Fw: Bcl-xL antisense oligonucleotide and cisplatin combination therapy extends survival in SCID mice with established mesothelioma xenografts.

----- Forwarded Message ----
From: HubMed - mesothelioma <rssfwd@rssfwd.com>
To: shell8377@yahoo.com
Sent: Wednesday, March 26, 2008 2:22:39 PM
Subject: Bcl-xL antisense oligonucleotide and cisplatin combination therapy extends survival in SCID mice with established mesothelioma xenografts.

[1]Int J Cancer. 2008 Mar 21;
Littlejohn JE, Cao X, Miller SD, Ozvaran MK, Jupiter D, Zhang L, Rodarte C, Smythe WR

Bcl-xL functions as a dominant regulator of apoptotic cell death and is implicated in chemotherapeutic resistance of malignant pleural mesothelioma (MPM). Mesothelioma cell lines demonstrate increasing levels of Bcl-xL as resistant clones are selected invitro. Moreover, upon introduction of antisense oligonucleotides specific to Bcl-xL mRNA, MPM cells are sensitized to chemotherapeutic agents. Here we describe the therapeutic effects of a novel combination therapy, Bcl-xL antisense oligonucleotide (ASO 15999) and cisplatin, on mesothelioma cell lines in vitro and invivo; in addition, efficacy of ASO 15999 in decreasing tumor load as well as its effect on survival in an animal model. Finally, we initiated preliminary toxicity studies involved with intraperitoneal (IP) injections of ASO 15999 into mice. This novel combination, with doses of cisplatin four times below established IC(50) levels, significantly decreased viability of MPM cell lines after 48 hr. The growth of established mouse flank human tumor xenografts was reduced with intra-tumor administration of ASO 15999. Local spread and development of IP xenografts was reduced with treatments of ASO alone, and survival of mice afflicted with these xenografts was prolonged after administration of ASO alone and ASO 15999 + cisplatin combination therapy. These findings suggest that ASO 15999 sensitizes MPM cell lines to the toxic effects of cisplatin. ASO 15999 induced reduction of Bcl-xL is effective in slowing the progression of human mesothelioma cell lines both in vitro and in vivo. More notably, the combination of Bcl-xL ASO and cisplatin extends survival in an orthotopic tumor xenograft model. (c) 2008 Wiley-Liss, Inc.



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Source: http://www.hubmed.org/display.cgi?uids=18360826
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Fw: Efficacy and safety of pemetrexed in elderly cancer patients: Results of an integrated analysis.

----- Forwarded Message ----
From: HubMed - mesothelioma <rssfwd@rssfwd.com>
To: shell8377@yahoo.com
Sent: Wednesday, March 26, 2008 2:22:39 PM
Subject: Efficacy and safety of pemetrexed in elderly cancer patients: Results of an integrated analysis.

[1]Crit Rev Oncol Hematol. 2008 Mar 19;
Kulkarni PM, Chen R, Anand T, Monberg MJ, Obasaju CK

PURPOSE: To analyze pemetrexed in elderly patients (>/=65 years) based on data collected in three randomized, phase III registration trials. METHODS: Patients who received pemetrexed as monotherapy or in combination with another drug were included in this analysis (N=764). In all studies, pemetrexed 500mg/m(2) was administered every 21 days. Data from patients receiving pemetrexed were stratified by age +/-65 years. RESULTS: Out of the 764 patients randomized, 271 were >/=65 years of age (35.4%). Of these, 28% had non-small cell lung cancer, 41% pancreatic cancer, and 31% had malignant pleural mesothelioma that was either locally advanced or metastatic. The overall response rate of the integrated database of elderly patients was 21.4%, with complete response in three patients (1.11% in >/=65 years vs. 1.01% in 

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Source: http://www.hubmed.org/display.cgi?uids=18358737
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Fwd: Government asbestos consultation launched (Insurance Window)

---------- Forwarded message ----------
From: Yahoo! News Search Results for asbestos cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Government asbestos consultation launched (Insurance Window)
To: mesothelioma77@gmail.com


A government consultation into a House of Lords ruling on asbestos-related condition pleural plaques will begin this month.

Thu, 05 Jun 2008 15:15:33 GMT

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Source: http://us.rd.yahoo.com/dailynews/rss/search/asbestos+cancer/SIG=138k6h174/*http%3A//www.insurancewindow.net/public/showPage.html?page=post_breakingnews_story&tempPageName=798042
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Fwd: Uroplakin is not a Reliable Immunohistochemical Marker for Malignant Mesothelioma of the Pleura.

---------- Forwarded message ----------
From: HubMed - mesothelioma cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Uroplakin is not a Reliable Immunohistochemical Marker for Malignant Mesothelioma of the Pleura.
To: mesothelioma77@gmail.com


[1]Appl Immunohistochem Mol Morphol. 2008 Jun 3;
Butnor KJ, Ordonez NG

AIM: To analyze the immunohistochemical expression of uroplakin (URO) in pleural malignant mesothelioma (PMM). METHODS AND RESULTS: We analyzed URO expression in PMM using similar immunohistochemical techniques at 2 separate institutions. At an antibody dilution of 1:10, 0/5 PMMs were immunoreactive for URO. At 1:8, diffuse weak cytoplasmic staining was seen in all 38 PMMs tested, but no membrane staining was observed. Adjacent nontumor tissue and positive control tissue showed cytoplasmic staining of equivalent intensity. Similar staining results were observed in 27 PMMs at a 1:5 dilution. CONCLUSIONS: At an antibody dilution for which positive and negative control tissues stain appropriately, PMM does not stain for URO. At higher antibody concentrations, PMM exhibits nonspecific cytoplasmic staining. We assert that URO is not a useful immunohistochemical marker for the detection of PMM. Further studies addressing whether URO is overexpressed at the mRNA level in PMM are warranted.



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Source: http://www.hubmed.org/display.cgi?uids=18528285
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Fwd: Malignant mesothelioma of the inguinal canal with an unusually long survival.

---------- Forwarded message ----------
From: HubMed - mesothelioma cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Malignant mesothelioma of the inguinal canal with an unusually long survival.
To: mesothelioma77@gmail.com


[1]Am J Clin Oncol. 2008 Jun; 31(3): 306-7
Walshe JM, Gal A, Murray DR, Premkumar A, Berman D, Hassan R





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Source: http://www.hubmed.org/display.cgi?uids=18525312
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Fwd: Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability.

---------- Forwarded message ----------
From: HubMed - mesothelioma cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability.
To: mesothelioma77@gmail.com


[1]J Transl Med. 2008; 6: 27
Verdina A, Cardillo I, Nebbioso A, Galati R, Menegozzo S, Altucci L, Sacchi A, Baldi A

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.



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Source: http://www.hubmed.org/display.cgi?uids=18498639
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