A5051129825- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Bone health and treatments
- Cancer-related Molecular Pathways
- Bone Metabolism and Diseases
- HIV/AIDS drug development and treatment
- Lymphoma Diagnosis and Treatment
- Biochemical and Molecular Research
- Axon Guidance and Neuronal Signaling
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Protease and Inhibitor Mechanisms
- Pancreatic and Hepatic Oncology Research
- Trauma and Emergency Care Studies
- Inflammatory mediators and NSAID effects
- Abdominal Trauma and Injuries
- Trauma Management and Diagnosis
- Cancer, Lipids, and Metabolism
University of Nebraska Medical Center
2014-2023
Nebraska Medical Center
2002-2020
Heinrich Heine University Düsseldorf
1990-2015
Düsseldorf University Hospital
2015
University of Nebraska–Lincoln
2013
Nagoya City University
2010
Ionis Pharmaceuticals (United States)
2010
University of Nebraska at Omaha
2005-2007
National Cancer Institute
2005
National Institutes of Health
2005
Abstract IL-8, a member of the chemokine family, has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective this study was determine mechanism IL-8-mediated angiogenesis. We examined direct IL-8 angiogenesis by examining receptor expression on endothelial cells their proliferation, survival, matrix metalloproteinases (MMPs) production. demonstrate that HUVEC human dermal microvascular constitutively express CXCR1 CXCR2 mRNA protein. Recombinant...
Melanoma, the most aggressive form of skin cancer, accounts for 75% all cancer-related deaths and current therapeutic strategies are not effective in advanced disease. In study, we have investigated efficacy orally active small-molecule antagonist targeting CXCR2/CXCR1.Human A375SM melanoma cells were treated with SCH-479833 or SCH-527123, their effect on proliferation, motility, invasion was evaluated vitro. We examined downstream signaling events following treatment antagonists. For vivo...
Abstract Breast cancer is one of the leading causes deaths among females. Many challenges exist in current management advanced stage breast as there are fewer recognized therapeutic strategies, often because therapy resistance. How cells evade chemotherapy and underlying mechanism remains unclear. We others have observed that malignant survive initial chemo- radiation express higher levels CXCR2 ligands, which may provide a survival benefit to In this report, we test hypothesis...
Abstract Tumor production of vascular endothelial cell growth factor (VEGF)-C is associated with tumor lymphangiogenesis and lymph node metastasis. In this study, we examined the effects small interfering RNA (siRNA)–mediated inhibition VEGF-C on murine mammary growth, metastasis, survival. The mRNA protein expression in cells stably transfected a siRNA vector were significantly lower compared VEGF-C-control vector-transfected cells. Cl66-siVEGFC tumors had levels spontaneous lung metastasis...
The aggressiveness of malignant melanoma is associated with differential expression CXCL-8 and its receptors, CXCR1 CXCR2. However, the precise functional role these receptors in progression remains unclear. In this study, we investigate CXCR2 progression. or were stably overexpressed human cell lines, SBC-2 (non-tumourigenic) A375P (low-tumourigenic) exhibiting low endogenous receptors. Functional assays performed to study resulting changes proliferation, motility invasion, vivo tumour...
Abstract The tropism of breast cancer cells for bone and their tendency to induce an osteolytic phenotype are a result interactions between stromal paramount importance metastasis. However, the underlying molecular mechanisms remain poorly understood. We hypothesize that tumor-stromal interaction alters gene expression in malignant tumor creating unique signature promotes metastasis inhibition such can be developed as targeted therapeutics. Microarray analysis was performed investigate...
We examined the expression of CXCL8 (interleukin-8), its receptors, CXCR1 and CXCR2, vessel density in human melanoma by immunohistochemical analysis tumors from different Clark levels, depths, thicknesses. Expression CXCR2 was lower level I II specimens than III through V metastases. observed ubiquitously majority tumor irrespective disease state, with highest intensity specimens. a significant difference between thin (≤0.75 mm) thick (>0.75 melanomas metastatic lesions. Positive...
Abstract Crucial steps in tumor growth and metastasis are proliferation, survival, neovascularization. Previously, we have shown that receptors for CXCL-8, CXCR1, CXCR2 expressed on endothelial cells has been to be a putative receptor angiogenic chemokines. In this report, examined whether angiogenesis of CXCL-8–expressing human melanoma regulated vivo by host CXCR2–dependent mechanism. We generated mCXCR2−/−, mCXCR2+/−, wild-type nude mice following crosses between BALB/c heterozygous...
Abstract Background KIAA1199 is a recently identified novel gene that up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity chemotactic cells revealed as protein target may be involved cellular chemotaxis and motility. In the present study, we examined functional significance of expression breast growth, motility invasiveness. Methods We validated previous microarray observation by tissue immunohistochemistry using TMA slide containing 12 tumor cores...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies. Desmoplasia and tumor-supporting inflammation are hallmarks PDAC. The tumor microenvironment contributes significantly to progression spread. Cancer-associated fibroblasts (CAFs) facilitate therapy resistance metastasis. Recent reports emphasized concurrence multiple subtypes CAFs with diverse roles, fibrogenic, secretory. C-X-C motif chemokine receptor 2 (CXCR2) is a known for its role during adverse...
The objective of this study was to evaluate the role tumour-associated macrophages (TAMs) in malignant melanoma progression, invasion and angiogenesis. We examined levels macrophage infiltration monocyte chemotactic protein-1 (MCP-1), neovascularization vascular endothelial growth factor-A (VEGF-A) different Clark's level melanomas with varying thicknesses metastases. TAM density significantly higher thick (>0.75 mm) than thin (<or=0.75 melanomas, positively correlated invasiveness...
Chemokines and their receptors have long been known to regulate metastasis in various cancers. Previous studies shown that CXCR2 expression is upregulated malignant breast cancer tissues but not benign ductal epithelial samples. The functional role of the metastatic phenotype still remains unclear. We hypothesize chemokine receptor, CXCR2, mediates tumor cell invasion migration promotes cancer. objective this study investigate potential mouse mammary cells.We evaluated by stably...
Semaphorin 5A (SEMA5A) is an axonal regulator molecule, which belongs to the family of proteins. Previously, we identified SEMA5A as a putative marker for aggressive pancreatic tumors. However, expression, localization and functional significance in tumors remain unclear. In our study, hypothesized that expression modulates tumor growth metastasis. We analyzed constitutive patient (n = 33) unmatched normal 8) tissues human cancer cell lines 16) with different histopathological...
CXCR1 and CXCR2 are receptors for CXCL-8 differentially expressed on melanoma endothelial cells. In this study, we determined the functional role of these in progression. We stably knock-down expression and/or A375-SM (SM; high metastatic) human cells by short-hairpin RNA transfection. Cell proliferation, migration, invasion, ERK phosphorlyation cytoskeletal rearrangements were carried out vitro. vivo growth was evaluated using murine subcutaneous xenograft model. Our data demonstrate that...
Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, promotes tumour growth metastasis. In this study, we examine whether (1) secrete SEMA5A (2) secreted modulates certain phenotypes associated with progression, angiogenesis metastasis through various other molecular factors signalling proteins. show human cell lines the extracellular domain (ECD) of (SEMA5A-ECD) overexpression mouse Sema5A-ECD Panc1 (not...
Abstract CXCL ‐8, a chemokine secreted by melanoma and stromal cells, serves as growth angiogenic factor for progression. This study evaluated how modulation of ‐8 levels in cell lines with different tumorigenic metastatic potentials affected multiple tumor phenotypes. A375P cells ( low expressor) were stably transfected mammalian expression vector to overexpress whereas A375SM high antisense suppress expression. Subsequent proliferation, migration, invasion, soft‐agar colony formation...