Endometrial and Cervical Cancer Treatments
- Uterine Myomas and Treatments
- Estrogen and related hormone effects
- Sarcoma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- HER2/EGFR in Cancer Research
- Growth Hormone and Insulin-like Growth Factors
- Endometriosis Research and Treatment
- Genetics and Neurodevelopmental Disorders
- Cytokine Signaling Pathways and Interactions
- Cervical Cancer and HPV Research
- PARP inhibition in cancer therapy
- Cancer-related gene regulation
- 14-3-3 protein interactions
- Genomics and Chromatin Dynamics
- Intraperitoneal and Appendiceal Malignancies
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- Cell Adhesion Molecules Research
- BRCA gene mutations in cancer
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
Yale University
2017-2024
Yale Cancer Center
2019-2024
Smilow Cancer Hospital
2021-2024
Albert Einstein College of Medicine
2010-2023
Johns Hopkins Hospital
2023
University of New Haven
2023
Women's Health Research Institute
2005-2023
Gynecologic Oncology Group
2023
Yale New Haven Hospital
2020-2021
Institute of Botany of the Slovak Academy of Sciences
2021
Enhanced levels of cytoplasmic Ca2+ due to membrane depolarization with elevated KCl or exposure the ionophore ionomycin stimulate serum response element (SRE)-dependent transcription in pheochromocytoma cell line PC12. By using altered binding specificity mutants factors that bind SRE, it was demonstrated contrast treatment purified growth factors, such as nerve factor, factor (SRF), but not Elk-1, mediates Ca(2+)-regulated SRE-dependent transcription. were found trigger via a...
Purpose There is a growing demand for BRCA1/ 2 mutation ( BRCAm) testing in patients with ovarian cancer; however, the limited number of genetic counselors presents potential barrier. To facilitate more widespread BRCAm cancer, pretest counseling by oncology team could shorten turnaround times and ease pressure on counselors. Patients Methods The prospective, observational Evaluating Streamlined Onco-genetic BRCA Testing Counseling Model Among With Ovarian Cancer (ENGAGE) study evaluated...
Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of uterus. We analyzed 83 uLMS sample genetics, including 56 Yale and 27 The Cancer Genome Atlas (TCGA). Among them, a total 55 samples two patient-derived xenografts (PDXs) TCGA have whole-exome sequencing (WES) data; 10 RNA-sequencing (RNA-Seq) 11 whole-genome (WGS) data. found recurrent somatic mutations in TP53, MED12, PTEN genes. Top mutated genes included ATRX, PTEN, MEN1 Somatic copy number...
Background Microsatellite instability–high (MSI‐H)/mismatch repair deficiency (dMMR) is a biomarker for responses to immune checkpoint inhibitors (ICIs). Whether mechanisms underlying microsatellite instability alter ICIs unclear. This article reports data from prospective phase 2 pilot study of pembrolizumab in patients with recurrent MSI‐H endometrial cancer (EC) analyzed by whole exome sequencing (WES) and potential primary/secondary ICI resistance (NCT02899793). Methods Patients...
This study was undertaken to examine the role of insulin-like growth factor (IGF) signaling pathway in response ovarian cancer cells Taxol and evaluate significance this human epithelial tumors.The effect treatment on AKT activation A2780 carcinoma evaluated using antibodies specific for phospho-AKT. To drug-resistant phenotype, we developed a Taxol-resistant cell line, HEY-T30, derived from HEY cells. IGF2 expression measured by real-time PCR. A type 1 IGF receptor (IGF1R) inhibitor,...
Significance Ovarian cancer has the propensity for early dissemination of microscopic metastases, making detection challenging. Development treatments patients with advanced/recurrent chemotherapy-resistant disease remains an unmet need. We sequenced primary, synchronous bilateral ovarian (SBOC), metastatic, and recurrent tumors. found primary metastatic tumors to be remarkably similar SBOC clonally related in all cases, suggesting represent intrinsic feature cancer. c-MYC PIK3CA...
The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most which harboring Human-Papillomavirus-type-16/18. found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, GNAS) a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) both adenocarcinoma (ACC) squamous carcinomas (SCCs). Somatic copy number variants (CNVs)...
Abstract Human trophoblast cell-surface marker (Trop-2) is a surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of epithelial solid tumors. We investigated the efficacy sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised humanized anti- Trop-2 antibody, conjugated with active metabolite irinotecan (SN-38), on positive cervical cancer cell lines xenograft model. expression was evaluated 147 primary...
High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.6% (42/64) of the Recurrent mutations were identified PIK3CA, KMT2D/MLL2, K-RAS, ARID1A, NOTCH2, and RPL10. The top mutated genes included RB1, PTEN, KMT2D / MLL2, WDFY3, a gene not yet implicated NETc. Somatic CNV analysis two copy number gains (3q27.1 19q13.12) five losses...
This retrospective review of patients undergoing total laparoscopic hysterectomy examines whether differences in outcomes exist on the basis body mass index (BMI).All cases performed from September 1996 to July 2002 for benign diagnoses, and microinvasive cervical, early endometrial, occult ovarian carcinoma were reviewed. There 330 analyzed by BMI category (range, 18.5-54.1): ideal (n = 150) less than 24.9 kg/m(2), overweight 95) 25 29.9 obese 78) 30 kg/m(2) or more. Seven converted...
Abstract Purpose: To evaluate the drug combination of discodermolide and Taxol in human ovarian cancer cells an vivo model carcinoma. Experimental Design: The index method was used to interaction SKOV-3 carcinoma cells. Data were correlated with alterations cell cycle distribution caspase activation. In addition, xenograft-bearing mice treated either Taxol, discodermolide, or a both drugs given concurrently antitumor efficacy toxicity this combination. Matrigel plug assay CD31...
To evaluate the safety and survival in women treated with adjuvant pelvic radiation "sandwiched" between six cycles of paclitaxel carboplatin chemotherapy completely resected UPSC.Surgically staged UPSC (FIGO stage 1-4) no visible residual disease were enrolled. Treatment involved (175 mg/m(2)) (AUC=6.0-7.5) every 21 days for 3 doses, followed by therapy (RT), an additional (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least RT.A total...
Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown radiotherapy (RT), systemic chemotherapy, or both. This first report describing and toxicity of ifosfamide plus cisplatin "sandwiched" RT in patients surgically staged completely resected carcinosarcoma.Women CS no gross residual disease were initially administered (1.2 g/m(2)/day×5 days) (20 mg/m(2)/day×5 every 3 weeks for cycles followed by pelvic external...
Uterine and ovarian carcinosarcomas (CS) are rare cancers with poor prognosis. Sacituzumab-govitecan (SG) is a new class of antibody-drug-conjugate (ADC) targeting the human-trophoblast-cell-surface marker (Trop-2) conjugated active metabolite irinotecan (SN-38). We evaluated efficacy SG against biologically aggressive CS.Trop-2 expression was in 10 formalin-fixed-paraffined-embedded (FFPE) CS by immunohistochemistry 9 primary cell-lines flow-cytometry. One Trop-2 low/negative (SARARK14) two...
5599 Background: Despite recent advances, there remains a significant need for targeted, efficacious treatments advanced and recurrent endometrial carcinoma (EC). Trop-2 has been demonstrated to be overexpressed in several EC including grade 3 endometrioid adenocarcinoma (96%), uterine serous (65%). overexpression found confer worse prognosis predicts disease recurrence. Sacituzumab govitecan-hziy (SG) is an antibody-drug conjugate comprised of humanized anti-Trop-2 antibody conjugated with...
Abstract Purpose: We report the results of a randomized phase II trial imiquimod, topical immune-response modulator versus imiquimod plus 9-valent human papillomavirus (HPV) vaccine (9vHPV) clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. Patients and Methods: randomly allocated 133 patients with untreated CIN2/3 equal proportions to 4-month treatment self-applied vaginal suppositories containing (Arm B) or 9vHPV C) A). The main outcome was efficacy, defined as...