A5002189188- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Phagocytosis and Immune Regulation
- Cancer, Stress, Anesthesia, and Immune Response
- Nanoplatforms for cancer theranostics
- Bone Metabolism and Diseases
- Pancreatic and Hepatic Oncology Research
- Enzyme function and inhibition
- Bone health and treatments
- Hepatitis Viruses Studies and Epidemiology
- Viral gastroenteritis research and epidemiology
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Genomics and Chromatin Dynamics
- Fibroblast Growth Factor Research
- Retinal and Macular Surgery
- Ferroptosis and cancer prognosis
- RNA Research and Splicing
- Acne and Rosacea Treatments and Effects
Stanford University
2012-2021
University of Bologna
2021
Stanford Medicine
2016
Centre Hospitalier de Luxembourg
2012
Agostino Gemelli University Polyclinic
2010
Cancer Institute (WIA)
2007
Roma Tre University
2003
Significance Here we report a fundamental and previously unknown role for the receptor tyrosine kinase AXL as direct hypoxia-inducible transcription factor target driving aggressive phenotype in renal clear cell carcinoma through regulation of SRC proto-oncogene nonreceptor MET kinase. Of therapeutic relevance, demonstrate that inactivation growth arrest-specific 6 (GAS6)/AXL signaling using soluble decoy reversed invasive metastatic (ccRCC) cells. Furthermore, define pathway by which...
Abstract Increasing evidence suggests that ionizing radiation therapy (RT) in combination with checkpoint immunotherapy is highly effective treating a subset of cancers. To better understand the limited responses to this we analysed genetic, microenvironmental, and immune factors tumours derived from transgenic breast cancer model. We identified two similar growth characteristics but different RT primarily due an antitumour response. The resulted cures responsive not unresponsive tumours....
Abstract Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine genes regulated by hypoxia that promote metastasis, we screen fifty inducible for their effects on invasion. In this study, identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as potent regulator of without affecting cell viability. MAFF expression is elevated metastatic breast cancer patients specifically correlated with hypoxic tumors. Combined ChIP-...
The bone microenvironment is composed of niches that house cells across variable oxygen tensions. However, the contribution gradients in regulating and blood homeostasis remains unknown. Here, we generated mice with either single or combined genetic inactivation critical oxygen-sensing prolyl hydroxylase (PHD) enzymes (PHD1–3) osteoprogenitors. Hypoxia-inducible factor (HIF) activation associated Phd2 Phd3 drove accumulation by modulating osteoblastic/osteoclastic cross-talk through direct...
Although the only effective drug against primary hepatocarcinoma, multikinase inhibitor Sorafenib (SFB) usually fails to eradicate liver cancer. Since SFB targets mitochondria, cell metabolic reprogramming may underlie intrinsic tumor resistance. To characterize cancer response SFB, we measured oxygen consumption, generation of reactive species (ROS) and ATP content in rat LCSC (Liver Cancer Stem Cells) -2 cells exposed drug. Genome wide analysis gene expression was performed by Affymetrix...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most metastatic and deadly cancers. Despite clinical significance spread, our understanding molecular mechanisms that drive PDAC ability remains limited. By generating a genetically engineered mouse model human PDAC, we uncover transient subpopulation cancer cells with exceptionally high ability. Global gene expression profiling functional analyses uncovered transcription factor BLIMP1 as driver metastasis. The highly enriched...
Significance Scaffold proteins can serve as critical focal points for association of signaling molecules and downstream pathways that regulate tumor growth invasion. We demonstrate low oxygen levels, common in solid tumors, expression one member the AKAP scaffold protein family, AKAP12, melanoma. Genetic inactivation AKAP12 leads to decreased migration, invasion, a mouse model Mechanistically, we discovered switch kinase A (PKA)-regulated phosphorylations under hypoxia are dependent on show...
Abstract Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 key mediators of cellular response to hypoxia. Both expressed osteoblasts. HIF1 is known be positive regulator bone formation. Conversely, role control osteoblast biology still poorly understood. In this study, we used mouse genetics demonstrate that an inhibitor osteoblastogenesis mass accrual. Moreover, provided evidence impairs...
The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as master transcriptional regulator. Differential gene activity is controlled transcription factors but also dependent on underlying chromatin structure, especially covalent histone modifications. After screening different lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B p53-inducible DNA damage. directly regulates JMJD2B expression binding...
Abstract In this paper, we investigated whether bcl-xL can be involved in the modulation of angiogenic phenotype human tumor cells. Using ADF glioblastoma and M14 melanoma lines, their derivative bcl-xL–overexpressing clones, showed that conditioned medium transfectants increased vitro endothelial cell functions, such as proliferation morphogenesis, vivo vessel formation Matrigel plugs, compared with control Moreover, overexpression induced an expression proangiogenic interleukin-8 (CXCL8),...
We recently reported that bcl-xL regulates interleukin 8 (CXCL8) protein expression and promoter activity in glioblastoma cells. In this paper we demonstrate CXCL8 induction by is mediated through a nuclear factor-kappa B (NF-kB)-dependent mechanism. Mutational studies on the showed NF-kB binding site was required for bcl-xL-induced an enhanced of subunits p65 p50 observed after over-expression. Electrophoretic mobility shift assay increased DNA-binding over-expressing cells use specific...
The induction of hypoxia-inducible factors (HIFs) is essential for the adaptation tumor cells to a low-oxygen environment. We found that expression apoptosis inhibitor ARC (apoptosis repressor with CARD domain) was induced by hypoxia in variety cancer cell types, and its primarily HIF1 dependent. Chromatin immunoprecipitation (ChIP) reporter assays also indicate gene regulated direct binding response element (HRE) located at bp -190 upstream transcription start site. HIFs play an role...
Abstract Purpose: To investigate how induced tumor heterogeneity influences immune responses to radiotherapy with different proportions of mixed immune-responsive and unresponsive cells in a triple-negative breast cancer model. It is hypothesized that studying the environment tumors could nominate active therapies enhance after radiotherapy. Experimental Design: Evaluate efficacy generated by immunologically responsive cells. Then study cellular transcriptomic differences between...
Abstract The induction of hypoxia inducible factors (HIFs) is essential for the adaptation tumor cells to a low oxygen environment. We found that expression apoptosis inhibitor ARC was induced by in variety cancer cell types and its primarily HIF1 dependent. Chromatin immunoprecipitation (ChIP) reporter assays also indicate gene regulated direct binding response element (HRE) located at -190 bp upstream transcription start site. HIFs play an role pathogenesis renal carcinoma (RCC) under...
Abstract There is increasing evidence that hypofractionated high dose ionizing radiation (RT) can enhance antitumor immune responses in many cancers. In some cases the combination of RT and checkpoint immunotherapy responses. Here, we developed a model to study genetic, microenvironmental, immunologic factors mediated after radiation. Two different tumor clones from same parental transgenic PyMT mammary carcinoma reveal similar growth characteristics but primarily due an response. The...
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