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Mesothelioma and Neoadjuvant Chemotherapy

Another interesting study is called, "Neoadjuvant Chemotherapy Followed by Extrapleural

Pneumonectomy in Malignant Pleural Mesothelioma" by Walter Weder, Peter Kestenholz, Christian Taverna, Stefan Bodis, Didier Lardinois, Monika Jerman, Rolf A. Stahel - Journal of Clinical Oncology, Vol 22, No 17 (September 1), 2004: pp. 3451-3457. Here is an excerpt: "PATIENTS AND METHODS: Eligible patients had MPM with clinical stage T1-3, N0-2, M0 disease considered to be completely resectable and a WHO performance status of 0 to 2. Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15, given every 28 days. Surgery had to consist of a complete extrapleural pneumonectomy, including resection of pericardium and diaphragm. Postoperative radiotherapy was to be considered for all patients.

RESULTS: Nineteen patients with MPM were included in this pilot study. According to the European Organization for Research and Treatment of Cancer prognostic score, two patients were in the good prognosis group, and 17 patients were in the poor prognosis group. The response rate to neoadjuvant chemotherapy was 32%. The major toxicity was thrombocytopenia. Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality. Major surgical complications occurred in six patients, and all were treated successfully. Thirteen patients received postoperative radiotherapy. The median survival time was 23 months. Two patients remain alive and free of disease 41 and 38 months after initiation of therapy.

CONCLUSION: For patients with potentially operable MPM, the availability of active and well-tolerated chemotherapy regimens, the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center, and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy."

Another interesting study is called, "Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma." By Cao XX, Mohuiddin I, Ece F, McConkey DJ, Smythe WR. - m J Respir Cell Mol Biol. 2001 Nov;25(5):562-8. Here is an excerpt: "Abstract - It has been shown that mesothelioma expresses the antiapoptotic protein BCL-XL, but not BCL-2, rendering bcl-xl gene expression a potential therapeutic target. Sodium butyrate (NaB) is a histone deacetylase inhibitor capable of alteration of bcl-2 family protein expression in other tumor types. Mesothelioma cell lines (REN, I-45) were exposed to NaB, and viability (colorimetric assay) and apoptosis (TUNEL, Hoescht staining, flow cytometry) were evaluated. Effects on bcl-2 family protein, fas-fas ligand, and caspases were examined by Western blot analysis and functional assay. An RNase assay evaluated bcl-2 family messenger RNA (mRNA) expression. Overexpressing BCL-XL mesothelioma clones were created by plasmid transfer. Cells were sensitive to NaB at low IC(50) (REN, 0.3 mM; I-45, 1 mM) and demonstrated apoptosis (percentage of cells below G1 phase by flow cytometry [sub-G1]: REN, 38.5%; I-45, 30.9%). A significant decrease in BCL-XL protein expression was noted with BAK, BAX, and BCL-2 unchanged, and this was corroborated at the transcriptional level with selectively decreased bcl-xl mRNA production after sodium butyrate exposure. Fas expression and fas-fas ligand sensitivity were unchanged. Caspases demonstrated low-level activation. Stable overexpressing BCL-XL clones were proportionally resistant to the NaB effect. This study suggests that mesothelioma cells are sensitive to the induction of apoptosis related to the attenuation of antiapoptotic bcl-xl gene and protein expression. Additional study of the therapeutic benefit of targeting bcl-xl gene expression in mesothelioma is warranted."

Another interesting study is called, "Ber-EP4 Antibody as a Discriminant in the Differential Diagnosis of Malignant Mesothelioma Versus Adenocarcinoma" - August 1991 - Volume 15 - Issue 8 - American Journal of Surgical Pathology by Sheibani, Khalil M.D.; Shin, Sung S. M.D.; Kezirian, Janice B.A.; Weiss, Lawrence M. M.D. Here is an excerpt: "Abstract - The pathologic diagnosis of malignant mesothelioma is often difficult, even with the benefit of special studies such as histochemistry, electron microscopy, and immunohistochemistry. Ber-EP4 is a newly characterized monoclonal antibody that reliably labels epithelial tissues but does not react with mesothelial cells. We evaluated Ber-EP4 on formalin-fixed, paraffin-embedded tissue sections from 115 malignant mesotheliomas and 83 adenocarcinomas. Although 72 cases (87%) of adenocarcinoma were positive for Ber-EP4, only one (1%) of the mesotheliomas was reactive. The only adenocarcinomas that did not stain were from the breast (eight of 25 cases nonreactive) and the kidney (all three cases nonreactive). The staining pattern in the positive adenocarcinomas was usually intense and membranous, but additional weak cytoplasmic staining was seen in many cases. The reactivity was diffuse in 59 cases and focal in 13 cases. The results of our study suggest that the Ber-EP4 antibody may have great use in the differential diagnosis of mesothelioma versus adenocarcinoma, particularly when only formalin-fixed tissue is available."

We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.

Mesothelioma and Neoadjuvant Chemotherapy

By: Montwrobleski77
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Mesothelioma and Neoadjuvant Chemotherapy