A5042175121- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
- ATP Synthase and ATPases Research
- Heat shock proteins research
- HER2/EGFR in Cancer Research
- Microtubule and mitosis dynamics
- Toxin Mechanisms and Immunotoxins
- Wnt/β-catenin signaling in development and cancer
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Click Chemistry and Applications
- Protist diversity and phylogeny
- Gastrointestinal Tumor Research and Treatment
- Cancer Mechanisms and Therapy
- Cellular transport and secretion
- Cancer-related gene regulation
- Infectious Diseases and Mycology
- Endoplasmic Reticulum Stress and Disease
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Bone health and treatments
- Cancer-related Molecular Pathways
- Photosynthetic Processes and Mechanisms
Novartis (United States)
2006-2021
BioMarin (United States)
2015-2019
Novartis Foundation
2015
Inserm
2014
Institut Pasteur
2014
UCSF Helen Diller Family Comprehensive Cancer Center
2014
Institut Gustave Roussy
2014
Novartis (Switzerland)
2012-2014
Novartis Institutes for BioMedical Research
2012-2013
University of California, San Francisco
2012
Abstract PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50, 0.011 μmol/L) and Cdk6 0.016 μmol/L), having no activity against panel 36 additional protein kinases. It potent antiproliferative agent retinoblastoma (Rb)-positive tumor cells in vitro, inducing an exclusive G1 arrest, with concomitant reduction phospho-Ser780/Ser795 on the Rb protein. Oral administration to mice bearing Colo-205 human colon carcinoma produces marked regression. Therapeutic doses...
We have developed video microscopy methods to visualize the assembly and disassembly of individual microtubules at 33-ms intervals. Porcine brain tubulin, free microtubule-associated proteins, was assembled onto axoneme fragments 37 degrees C, dynamic behavior plus minus ends analyzed for tubulin concentrations between 7 15.5 microM. Elongation rapid shortening were distinctly different phases. At each end, elongation phase characterized by a second order association substantial first...
Individual microtubule dynamics were observed in real time primary cultures of newt lung epithelium using video-enhanced differential interference contrast microscopy and digital image processing. The linear filaments cells corresponded to microtubules based on three criteria: (a) small particles translocated along them; (b) the majority them disappeared after incubation nocodazole; (c) distribution by correlated with anti-tubulin immunofluorescence staining same cell. Microtubules most...
Increased numbers of tumor-infiltrating macrophages correlate with poor disease outcome in patients affected by several types cancer, including breast and prostate carcinomas. The colony stimulating factor 1 receptor (CSF1R) signaling pathway drives the recruitment tumor-associated (TAMs) to neoplastic microenvironment promotes differentiation TAMs toward a pro-tumorigenic phenotype. Twelve clinical trials are currently evaluating agents that target CSF1/CSF1R as treatment against multiple...
We used video assays to study the dynamic instability behavior of individual microtubules assembled in vitro with purified tau, MAP2 or a preparation unfractionated heat-stable MAPs. Axoneme-nucleated were from pure tubulin at concentrations between 4 and 9 microM presence MAPs, observed by video-differential interference contrast microscopy. Microtubules co-assembled each MAP exhibited elongation rapid shortening phases abrupt transitions (catastrophe rescue) characteristic instability....
Although the mechanism of microtubule dynamic instability is thought to involve hydrolysis tubulin-bound GTP, GTP and basis stability are controversial. Video microscopy individual microtubules dilution protocols were used examine size lifetime stabilizing cap. Purified porcine brain tubulin (7-23 microM) was assembled at 37 degrees C onto both ends isolated sea urchin axoneme fragments in a miniature flow cell give 10-fold variation elongation rate. The concentration region growth could be...
The SEC13 gene of Saccharomyces cerevisiae is required in vesicle biogenesis at a step before or concurrent with the release transport vesicles from ER membrane. encodes 33-kD protein sequence homology to series conserved internal repeat motifs found beta subunits heterotrimeric G proteins. product this gene, Sec13p, cytosolic peripherally associated membranes. We developed cell-free Sec13p-dependent formation reaction. Sec13p-depleted membranes and cytosol fractions were generated by urea...
Abstract A novel oral Hsp90 inhibitor, NVP-HSP990, has been developed and characterized in vitro vivo. In vitro, NVP-HSP990 exhibits single digit nanomolar IC50 values on three of the isoforms (Hsp90α, Hsp90β, GRP94) 320 value fourth (TRAP-1), with selectivity against unrelated enzymes, receptors, kinases. c-Met amplified GTL-16 gastric tumor cells, dissociated Hsp90-p23 complex, depleted client protein c-Met, induced Hsp70. potently inhibited growth human cell lines primary patient samples...
Purpose: c-KIT overexpression is well recognized in cancers such as gastrointestinal stromal tumors (GIST), small cell lung cancer (SCLC), melanoma, non-small (NSCLC), and acute myelogenous leukemia (AML). Treatment with the small-molecule inhibitors imatinib, sunitinib, regorafenib resulted resistance (c-KIT mutant tumors) or limited activity wild-type tumors). We selected an anti-c-KIT ADC approach to evaluate anticancer multiple disease models.Experimental Design: A humanized antibody...
Recently, we have reported the purification and cloning of a novel G protein βγ subunit-activated phosphoinositide 3-kinase from pig neutrophils. The enzyme comprises p110γ catalytic subunit p101 regulatory subunit. Now cloned human ortholog generated panels truncations deletions used these in vitro vivo assays to determine domains responsible for interaction activation by subunits. Our results suggest large areas including both N- C-terminal portions interact with N-terminal half p110γ....
Abstract Purpose: The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) results from a t(4;14) chromosomal translocation that occurs in ∼15% of multiple myeloma (MM) patients confers particularly poor prognosis. This study assesses the antimyeloma activity CHIR-258, small-molecule inhibitor tyrosine kinases is currently phase I trials, newly developed FGFR3-driven preclinical MM animal model. Experimental Design: We an orthotopic model mice using...
Abstract Selective RAF inhibitors have significant activity in patients with metastatic melanoma whose tumors express BRAFV600E. However, not all respond equally well to treatment and the duration of response is often limited less than 6 months. LGX818 was developed hypothesis that a more potent inhibitor excellent pharmacological properties would maximize degree patient response. highly selective anti-proliferative apoptotic cells expressing In A375 (BRAFV600E) human cell line suppresses...
RAV12 is a chimeric antibody that recognizes an N-linked carbohydrate antigen (RAAG12) strongly expressed on multiple solid organ cancers. More than 90% of tumors colorectal, gastric, and pancreatic origin express RAAG12, majority these exhibit uniform RAAG12 expression. exhibits potent cytotoxic activity in vitro against COLO 205 colon tumor cells via oncotic cell death mechanism. RAV12-treated undergo morphologic changes consistent with oncosis, including cytoskeletal rearrangement, rapid...
Treatment with RAF inhibitors such as vemurafenib causes the development of cutaneous squamous cell carcinomas (cSCC) or keratoacanthomas a side effect in 18% to 30% patients. It is known that activate mitogen-activated protein kinase (MAPK) pathway and stimulate growth RAS-mutated cells, possibly accounting for up 60% cSCC keratoacanthoma lesions RAS mutations, but other contributing events are obscure. To identify events, we evaluated tumors from patients treated presence human papilloma...
Abstract In this report, we describe an in vitro system for analyzing microtubule‐based movements supernatants of sea urchin egg and embryo homogenates. Using video enhanced DIC microscopy, have observed bidirectional saltatory particle on native taxol‐stabilized microtubules assembled low speed Lytechinus homogenates, gliding these across a glass surface. A high supernatant soluble proteins, depleted organelles, microtubules, their associated proteins supports the exogenous translocation...