Search results for "Oncogene protein"
showing 10 items of 812 documents
Entrectinib: a potent new TRK, ROS1, and ALK inhibitor
2015
Abstract: Introduction: Receptor tyrosine kinases (RTKs) and their signaling pathways, control normal cellular processes; however, their deregulation play important roles in malignant transformation. In advanced non-small cell lung cancer (NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the development of molecularly targeted agents that only benefit roughly 20% of patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent anti-neoplastic activity and tolerability in various neoplastic conditions, particularly NSCLC. Areas covered: This review outlines the pharmacokinetics, pharmacodynamics, mechanism of action, safety, tolerability, pre-cl…
Soluble interleukin 6 (IL-6) receptor influences the expression of the protooncogene junB and the production of fibrinogen in the HepG2 human hepatom…
1998
Abstract Interleukin 6 (IL-6) belongs to a family of cytokines using receptors sharing a common signal-transducing chain, gp130 and containing a specific ligand-binding chain (IL-6Rα). It was shown that both the membrane-bound and the soluble form (sIL-6R) of this ligand specific receptor chain occurs naturally. The soluble form of IL-6 receptor was found to be able to associate with the membrane-bound gp130 and to generate active IL-6 receptor complex capable of inducing signal transduction. This study on a human hepatoma cell line and primary rat hepatocytes examined how the effectiveness of IL-6 is modified by the presence of soluble IL-6 receptor and whether the sIL-6R in the absence of…
Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics
2009
Abstract Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor–positive cancers (34.5%; P = 0.32), 17 of 75 HER-2–positive samples (22.7%; P = 0.04), 20 of 240 basal-like c…
Hamster Bcl-2 Protein Is Cleaved in Vitro and in Cells by Caspase-9 and Caspase-3
2001
Full-length cDNA of hamster bcl-2 (771 nt) was cloned by RT-PCR and inserted into pGEX-4T-1 to produce the recombinant hamster Bcl-2 protein. The purified recombinant Bcl-2 protein (26.4 kDa) was used as a substrate for the active human caspase-3 and caspase-9 in vitro. It is shown here that Bcl-2 is efficiently cleaved by caspase-3 to a 23 kDa fragment. Although not possessing a putative caspase-9 cleavage site in its sequence, hamster Bcl-2 was also cleaved by caspase-9 into exactly the same 23 kDa cleavage product, indicating that cleavage occurred at the same site. Caspase-3- and caspase-9-mediated cleavage of Bcl-2 was efficiently blocked by caspase-3 (zDEVD) and caspase-9 (zLEHD) inhi…
SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells
2012
Abstract SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERα−positive MCF-7 and the ERα−negative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show…
Development of type-specific and cross-reactive serological probes for the minor capsid protein of human papillomavirus type 33.
1993
Human papillomavirus type 33 (HPV33) is associated with malignant tumors of the cervix. In an attempt to develop immunological probes for HPV33 infections, antisera against various bacterial fusion proteins carrying sequences of the minor capsid protein encoded by L2 were raised in animals. Antigenic determinants on the HPV33 L2 protein were identified by using truncated fusion proteins and were classified as type specific or cross-reactive with respect to HPV1, -8, -11, -16, and -18. Cross-reactive epitopes map to amino acids 98 to 107 or to amino acids 102 to 112 and 107 to 117, respectively, depending on the fusion protein used for immunization. Antibodies directed toward these epitopes …
Case of multifocal glioblastoma with four fusion transcripts of ALK, FGFR2, NTRK2, and NTRK3 genes stresses the need for tumor tissue multisampling f…
2021
Glioblastoma multiforme (GBM) is the most malignant brain tumor with patient mortality rate close to 100%, 5-yr survival rate of ∼5%, and a median survival of 14 mo. GBMs have notorious histomorphologic and molecular heterogeneities thus giving hope for development of future personalized therapies. We describe here a case of a 48-yr-old male patient with three-nodular GBM. To address the question of intratumoral molecular heterogeneity, a comparative analysis of gene expression was performed by using multiple samples collected from different tumor sites with the aid of intraoperative magnetic resonance imaging (MRI). Sixteen GBM biosamples from parietal, temporal, and temporo-polar localiza…
Vesicle transport and photoreceptor death: fishing for molecular links.
2013
Intracellular vesicle transport defects can induce retinal degeneration and photoreceptor cell death, but the molecular connections between these processes remains poorly understood. Reporting in Developmental Cell, Nishiwaki et al. (2013) suggest that a vesicle fusion cis-SNARE complex component translates vesicular transport defects into photoreceptor cell apoptosis.
DICER and ZRF1 contribute to chromatin decondensation during nucleotide excision repair
2016
Abstract Repair of damaged DNA relies on the recruitment of DNA repair factors in a well orchestrated manner. As a prerequisite, the chromatin needs to be decondensed by chromatin remodelers to allow for binding of repair factors and for DNA repair to occur. Recent studies have implicated members of the SWI/SNF and INO80 families as well as PARP1 in nucleotide excision repair (NER). In this study, we report that the endonuclease DICER is implicated in chromatin decondensation during NER. In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated manner. The H2A–ubiquitin binding protein ZRF1 and DICER together impact on the chromatin conformation via PARP1. Moreover, …
GAM/ZFp/ZNF512B is central to a gene sensor circuitry involving cell-cycle regulators, TGF beta effectors, Drosha and microRNAs with opposite oncogen…
2010
MicroRNAs (miRNAs) are small regulatory RNAs targeting multiple effectors of cell homeostasis and development, whose malfunctions are associated with major pathologies such as cancer. Herein we show that GAM/ZFp/ZNF512B works within an intricate gene regulatory network involving cell-cycle regulators, TGFβ effectors and oncogenic miRNAs of the miR-17-92 cluster. Thus, GAM impairs the transcriptional activation of the miR-17-92 promoter by c-Myc, downregulates miR-17-92 miRNAs differentially, and limits the activation of genes responsive to TGFβ canonical pathway. In contrast, TGFβ decreases GAM transcripts levels while differentially upregulating miR-17-92 miRNAs. In turn, miR-17, miR-20a a…