• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4481-4485
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• 2012

Background: Chemotherapy induced leutropenia has been shown to be associated with improved treatment outcomes in selected solid tumors. We studied the association of chemotherapy induced leutropenia with treatment related outcomes in advanced non-small-cell lung cancer. Methods: This is a prospective analysis of patients receiving chemotherapy for advanced NSCLC at the Shandong Cancer Hospital from 2005-07.The chemotherapy included cisplatin $35mg/m^2$, IV on $d_{1,2}$ and vinorelbine $25mg/m^2$ IV on $d_{1,8}$ every 21 days. Patients were stratified into three groups (A) those experiencing grades 0 leucopenia, group (B) grades 1-2 and group (C) grades 3-4. The outcomes studied were response rate (RR), disease control rate (DCR), and time to progression (TTP). Results: 128 patients were studied. The RRs in groups A, B and C were 30.8%, 56.8% and 71.4%, respectively, p=0.010. The DCRs were 61.5%, 83.8% and 92.9%, respectively, p=0.009 and the median TTPs were 150 days (95%CI: 91-209), 189 days (95%CI: 181-197) and 207 days (95%CI: 172-242), p=0.009. The differences in RR and TTP were significant. In patients whose CIL kept on 10 days at least, the TTP was significantly prolonged, p=0.0213, and the same was the case for those experiencing grades 1-2 leucopenia and ECOG 0, p=0.0412. Conclusions: Occurrence of CIL correlated with RR and TTP in patients with advanced NSCLC receiving cisplatin and vinorelbine chemotherapy, especially in patients experiencing grades 1-2 leucopenia and ECOG 0, and the same for those with CIL persisting for 10 days at least. CIL could be a biological measure of drug activity and a marker of efficacy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9557-9565
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• 2014

MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6305-6309
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• 2013

Background: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. Materials and Methods: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. Results: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down-regulate the expression of MMP-3, Twist and Snail. Conclusions: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5753-5757
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• 2014

Background: The purpose of this study is to determine whether the IGF1R expression has a prognostic role in non-small cell lung cancer. Materials and Methods: Forty-seven patients histopathologically diagnosed with small cell lung cancer upon bronchoscopic biopsy or resection materials were included in the study. IGF1R expression was examined via immunohistochemical methods. In samples, >10% staining were assessed as positive and ${\leq}10%$ as negative. Information about demographic datas and treatments was obtained by retrospective searches of patient files. Results: IGF1R expression was determined as positive in 38 (80.9%) and as negative in 9 (19.1%) patients. There was no significant relation between IGF1R expression and histological sub-type, local invasion, lymph node and metastasis status (p=0.842, p=0.437, 0.064, 0.447, respectively). There was also no correlation with IGF1R expression and survival (p=0.141). Conclusions: There are conflicting results between IGF1R and its prognostic effects in the various studies. It has been claimed in some studies it is not related to prognosis as in our study, and in some studies it has been claimed that it is a good prognostic factor whereas in some studies it has been claimed as being a factor for worse prognosis. We think that IGF1R expression in non-small cell lung carcinoma patients deserves further analysis, because of its potential prognostic and predictive roles.

• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.8-14
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• 2014

Non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) sensitizing mutations has a distinct disease entity. Patients with this cancer have better prognosis, and frequently achieve long-term survival. EGFR-tyrosine kinase inhibitor (TKI) is the drug of choice for this cancer; but the disease inevitably progresses, after durable response. The tumor is a mixture of EGFR-TKI sensitive clones and resistant clones, regardless of their molecular mechanisms. EGFR-TKI sensitive clones are very susceptible to this drug, but rarely eradicated; so, withdrawal of the drug permits rapid regrowth of drug sensitive clones, possibly causing "disease flare." Re-administration or continuation of EGFR-TKI can effectively suppress the expansion of drug sensitive clones, even when the total tumor volume continuously increases. Chemotherapy can definitely prolong the survival of patients experiencing EGFR-TKI failure. Prospective clinical trials are warranted to compare efficacies of chemotherapeutic agents. A few retrospective studies suggested that a taxanebased regimen may be superior to others. Here, we reviewed therapeutic options and clinical evidence about this unique disease entity.

• Radiation Oncology Journal
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• v.35 no.1
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• pp.16-24
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• 2017

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.71 no.4
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• pp.259-265
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• 2011

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2355-2362
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• 2012

The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.

• Journal of Chest Surgery
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• v.52 no.4
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• pp.195-204
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• 2019

Lobectomy is considered the standard strategy for early-stage non-small cell lung cancer (NSCLC). However, sublobar resection for NSCLC has recently received increased attention. The objective of this study was to compare 5-year survival, recurrence-free survival, postoperative mortality, and postoperative morbidities in patients who received segmentectomy versus those who received lobectomy through a meta-analysis. Sixteen studies were included and the combined hazard ratios or odds ratios were calculated. The results revealed that the 5-year survival rate after segmentectomy was comparable to that of lobectomy for stage IA NSCLC. However, segmentectomy for stage I NSCLC had lower rates of postoperative mortality and morbidities than lobectomy.