A5017882783- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Brain Metastases and Treatment
- Cancer Treatment and Pharmacology
- RNA modifications and cancer
- Synthesis of Tetrazole Derivatives
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- HER2/EGFR in Cancer Research
- Cancer-related molecular mechanisms research
- Chemical Reactions and Isotopes
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Helicobacter pylori-related gastroenterology studies
- Cancer Diagnosis and Treatment
- Lung Cancer Research Studies
- Advanced Breast Cancer Therapies
- Radiology practices and education
- Foot and Ankle Surgery
- Adenosine and Purinergic Signaling
- Genomics and Chromatin Dynamics
- Folate and B Vitamins Research
- Bioactive Compounds in Plants
University of Michigan
2014-2023
Khyber Medical College
2023
Michigan Medicine
2022
VA Ann Arbor Healthcare System
2021
University of North Carolina at Chapel Hill
2018
Ohio University
2018
William Harvey Research Institute
2018
Michigan Center for Translational Pathology
2016-2017
National Cancer Institute
2011-2013
Center for Cancer Research
2011-2013
Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that receptor discoidin domain 2 (DDR2) is essential for stromal-BC communication. In human BC DDR2 concordantly upregulated in metastatic and multipotent cells. MSCs isolated from maintains a fibroblastic phenotype with induces pathological activation of signaling Loss impairs their ability to promote...
Abstract Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. has been mainly studied as the catalytic component Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how drives metastasis despite low H3K27me3 levels observed ER- is unknown. Here we show human invasive carcinomas and distant metastases, cytoplasmic phosphorylated T367 significantly associated with disease...
Abstract Brain metastases of breast and other cancers remain resistant to chemotherapeutic regimens that are effective systemically, in part due the blood–brain barrier. We report TPI-287, a new microtubule-stabilizing agent, displays vitro cytotoxic activity similar taxanes epothilones. Unlike taxanes, TPI-287 is permeable through Brain-to-plasma ratios after single injection typically exceeded one were as high 63.8 rat 14.1 mouse. A brain-tropic derivative MDA-MB-231 triple-negative cancer...
Twenty percent of breast cancer (BC) patients develop distant metastasis for which there is no cure. Mesenchymal stem/stromal cells (MSCs) in the tumor microenvironment were shown to stimulate metastasis, but mechanisms are unclear. Here, we identified and quantified engulfing stromal clinical samples BC by dual immunostaining EZH2 ALDH1 expression. Using flow cytometry a microfluidic single-cell paring retrieval platform, show that MSC engulfment capacity associated with cell metastatic...
Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. colonization cells occurs a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although neuroinflammatory response has been documented brain metastasis, its contribution to progression therapy remains poorly understood. Using an experimental metastasis model, we characterized the microenvironment tropic, HER2-transfected...
Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, functions a positive regulator of melanoma progression and metastasis. In contrast, the Raf kinase inhibitor, RKIP, negative modulator RAF-stimulated MEKK activation, is strongly downregulated in metastatic cells. this study, we explored hypothesized inverse relationship between MDA-9 RKIP melanoma. Tumor array cell line analyses confirmed an expression during progression. We found that transcriptionally support...
Triple-negative breast cancers (TNBCs) are frequently poorly differentiated with high propensity for metastasis. Enhancer of zeste homolog 2 (EZH2) is the lysine methyltransferase polycomb repressive complex that mediates transcriptional repression in normal cells and cancer through H3K27me3. However, H3K27me3-independent non-canonical functions EZH2 incompletely understood. We reported phosphorylation at T367 by p38α induces TNBC metastasis an manner. Here, we show cytosolic methylates 139...
Pazopanib is an FDA approved Vascular Endothelial Growth Factor Receptor inhibitor. We previously reported that it also inhibits tumor cell B-Raf activity in experimental brain metastatic setting. Here, we determine the effects of different genotypes on pazopanib efficacy, terms primary growth and anti-angiogenesis. A panel seven human breast cancer melanoma lines harboring mutations Ras-Raf pathway was implanted orthotopically mice, growth, ERK1/2, MEK1/2 AKT activation, blood vessel...
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and major cause gastric adenocarcinoma. The mechanisms link H. infection to carcinogenesis are not well understood. In present study, we report Raf-kinase inhibitor protein (RKIP) has role in induction apoptosis by epithelial cells. Western blot luciferase transcription reporter assays demonstrate pathogenicity island rapidly phosphorylates RKIP, which then...
Abstract Background: Breast cancer accounts for more than 40,000 deaths yearly in the United States, majority of which are due to metastatic disease. The histone methyltransferase EZH2 (Enhancer Zeste Homolog 2) is a member polycomb repressive complex 2 (PRC2) responsible transcriptional repression by trimethylation H3 at lysine 27. an independent predictor recurrence and mortality that overexpressed 55% invasive breast carcinomas. We previously identified novel link between p38...
Abstract Background: Triple negative (estrogen receptor, progesterone HER2-neu negative) breast cancers (TNBC) comprise 15% of all but are responsible for a disproportionately high number deaths. Overexpression the histone methyltransferase EZH2 (Enhancer Zeste Homolog 2) is an independent prognostic biomarker significantly associated with poorly-differentiated TNBCs and poor patient outcome. We previously identified novel link between p38 mitogen-activated protein kinase, important mediator...
Abstract Background: Triple negative (estrogen receptor, progesterone HER2-neu negative) breast cancers (TNBC) account for 15% of all but are responsible a disproportionate number deaths. Overexpression the histone methyltransferase EZH2 (Enhancer Zeste Homolog 2) is an independent prognostic biomarker significantly associated with poorly-differentiated TNBCs and poor patient outcome. As member polycomb repressive complex 2 (PRC2), canonical function to mediate transcriptional repression...
Abstract Brain metastases occur in approximately 35% of metastatic breast cancer patients whose tumors overexpress HER2. colonization cells occurs a unique environment, containing microglia, oligodendrocytes, astrocytes and neurons. While neuroinflammatory response has been documented brain metastasis, its contribution to progression therapy remains poorly understood. Using model system study experimental metastasis cancer, we intensively characterized the microenvironment tropic,...
Abstract Raf kinase inhibitory protein (RKIP) is a negative regulator of the mitogen activated (MAPK) cascade initiated by Raf-1 and nuclear factor kappa B (NF-κB) an activator apoptosis in human cancers. STAT3 (signal transducer activators transcription) often constitutively phosphorylated gastric cancer. RKIP has been positively correlated with higher survival rate cancer patients (Chatterjee, et al., Clin. Cancer Res., 14:2994-3001, 2008). Helicobacter pylori (H. pylori) infection...
<p>PDF file - 652K, Characterization of MDA-9 overexpressed FM-516 clones</p>
<p>PDF file - 205K, Expression of RKIP mRNA in different melanoma cells</p>