Fwd: The Role of Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Tumor Behavior.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:39 PM
Subject: The Role of Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Tumor Behavior.
To: mesothelioma77@gmail.com


[1]Nucleosides Nucleotides Nucleic Acids. 2008 Jun; 27(6): 681-691
Bijnsdorp IV, de Bruin M, Laan AC, Fukushima M, Peters GJ

Platelet-derived endothelial cell growth-factor (PD-ECGF) is similar to the pyrimidine enzyme thymidine phosphorylase (TP). A high TP expression at tumor sites is correlated with tumor growth, induction of angiogenesis, and metastasis. Therefore, high TP is most likely associated with a poor prognosis. TP is not only expressed in tumor cells but also in tumor surrounding tissues, such as tumor infiltrating macrophages. TP catalyzes the conversion of thymidine to thymine and doxyribose-1-phosphate (dR-1-P). The latter in its parent form or in its sugar form, deoxyribose (dR) may play a role in the induction of angiogenesis. It may modulate cellular energy metabolism or be a substrate in a chemical reaction generating reactive oxygen species. L-deoxyribose (L-dR) and thymidine phosphorylase inhibitor (TPI) can reverse these effects. The mechanism of TP induction is not yet completely clear, but TNF, IL10 and other cytokines have been clearly shown to induce its expression. The various complex interactions of TP give it an essential role in cellular functioning and, hence, it is an ideal target in cancer therapy.



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Source: http://www.hubmed.org/display.cgi?uids=18600526
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Fwd: Overexpression of Dihydrodiol Dehydrogenase as a Prognostic Marker in Resected Gastric Cancer Patients.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:39 PM
Subject: Overexpression of Dihydrodiol Dehydrogenase as a Prognostic Marker in Resected Gastric Cancer Patients.
To: mesothelioma77@gmail.com


[1]Dig Dis Sci. 2008 Jul 5;
Chang HC, Chen YL, Chan CP, Yeh KT, Kuo SJ, Ko CJ, Fang HY

The cytoplasmic enzyme dihydrodiol dehydrogenase (DDH) plays an important role in detoxification. Patients with DDH overexpression have a significantly higher incidence of early tumor recurrence and distant metastasis. This study evaluated the correlation between clinicopathological data and DDH expression and the prognostic significance of DDH expression in patients with resected gastric cancer. Between January 1998 and September 2004, we retrospectively enrolled 81 patients who received surgical treatment for gastric cancer. Pathology samples were immunostained with monoclonal antibody to DDH. The relationship between DDH expression and clinicopathological data (age, gender, histological type, stage) was analyzed by chi-square analysis. Survival curves were plotted using the Kaplan-Meier method and compared using a log-rank test. The overexpression rate of DDH was 41.9%. Of patients with overexpressed DDH, 13% had stage I, 24% had stage II, 52% had stage III, and 78% had stage IV tumors. Among patients who died, DDH expression level differed significantly between high and low-expression groups (P = 0.042). Survival was significantly better in patients with low DDH expression (P = 0.048). Thus, DDH expression may be useful in identifying high-risk gastric cancer patients and distinguishing future candidates for curative and palliative treatment.



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Source: http://www.hubmed.org/display.cgi?uids=18600452
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Fwd: Pharmacokinetics of 5-Fluorouracil in Patients Heterozygous for the IVS14+1G > A Mutation in the Dihydropyrimidine Dehydrogenase Gene.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:39 PM
Subject: Pharmacokinetics of 5-Fluorouracil in Patients Heterozygous for the IVS14+1G > A Mutation in the Dihydropyrimidine Dehydrogenase Gene.
To: mesothelioma77@gmail.com


[1]Nucleosides Nucleotides Nucleic Acids. 2008 Jun; 27(6): 692-698
van Kuilenburg AB, Maring JG, Schalhorn A, Terborg C, Schmalenberg H, Behnke D, Schwabe W, Jabschinsky K, Hausler P

5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clearance were weak parameters with respect to the identification of patients with a DPD deficiency. However, highly significant differences were observed for the terminal half life of 5FU between DPD patients and controls. Thus, a DPD deficiency could be predicted from 5FU blood concentrations measured after the administration of a test dose of 5FU.



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Source: http://www.hubmed.org/display.cgi?uids=18600527
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Fwd: Baron & Budd Attorney Denyse Clancy Speaks at International Mesothelioma Program's First Annual Harvard Medical School ... (PR Newswire via Yahoo! Finance)

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From: Yahoo! News Search Results for asbestos cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:40 PM
Subject: Baron & Budd Attorney Denyse Clancy Speaks at International Mesothelioma Program's First Annual Harvard Medical School ... (PR Newswire via Yahoo! Finance)
To: mesothelioma77@gmail.com


Denyse Clancy, an attorney and shareholder with the Dallas-based law firm Baron & Budd, P.C., spoke at the International Mesothelioma Program's First Annual Harvard Medical School Course, entitled Surgery-Based Multimodality Therapy for Malignant Pleural Mesothelioma.

Mon, 07 Jul 2008 18:20:00 GMT

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Source: http://us.rd.yahoo.com/dailynews/rss/search/asbestos+cancer/SIG=11peo6bst/*http%3A//biz.yahoo.com/prnews/080707/lam066.html?.v=101
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Fwd: Mapping proteolytic cancer cell-extracellular matrix interfaces.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:40 PM
Subject: Mapping proteolytic cancer cell-extracellular matrix interfaces.
To: mesothelioma77@gmail.com


[1]Clin Exp Metastasis. 2008 Jul 4;
Wolf K, Friedl P

For cancer progression and metastatic dissemination, cancer cells migrate and penetrate through extracellular tissues. Cancer invasion is frequently facilitated by proteolytic processing of components of the extracellular matrix (ECM). The cellular regions mediating proteolysis are diverse and depend upon the physical structure, composition, and dimensionality of the ECM contacted by the cell surface. Cancer cells migrating across 2D substrate contain proteolytic structures such as lamellipodia, invadopodia, and the trailing edge. Likewise, invasive mesenchymal migration through 3D fibrillar ECM, as monitored for HT1080 fibrosarcoma and MDA-MB-231 breast carcinoma cells by submicron-resolved imaging, is mediated by several types of proteolytic structures rich in filamentous actin, ss1 integrin, and MT1-MMP with distinct location and function. These comprise (i) anterior pseudopod bifurcataions and the nucleus corresponding to zones of local cell compression by constraining collagen fibers, (ii) lateral small spikes that protrude into the ECM and cause small spot-like proteolytic foci, and (iii) a strongly proteolytic trailing edge sliding along reorganized ECM fibers. Through their combined action these proteolytic surface structures cleave, remove, and realign ECM barriers, support rear end retraction, generate tube-like matrix defects and laterally widen existing tracks during 3D tissue invasion.



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Source: http://www.hubmed.org/display.cgi?uids=18600304
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Fwd: The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:40 PM
Subject: The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype.
To: mesothelioma77@gmail.com


[1]Am J Pathol. 2008 Jul 3;
Xiao Y, Ye Y, Yearsley K, Jones S, Barsky SH

Inflammatory breast carcinoma (IBC) is a particularly lethal form of breast cancer characterized by exaggerated lymphovascular invasion, which is a phenotype recapitulated in our human xenograft MARY-X. MARY-X generated spheroids in vitro that resemble the embryonal blastocyst. Because of the resemblance of the spheroids to the embryonal blastocyst and their resistance to traditional chemotherapy/radiotherapy, we hypothesized that the spheroids expressed a stem cell-like phenotype. MARY-X spheroids expressed embryonal stem cell markers including stellar, rex-1, nestin, H19, and potent transcriptional factors, oct-4, nanog, and sox-2, which are associated with stem cell self-renewal and developmental potential. Most importantly, MARY-X spheroids expressed a cancer stem cell profile characterized by CD44(+)/CD24(-/low), ALDH1, and most uniquely, CD133. A significant percentage of single cells of MARY-X exhibited distinct proliferative and morphogenic potencies in vitro. As few as 100 cells derived from single-cell clonogenic expansion were tumorigenic with recapitulation of the IBC phenotype. Prototype stem cell signaling pathways such as notch3 were active in MARY-X. The stem cell phenotype exhibited by MARY-X also was exhibited by the lymphovascular emboli of human IBC cases independent of their molecular subtype. This stem cell-like phenotype may contribute to the aggressive nature of IBC but also may lend itself to selective targeting.



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Source: http://www.hubmed.org/display.cgi?uids=18599608
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Fwd: Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Mon, Jul 7, 2008 at 2:40 PM
Subject: Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues.
To: mesothelioma77@gmail.com


[1]Eur J Pharm Sci. 2008 Jun 11;
Han Y, Riwanto M, Go ML, Rachel Ee PL

Chalcones are biosynthetic precursors of flavonoids found to possess cytotoxic and chemopreventive activities. In this study, 17 non-basic chalcone analogues were synthesized and evaluated for their ability to modulate the function of either the human wild-type (482R) or mutant (482T) breast cancer resistance protein (BCRP/ABCG2) stably expressed in breast cancer MDA-MB-231 cells. At 5muM, chalcones with 2,4-dimethoxy groups or 2,4-dihydroxyl groups on ring A were found to increase mitoxantrone accumulation to a greater extent than an established BCRP inhibitor, fumitremorgin C. At the same time, these chalcones had negligible effect on calcein accumulation in P-glycoprotein overexpressing MDCKII cells, indicating their potential as selective BCRP inhibitors. Functionally, these compounds were able to increase the sensitivity of BCRP-overexpressing cancer cells to mitoxantrone by 2-5-fold. The effect of chalcone compounds on both wild-type and mutant BCRP ATPase activity was also examined and variable effects were observed. A stimulatory effect was mostly observed with chalcones with 2,4-dimethoxy substitution on ring A which were earmarked as good BCRP inhibitors in the MX accumulation and cytotoxicity assays. These findings underscore the potential of methoxylated and hydroxylated chalcones as selective and potent inhibitors of BCRP whose mode of action may not involve the inhibition of ATPase activity.



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Source: http://www.hubmed.org/display.cgi?uids=18598762
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