- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Endometrial and Cervical Cancer Treatments
- Angiogenesis and VEGF in Cancer
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Blood properties and coagulation
- PARP inhibition in cancer therapy
- Axon Guidance and Neuronal Signaling
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Cancer, Stress, Anesthesia, and Immune Response
- Cell Adhesion Molecules Research
- Cancer Mechanisms and Therapy
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Metal complexes synthesis and properties
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Cervical Cancer and HPV Research
- Drug Transport and Resistance Mechanisms
University of Southern California
2012-2023
Gynecologic Oncology Group
2006-2023
Epic Sciences (United States)
2023
University of California San Francisco Medical Center
2022
The University of Texas MD Anderson Cancer Center
2006-2021
USC Norris Comprehensive Cancer Center
2012-2020
Roche (United States)
2015-2017
Southern California University for Professional Studies
2014
Los Angeles Medical Center
2013
LAC+USC Medical Center
2012
Abstract Purpose: Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-κB (NF-κB). This study evaluates effects curcumin on ovarian cancer growth using an orthotopic murine model cancer. Experimental Design: In vitro in vivo experiments with without docetaxel were done human cell lines SKOV3ip1, HeyA8, HeyA8-MDR athymic mice. NF-κB modulation was ascertained electrophoretic mobility shift...
To evaluate the addition of humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC).This multicenter placebo-controlled double-blind randomized phase trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with untreated International Federation Gynecology Obstetrics (FIGO) OC who either had undergone primary cytoreductive surgery macroscopic residual...
Chronic stress is associated with hormonal changes that are known to affect multiple systems, including the immune and endocrine but effects of on cancer growth progression not fully understood. Here, we demonstrate human ovarian cells exposed either norepinephrine or epinephrine exhibit lower levels anoikis, process by which enter apoptosis when separated from ECM neighboring cells. In an orthotopic mouse model cancer, restraint increases in protected tumor anoikis promoted their activating...
Focal adhesion kinase (FAK) plays a critical role in ovarian cancer cell survival and various steps the metastatic cascade. Based on encouraging vitro results with FAK silencing, we examined vivo therapeutic potential of this approach using short interfering RNA (siRNA) neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).Therapy experiments siRNA or without docetaxel were done human lines SKOV3ip1, HeyA8, HeyA8MDR nude mice. Additional cisplatin-resistant line (A2780-CP20)...
Interleukin-8 (IL-8) is a proangiogenic cytokine that overexpressed in many human cancers. We investigated the clinical and biologic significance of IL-8 ovarian carcinoma using samples orthotopic mouse models.Tumor expression was assessed by immunohistochemistry among cancer patients (n = 102) with available survival data. examined effect gene silencing small interfering RNAs incorporated into neutral liposomes (siRNA-DOPCs), alone combination docetaxel, on vivo tumor growth, angiogenesis...
Metastasis is a complex, multistep process that begins with the epithelial-mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection such cells. However, most current CTC methods target only EpCAM cytokeratin (CK) enrich CTCs, resulting in failure recognize other, perhaps more important, phenotypes expression these markers. Here, we describe population...
Surgical stress has been suggested to facilitate the growth of preexisting micrometastases as well small residual tumor postoperatively. The purpose this study was examine effects surgical on ovarian cancer and determine underlying mechanisms responsible for increased growth.To mimic surgery, we did a laparotomy or mastectomy under isoflurane inhalation athymic nude mice 4 days after i.p. cell injection. Propranolol infusion via Alzet pumps used block influence sympathetic nervous system...
Abstract Focal adhesion kinase (FAK) overexpression is frequently found in ovarian and other cancers predictive of poor clinical outcome. In the current study, we characterized biological therapeutic effects a novel FAK inhibitor, TAE226. Taxane-sensitive (SKOV3ip1 HeyA8) taxane-resistant (HeyA8-MDR) cell lines were used for vitro vivo therapy experiments using TAE226 alone combination with docetaxel. Assessment cytotoxicity, proliferation [proliferating nuclear antigen (PCNA)], angiogenesis...
Abstract Purpose: Vascular endothelial growth factor (VEGF) is critical for angiogenesis and tumor progression; however, its role in endometrial cancer not fully known. Therefore, we examined the clinical therapeutic significance of VEGF carcinoma using patient samples an endometrioid orthotopic mouse model. Experimental Design: Following Institutional Review Board approval, expression microvessel density (MVD) counts were evaluated immunohistochemistry 111 invasive cancers by two...
Targeting kinases is central to drug-based cancer therapy but remains challenging because the drugs often lack specificity, which may cause toxic side effects. Modulating effects difficult are evolutionarily and hence structurally related. The of specificity anticancer drug imatinib enables it be used treat chronic myeloid leukemia, where its target Bcr-Abl kinase, as well a proportion gastrointestinal stromal tumors (GISTs), C-Kit kinase. However, also has cardiotoxic traceable impact on...
Neuropilin-2 (NRP2) is a high-affinity kinase-deficient receptor for vascular endothelial growth factor (VEGF) and semaphorin 3F. We investigated its function in human colorectal cancers.Immunohistochemistry immunoblotting were used to assess NRP2 expression levels tumors cancer cell lines, respectively. HCT-116 cells stably transfected with short hairpin RNA (shRNAs) against or control shRNAs assayed proliferation by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium...
Abstract Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine in ovarian carcinoma. Experimental Design: kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial cancers), and variables were collected retrospective chart review. Centrosome amplification immunofluorescence cell lines, patient samples. Results: All cancer lines exhibited significant protein overexpression, all except...
Abstract Purpose: Defects in the antigen processing machinery (APM) may provide tumor cells with a mechanism to escape immune recognition. The purpose of this study is determine clinical significance APM component down-regulation and tumor-infiltrating T ovarian carcinoma. Experimental Design: After institutional review board approval, samples from 150 patients invasive epithelial cancers were examined for TAP1, TAP2, tapasin, HLA class I heavy chain (HLA-HC), β2 microglobulin, T-cell (CD3+...
Abstract Metronomic chemotherapy is the frequent administration of low doses chemotherapeutic agents targeting tumor-associated endothelial cells. We examined efficacy metronomic taxanes alone and in combination with AEE788—a dual epidermal growth factor receptor (EGFR) vascular (VEGFR) inhibitor—in an orthotopic mouse model ovarian cancer. Growth-modulating effects maximum tolerated dose (MTD) regimens on overall survival were tested vivo using both chemotherapy-sensitive (HeyA8 SKOV3ip1)...
Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting critical resistance gene, ATP7B, using both vitro vivo models.Expression ATP7A ATP7B was cancer cell lines by real-time reverse transcription-PCR Western blot analysis. gene silencing achieved with targeted small interfering RNA (siRNA) its effects on viability DNA adduct formation were examined. For therapy experiments,...
Abstract Vascular endothelial growth factor receptor (VEGFR) has recently been discovered on ovarian cancer cells, but its functional significance is unknown and the focus of this study. By protein analysis, A2780‐par HeyA8 cell lines expressed VEGFR‐1 A2774, SKOV3ip1 VEGFR‐2. in situ hybridization (ISH), 85% human specimens showed moderate to high VEGFR‐2 expression, whereas only 15% expression. immunofluorescence, little or no was detected normal surface epithelial expression 75% invasive...
Despite standard chemoradiotherapy (CRT), most women with lymph node (LN)-positive cervical cancer experience disease recurrence. Immunotherapy is being investigated in the up-front treatment setting.To assess safety of sequential immunotherapy after CRT and to investigate human papillomavirus (HPV) genotype HLA allele status on survival programmed cell death 1 (PD-1) expression before immunotherapy.This prospective phase trial conducted 29 Gynecology Oncology Cooperative Group member...
Abstract The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired variants, here we establish epigenomic transcriptomic landscapes primary OCs using H3K27ac ChIP-seq RNA-seq, then integrate these with whole genome sequencing data from 232 OCs. We 25 frequently mutated elements, including an enhancer at 6p22.1 which associates differential expression ZSCAN16 (P = 6.6 × 10-4) ZSCAN12...
Objective To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. Methods In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial ( NCT04300647 ), patients with (SP263 tumor area positivity ≥5%) recurrent/persistent cancer after 1–2 chemotherapy lines (≥1 platinum-based) were 3:1 to 1200 mg with/without 600 every 3 weeks until disease progression unacceptable toxicity....