Animal Models of Lung Cancer: Characterization and Use for Chemoprevention Research

ArticleinProgress in molecular biology and translational science 105:211-26 · January 2012with23 Reads
DOI: 10.1016/B978-0-12-394596-9.00007-X · Source: PubMed
Abstract
Of the potential sites of cancer development, cancer of the lung accounts for the highest number of cancer deaths each year in the United States (Jemal et al., 2010(1)). Based on its histopathological features, lung cancer is grouped into small cell lung cancer (SCLC; ∼20%) and non-SCLC (NSCLC; ∼80%), which is further divided into three subtypes: squamous cell carcinoma (∼30%), adenocarcinoma (∼50%), and large cell lung carcinoma. Every subtype of lung cancer has a relatively low 5-year survival rate that is attributed, in part, to the fact that they are routinely diagnosed at later histologic stages. Due to this alarming statistic, it is necessary to develop not only new and effective means of treatment but also of prevention. One of the promising approaches is chemoprevention which is the use of synthetic or natural agents to inhibit the initial development of or further progression of early lung lesions (Hong and Sporn, 1997). Many compounds have been identified as potentially effective chemopreventive agents using animal models. Most chemopreventive studies have been performed using mouse models which were developed to study lung adenomas or adenocarcinomas. More recently, models of squamous cell lung cancer and small cell lung cancer have also been developed. This review seeks to highlight mouse models which we helped to develop and presents the results of recent chemopreventive studies that we have performed in models of lung adenocarcinoma, squamous cell carcinoma, and small cell lung cancer.
    • "Chemoresistance and/or recurrence of cancer after chemotherapy are frequent events seen with treatment of this disease [2]. Thus, different research groups are now focused on finding novel drugs or anticancer compounds [3, 4] while others are developing methodologies for the evaluation of these drugs567. One of the current approaches for investigating novel antineoplastic or chemopreventive compounds is based on natural products research. "
    [Show abstract] [Hide abstract] ABSTRACT: Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control) decreased significantly ( P < 0.05 ); however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.
    Full-text · Article · May 2015
    • "However, the efficacy of ginseng on lung squamouse cell carcinoma has never been explored. In this study, we used a NTCU-induced lung SCC model, which has been used for years in our lab as a successful mouse lung SCC model, is organ specific and captures well-defined pathologic development from normal to bronchiolar hyperplasia, metaplasia, SCC in situ, and finally, SCC as seen in human (19, 21, 25). During the study, KWG did not cause any visible sign of toxicity or ill health, nor have any significant effect on body weight in mice. "
    [Show abstract] [Hide abstract] ABSTRACT: In this study, we investigated the chemopreventive activity of Korea white ginseng (KWG) in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to induce lung tumors in female Swiss mice, and KWG was given orally. KWG significantly reduced the percentage of lung SCCs from 26.5% in the control group to 9.1% in the KWG group, meantime, increased percentage of normal bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell lung tumor area from an average of 9.4% in control group to 1.5% in the KWG group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung tumor inhibitory effects of KWG were partly through inhibition of proliferation. HPLC/MS identified 10 ginsenosides from KWG extracts, Rb1 and Rd being most abundant as detected in mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by inhibition of AP-1, as demonstrated by in vitro study conducted on AP-1/ NFkB dependent mouse NSCLC cell lines. Western blotting of lung tissues also indicated that NTCU upregulated AP-1 through phosphorylation of JNK,which was down regulated by KWG in concurrence with its chemoprevention function.
    Article · Apr 2013
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    Article · Nov 2012
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