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
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
  • [Show abstract] [Hide abstract] ABSTRACT: Introduction: In a variety of cancers there is evidence that specific regimens can prevent or significantly delay the development of cancer. Thus, for breast cancer (ER+) use of SERMs or aromatase inhibitors can substantially decrease tumor incidence. For cervical cancer, HPV vaccination will inhibit long term cancer incidence. For colon cancer, the second greatest cancer killer, administration of aspirin and other NSAIDs decreases advanced colon adenomas in Phase II trials and epidemiologic data support their ability to prevent colon cancer. To date prevention trials in the area of lung cancer have shown minimal efficacy. Areas covered: The paper examines and discusses in greater detail certain promising agents which the authors have tested either preclinically and or in early phase clinical trials. These agents include RXR agonists, EGFr inhibitors, NSAIDs and Triterpenoids. Other agents including glucocorticoids, pioglitazone and iloprost are briefly mentioned. In addition, the paper presents various types of potential Phase II lung cancer prevention trials and describes their strengths and weaknesses. The potential use of various biomarkers as endpoints in trials e.g. histopathology, non-specific biomarkers (e.g., Ki67, cyclin D expression, apoptosis) and molecular biomarkers (e.g. specific phosphorylated proteins, gene expression etc.) is presented. Finally, we examine at least one approach, the use of aerosols, which may diminish the systemic toxicity associated with certain of these agents. Expert opinion: The manuscript presents: a) a number of promising agents which appear applicable to further Phase II prevention trials; b) approaches to defining potential preventive agents as well; c) approaches which might mitigate the side effects associated with potential agents most specifically the use of aerosols. Finally, we discuss biomarker studies both preclinical and clinical which might help support potential Phase II trials. The particular appeal to the preclinical studies is that they can be followed to a tumor endpoint. We hope that this will give the reader further background and allow one to appreciate the potential and some of the hurdles associated with lung cancer chemoprevention.
    Article · Nov 2012
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