A5062190577- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Brain Metastases and Treatment
- RNA modifications and cancer
- Ovarian cancer diagnosis and treatment
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- Cancer, Lipids, and Metabolism
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Cancer, Stress, Anesthesia, and Immune Response
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Nanoplatforms for cancer theranostics
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Breast Cancer Treatment Studies
- DNA Repair Mechanisms
- Multiple and Secondary Primary Cancers
- Chronic Lymphocytic Leukemia Research
National Cancer Institute
2016-2025
National Institutes of Health
2016-2025
Center for Cancer Research
2016-2025
Yale University
2020
Harvard University
2020
Rockefeller University
2020
Brigham and Women's Hospital
2020
Cornell University
1978-2020
Princeton University
2020
Federation of American Societies for Experimental Biology
2020
Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling receptor may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients Methods This phase I study tested durvalumab doublets parallel 3 + dose escalations. Durvalumab was...
Abstract Purpose: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial PARPi olaparib and anti–PD-L1 durvalumab collected paired fresh core biopsies blood samples to test this hypothesis. Patients Methods: In single-center, proof-of-concept study, we enrolled women aged ≥18 with recurrent cancer. All patients were inhibitor–naïve had measurable...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 [Apo2L]) is a member of the TNF superfamily and has been shown to have selective antitumor activity. Although it known that TRAIL (Apo2L) induces apoptosis activates NF-κB Jun N-terminal kinase (JNK) through receptors such as TRAIL-R1 (DR4) TRAIL-R2 (DR5), components its signaling cascade not well defined. In this report, we demonstrated death domain RIP essential for TRAIL-induced IκB (IKK) JNK activation. We found...
Aberrant NLRP3 inflammasome activation contributes to the development of endotoxemia. The importance negative regulation inflammasomes remains poorly understood. Here, we show that E3 ubiquitin ligase Cbl-b is essential for preventing endotoxemia induced by a sub-lethal dose LPS via caspase-11/NLRP3–dependent manner. Further studies undergoes both K63- and K48-linked polyubiquitination. binds K63-ubiquitin chains attached leucine-rich repeat domain (LRR) its ubiquitin-associated region (UBA)...
<h3>Background</h3> Strategies to improve activity of immune checkpoint inhibitors are needed. We hypothesized enhanced DNA damage by olaparib, a PARP inhibitor, and reduced VEGF signaling cediranib, VEGFR1–3 would complement anti-tumor durvalumab, PD-L1 the 3-drug combination be tolerable. <h3>Methods</h3> This phase 1 study tested in 3 + dose escalation. Cediranib was taken intermittently (5 days on/2 off) at 15 or 20 mg (dose levels 2, respectively) with durvalumab 1500 IV every 4 weeks,...
We report a novel mechanism of action ONC201 as mitochondria-targeting drug in cancer cells. was originally identified small molecule that induces transcription TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cells by activating TRAIL death receptors. In this study, we examined toxicity on multiple human breast endometrial cell lines. attenuated viability all lines tested. Unexpectedly, not dependent either receptors nor caspases. Time-lapse live imaging revealed...
The Cbl family of ubiquitin ligases in mammals contains three members, Cbl, Cbl-b, and Cbl-3, that are involved down-regulation receptor tyrosine kinases (RTKs) by mediating ubiquitination degradation. More recently, a novel pathway has been identified whereby promotes internalization EGF via CIN85/endophilin is functionally separable from the ligase activity (1Soubeyran P. Kowanetz K. Szymkiewicz I. Langdon W.Y. Dikic Nature. 2002; 416: 183-187Crossref PubMed Scopus (489) Google Scholar)....
Stimulation of the T cell antigen receptor (TCR)·CD3 complex induces rapid tyrosine phosphorylation Cbl, a protooncogene product which has been implicated in intracellular signaling pathways via its interaction with several molecules. We found recently that Cbl associates directly member 14-3-3 protein family (14-3-3τ) cells and association is increased as consequence anti-CD3-mediated activation. report here phorbol 12-myristate 13-acetate stimulation also enhanced between two isoforms (τ...
We report here the molecular cloning and chromosomal localization of an additional member helix-loop-helix (HLH) family transcription factors, NSCL. The NSCL gene was identified based on its hybridization to previously described hemopoietic HLH gene, SCL. Murine cDNA clones were obtained from a day 11.5 mouse embryo library. coding region is 399 base pairs encodes predicted protein 14.8 kDa. nucleotide sequence shows 71% identity amino acid 61% murine SCL in domain. protein-coding terminates...
In this paper, using polymerase chain reaction (PCR), we demonstrated the occurrence of hybrid genes formed by interlocus recombination between T cell receptor gamma (TCR-gamma) variable (V) regions and TCR-beta joining (J) in peripheral blood lymphocytes (PBL) from normal individuals patients with ataxia-telangiectasia (AT). Sequence analysis PCR-derived confirmed that site-specific V gamma-J beta had occurred showed 10 23 genomic maintained a correct open reading frame. By dilution...