A5074434719- MicroRNA in disease regulation
- Natural Compounds in Disease Treatment
- Cancer Cells and Metastasis
- Histone Deacetylase Inhibitors Research
- Skin and Cellular Biology Research
- Cancer and Skin Lesions
- Signaling Pathways in Disease
- Cancer Research and Treatment
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Hedgehog Signaling Pathway Studies
- Cancer Mechanisms and Therapy
- Cancer, Stress, Anesthesia, and Immune Response
- Wnt/β-catenin signaling in development and cancer
- Biological Research and Disease Studies
- Endoplasmic Reticulum Stress and Disease
- Sirtuins and Resveratrol in Medicine
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- Estrogen and related hormone effects
Magee-Womens Research Institute
2022-2024
UPMC Hillman Cancer Center
2022-2024
Cancer Research Center
2022
University of Colorado Anschutz Medical Campus
2017-2022
University of Pittsburgh
2022
University of Minnesota
2012-2017
University of Minnesota System
2013-2017
Pancreatic cancer, the fourth most prevalent cancer-related cause of death in United States, is a disease with dismal survival rate 5% 5 years after diagnosis. One proteins responsible for its extraordinary ability to evade cell HSP70. A naturally derived compound, triptolide, and water-soluble prodrug, Minnelide, down-regulate expression this protein pancreatic cancer cells, thereby causing death. However, mechanism action triptolide has not been elucidated. Our study shows that...
Pancreatic cancer stromal microenvironment is considered to be the major reason for failure of conventional and targeted therapy this disease. The desmoplastic stroma, comprising mainly collagen glycosaminoglycans like hyaluronan (HA), responsible compression vasculature in tumor resulting impaired drug delivery poor prognosis. Minnelide, a water-soluble prodrug triptolide currently phase I clinical trial, has been very effective multiple animal models pancreatic cancer. However, whether...
Abstract Estrogen receptor alpha (ER/ ESR1 ) is frequently mutated in endocrine resistant ER-positive (ER+) breast cancer and linked to ligand-independent growth metastasis. Despite the distinct clinical features of mutations, their role intrinsic subtype switching remains largely unknown. Here we find that mutant cells samples show a significant enrichment basal markers, six cytokeratins (BCKs) are most enriched genes. Induction BCKs independent ER binding instead associated with chromatin...
Chemoresistance in pancreatic cancer has been attributed to tumor-initiating cells (TICs), a minor sub-population of tumor cells. However, the mechanism chemo-resistance these is still unclear.In current study, immunohistochemical analysis LSL-KrasG12D; LSL-Trp53R172H;PdxCre (KPC) murine tumors indicated that hypoxic regions developed through progression. This "niche" correlated with increased CD133+ population had an HIF1A activity. Consistent this observation, glucose uptake and activity...
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number hypoxia mediated signaling pathways including cell proliferation, metabolism and survival. Previous studies from our laboratory have shown that Minnelide, water-soluble pro-drug triptolide (anti-cancer compound), decreases viability cancer cells vitro as well vivo. However, its mechanism action remain elusive. In the current study we evaluated effect on oncogenic stemness pancreatic...
Abstract Endoplasmic reticulum (ER) stress initiates an important mechanism for cell adaptation and survival, named the unfolded protein response (UPR). Severe or chronic/prolonged UPR can breach threshold survival lead to death. There is a fundamental gap in knowledge on molecular of how chronic ER stimulated leads death pancreatic ductal adenocarcinoma (PDAC). Our study shows that downregulating specificity 1 (Sp1), transcription factor overexpressed cancer, activates results stress. In...
Pancreatic Ductal Adenocarcinoma (PDAC) is a devastating disease hallmarked by limited patient survival. Resistance to chemotherapy, major cause of treatment failure in PDAC patients, often attributed Cancer Stem Cells (CSCs). CSCs are small subset quiescent cells within tumor represented surface markers like CD133. These responsible not only for recurrence, but also poor prognosis based on their "stem-like" characteristics. At present, conventional therapy directed towards rapidly dividing...
Abstract Basal-like breast cancers (BLBC) are the most common triple-negative subtype (hormone receptor and HER2 negative) with poor short-term disease outcome commonly identified by expression of basal cytokeratins (CK) 5 17. The goal this study was to investigate whether CK5 CK17 play a role in adverse behavior BLBC cells. cell lines contain heterogeneous populations cells expressing CK5, CK17, mesenchymal filament protein vimentin. Stable shRNA knockdown either or compared non-targeting...
Abstract Breast cancer affects 1/8 of women throughout their lifetimes, with 90% deaths being caused by metastasis. However, metastasis poses unique challenges to research, as complex changes in the microenvironment different metastatic sites and difficulty obtaining tissue for study hinder ability examine depth that occur during Rapid autopsy programs thus fill a need advancing research. Here, we describe our protocol processes establishing improving US-based Hope OTHERS (Our Tissue Helping...
Abstract Background: Pancreatic ductal adenocarcinoma is currently the fourth most frequent cause of cancer-related death in United States with poor survival. Tumor recurrence this devastating disease adds to its grim Relapse any tumor largely attributed presence tumor-initiating cells (TIC). Chemo-resistance considered a hallmark TICs. Standard chemotherapy typically targets rapidly growing as result which quiescent TICs often evade cell by these agents. However, mechanism involved...
Response of tumors derived from MIA PaCa-2 cells overexpressing CD133 to Minnelide treatment. (TIF 788Â kb)
<p>Gene expression in normal ductal cells and cancer cells</p>
<p>Gene expression of collagen stabilization genes</p>
<p>Quantitation of area stained in immunohistochenistry</p>
<p>Expression and activity of HA synthesis degradation genes</p>