A5007491235- Cell Adhesion Molecules Research
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Lymphatic System and Diseases
- Protease and Inhibitor Mechanisms
- Ferroptosis and cancer prognosis
- Caveolin-1 and cellular processes
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- Pancreatitis Pathology and Treatment
- Epigenetics and DNA Methylation
- S100 Proteins and Annexins
- Chemokine receptors and signaling
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- Vascular Malformations and Hemangiomas
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
University of California, San Diego
2016-2025
Moores Cancer Center
2006-2024
Ecological Society of America
2020
Sunnybrook Health Science Centre
2011
Health Sciences Centre
2011
Technion – Israel Institute of Technology
2011
Ewha Womans University
2011
University of Washington
2010
University of California System
2009
Sidney Kimmel Comprehensive Cancer Center
2006
Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist defined by their dependency distinct integrins. In vivo in corneal or chorioallantoic membrane models induced basic fibroblast growth factor tumor necrosis factor-α depended α v β 3 , whereas initiated endothelial factor, transforming factor-α, phorbol ester 5 . Antibody each integrin selectively blocked one these pathways, a cyclic peptide antagonist both...
Pancreas ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates all solid tumors, and thus new treatment strategies are urgently needed. Here, we report that targeting Bruton tyrosine kinase (BTK), a key B-cell macrophage kinase, restores T cell-dependent antitumor immune responses, thereby inhibiting PDAC growth improving responsiveness to standard-of-care chemotherapy. We tumor depends on cross-talk between B cells FcRγ(+) tumor-associated macrophages, resulting in...
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved responsiveness standard-of-care chemotherapy in animal models PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming macrophages inhibits adaptive...
Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of do not benefit from these agents. To improve checkpoint inhibitors, intratumoral (i.t.) injection innate immune activators, TLR7 TLR9 agonists, were tested along programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at primary injected distant sites human papillomavirus-negative (HPV-negative)...
Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing progression. Recruitment of these is regulated by integrins, a family adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, CD11b does not regulate myeloid cell recruitment tumors but instead controls polarization growth. activation promotes pro-inflammatory macrophage stimulating expression microRNA Let7a. In contrast, inhibition prevents...
Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway correlates with resistance. We report a phase I trial JAK ruxolitinib anti-PD-1 antibody nivolumab Hodgkin lymphoma patients relapsed or refractory following immunotherapy. The combination yielded best overall response rate 53% (10/19)....
Cells selected for overexpression of the integrin alpha 5 beta 1 show decreased proliferation and loss transformed phenotype. We provide evidence that de novo expression in HT29 colon carcinoma cells results growth arrest these as characterized by reduced DNA synthesis cellular vitro. In fact, on induces transcription specific gene (gas-1), a product known to induce quiescence, but blocks immediate early genes c-fos, c-jun, jun B. vivo, transfectants display dramatically tumorigenicity well...
CD34+ bone marrow-derived progenitor cells contribute to tissue repair by differentiating into endothelial cells, vascular smooth muscle hematopoietic and possibly other cell types. However, the mechanisms which circulating home remodeling tissues remain unclear. Here we show that integrin alpha4beta1 (VLA-4) promotes homing of ligands VCAM cellular fibronectin, are expressed on actively neovasculature. Progenitor express alpha4beta1, homed sites active tumor neovascularization but not...
Recent studies indicate that angiogenesis depends, in part, on ligation of integrin α5β1 by fibronectin. Evidence is now provided regulates the function αvβ3 endothelial cells during their migration vitro or angiogenesisin vivo. Secretion fibronectin leads to α5β1, which potentiates αvβ3-mediated vitronectin without influencing cell adhesion. Endothelial attachment suppresses protein kinase A (PKA) activity, while addition soluble anti-α5β1 restores this activity. Moreover, agents activate...
Neovascularization depends on vascular cell proliferation and the stabilization of vessels by association smooth muscle-like pericytes with ECs. Here we show that integrin alpha4beta1 (VLA-4) VCAM-1 promote close intercellular adhesion between ECs this interaction is required for blood vessel formation. Integrin expressed proliferating but not quiescent ECs, while its ligand mural cells. Antagonists integrin-ligand pair block cells to endothelia in vitro vivo, thereby inducing apoptosis...
Myeloid cells are a heterogeneous population of bone marrow-derived that play critical role during growth and metastasis malignant tumors. Tumors exhibit significant myeloid cell infiltrates, which actively recruited to the tumor microenvironment. promote by stimulating angiogenesis, suppressing immunity, promoting distinct sites. In this review, we discuss in angiogenesis. Furthermore, describe subset with immunosuppressive activity (known as myeloid-derived suppressor cells). Finally, will...
Abstract Recent studies have shown that lymphangiogenesis or the growth of lymphatic vessels at periphery tumors promotes tumor metastasis to lymph nodes. We show here fibronectin-binding integrin α4β1 and its ligand fibronectin are novel functional markers proliferative endothelium. Tumors lymphangiogenic factors, such as vascular endothelial factor-C (VEGF-C) VEGF-A, induce vessel expression α4β1. Integrin then factor tumor-induced lymphangiogenesis, genetic loss in Tie2Cre+ α4loxp/loxp...
Abstract Despite the promise of ribonucleic acid interference therapeutics, delivery oligonucleotides selectively to diseased tissues in body, and specifically cellular location needed provide optimal therapeutic outcome, remains a significant challenge. Here, key material properties biological mechanisms for short interfering RNAs (siRNAs) effectively silence target‐specific cells vivo are identified. Using porous silicon nanoparticles as siRNA host, tumor‐targeting peptides selective...
Triple-negative breast cancer (TNBC) is an aggressive subtype of with a poor prognosis particularly in the metastatic setting. Treatments anti-programmed cell death protein-1/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICI) combination chemotherapies have demonstrated promising clinical benefit TNBC (mTNBC) but there still unmet need, for patients PD-L1 negative tumors. Mechanisms resistance to ICIs mTNBC include presence immunosuppressive tumor-associated macrophages...