Archive for the 'Gene Therapy' Category
December 3rd, 2008. Opposite effects of Notch-1 and Notch-2 on mesothelioma cell survival under hypoxia are exerted through the Akt pathway
The mechanism of Notch-2 toxicity to MM cells countered that of Notch-1, as it was the result of positive transcriptional regulation of PTEN and inhibition of the PI3K/Akt/mTOR signaling pathway. These results provide new insight into the role of Notch in MM and suggest that Notch pathway inhibitors may be useful in the treatment of this deadly disease.
November 1st, 2008. Genomic events associated with progression of pleural malignant mesothelioma
Imbalances seen by ROMA were confirmed by Affymetrix genome analysis in a subset of samples. © 2008 Wiley-Liss, Inc.
October 18th, 2008. The cytotoxic ribonuclease onconase targets RNA interference (siRNA)
The data thus provide evidence that one of the targets of Onc is siRNA, likely within the RNA-induced silencing complex (RISC). In light of the findings that microRNAs are involved in tumor pathogenesis as well as in enhancing cell resistance to anticancer therapy the present data may provide explanation for both, the antitumor Onc activity and its propensity to enhance effectiveness of cytotoxic drugs.
October 17th, 2008. Down-regulation of Inhibition of Differentiation-1 via Activation of Activating Transcription Factor 3 and Smad Regulates REIC/Dickkopf-3–Induced Apoptosis
In summary, we first showed that both ATF3 and Smad were crucially and synergistically involved in down-regulation of Id-1, which regulated JNK phosphorylation in REIC/Dkk-3-induced apoptosis. Thus, gene therapy with REIC/Dkk-3 may be a promising therapeutic tool for MM.
October 2nd, 2008. Inhibition of Hsp90 leads to cell cycle arrest and apoptosis in human malignant pleural mesothelioma
Conclusion: These results suggest that Hsp90 is strongly associated with the growth and survival of MM and that inhibition of Hsp90 may have therapeutic potential in the treatment of MM.
September 2nd, 2008. Malignant Pleural Mesothelioma–Targeted CREBBP/EP300 Inhibitory Protein 1 Promoter System for Gene Therapy and Virotherapy
Moreover, these viruses showed antitumor effects in a mesothelioma xenograft mouse model. Here, we describe a novel strategy to target malignant mesothelioma using the CRI1(-138 4x) promoter system.
September 2nd, 2008. Recent advances in the treatment of malignant pleural mesothelioma
Vorinostat, a small molecule inhibitor of HDAC, which targets select members of class I and II HDACs, has shown early evidence of activity and is currently being evaluated in a randomized study for patients who progress with standard therapy for advanced mesothelioma. It is hoped that the HDAC inhibitors and other novel targeted agents will pave the way for improved outcomes for patients with this disease.
Posted in Chemotherapy, Cisplatin (Platinol ®), Determining Efficacy, Extrapleural Pneumonectomy (EPP), Full Archive, Gene Therapy, Pemetrexed (Alimta), Pleural, Pleurectomy/decortication, Radiation, Surgery, Treatment, Type of Assessment:, Type of Mesothelioma: | No Comments »
August 30th, 2008. YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation
Future studies of transcriptional targets of YAP1 in MPMs may shed light on the molecular mechanisms of MPM development and lead to new therapeutic strategies. Abbreviations: BAC, bacterial artificial chromosome; CGH, comprehensive genomic hybridization; EGFP, enhanced green fluorescent protein; GST, glutathione S-transferase; MPM, malignant pleural mesothelioma; NF2, neurofibromatosis type 2; NHERF1, Na(+)/H(+) exchanger regulatory factor 1; PCR, polymerase chain reaction; RNAi, RNA interference; SDS, sodium dodecyl sulfate; sh, short hairpin.
August 30th, 2008. Novel Oncolytic Agent GLV-1h68 Is Effective Against Malignant Pleural Mesothelioma
GLV-1h68 was successfully used to treat MPM in vitro and in an orthotopic model (in vivo). These promising results warrant clinical investigation of GLV-1h68 as a novel agent in the treatment of MPM.
August 8th, 2008. Novel Functional View of the Crocidolite Asbestos-Treated A549 Human Lung Epithelial Transcriptome Reveals an Intricate Network of Pathways with Opposing Functions
Conclusions: Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.
May 14th, 2008. Molecular targets and targeted therapies for malignant mesothelioma
Alternative approaches are based on inhibitors of the ubiquitin-proteasome pathway and of histone deacetylases which, notwithstanding the functional divergence of the corresponding targets, share the ability to determine a wide modulation of the cancer cell phenotype that can lead to cell cycle arrest, apoptosis and sensitization to different antineoplastic treatments. A recombinant immunotoxin targeted to the membrane antigen mesothelin is an additional agent whose activity is being evaluated in mesothelioma patients.
May 6th, 2008. Overexpression and altered glycosylation of MUC1 in malignant mesothelioma
CA15-3 in effusions could differentiate malignant from benign effusions but were not specific for mesothelioma. Thus, as in other cancers, alterations in MUC1 biology occur in mesothelioma and these results suggest that specific MUC1 characteristics may be useful for mesothelioma diagnosis and should also be investigated as a potential therapeutic target.
April 21st, 2008. Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases
Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes.
April 9th, 2008. Frequent p16 inactivation by homozygous deletion or methylation is associated with a poor prognosis in Japanese patients with pleural mesothelioma
Our study showed that P16 inactivation by homozygous deletions or methylation is a frequent event in Japanese patients with MPMs, relating to poor prognosis. Homozygous deletion is the major cause of P16 inactivation, but methylation also lead to the inactivation of P16 when the P16 alleles are retained.
April 4th, 2008. Inhibition of both mesothelioma cell growth and Cdk4 activity following treatment with a TATp16INK4a peptide
Conclusion: Therapeutic strategies which introduce either TATp16INK4a peptide, or small molecule mimetic, could be an effective strategy for mesothelioma treatment.
March 28th, 2008. Cell-cycle molecules in mesothelioma: an overview
Several studies report the importance of cell cycle regulator proteins in the pathogenesis and the prognosis of mesothelioma. This article will review the most recent data from the literature about the expression and the diagnostic and prognostic significance of cell cycle molecules in mesothelioma.
March 7th, 2008. Characterization of Human Mesothelioma Cell Lines as Tumor Models for Suicide Gene Therapy
Conclusion: The characterized cell lines described here may serve as a model for in vitro and in vivo preclinical gene therapy for the treatment of MPM using rAAV2 suicide vectors.
March 4th, 2008. Asbestos exposure predicts cell cycle control gene promoter methylation in pleural mesothelioma
05) after controlling for age, gender, and tumor histology. These data suggest a novel tumorigenic mechanism of action of asbestos, and may contribute to the understanding of precisely how asbestos exposure influences the etiology and clinical course of malignant mesothelioma.
February 28th, 2008. Transcriptome sequencing of malignant pleural mesothelioma tumors
Of the seven point mutations, three were observed in at least one tumor from 49 other MPM patients. The mutations were in genes that could be causally related to cancer and included XRCC6, PDZK1IP1, ACTR1A, and AVEN.
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