• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4797-4800
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• 2015

Background: This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Materials and Methods: Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. Conclusions: This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.

• Journal of Chest Surgery
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• v.30 no.6
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• pp.566-572
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• 1997

A major obstacles to evaluation of newly-developed treatment strategy for human lung cancer has been the lack of appropriate experimental animal models. We describe a new experimental model of orthotopically-developed non-small cell lung cancer in nude rat, involving inoculation of tumor cell suspension by thoracotomy. Over 40 direct implantation to the periphery of the lung has been performed to date, each requiring less than'1 hour for completion. This model has been used to perform a series of experiments to investigate whether the rat lung and surrounding structures trapped tumor cells with 2 different non-small cell lung cancer cell lines(NCI-H46O and NCI-H1299). Every animal showed development of tumor masses, which were loculated at the periphery of the lung karenchyma and identified also by radiography. After 3 weetu of the inoculation, tumor develop meat at the mediastinal strutures were identified. The life expectancies of the victims were different between the cell lines, but were approximately 5 weeks when NCI-H46O cell line was used. This new orthotopic lung cancer model may be facilitate future studies of the new therapeutics of localized non-small cell lung cancer .

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.761-766
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• 2012

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

• Journal of Chest Surgery
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• v.39 no.9 s.266
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• pp.668-673
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• 2006

Background: Docetaxel has been effectively used as an anti-cancer chemotherapuetic agent for various tumor treatments including lung cancer. However, the cell death induction mechanism(s) involved with docetaxel treatment in lung cancer cells has not been known yet. Material and Method: In the present study, the cellular and biochemical changes of NCI-H1703 cells (non-small cell lung cancer cell line, p53-mutant) after docetaxel treatment have been monitored by flow cytometry, fluorescence microscopy and western blot. Result: Docetaxel treatment significantly resulted in decrease of S phase as well as increase of G2 phase, and consequently evoked an increase of cell death in NCI-H1703 cells. After docetaxel exposure the activations of caspase-3 and caspase-9 were detected. Conclusion: Take together, it is suggested that the docetaxel induces NCI-H1703 cell death by caspase-9 and caspase-3 dependent mitochondrial apoptotic pathway.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.796-805
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• 1997

Background : It is clear that deregulation of cell cycle progression is a hallmark of neoplastic transformation and genes involved in the $G_1$/S transition of the cell cycle are especially frequent targets for mutations in human cancers, including lung cancer. p16 gene product, one of the G1 cell-cycle related proteins, that is recently identified plays an important role in the negative regulation of the the kinase activity of the cyclin dependent kinase (cdk) enzymes. Therefore p16 gene is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressor 1). No more oncogenes have been reported to be frequently related to multiple different malignancies than the alterations of p16 gene. Especially when it comes to non-small cell lung cancer, there was no expression of p16 in more than 70% of cell lines examined. And also it is speculated that p16 gene could exert a key role in the development of non-small cell lung cancer. This study was designed to evaluate whether p16 gene could be used as a candidate for gene therapy of non-small cell lung cancer. Methods : After the extraction of total RNA from normal fibroblast cell line and subsequent reverse transcriptase reaction and polymerase chain reaction, the amplified p16 cDNA was subcloned into eukaryotic expression plasmid vector, pRC-CMV. The constructed pRC-CMV-p16 was transfected into the NCI-H441 NSCLC cell line using lipofectin. The changes of G1 cell-cycle related proteins were investigated with Western blot analysis and immunoprecipitation after extraction of proteins from cell lysates and tumor suppressive effect was observed by clonogenic assay. Results : (1) p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 showed the formation of p16 : cdk 4 complex and decreased phosphorylated Rb protein, while control cell line did not. (2) Clonogenic assay demonstrated that the number of colony formation was markedly decreased in p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 than the control cell line. Conclusion : It is confirmed that the expression of p16 protein in p16 absent NSCLC cell line with the gene transfection leads to p16 : cdk4 complex formation, subsequent decrease of phosphorylated pRb protein and ultimately tumor suppressive effects. And also it provides the foundation for the application of p16 gene as a important candidate for the gene therapy of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6267-6271
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• 2013

Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1507-1513
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• 2015

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4917-4920
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• 2016

For advanced non-small-cell lung cancer (NSCLC) cases, a platinum-based regimen is the first-line chemotherapy treatment. The excision repair cross-complementing group 1 (ERCC1) plays an important role in DNA repair and has been related to resistance to platinum chemotherapy. This study aimed to investigate the effects of the ERCC1 (C118T) polymorphism on treatment response in 26 Thai advanced NSCLC patients receiving first line platinum-based chemotherapy during January to July 2015 at King Chulalongkorn Memorial Hospital (KCMH). DNA was extracted from peripheral blood lymphocytes and the single nucleotide polymorphism of ERCC1 was genotyped using a real-time PCR method with the TaqMan assay. The distribution of C/C, C/T and T/T genotypes was 57.7 %, 34.6 % and 7.7 %, respectively. The response rate to platinum-based chemotherapy in the wild type (C/C) of ERCC1 (C118T) was better than with the variant types (C/T and T/T) but the difference was not statistically significant (29.7% vs 9.1%, P=0.274). The results showed that a genetic polymorphism in ERCC1 might influence patient response to platinum-based chemotherapy. Further multicenter studies are now required to confirm the results of our study.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4485-4494
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• 2013

Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1281-1284
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• 2012

Background: Platinum-hased chemotherapy for advanced non-small cell lung cancer (NSCLC) is still considered the first choice, presenting a modest survival advantage. However, the patients eventually experience disease progression and require second-line therapy. While there are reliable predictors to identify patients receiving first-line chemotherapy, very little knowledge is available about the prognostic factors in patients who receive second-line treatments. The present study was therefore performed. Methods: We retrospectively reviewed 107 patients receiving second-line treatments from August 2002 to March 2012 in the Dicle University, School of Medicine, Department of Medical Oncology. Fourteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Result: The results of univariate analysis for overall survival (OS) were identified to have prognostic significance: performance status (PS), stage, response to first-line chemotherapy response to second-line chemotherapy and number of metastasis. PS, diabetes mellitus (DM), response to first-line chemotherapy and response to second-line chemotherapy were identified to have prognostic significance for progression-free survival (PFS). Multivariate analysis showed that PS, response to first-line chemotherapy and response to second-line chemotherapy were considered independent prognostic factors for OS. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. Conclusion: In conclusion, PS, response to first and second-line chemotherapy were identified as important prognostic factors for OS in advanced NSCLC patients who were undergoing second-line palliative treatment. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. It may be concluded that these findings may facilitate pretreatment prediction of survival and can be used for selecting patients for the correct choice of treatment.