Expression of bcl-2 — protein in small cell lung cancer

Kaiser, Ulrich; Schilli, M.; Haag, Uwe; Neumann, Kurt; Kreipe, Hans; Kogan, E. A.; Havemann, K.

doi:10.1016/0169-5002(96)00568-5

Cited by 88 publications

(45 citation statements)

References 15 publications

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“…A total of 29 trials, published between 1993 and 1999, were selected (Pezzella et al, 1993;Fontanini et al, 1995Fontanini et al, , 1996Walker et al, 1995;Brambilla et al, 1996;Kaiser et al, 1996;Ohsaki et al, 1996;O'Neill et al, 1996;Rao et al, 1996;Takayama et al, 1996;Anton et al, 1997;Apolinario et al, 1997;Higashiyama et al, 1997;Ishida et al, 1997;Koukourakis et al, 1997;Pastorino et al, 1997;Greatens et al, 1998;Kim et al, 1998;Kwiatkowski et al, 1998;Chen et al, 1999;D'Amico et al, 1999;Dingemans et al, 1999;Dosaka-Akita et al, 1999;Eerola et al, 1999;Ghosh et al, 1999;Huang et al, 1999;Laudanski et al, 1999;Maitra et al, 1999;Santinelli et al, 1999). They all report on the prognostic value for survival of Bcl-2 status in lung cancer patients, assessing Bcl-2 protein expression in the primary tumour.…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

et al. 2003

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The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-2 in lung cancer and reported analysis of survival data according to Bcl-2 status. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a quality scale designed by the European Lung Cancer Working Party (including study design, laboratory methods and analysis). Of 28 studies, 11 identified Bcl-2 expression as a favourable prognostic factor and three linked it with poor prognosis; 14 trials were not significant. No differences in scoring measurement were detected between the studies, except that significantly higher scores were found in the trials with the largest sample sizes. Assessments of methodology and of laboratory technique were made independently of the conclusion of the trials. A total of 25 trials, comprising 3370 patients, provided sufficient information for the meta-analysis. The studies were categorised according to histology, disease stage and laboratory technique. The combined hazard ratio (HR) suggested that a positive Bcl-2 status has a favourable impact on survival: 0.70 (95% confidence interval 0.57 -0.86) in seven studies on stages I -II NSCLC; 0.50 (0.39 -0.65) in eight studies on surgically resected NSCLC; 0.91 (0.76 -1.10) in six studies on any stage NSCLC; 0.57 (0.41 -0.78) in five studies on squamous cell cancer; 0.75 (0.61 -0.93) and 0.71 (0.61 -0.83) respectively for five studies detecting Bcl-2 by immunohistochemistry with Ab clone 100 and for 13 studies assessing Bcl-2 with Ab clone 124; 0.92 (0.73 -1.16) for four studies on small cell lung cancer; 1.26 (0.58 -2.72) for three studies on neuroendocrine tumours. In NSCLC, Bcl-2 expression was associated with a better prognosis. The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value.

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Section: Studies Selection and Characteristicsmentioning

confidence: 99%

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

et al. 2003

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“…Finally, overexpression of the proto-oncogene BCL-2 is often found in lung cancer (Pezzella et al 1993;Kaiser et al 1996). BCL-2 is an antiapoptotic protein and is expressed in 75%-95% of SCLCs (Jiang et al 1995), whereas it is expressed in 25%-30% of the squamous cell carcinomas and ∼10% of adenocarcinomas (Pezzella et al 1993).…”

Section: Prominent Molecular Abnormalities In Lung Cancermentioning

confidence: 99%

Mouse models for human lung cancer

Meuwissen

Berns²

2005

Genes Dev.

271

243

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In recent years several new mouse models for lung cancer have been described. These include models for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Tumorigenesis in these conditional mouse tumor models can be initiated in adult mice through Cre-recombinase-induced activation of oncogenic mutations in a subset of the cells. They present a marked improvement over mouse models that depend on carcinogen induction of tumors. These models permit us to study the consecutive steps involved in initiation and progression and allow us to address questions like the cell of origin, and the role of cancer stem cells in the maintenance of these tumors. They now need to be validated as suitable preclinical models for intervention studies in which questions with respect to therapy response and resistance can be addressed.During the last decades lung cancer has become the leading cause of cancer deaths in the world, accounting for even more solid tumor deaths than breast, pancreatic, prostate, and colorectal combined (Landis et al. 1999). More then 170,000 new cases are being diagnosed each year in the United States alone, of whom ∼160,000 will eventually die, representing 28% of all cancer deaths (Jemal et al. 2004). Worldwide more than a million deaths are due to lung cancer. Tobacco smoking is the major causal agent, being responsible for ∼85% of the lung cancer incidence. Other respiratory exposure to occupational or environmental carcinogens, such as asbestos or radon, and yet unknown genetic factors contribute to the remaining 15% . Although smoking cessation before the age of 30 does substantially reduce the risk of lung cancer, this is significantly less for those who stop smoking at 50 or 60 yr (Peto et al. 2000;Doll et al. 2004). Interestingly, nearly 50% of all first diagnosed lung cancers in the United States are from people who stopped smoking at least 5 or more years ago (Peto and Lopez 2001). This indicates that extensive damage to the respiratory tract can persist over many years. Indeed, recent studies (Mao 2002;Pfeifer et al. 2002;Wistuba et al. 2002) showed the presence of multiple genetic lesions, often manifested in clonal patches of cells in respiratory epithelium of current and former smokers.Lung cancer can be divided into two major histopathological groups: non-small-cell lung cancer (NSCLC) (Van Zandwijk et al. 1995) SCLC and NSCLC show major differences in histopathologic characteristics that can be explained by the distinct patterns of genetic lesions found in both tumor classes . Responsiveness to treatment with chemotherapy and/or radiation also differs significantly between NSCLC and SCLC and has a dramatic effect on clinical treatment outcome. The overall 5-yr survival rate for lung cancer is ∼14% (Travis et al. 1995); for SCLC alone it is even worse, ∼5% (Worden and Kalemkerian 2000).Spontaneous lung tumors in mice are similar in morphology, histopathology, and molecular characteristics to human adenocarcinomas. Mouse models for lung cancer can thus serve as a valua...

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“…In SCLC patients, the overexpression of Bcl-2 has been reported to occur in 55% to 90% of all SCLC cases, and it has been suggested to be a key factor involved in both the genesis and maintenance of SCLC (24)(25)(26)(27)(28). Studies have shown that Bcl-2 also plays a direct role in SCLC cell resistance to external apoptotic stimuli (8,9,29,30).…”

Section: Introductionmentioning

confidence: 99%

Influence of Bcl-2 Family Members on the Cellular Response of Small-Cell Lung Cancer Cell Lines to ABT-737

et al. 2007

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ABT-737 is a novel and potent Bcl-2 antagonist with singleagent activity against small-cell lung cancer (SCLC) cell lines. Here, we evaluated the contribution of Bcl-2 family members to the in vitro cellular response of several SCLC cell lines to ABT-737. Relatively higher levels of Bcl-2, Bcl-X L , Bim and Noxa, and lower levels of Mcl-1 characterized naïve SCLC cell lines that were sensitive to ABT-737. Conversely, a progressive decrease in the relative levels of Bcl-2 and Noxa and a progressive increase in Mcl-1 levels characterized the increased resistance of H146 cells following chronic exposure to ABT-737. Knockdown of Mcl-1 with small interfering RNA sensitized two resistant SCLC cell lines H196 and DMS114 to ABT-737 by enhancing the induction of apoptosis. Likewise, up-regulation of Noxa sensitized H196 cells to ABT-737. Combination treatment with DNA-damaging agents was extremely synergistic with ABT-737 and was associated with the down-regulation of Mcl-1 and the up-regulation of Noxa, Puma, and Bim in H196 cells. Thus, SCLC cells sensitive to ABT-737 expressed the target proteins Bcl-2 and Bcl-X L , whereas Mcl-1 and factors regulating Mcl-1 function seem to contribute to the overall resistance of SCLC cells to ABT-737. Overall, these observations provide further insight as to the mechanistic bases for ABT-737 efficacy in SCLC and will be helpful for profiling patients and aiding in the rational design of combination therapies. [Cancer Res 2007;67(3):1176-83]

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Expression of bcl-2 — protein in small cell lung cancer

Cited by 88 publications

References 15 publications

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

Mouse models for human lung cancer

Influence of Bcl-2 Family Members on the Cellular Response of Small-Cell Lung Cancer Cell Lines to ABT-737

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