Archive for the 'New & Novel' Category
February 8th, 2008. Ensemble methods for classification of patients for personalized medicine with high-dimensional data
Conclusion: The statistical classification method for individualized treatment of diseases developed in this study is expected to play a critical role in developing safer and more effective therapies that replace one-size-fits-all drugs with treatments that focus on specific patient needs.
January 30th, 2008. Advances in the systemic therapy of malignant pleural mesothelioma
Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.
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.
December 21st, 2007. Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin
The preclinical data obtained from our studies warrants pursuing clinical testing of MORAb-009. We have in fact initiated a Phase I clinical study enrolling patients with mesothelin-positive pancreatic, mesothelioma, non-small cell lung and ovarian cancers.
December 7th, 2007. CD200: A putative therapeutic target in cancer
Moreover, we show that CD200 expression is associated with tumor progression in various cancers. Taken together, these data suggest that CD200 is a potential therapeutic target and prognostic factor for a large array of malignancies.
December 6th, 2007. A genetic mouse model for metastatic lung cancer with gender differences in survival
Additionally, the presence of both mutations induced pleural mesotheliomas in 23% of these mice. This mouse model recapitulates the metastatic nature of human lung cancer and will be invaluable to further probe the molecular basis of metastatic lung cancer and for translational studies.
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.
November 3rd, 2007. Novel expression of kallikreins, kallikrein-related peptidases and kinin receptors in human pleural mesothelioma
KRP/hK2, 6, 8 and 9 were also expressed in the cytoplasm and nuclei of mesothelioma cells, whereas KRP/hK5 and hK7 showed predominantly cytoplasmic localisation. This is a first report, but further studies are required to determine whether these proteins have a functional role in the pathogenesis of mesothelioma and/or may be potential biomarkers for pleural mesothelioma.
Posted in Biphasic or Mixed, Diagnosis & Differentiation, Epithelioid, Full Archive, New & Novel, Pleural, Sarcomatoid, Serum Marker/Blood Test, Treatment, Type of Assessment:, Type of Mesothelioma: | No Comments »
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.
October 24th, 2007. Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin
Conclusions: Our results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.
October 20th, 2007. Mesothelin targeted cancer immunotherapy
These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy.
October 20th, 2007. Phase II Study of Vinflunine in Malignant Pleural Mesothelioma
Conclusion: Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.
October 17th, 2007. Malignant mesothelioma cells are rapidly sensitized to TRAIL-induced apoptosis by low-dose anisomycin via Bim
Overall, our data indicate that the rapid and selective sensitization by anisomycin in mesothelioma cells is mediated by posttranslational potentiation of Bim, which primes the cells for apoptosis via the death receptor pathway. Such subtoxic approaches to sensitization may enhance the value of TRAIL in cancer therapy.
October 9th, 2007. Alpha-Tocopheryl succinate: Toxicity and lack of anti-tumour activity in immuno-competent mice
Toxicity of α-TOS has not been reported to date perhaps due to a lack of studies conducted in fully immuno-competent hosts. Our results suggest that the translation of animal studies to clinical treatment with α-TOS requires careful consideration.
October 5th, 2007. A microaliquoting technique for precise histological annotation and optimization of cell content in frozen tissue specimens
High yield and quality RNA was extracted from precision annotated, tumor-enriched subsamples prepared by combining individual microaliquots with the highest tumor cellularity estimates. Microaliquoting provides accurate cell content annotation and permits genomic analysis of enriched subpopulations of cells without fixation or amplification.
October 3rd, 2007. The Therapeutic Efficacy of Anti–Vascular Endothelial Growth Factor Antibody, Bevacizumab, and Pemetrexed against Orthotopically Implanted Human Pleural Mesothelioma Cells in Severe Combined Immunodeficient Mice
Conclusions: These results suggest that the combined use of bevacizumab and pemetrexed may therefore be promising for controlling the progression of MPM highly expressing VEGF.
Posted in Bevacizumab (Avastatin), Chemotherapy, Determining Efficacy, EGFR, Full Archive, New & Novel, Pemetrexed (Alimta), Pleural, Treatment, Type of Assessment:, Type of Mesothelioma: | No Comments »
October 3rd, 2007. Bortezomib Inhibits Nuclear Factor-κB–Dependent Survival and Has Potent In vivo Activity in Mesothelioma
Conclusions: Inhibition of NF-κB constitutive activation in MMe cells by Bortezomib resulted in in vitro cytotoxicity along with apoptosis and in vivo tumor regression. Our results support the use of Bortezomib in the treatment of MMe and has led to a phase II clinical trial currently enrolling in Europe.
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.
September 11th, 2007. α-Tocopheryl succinate inhibits angiogenesis by disrupting paracrine FGF2 signalling
The role of FGF2 was confirmed by its down-regulation by treating MM cells with siRNA, abolishing EC proliferation and wound healing enhancement afforded by MM cells. We conclude that α-TOS disrupts angiogenesis mediated by MM cells by inhibiting FGF2 paracrine signalling.
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