Adenoviral Gene Transfer and Mesothelioma Cancer Cell Lines

Author: Montwrobleski77

Another interesting study is called, “Adenovirus-mediated Bak gene transfer induces apoptosis in mesothelioma cell lines” by Abujiang Pataer, MD, PhD, W. Roy Smythe, MD, Robert Yu, MS, Bingliang Fang, MD, PhD, Tim McDonnell, MD, PhD, Jack A. Roth, MD, Stephen G. Swisher, MD – From the Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, and the Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Tex. – General Thoracic Surgery J Thorac Cardiovasc Surg 2001;121:0061-0067. Here is an excerpt: “Objective: Conventional treatment for mesothelioma is largely ineffective. We therefore evaluated the novel approach of adenoviral gene transfer of the proapoptotic Bcl-2 family member Bak in mesothelioma cancer cell lines, which are sensitive and resistant to adenoviral p53.

Methods: Binary adenoviral Bak (Ad/GT-Bak and Ad/GV16) and LacZ (Ad/GT-LacZ and Ad/GV16) vectors were used for transduction of the mesothelioma cell lines I-45 (p53 resistant) and REN (p53 sensitive). Protein levels were determined by Western blotting. Apoptosis was assessed by morphologic changes, caspase-3 cleavage, and fluorescence-activated cell sorter analysis of subdiploid populations. Cell viability was determined with the XTT assay. Statistical analysis was performed with analysis of variance and the Student test.

Results: High levels of Bak gene transfer were seen after coadministration of Ad/GT-Bak and Ad/GV16 in both mesothelioma cell lines. Apoptosis was induced 24 hours after Bak but not LacZ gene transfer ([Bak: I-45, 36%; REN, 25%] vs [LacZ: I-45, 1%; REN, 3%], P < .05]) in p53-sensitive (REN) and p53-resistant (I-45) cell lines. Cellular viability was significantly decreased 48 to 72 hours after Bak gene transfer compared with control vector in both cell lines (72 hours: Bak I-45, 1.4% ± 1.0%, and Bak REN, 4.7% ± 1%, vs Lac-Z I-45, 83% ± 3%, and Lac-Z REN, 100% ± 1%; P < .05).

Conclusions: Adenovirus-mediated overexpression of the Bak gene induces apoptosis and decreased cellular viability in p53-sensitive and p53-resistant mesothelioma cells. These data suggest that the gene transfer of proapoptotic Bcl-2 family members may represent a novel gene therapy strategy to treat mesothelioma.

Another interesting study is called, “Palliative surgical debulking in malignant mesothelioma : Predictors of survival and symptom control” by A. E. Martin-Ucara, J. G. Edwardsa, A. Rengajarana, S. Mullerb and D. A. Waller, – Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK. Here is an excerpt: “Abstract – Objective: Malignant mesothelioma (MM) typically presents at an advanced stage. In the UK surgical intervention has been mostly reserved for tissue diagnosis or chemical pleurodesis. However, the role of debulking surgery in symptom control has not been fully explored. Methods: In a prospective cohort study, 51 consecutive patients presenting with MM underwent palliative surgical debulking for symptomatic relief (all patients presented with dyspnoea, 39 also had pain and two had a co-existing pleural empyema). Patients with early disease who underwent extrapleural pneumonectomy were excluded. The treatment aims were pleural drainage, lung re-expansion, pleurodesis and pleural debulking for symptom control. If the lung re-expanded after drainage of the effusion a subtotal parietal pleurectomy was performed via Video Assisted Thoracic Surgery (VATS). If the lung remained entrapped, a parietal and visceral decortication using VATS or thoracotomy was performed. The changes in subjective dyspnoea and pain scores were recorded at 6 weeks and 3, 6 and 12 months after surgery. Prognostic factors were analyzed to determine their influence on survival and symptom control. Results: VATS pleurectomy was possible in 17 patients (34%), whilst decortication was required in the remainder (three by VATS and 31 by thoracotomy). Median postoperative stay was 7 days (range 2–17) with 30-day mortality of 7.8% (four of 51 patients). Morbidity included postoperative empyema in two patients (4%) and prolonged air-leak in five (9.8%). Overall significant symptomatic benefit was obtained up to 3 months after surgery but subsequently increasing mortality offset these benefits. Epithelial cell type and absence of weight loss prior to surgery were found to predict longer survival and successful symptom control. Conclusions: Debulking surgery has a beneficial role in symptom control for unresectable MM. However, this surgery should be reserved for those patients who present with epithelial cell type and before significant loss of weight.”

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