• Title/Summary/Keyword: Non-small-cell lung

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Prognostic Value of Phosphorylated mTOR/RPS6KB1 in Non-small Cell Lung Cancer

  • Zhang, Yong;Ni, Huan-Juan;Cheng, De-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3725-3728
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    • 2013
  • Background: The mammalian target of rapamycin (mTOR) /RPS6KB1 activation has recently been implicated in tumour development, but its role in lung cancer remains unclear. The aim of this study was to explore the role of mTOR/RPS6KB1 signaling pathway in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemistry was performed to assess the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and its downstream ribosomal phosphorylated RPS6KB1 (p-RPS6KB1) in NSCLC patients. We also analyzed p-mTOR/p-RPS6KB1 protein expression in 45 fresh NSCLC tissues using Western blotting. Results: The expression level of p-mTOR and p-RPS6KB1 was significantly higher in NSCLC tumor specimens than that in adjacent noncancerous normal lung tissues (P<0.01). p-mTOR expression correlated with p-RPS6KB1. Furthermore, high expression level of p-mTOR or p-RPS6KB1 in NSCLC was associated with a shorter overall survival (both P<0.01). Multivariate analysis indicated high level of p-mTOR expression was an independent prognostic factor (HR=2.642, 95%CI 1.157-4.904, p=0.002). Conclusions: p-mTOR and p-RPS6KB1 could be useful prognostic markers for NSCLC.

Kanahia Laniflora Methanolic Extract Suppressed Proliferation of Human Non-Small Cell Lung Cancer A549 Cells

  • Alfaif, Mohammad Yahya
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4755-4759
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    • 2016
  • Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells. Results: The extract showed strong cytotoxic activity against A549 cells with an $IC_{50}$ value of $0.13{\mu}g/ml$ compared to $0.21{\mu}g/ml$ for doxorubicin. The extract also significantly increased the percentage of apoptotic cells to 49.7% as compared to 1.4% and 47.4% for control and doxorubicin respectively. Conclusion: These results showed, for the first time, that a methanolic extract of Kanahia laniflora leaves can inhibit the proliferation of human non-small cell lung cancer cells (A549). Further attention to its potential as a new effective anticancer agent is warranted.

Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

  • Zheng, De-Jie;Yu, Guo-Hua;Gao, Jian-Feng;Gu, Jun-Dong
    • 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.

Poor Prognostic Factors in Surgically Resected Stage I Non-small Cell Lung Cancer: Histopathologic and Immunohistochemical Analysis

  • Cho, Suk-Ki;Park, Tae-In;Lee, Eung-Bae;Son, Shin-Ah
    • Journal of Chest Surgery
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    • v.45 no.2
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    • pp.101-109
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    • 2012
  • Background: A better understanding of the histopathology and molecular biology of lung cancer might improve our capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I non-small cell lung cancer. Materials and Methods: One hundred ten patients at the Kyungpook National University Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. Results: Univariate analysis showed that the T stage, differentiation, visceral pleural invasion, and survivin expression were significantly associated with recurrence. Multivariate analysis demonstrated that differentiation and survivin overexpression emerged as independent prognostic factors of recurrence. Conclusion: In resected stage I non-small cell lung cancer, poor differentiation and survivin overexpression have been identified as independent predictors of poor disease-free survival.

Antimetastatic effect of fucoidan against non-small cell lung cancer by suppressing non-receptor tyrosine kinase and extracellular signal-related kinase pathway

  • Nareenath Muneerungsee;Supita Tanasawet;Wanida Sukketsiri
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.844-854
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    • 2023
  • BACKGROUND/OBJECTIVES: Fucoidan, a polysaccharide content in brown algae, has been reported to inhibit the growth of cancer cells. The present study aimed to investigate the suppression effects of fucoidan on A549 non-small cell lung cancer cells migration. MATERIALS/METHODS: The anti-migratory activity of fucoidan in A549 cells was examined by wound healing assay and phalloidin-rhodamine staining in response to fucoidan (0-100 ㎍/mL) treatment for 48 h. Western blot analysis was performed to clarify the protein expressions relevant to migratory activity. RESULTS: Fucoidan (25-100 ㎍/mL) significantly suppressed A549 cells migration together with reduced the intensity of phalloidin-rhodamine which detect filopodia and lamellipodia protrusions at 48 h of treatment. The protein expression indicated that fucoidan significantly suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-related kinase (ERK). In addition, the phosphorylation of p38 in A549 cells was found to be increased. CONCLUSIONS: Our data conclude that fucoidan exhibits anti-migratory activities against lung cancer A549 cells mediated by inhibiting ERK1/2 and FAK-Src pathway.

Alternative drug therapies are superior to epidermal growth factor receptor -targeted chemotherapeutic drug responses in non-small cell lung cancer

  • Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.3 no.2
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    • pp.10.1-10.8
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    • 2013
  • Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

Cell Death Induction Mechanism of Non-small Cell Lung Cancer Cell Line, NCI-H1703 by Docetaxel (Docetaxel에 의한 비소세포폐암세포주 NCI-H1703의 세포사멸 유도기전)

  • Ha Hyeon-Cheol;Song Seung-Hwan;Park Chin-Su;Kim Jong-Won;Kim Yeong-Dae
    • 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.

Druggable Targets of Squamous Cell Lung Cancer

  • Kim, Cheol Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.6
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    • pp.231-235
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    • 2013
  • Knowledge of molecular pathogenesis of non-small cell lung cancer has increased remarkably and changed the principles of treatment, especially during the past decade. These advancements have been limited mainly to adenocarcinoma of the lung. Recently, genetic alterations in squamous cell lung cancer (SQCLC) have been detailed and positive results of clinical trials using agents targeting these changes have indicated the potential for improved treatment outcomes for SQCLC.

Expression of ERCC1, MSH2 and PARP1 in Non-small Cell Lung Cancer and Prognostic Value in Patients Treated with Platinum-based Chemotherapy

  • Xie, Ke-Jie;He, Hong-Er;Sun, Ai-Jing;Liu, Xi-Bo;Sun, Li-Ping;Dong, Xue-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2591-2596
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    • 2014
  • Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation group l (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lung cancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancer paraffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used to determine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled 111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%, 36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with the survival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negative cancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positive alone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter than those with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1 negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.

The Relationship Between Loss of Blood Group Antigen A in Cancer Tissue and Survival Time in the Antigen A Positive Non-Small Cell Lung Cancer (A 항원 양성 원발성 비소세포폐암 조직에서의 A 항원 소실과 생존기간과의 관계)

  • Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.3
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    • pp.339-346
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    • 2000
  • Background : The moot important prognostic factor in non-small cell lung cancer is the TNM stage. Even after complete resection in early non-small cell lung cancer, the five-year survival rate is still low. However, new prognostic factors, including molecular biologic factors, have recently been found to guide the treatment of patients with non-small cell lung cancer. We evaluated the prognostic value of the loss of blood-group antigen A in tumor tissue, which has been implicated as an important prognostic factor for overall survival and the timing of the disease progression. Methods : The loss of blood-group antigen A was assessed immunohistochemically in paraffin-embedded tumor samples from 26 patients with blood types A or AB, who had undergone curative surgery. Monoclonal antibody was used to detect the blood group antigen A expression. Results : Fifteen patients (58%) expressed antigen A in their tumor tissue, whereas 11 patients (42%) did not show antigen A. The median survival time of the blood A antigen positive group was 11 months, while the median survival time of the blood A antigen negative group was 18 months. The difference in survival between the two groups was not statistically significant. Conclusion : The loss of blood-group antigen A in tumor tissue was not found to be a significant prognostic factor in patients with non-small cell lung cancer. This study needs to be extended for further evaluation.

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