A5016006904- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Lung Cancer Research Studies
- Ion Channels and Receptors
- Helicobacter pylori-related gastroenterology studies
- Peptidase Inhibition and Analysis
- Metabolism, Diabetes, and Cancer
- Endoplasmic Reticulum Stress and Disease
- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- Calcium signaling and nucleotide metabolism
- Cancer-related Molecular Pathways
- Radiopharmaceutical Chemistry and Applications
- Thyroid Cancer Diagnosis and Treatment
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- Medical Imaging and Pathology Studies
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Microbial Natural Products and Biosynthesis
- Hedgehog Signaling Pathway Studies
- 14-3-3 protein interactions
Wayne State University
2018-2023
The Barbara Ann Karmanos Cancer Institute
2019-2023
Pancreatic ductal adenocarcinoma (PDAC) remains an unmet clinical problem in urgent need of newer molecularly driven treatment modalities. Calcium signals, particularly those associated with calcium release-activated (CRAC) channels, are known to influence the development, growth, and metastasis many cancers. This is first study investigating impact CRAC channel inhibition on PDAC cell lines patient-derived tumor models. were exposed a novel inhibitor, RP4010, presence or absence standard...
Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) that shows improved median progression-free survival (PFS) in patients with thyroid carcinomas. However, virtually all ultimately progress, indicating the need for better understanding of mechanisms resistance. Here, we examined molecular profile anaplastic cancer cells (8505C) exposed to lenvatinib and found long-term exposure caused phenotypic changes. Consistent change toward mesenchymal morphology, activation pro-survival...
Pancreatic neuroendocrine tumors (PNET) remain an unmet clinical need. In this study, we show that targeting both nicotinamide phosphoribosyltransferase (NAMPT) and p21-activated kinase 4 (PAK4) could become a synthetic lethal strategy for PNET. The expression of PAK4 NAMPT was found to be higher in PNET tissue compared normal cells. PAK4-NAMPT dual RNAi suppressed proliferation cell lines. Treatment with KPT-9274 (currently Phase I trial or analogs, PF3758309 (the selective inhibitor) FK866...
Abstract Metastatic pancreatic neuroendocrine tumors (PNET) remain an unmet clinical problem. Chronologic treatment in PNETs includes observation (watchful protocol), surgery, targeted therapy, and chemotherapy. However, increasing evidence illustrates that the outcomes of therapeutic options for advanced show minimal response. The FDA-approved mTOR inhibitor everolimus does not shrink these tumors. It only delays disease progression a subset patients, while significant fraction acquires...
Abstract Background: Dihydroorotate dehydrogenase (DHODH) is an enzyme which critically involved in process of de novo pyrimidine biosynthesis. Therefore, it plays important roles cell proliferation, mitosis and cellular metabolism. Importantly, overexpression DHODH has been found various types malignant tumors including melanoma, myeloma, lymphoma. Moreover, from Oncomine database, we observed that colorectal kidney cancers lymphoma have much higher expression compared to normal cells....
Background: Calcium Ca(2+) signals and the underlying channels transporters are known to influence development, growth, metastasis of many cancers. release-activated calcium (CRAC) channel proteins, STIM Orai, have been shown play a role in cancer progression metastasis. Here we investigate impact RP4010, CRAC inhibitor, GI [pancreatic ductal adenocarcinoma (PDAC), gastric (GC) pancreatic neuroendocrine tumors (PNETs)] cellular patient derived tumor models.Methods: cell lines [3 PDAC one...
<div>Abstract<p>Metastatic pancreatic neuroendocrine tumors (PNET) remain an unmet clinical problem. Chronologic treatment in PNETs includes observation (watchful protocol), surgery, targeted therapy, and chemotherapy. However, increasing evidence illustrates that the outcomes of therapeutic options for advanced show minimal response. The FDA-approved mTOR inhibitor everolimus does not shrink these tumors. It only delays disease progression a subset patients, while significant...
<div>Abstract<p>Metastatic pancreatic neuroendocrine tumors (PNET) remain an unmet clinical problem. Chronologic treatment in PNETs includes observation (watchful protocol), surgery, targeted therapy, and chemotherapy. However, increasing evidence illustrates that the outcomes of therapeutic options for advanced show minimal response. The FDA-approved mTOR inhibitor everolimus does not shrink these tumors. It only delays disease progression a subset patients, while significant...
<p>Supplementary Figures</p>
<p>Supplementary Figures</p>
Abstract Our studies in pancreatic neuroendocrine tumor (pNET) cell lines demonstrate hyper-activation of the Rho GTPase effector p21 activated kinase 4 (PAK4) and nicotinamide adenine dinucleotide (NAD) salvage pathway rate limiting enzyme phosphoribosyltransferase (NAMPT). The PAK4 protein is known to regulate a myriad signaling proteins mTOR including mTORC1, mTORC2, PI3K, IGF-1. Similarly, NAMPT recognized through energy sensor protein, AMPK. In this study, pNET QGP-1 Bon-1 were...
Abstract Background: Calcium Ca(2+) signals and the underlying channels transporters are known to influence development, growth, metastasis of many cancers. release-activated calcium (CRAC) channel proteins, STIM Orai, have been shown play a role in cancer progression metastasis. Here we investigate impact RP4010, CRAC inhibitor, GI [pancreatic ductal adenocarcinoma (PDAC), gastric (GC) pancreatic neuroendocrine tumors (PNETs)] cellular patient derived tumor models. Methods: cell lines [3...
Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease in urgent need of newer therapeutic modalities. Earlier we have shown that PDAC, the over-expression nuclear exporter protein Exportin-1 (XPO1) leads to functional inactivation tumor suppressor proteins (TSPs; FOXO3a, p27, Par-4 etc.) through mis-localization. We demonstrated inhibition XPO1 by CRISPR/Cas9 validated Selective Inhibitor Nuclear Export (SINE) Selinexor and analogs restores anti-tumor function...
Background: Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease in urgent need of newer therapeutic modalities. Earlier we have shown that PDAC, the over-expression nuclear exporter protein Exportin-1 (XPO1) leads to functional inactivation tumor suppressor proteins (TSPs; FOXO3a, p27, Par-4 etc.) through mis-localization. We demonstrated inhibition XPO1 by CRISPR/Cas9 validated Selective Inhibitor Nuclear Export (SINE) Selinexor and analogs restores anti-tumor function multiple...
Abstract Pancreatic Neuroendocrine Tumors (PNETs) remains an unmet clinical problem and epidemiologic studies indicate that their incidence has significantly increased over the years. Surgery only curative option in patients with localized tumors. However, there is no effective therapy advanced or metastatic disease. Thus, unfortunately, 65% of PNET advanced/unresectable disease die within 5 years after diagnosis. Current therapeutic approaches for include chemotherapy (Capecitabine,...