Archive for the 'Kinase Inhibitors' Category
January 20th, 2011. Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma
HSP90 inhibition also suppressed phosphorylation of downstream signaling intermediates (AKT, mitogen-activated protein kinase, and S6); upregulated the p53, p21, and p27 cell cycle checkpoints; induced G(2) phase arrest; induced caspase 3/7 activity; and led to an increase in the sub-G(1) apoptotic population. These compelling proapoptotic and antiproliferative responses indicate that HSP90 inhibition warrants clinical evaluation as a novel therapeutic strategy in mesothelioma.
January 14th, 2011. Dasatinib: An Anti-Tumour Agent via Src Inhibition
The most common non-haematologic adverse events include gastrointestinal symptoms (diarrhoea, nausea, vomiting, abdominal pain and anorexia), headache, peripheral edema, and pleural effusion. In respect of these encouraging studies investigating dasatinib in the treatment of patients with GIST, prostate cancer, multiple myeloma and sarcomas, ongoing phase III clinical trials warrant the drug evaluation as recommended agent for the treatment of these diseases, also in association with chemoterapy or other targeted therapies.
January 12th, 2011. Phase I Studies of CBP501,a G2 Checkpoint Abrogator, as Monotherapy and in Combination with Cisplatin in Patients with Advanced Solid Tumors
Conclusions: CBP501 is well tolerated in patients as monotherapy and with cisplatin. At the recommended phase 2 dose (RP2D) the combination is feasible and HRS manageable with prophylaxis. Evidence of anti-tumor activity was observed in platinum-resistant patients.
January 6th, 2011. Summary of Presentations from the 46th Annual Meeting of the American Society of Clinical Oncology (2010) Focus on Tumor Biology and Biomarkers Related to Lung Cancer
Novel genetic mutations were identified in pleural mesothelioma using array-based technologies. Several studies on the development and testing of new molecular diagnostic tests to detect epidermal growth factor receptor tyrosine kinase mutations and EML4-ALK (Echinoderm Microtubule-associated Protein like 4 Anaplastic Lymphoma Receptor Tyrosine Kinase) fusion gene were presented as well.
January 5th, 2011. Antiangiogenic therapies for malignant pleural mesothelioma
Further understanding of the functional characteristics of tumor angiogenesis may be essential to improve targeting therapies in MPM. In this review, we introduce current status of clinical strategies and novel therapeutic approaches against angiogenesis in MPM.
October 18th, 2008. Expression and Regulation of Epithelial Na+ Channels by Nucleotides in Pleural Mesothelial Cells
Furthermore, we found that both forskolin and cGMP increased the short-circuit currents in mouse pleural tissues. Taken together, our data demonstrate that the ENaC channels are biochemically and functionally expressed in human pleural mesothelial cells, and can be up-regulated by cAMP and cGMP.
September 5th, 2008. Systemic Treatments for Mesothelioma: Standard and Novel
These include drugs targeted against the epidermal growth factor, platelet-derived growth factor, vascular endothelial growth factor, src kinase, histone deacetylase, the proteasome, and mesothelin. Given the progress made in recent years, there is reason to believe that more effective treatments will continue to be developed.
Posted in Chemotherapy, Cisplatin (Platinol ®), Determining Efficacy, EGFR, Full Archive, Gemcitabine (Gemzar), General, Irinotecan, Kinase Inhibitors, New & Novel, Pemetrexed (Alimta), Raltitrexed (Tomudex), Staging, Treatment, Type of Assessment:, Vinorelbine | No Comments »
September 4th, 2008. Protein kinase C beta in malignant pleural mesothelioma
Enzastaurin has preclinical activity against MPM, and exhibited synergism with cisplatin. PKC[beta] inhibition in MPM might be able to reduce the invasiveness of MPM by affecting cytoskeletal function.
August 14th, 2008. Enhanced antitumor therapy by inhibition of p21waf1 in human malignant mesothelioma
Conclusions: These results indicated that p21 might play an important role in chemosensitivity to anticancer agents, and the suppression of its expression might be a potential therapeutic target for MPM.
August 2nd, 2008. MET as a target for treatment of chest tumors
These drugs function at a variety of steps within the HGF-MET pathway, including MET expression at the RNA or protein level, the ligand-receptor interaction, and tyrosine kinase function. This paper will review the structure, function, mechanisms of tumorigenesis, and potential for therapeutic inhibition of the MET receptor in lung cancer and mesothelioma.
June 27th, 2008. The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies
The NSCLC trials include patients with squamous cell histologic features and treated brain metastases, populations for which bevacizumab is currently not indicated. These trials will determine whether cediranib will join the growing armamentarium of therapeutic options for thoracic malignancies and broaden the number of patients with NSCLC who could potentially benefit from antiangiogenic therapy.
June 24th, 2008. Phosphorylation and localization of protein-zero related (PZR) in cultured endothelial cells
To see if tyrosine kinases other than Src are also capable of phosphorylating PZR, the authors cotransfected HEK293 cells with PZR and one of several tyrosine kinases and found that c-Src, c-Fyn, c-Lyn, Csk, and c-Abl, but not c-Fes, phosphorylated PZR and increased PZR/SHP-2 interaction. These results suggest that PZR is a cell adhesion protein that may be involved in SHP-2-dependent signaling at interendothelial cell contacts.
April 9th, 2008. Epidermal growth factor receptor gene mutation, amplification and protein expression in malignant pleural mesothelioma
In MPM, EGFR seems to play a role in a limited subset of patients. To identify possible candidates for EGFR tyrosine kinase in inhibitor therapy, the information on the EGFR gene status may be valuable.
Posted in Diagnosis & Differentiation, EGFR, Epithelioid, Full Archive, Immunohistochemistry or IHC, Kinase Inhibitors, New & Novel, Sarcomatoid, Treatment, Type of Assessment:, Type of Mesothelioma: | No Comments »
March 28th, 2008. Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement
In contrast, the selective EGFR tyrosine kinase inhibitor, gefitinib, had no effect against EHMES-10 cells both in vitro and in vivo. Our results suggest that using vandetanib to target RET-dependent tumor cell proliferation and survival and VEGFR-2-dependent tumor angiogenesis may be promising against MPM expressing RET oncogenic rearrangement and VEGF.
February 28th, 2008. Pleural mesothelioma: diagnostic problems and evaluation of prognostic factors
Conclusion: MPM is an increasing disaster in Egypt which is underestimated and neglected. A panel of immunohistochemical markers should be used for proper evaluation. p27 has proven to be a potential biologic prognostic marker for mesothelioma and more studies as regard its significance are recommended on a larger number.
January 29th, 2008. Imatinib mesylate enhances therapeutic effects of gemcitabine in human malignant mesothelioma xenografts
Conclusions: Imatinib mesylate enhances the therapeutic response to gemcitabine, in accordance with our previous in vitro data. These in vivo results validate imatinib mesylate and gemcitabine as a combination treatment of malignant mesothelioma, also in view of its known positive effects on tumor drug uptake. These evidences provide the rationale for the currently ongoing clinical trials.
November 28th, 2007. Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: Therapeutic targets
Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies.
November 23rd, 2007. Survivin is highly expressed and promotes cell survival in malignant peritoneal mesothelioma
Conclusion: Our results show for the first time that survivin, as well as other IAPs, is largely expressed in clinical MPMs and suggest that strategies aimed at down-regulating survivin may provide a novel approach for the treatment of the malignancy.
October 24th, 2007. Receptor EphA2 activation with ephrinA1 suppresses growth of malignant mesothelioma (MM)
Ligand activated and ephrinA1 vector (pcDNA/EFNA1) transfected MMC demonstrated decreased clonal growth in 3-D matrigels when compared to resting MMC. These studies suggest that EphA2 activation by its ligand ephrinA1 transmits intracellular signals from cell membrane to nucleus via ERK1/2 signaling cascade and inhibits MM growth.
September 18th, 2007. HGF Mediates Cell Proliferation of Human Mesothelioma Cells Through a PI3K/MEK5/Fra-1 Pathway
HGF also caused increased MM cell viability and proliferating cell nuclear antigen (PCNA) expression that were abolished by knockdown of MEK5 or Fra-1. Data suggest that HGF-induced effects in the some MM cells are mediated via activation of a novel PI3K/ERK5/Fra-1 feedback pathway that might explain tumor-specific effects of c-Met inhibitors on MM and other tumors.
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