A5054476619- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- Sirtuins and Resveratrol in Medicine
- Mechanisms of cancer metastasis
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Galectins and Cancer Biology
- Protease and Inhibitor Mechanisms
- MicroRNA in disease regulation
- PARP inhibition in cancer therapy
- Autophagy in Disease and Therapy
- Blood Coagulation and Thrombosis Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Circular RNAs in diseases
- Glycosylation and Glycoproteins Research
- Immune cells in cancer
- Cancer, Lipids, and Metabolism
- Child Abuse and Trauma
- Calcium signaling and nucleotide metabolism
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
National Cancer Institute
2019-2025
National Institutes of Health
2020-2025
Johns Hopkins University
2024
Johns Hopkins Medicine
2024
Translational Research Institute
2014-2021
The University of Queensland
2014-2021
Mater Research
2014-2021
University of Pennsylvania
2019-2021
Michigan State University
2019
Retina Institute
2014
<h3>Background</h3> The long-term prognosis of Henoch-Schönlein Purpura (HSP) is predominantly determined by the extent renal involvement. There no consensus as to whether treatment with prednisolone at presentation can prevent or ameliorate progression nephropathy in HSP. <h3>Methods</h3> Children under 18 years age new-onset HSP were randomly assigned receive placebo for 14 days. primary outcomes (a) presence proteinuria 12 months (defined urine protein : creatinine ratio (UP UC) >20...
Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action due to a slow cumulative decrease activated lymphocytes homing inflamed gut. We examined the role of host metabolism, microbiome amelioration colitis by related thioguanine (TG).C57Bl/6 mice with or without specific genes altered elucidate mechanisms responsible TG's actions were treated daily intrarectal TG, MP water. Disease...
Whereas many components regulating the progression from S phase through G2 into mitosis have been identified, mechanism by which these control this critical cell cycle is still not fully elucidated. Cyclin A/Cdk2 has shown to regulate timing of B/Cdk1 activation and although occurs only poorly understood. Here we show that depletion A or inhibition Cdk2 during late S/early maintains arrest reducing Cdh1 transcript protein levels, thereby stabilizing Claspin maintaining elevated levels...
Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface elevated in lung, colorectal, pancreas, renal and clear cell cancer. was examined by immunohistochemistry HGSC fallopian tube. The impact targeting CDCP1 on growth migration vitro, intraperitoneal xenograft mice examined. Three patient-derived (PDX) mouse...
Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination these tumors is characteristically via direct extension the primary tumor into nearby organs and spread exfoliated cells throughout peritoneum, initially peritoneal fluid, later ascites that accumulates as a result disruption lymphatic system. The molecular mechanisms orchestrating processes uncertain. In particular, signaling pathways used by malignant to survive stresses...
Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity refractory skeletal complications. Macrophages are abundant in bone marrow can influence both osteoblast osteoclast function physiology pathology. Herein, we examined the role of macrophages lesions, particularly response. First, macrophage lymphocyte distributions were qualitatively assessed patient's by...
Disease recurrence is the major cause of morbidity and mortality ovarian cancer (OC). In terms maintenance therapies after platinum-based chemotherapy, PARP inhibitors significantly improve overall survival patients with BRCA mutations but little benefit to without homologous recombination deficiency (HRD). The stem-like tumor-initiating cell (TIC) population within OC tumors are thought contribute disease chemoresistance. Therefore, there a need identify drugs that target TICs prevent...
Abstract Ovarian cancer follows a characteristic progression pattern, forming multiple tumor masses enriched with stem cells (CSCs) within the abdomen. Most patients develop resistance to standard platinum-based drugs, necessitating better treatment approaches. Targeting CSCs by inhibiting NAD+ synthesis has been previously explored. Nicotinamide phosphoribosyltransferase (NAMPT), which is rate limiting enzyme in salvage pathway for an attractive drug target this pathway. KPT-9274 innovative...
Abstract Ovarian cancer (OV) has the highest mortality rate among gynecological cancers. As OV progresses, tumor cells spread outside ovaries to peritoneal and abdominal cavities, forming cell clusters that float in ascitic fluid caused by peritonitis carcinomatosa, leading further dissemination metastasis. These are enriched with stem (CSCs) which responsible for treatment resistance, recurrence, Therefore, targeting CSCs is a potentially effective approach treating OV. However,...
CUB-domain containing protein 1 (CDCP1) is a cancer associated cell surface that amplifies pro-tumorigenic signalling by other receptors including EGFR and HER2.Its potential as target supported studies showing anti-CDCP1 antibodies inhibit migration survival in vitro, tumor growth metastasis vivo.Here we characterize two antibodies, focusing on immuno-conjugates of one these tool to detect ovarian cancer.Methods: A panel lines was examined for expression CDCP1 loss induced 10D7 41-2 using...
Epithelial ovarian cancer (EOC) is a global health burden and remains the fifth leading cause of related death in women worldwide with poorest five-year survival rate gynecological malignancies. EOC recurrence considered to be driven by chemoresistant, stem-like tumor-initiating cells (TICs). We previously showed that disulfiram, an ALDH inhibitor, effectively targeted TICs compared adherent terms viability, spheroid formation, oxidative stress also prevented relapse vivo model EOC. In this...
Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC driven by chemoresistant, stem-like tumor-initiating cells (TICs) that are supported complex extracellular matrix immunosuppressive microenvironment. To target TICs prevent recurrence, we identified genes critical for TIC viability from whole genome siRNA screen. A top hit was...
Signaling pathways regulated by the receptor CDCP1 play central roles in promoting cancer and mediating resistance to chemo-and targeted-therapies.In this perspective we briefly summarize these findings as well data demonstrating poorer outcomes for several malignancies that exhibit elevated expression.Promising from preclinical studies suggest targeted agents, including therapeutic antibodies, could be useful treatment of patients selected on basis activation its signaling partners EGFR,...
Epithelial ovarian cancer (EOC) remains the fifth leading cause of cancer-related death in women worldwide, partly due to survival chemoresistant, stem-like tumor-initiating cells (TICs) that promote disease relapse. We previously described a role for NF-κB pathway promoting TIC chemoresistance and through transcription factors (TFs) RelA RelB, which regulate genes important inflammatory response those associated with cancer, including microRNAs (miRNAs). hypothesized signaling...
High stage and recurrent ovarian clear cell carcinoma (OCC) are associated with poor prognosis resistance to chemotherapy. A distinguishing histological feature of OCC is abundant cytoplasmic stores glucose, in the form glycogen, that can be mobilized for cellular metabolism. Here, we report effect on preclinical models disrupting glycogen utilization using glucose analogue 2-deoxy-D-glucose (2DG). At concentrations significantly lower than previously reported other cancers, 2DG markedly...
Abstract The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 cleaved by serine proteases at adjacent sites, arginine 368 (R368) lysine 369 (K369), which induces cell migration vitro metastasis vivo . We demonstrate that membrane localization protease activity increases efficacy cleavage CDCP1, both secreted anchored can have distinct preferences for cleaving CDCP1-R368 CDCP1-K369. Approaches disrupt may...
Abstract Ovarian cancer follows a characteristic progression pattern, forming multiple tumor masses enriched with stem cells (CSCs) within the abdomen. Most patients develop resistance to standard platinum-based drugs, necessitating better treatment approaches. To target CSCs, inhibition of nicotinamide phosphoribosyltransferase (NAMPT), which is rate-limiting enzyme in salvage pathway for NAD + synthesis, has been explored ovarian cancer. KPT-9274 an innovative drug targeting both NAMPT and...