Mesothelioma and Frequent Promoter Hypermethylation

Mesothelioma and Frequent Promoter Hypermethylation

Another study is called, “Secreted Frizzled-Related Protein 4 Is Silenced by Hypermethylation and Induces Apoptosis in β-Catenin–Deficient Human Mesothelioma Cells” by Biao He, Amie Y. Lee, Sina Dadfarmay, Liang You, Zhidong Xu, Noemi Reguart, Julien Mazieres, Iwao Mikami, Frank McCormick, and David M. Jablons – Cancer Res February 1, 2005 65; 743.  Here is an excerpt: “Abstract – The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in tumorigenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancer. Restoration of SFRP function attenuates Wnt signaling and induces apoptosis in a variety of cancer types. Wnt signaling is known to inhibit apoptosis through activation of β-catenin/Tcf–mediated transcription. Recently, we identified aberrant Wnt activation as a result of Dishevelled overexpression in malignant mesothelioma. Here, we report that silencing of SFRP4 is correlated with promoter hypermethylation in β-catenin–deficient mesothelioma cell lines. Reexpression of SFRP4 in these β-catenin–deficient mesothelioma cell lines blocks Wnt signaling, induces apoptosis, and suppresses growth. Conversely, knocking down SFRP4 by small interfering RNA in cell lines expressing both SFRP4 and β-catenin stimulates Wnt signaling, promotes cell growth, and inhibits chemodrug-induced apoptosis. Our results suggest that methylation silencing of SFRP4 may play an important role in aberrant Wnt activation in mesothelioma even in the absence of β-catenin. Our data also suggest that β-catenin–independent noncanonical pathway(s) may be involved in the apoptotic inhibition caused by activation of Wnt signaling.”

Another interesting study is called, “The cytopathology of mesothelioma.  Tao LC.” – Acta Cytol. 1979 May-Jun;23(3):209-13.  Here is an excerpt: “Abstract – Fifty-seven cases of mesothelioma from the Toronto General Hospital during the period 1965 to 1976 have been reviewed. Pleural effusions or ascites were present in 34 patients. The value of cytologic examination of effusion specimens was assessed, and the criteria for cytologic diagnosis were elucidated. It appears that patients with predominantly fibrous or sarcomatous mesothelioma were not prone to develop pleural effusions or ascites; few tumor cells, if any, from these mesotheliomas were exfoliated into effusions. Cytologic examinations of effusion specimens were positive in 12 of 14 cases of carcinomatous mesothelioma and in three of four cases of undifferentiated mesothelioma. However, only four of seven casee of benign mesothelioma (mostly epithelial type) showed positive results, as did two of four cases of sarcomatous mesothelioma. It appears that cytologic diagnosis of mesothelioma is more useful for the carcinomatous and undifferentiated types. The cytomorphologic features of the various types of mesothelioma are different, and by cytologic examination of effusion specimens, typing of mesothelioma is possible and correlates well with the histologic typing.”

Another interesting study is called, “Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma.” By Fizazi K, Caliandro R, Soulié P, Fandi A, Daniel C, Bedin A, Doubre H, Viala J, Rodier J, Trandafir L, Le Chevalier T, Cvitkovic E, Armand J, Ruffié P – Eur J Cancer. 2000 Aug;36(12):1514-21.  Here is an excerpt: “Abstract – The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.”

Monty Wrobleski is the author of this article.  For more information please click on the following links

Depuy Hip Recall Attorney

Depuy Hip Recall Attorney

Malignant Mesothelioma


Article from articlesbase.com

Comments are closed.

Categories