A5080849182- Ovarian cancer diagnosis and treatment
- HER2/EGFR in Cancer Research
- Protein Degradation and Inhibitors
- Endometrial and Cervical Cancer Treatments
- Uterine Myomas and Treatments
- Chromatin Remodeling and Cancer
- Estrogen and related hormone effects
- PARP inhibition in cancer therapy
- Cervical Cancer and HPV Research
- Monoclonal and Polyclonal Antibodies Research
- Intraperitoneal and Appendiceal Malignancies
- Cell Adhesion Molecules Research
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Multiple Myeloma Research and Treatments
- Endometriosis Research and Treatment
- Renal cell carcinoma treatment
- Lung Cancer Research Studies
- Sarcoma Diagnosis and Treatment
- Drug-Induced Adverse Reactions
- DNA Repair Mechanisms
- Reproductive System and Pregnancy
Yale University
2015-2024
Smilow Cancer Hospital
2021-2024
Johns Hopkins Hospital
2023
University of New Haven
2023
Yale New Haven Hospital
2020-2021
Foundation for the National Institutes of Health
2011
National Cancer Institute
2011
Center for Cancer Research
2011
University of Iowa
2007
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...
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...
Purpose: Carcinosarcomas (CS) are highly aggressive gynecologic malignancies containing both carcinomatous and sarcomatous elements with heterogeneous HER2/neu expression. We compared the efficacy of SYD985 (Synthon Biopharmaceuticals BV), a novel HER2-targeting antibody-drug conjugate (ADC), to trastuzumab emtansine (T-DM1, Genentech-Roche) against primary uterine ovarian CS.Experimental Design: Eight CS cell lines were evaluated for surface expression by IHC gene amplification FISH assays....
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...
Background Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Sacituzumab govitecan (SG) a novel antibody-drug-conjugate (ADC) targeting trophoblast-antigen-2 (Trop-2), cell surface glycoprotein highly expressed in many epithelial tumors, to deliver SN-38, active metabolite of irinotecan. This study aimed evaluate Trop-2 expression EOC tissues and preclinical activity SG against primary lines xenografts. Methods was assessed 90 formalin-fixed-paraffin-embedded tumors...
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...
Aims: To compare baseline risk factors for type 1 vs. 2 endometrial cancers and analyze these association with overall survival time to recurrence. Methods: Retrospective review of 816 consecutive cancer cases was conducted diagnosis from January 2005 December 2010 clinical course until 2016. Risk factors, treatment, recurrence, death were compared using sample t tests, χ2 test Cox Regression models. Results: There 550 266 cancer. Patients disease older (p < 0.001), less obese = 0.03),...
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...
We evaluated the role of PIK3CA-mutations as mechanism resistance to trastuzumab in primary HER2/neu-amplified uterine-serous-carcinoma (USC) cell lines. Fifteen whole-exome-sequenced USC lines were tested for HER2/neu-amplification and PIK3CA-mutations. Four (2-harbouring wild-type-PIK3CA-genes 2-harbouring oncogenic-PIK3CA-mutations) vitro dose-titration-proliferation-assays, cell-viability HER2 S6-protein-phosphorylation after exposure trastuzumab. harbouring wild-type-PIK3CA transfected...
Ovarian cancer is the most lethal gynecologic cancer. Claudin-3 and -4, receptors for Clostridium perfringens enterotoxin (CPE), are overexpressed in more than 70% of these tumors. Here, we synthesized characterized poly(lactic-co-glycolic-acid) (PLGA) nanoparticles (NPs) modified with carboxy-terminal-binding domain CPE (c-CPE-NP) delivery suicide gene therapy to chemotherapy-resistant ovarian cells. As a therapeutic payload, generated plasmid encoding diphtheria toxin subunit-A (DT-A)...
Endometrial cancer is the most common gynecologic malignancy in developed countries. The antibody-drug conjugate (ADC) sacituzumab govitecan (SG) targets trophoblast cell-surface antigen-2 (Trop-2) - a glycoprotein highly expressed many epithelial tumors and delivers active metabolite of irinotecan SN-38 to Trop-2-positive tumor cells. We evaluated Trop-2 expression endometrial endometrioid carcinoma (EC) tissues activity SG against primary poorly differentiated EC cell lines xenografts. was...