• Tuberculosis and Respiratory Diseases
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• v.77 no.3
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• pp.111-115
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• 2014

Lung cancer is the leading cause of cancer-related mortality worldwide, and more than 80% of cases are of non-small cell lung cancer. Although chemotherapy and molecularly targeted therapy may provide some benefit, there is a need for newer therapies for the treatment of patients with advanced NSCLC. Immunotherapy aims to augment the recognition of cancer as foreign, to stimulate immune responsiveness, and to relieve the inhibition of the immune response that allows tolerance to tumor survival and growth. Two immunotherapeutic approaches showing promise in NSCLC are immune checkpoint inhibition and cancer vaccination. Although currently immunotherapy does not have an established role in the treatment of NSCLC, these patients should be enrolled in formal clinical trials.

• BMB Reports
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• v.52 no.2
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• pp.113-118
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• 2019

The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.536-546
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• 1996

Background : The survival benefit of combination chemotherapy comparing supportive care to patients with advanced non-small cell lung cancel, especially stage IV non-small cell lung cancer patients with metastatic disease, is controversial. The main goal of this study was to evaluate the difference in survival between patients treated with chemotherapy and those who were not and to identify prognostic factors in the patients with stage IV non-small cell lung cancer. Methods : From January 1989 to December 1994, total 67 patients including 20 patients treated with combination chemotherapy and 47 patients treated with only supportive care in stage IV non-small cell lung cancer patients with metastatic disease were enrolled in this study. Combination chemotherapy consisted of etoposide $120mg/m^2$ iv for 3 days and cis-platin iv day 1 every 4 weeks. The treatment groups were retrospectively analyzed by age, sex, histologic cell type, weight loss, serum LDH level, ECOG performance status and major organ metastasis. Results : The significant prognostic factors influencing survival on this study were ECOG performance status and histologic subtype. Overall response rate by combination chemotherapy was 30%(complete response 0%, partial response 30%). Median survival of overall patients was 13.6 weeks and median survival of Chemotherapy group, 20 weeks, was significantly longer than that of supportive care group, 11.7 week(p<0.01). Median survival of responded in patients receiving chemotherapy, 45.5 weeks, was significantly longer than that of non-responder, 17.3 weeks(p<0.05). 1 year-survival rate of chemotherapy group and supportive care group was 15N and 8%, respectively. Nausea or vomiting, alopecia and anemia were seen in nearly most cases after this combination chemotherapy. Toxicities above grade 3 included neutropenia, anemia, thrombocytopenia, infection, fever, nausea, vomiting and alopecia. But this combination chemotherapy was relatively well tolerated except one treatment-related death from sepsis associated with severe granulocytopenia. Conclusion : These results suggest that systemic chemotherapy might be helpful to the stage IV non-small cell lung cancer patients with good performance status and large scale randomized prospective trials should be performed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.139-143
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• 2014

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.253-258
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• 2015

Background: Development of squamous cell cancer of head and neck (SCCHN) is associated with human papillomavirus (HPV) infection, which in turn is closely related with expression of $p16^{INK4A}$. Loss of $p16^{INK4A}$ expression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated $p16^{INK4A}$ as a prognostic marker of treatment response and survival in our SCCHN patients with laryngeal, hypopharyngeal or nasopharyngeal cancers. Materials and Methods: 131 patients diagnosed with SCCHN between January 2,2006 and July 17, 2010 were examined for $p16^{INK4A}$. The median age was 60 years (15-82 years). Fifty one patients were stage I-II and 80 were stage III-IV. Immunohistochemical expression of $p16^{INK4A}$ was analyzed in pretreatment paraffin-embedded tumor blocks. The influence of $p16^{INK4A}$ status on disease-free survival, and overall survival after treatment was evaluated. Results: $p16^{INK4A}$ positivity was found in 58 patients (44%). Tumor-positivity for$ p16^{INK4A}$ was correlated with improved disease free survival (70.1 months vs 59 months) and improved overall survival (2, 3 and 5-year values; 77% vs 72%, 70% vs 63% and, 63% vs 55%; respectively). On multivariate analysis, stage was determined as independent prognostic factor for disease-free survival. Conclusions: Stage was the major prognostic factor on treatment response and survival in our patients. $p16^{INK4A}$ status predicts better outcome in laryngeal, hypopharyngeal or nasopharyngeal cancer cases treated with surgery plus adjuvant radiochemotherapy as well as with definitive radiation therapy and/or chemotherapy.

• Journal of Chest Surgery
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• v.56 no.6
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• pp.403-411
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• 2023

Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). Conclusion: After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2873-2877
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• 2012

Objective: To determine STAT3, P-STAT3, and VEGF-C expression levels in small cell lung cancers (SCLCs), and discuss their role and clinical significance in SCLC development. Method: Immunohistochemical methods were applied to 128 cases of SCLC and 40 cases of adjacent normal tissue. Results: The expression levels of STAT3, P-STAT3, and VEGF-C were higher in SCLC than in normal tissue (P<0.05). Pairwise comparisons showed positive correlations with lymph node metastasis, clinical stage, and tumor size (P<0.05). The expression levels were also related with the overall survival rates. Conclusion: STAT3 and VEGF-C play important roles in the development of SCLC, and might be expected to become new targets for SCLC treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2971-2977
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• 2014

Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

• 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.

• Journal of Acupuncture Research
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• v.31 no.2
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• pp.87-98
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• 2014

Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.