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Monday, August 25, 2008

Fwd: Farnesol, a fungal quorum-sensing molecule triggers apoptosis in human oral squamous carcinoma cells.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Thu, Aug 21, 2008 at 9:30 PM
Subject: Farnesol, a fungal quorum-sensing molecule triggers apoptosis in human oral squamous carcinoma cells.
To: mesothelioma77@gmail.com


[1]Neoplasia. 2008 Sep; 10(9): 954-63
Scheper MA, Shirtliff ME, Meiller TF, Peters BM, Jabra-Rizk MA

Farnesol is a catabolite within the isoprenoid/cholesterol pathway that has exhibited significant antitumor activity. Farnesol was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. In this study, we hypothesize that synthetic and Candida-produced farnesol can induce apoptosis in vitro in oral squamous cell carcinoma (OSCC) lines. Cell proliferation, apoptosis, mitochondrial degradation, and survivin and caspase expressions were examined. In addition, global protein expression profiles were analyzed using proteomic analysis. Results demonstrated significant decrease in proliferation and increase in apoptosis in cells exposed to farnesol and C. albicans culture media. Concurrently, protein expression analysis demonstrated a significant decrease in survivin and an increase in cleaved-caspase expression, whereas fluorescent microscopy revealed the presence of active caspases with mitochondrial degradation in exposed cells. A total of 36 differentially expressed proteins were identified by proteomic analysis. Among the 26 up-regulated proteins were those involved in the inhibition of carcinogenesis, proliferation suppression, and aging. Most notable among the 10 down-regulated proteins were those involved in the inhibition of apoptosis and proteins overexpressed in epithelial carcinomas. This study demonstrates that farnesol significantly inhibits the proliferation of OSCCs and promotes apoptosis in vitro through both the intrinsic and extrinsic apoptotic signaling pathways. In addition, we report for the first time the ability of Candida-produced farnesol to induce a similar apoptotic response through the same pathways. The capability of farnesol to trigger apoptosis in cancer cells makes it a potential tool for studying tumor progression and an attractive candidate as a therapeutic agent.



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Source: http://www.hubmed.org/display.cgi?uids=18714396
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Fwd: Preventing Growth of Brain Tumors by Creating a Zone of Resistance.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Thu, Aug 21, 2008 at 9:30 PM
Subject: Preventing Growth of Brain Tumors by Creating a Zone of Resistance.
To: mesothelioma77@gmail.com


[1]Mol Ther. 2008 Aug 19;
Maguire CA, Meijer DH, Leroy SG, Tierney LA, Broekman ML, Costa FF, Breakefield XO, Stemmer-Rachamimov A, Sena-Esteves M

Glioblastoma multiforme (GBM) is a devastating form of brain cancer for which there is no effective treatment. Here, we report a novel approach to brain tumor therapy through genetic modification of normal brain cells to block tumor growth and effect tumor regression. Previous studies have focused on the use of vector-based gene therapy for GBM by direct intratumoral injection with expression of therapeutic proteins by tumor cells themselves. However, as antitumor proteins are generally lethal to tumor cells, the therapeutic reservoir is rapidly depleted, allowing escape of residual tumor cells. Moreover, it has been difficult to achieve consistent transduction of these highly heterogeneous tumors. In our studies, we found that transduction of normal cells in the brain with an adeno-associated virus (AAV) vector encoding interferon-beta (IFN-beta) was sufficient to completely prevent tumor growth in orthotopic xenograft models of GBM, even in the contralateral hemisphere. In addition, complete eradication of established tumors was achieved through expression of IFN-beta by neurons using a neuronal-restricted promoter. To our knowledge this is the first direct demonstration of the efficacy of targeting gene delivery exclusively to normal brain cells for brain tumor therapy.Molecular Therapy (2008); doi:10.1038/mt.2008.168.



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Source: http://www.hubmed.org/display.cgi?uids=18714312
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Fwd: Cell membrane proteomic analysis identifies proteins differentially expressed in osteotropic human breast cancer cells.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Thu, Aug 21, 2008 at 9:30 PM
Subject: Cell membrane proteomic analysis identifies proteins differentially expressed in osteotropic human breast cancer cells.
To: mesothelioma77@gmail.com


[1]Neoplasia. 2008 Sep; 10(9): 1014-20
Kischel P, Guillonneau F, Dumont B, Bellahcène A, Stresing V, Clézardin P, De Pauw EA, Castronovo V

Metastatic breast cancer cells are characterized by their high propensity to colonize the skeleton and form bone metastases, causing major morbidity and mortality. Identifying key proteins involved in the osteotropic phenotype would represent a major step toward the development of both new prognostic markers and new effective therapies. Cell surface proteins differentially expressed in cancer cells are preferred potential targets for antibody-based targeted therapies. In this study, using cell surface biotinylation and a mass spectrometric approach, we have compared the profile of accessible cell surface proteins between the human breast cancer cell line MDA-MB-231 and its highly osteotropic B02 subclone. This strategy allowed the identification of several proteins either up- or downregulated in the osteotropic cell line, and differential protein expressions were validated using antibody-based techniques. Class I HLAs were down-regulated in the bone metastatic variant, whereas alpha(v)beta(3) integrins, among others, were consistently up-regulated in this latter cell line. These results show that comprehensive profiling of the cell surface proteome of mother cancerous cell lines and derived organ-specific metastatic cell lines provides an effective approach for the identification of potential accessible marker proteins for both prognosis and antibody-based targeted therapies.



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Source: http://www.hubmed.org/display.cgi?uids=18714363
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