• IMMUNE NETWORK
• /
• 제4권3호
• /
• pp.184-189
• /
• 2004

Background: Hu syndrome, a neurological disorder, is characterized by the remote effect of small cell lung cancer on the neural degeneration. The suspicious effectors for this disease are anti-Hu autoantibodies or Hu-related CD8+ T lymphocytes. Interestingly, the same effectors have been suggested to act against tumor growth and this phenomenon may represent natural tumor immunity. For these diagnostic and therapeutic reasons, the demand for antibodies against Hu protein is rapidly growing. Methods: Polyclonal and monoclonal antibodies were generated using recombinant HuR protein. Western blot analyses were performed to check the specificity of generated antibodies using various recombinant proteins and cell lysates. Extracellular stimuli for HuR expression had been searched and HuR-associated proteins were isolated from polysome lysates and then separated in a 2-dimensional gel. Results: Polyclonal and monoclonal antibodies against HuR protein were generated and these antibodies showed HuR specificity. Antibodies were also useful to detect and immunoprecipitate endogenous HuR protein in Jurkat and BJAB. This report also revealed that TNF-${\alpha}$ treatment in BJAB up-regulated HuR expression. Lastly, protein profile in HuR-associated mRNAprotein complexes was mapped by 2-dimensional gel electrophoresis. Conclusion: This study reported that new antibodies against HuR protein were successfully generated. Currently, project to develop a diagnostic kit is in process. Also, this report showed that TNF-${\alpha}$ up-regulated HuR expression in BJAB and protein profile associated with HuR protein was mapped.

• Journal of Microbiology and Biotechnology
• /
• 제25권5호
• /
• pp.648-657
• /
• 2015

H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권6호
• /
• pp.2465-2472
• /
• 2014

Background: The American Joint Committee on Cancer (AJCC) published a new staging system ($7^{th}$ edition) in 2009. In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with this new system. Materials and Methods: We retrospectively evaluated the files of 122 T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, treated at two centers between November 2003 and June 2012. Variables correlating with univariate survival at p<0.20 were later included in multivariate Cox regression analysis. Here, selection of relevant predictors of survival was carried out in accordance with the likelihood ratio formula with p<0.05 regarded as significant. Results: The median age was 60 and the median follow-up period was 17.4 months. Median overall survival (OS) was 18.3 months, the 1 year overall survival (OS) rate was 72%, and the 5 year OS rate was 28%. Statistically significant predictors of survival were (p<0.20) ECOG-PS (Eastern Cooperative Oncology Group Performance Status), age, T4 factor subgroup, stage and primary treatment in OS univariate analysis. On multivariate analysis for OS ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004) were significant. In the group receiving non-curative treatment, the median OS was 11.0 months, while it was 19.0 months in the definitive RT group and 26.6 months in the curative treatment group. There was a significant difference between the non-curative group and the groups which had definitive RT and curative operations (respectively p<0.001 and p=0.001) in terms of OS, but not between the groups which had definitive RT and curative operations. The median event free survival (EFS) rate was 9.9 months, with rates of 46% and 19% at 3 and 5 years, respectively. On univariate analysis of EFS rate with ECOG-PS, weight loss and staging, statistical significance was found only for thorax computerized tomography (CT)+18F-fluorodeoxy-glucose positron emission tomography-CT (PET-CT) use, stage and primary treatment (p<0.20). In multivariate analysis with EFS, only the primary treatment was statistically significant (p=0.001). In the group receiving non-curative treatment, the median EFS was 10.5 months while in the curative operation group it was 14.7 months. When all the primary treatment groups were taken into consideration, grade III/IV side effect swas observed in 57 patients (46.6%). Esophagitis was most prominent among those that received definitive radiotherapy. Conclusions: Independent prognostic factors among these 122 heterogeneous LA-NSCLC T4 N0-3 M0 patients were age at diagnosis, ECOG-PS, stage and primary treatment, the last also being a significant prognostic indicator of EFS. Our findings point to the importance of appropriate staging and a multidisciplinary approach with modern imaging methods in this patient group. In those with T4 lesions, treatment selection and the effective use of curative potential should be the most important goal of clinical care.

• Radiation Oncology Journal
• /
• 제27권3호
• /
• pp.163-168
• /
• 2009

목 적: 4개 이상의 다발성 전이성 뇌종양에서 정위적 방사선수술의 효용성에 대해서 검증하기 위하여 후향적으로 시행하였다. 대상 및 방법: 2004년 1월부터 2006년 12월까지 본원에서 4개 이상의 다발성 전이성 뇌종양으로 진단되어 정위적 방사선수술을 받은 29명의 환자와 전뇌 방사선조사를 받은 39명의 환자를 대상으로 후향적으로 분석하였다. 소세포 폐암과 흑색종으로 진단받은 환자는 제외하였고, 원발 병소는 정위적 방사선수술군에서는 폐암이 69.0%, 유방암이 13.8%였고, 전뇌 방사선조사군에서는 폐암이 64.1%, 유방암이 15.4%, 대장-직장암이 12.8%였다. 정위적 방사선수술은 감마나이프를 이용하여 시술하였고, 50% 등선량 곡선에 10~20 Gy를 1회 조사하였다. 전뇌 방사선조사는 30 Gy, 10회 분할조사 하였다. 치료 후 뇌 자기공명영상 또는 조영 증강 컴퓨터 단층촬영을 시행하여 두 군에서 치료 후 전이성 뇌종양이 진행되기까지 걸린 기간과 전체 생존율에 대해 비교 분석하였다. 결 과: 두 군의 추척 관찰 기간은 2개월에서 23개월이었고, 정위적 방사선수술군의 추적관찰 기간 중앙값은 5개월, 전뇌 방사선조사군의 경우에는 6개월이었다. 뇌전이 숫자의 중앙값이 정위적 방사선수술군에서는 6개, 전뇌 방사선조사군에서는 5개였다. 전이성 뇌종양의 진행을 억제하는 효과를 보여주는 두개내 무진행 생존율은 정위적 방사선수술군에서는 5.1개월, 전뇌 방사선조사군에서는 6.1개월이었고, 정위적 방사선수술을 시행한 환자들의 전체 생존율의 중앙값은 5.6개월, 전뇌 방사선조사를 시행한 환자들은 7.2개월이었다. 결 론: 4개 이상의 다발성 뇌 전이에 있어서 정위적 방사선수술은 전뇌 방사선조사에 비해 그 효용성이 낮으며 전뇌 방사선조사를 시행하는 것이 바람직할 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권11호
• /
• pp.4623-4627
• /
• 2014

Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권15호
• /
• pp.6445-6449
• /
• 2015

Background: NSCLC is a disease involving uncontrolled cell growth, which could result in metastases into nearby tissues beyond the lungs. Materials and Methods: The aim of the present study was to analyze the influence of epidermal growth factor receptor (EGFR) gene expression on metastasis and survival in NSCLC patients. The present case-control study included 100 cases of NSCLC patients and 100 age and sex matched controls. EGFR gene expression was analyzed by quantitative real time PCR using serum RNA. Association with NSCLC patient survival was analyzed by the Kaplan-Meier method. Results: We analyzed EGFR gene expression and observed mean increased gene expression of 13.5 fold in NSCLC patients. Values reflected overall survival of patients with a median of 15.8 months in the cases of <13 fold increased gene expression vs 6.7 months with >13 fold increased EGFR gene expression (p=0.005). Distant metastatic patients with <13 fold increased EGFR gene expression had 7.9 months of median survival time while>13 fold increased EGFR gene expression had only 5 months of median survival time (p=0.03). Non metastatic patients with <13 fold increased EGFR gene expression had 18 months of median survival time as compared to only 7.1 months with >13 fold increased expression. Conclusions: Higher cell free EGFR mRNA expression may play an important role in causing distant metastases and reducing overall survival of NSCLC patients in the Indian population.

• Journal of Chest Surgery
• /
• 제38권9호
• /
• pp.616-621
• /
• 2005

배경: 비소세포폐암에서 전폐절제술은 총 시행 술식 중 $20 {\~}35\%$를 차지하고 있으며 특히 우측 전폐 절제술의 경우 $10{\~}25\%$의 높은 사망률이 보고되고 있다. 이에 저자들은 전폐 절제술 후 일어날 수 있는 합병증의 양상을 알아보고 술식에 따른 합병증의 양상과 원인, 그리고 사망률에 미치는 원인을 알아보고자 하였다. 대상 및 방법: 1987년 8월부터 2002년 4월까지 원자력병원 흥부외과에서 비소세포폐암으로 전폐절제술을 시행 받은 환자들의 의무기록을 후향적으로 조사하였다. 결과: 총 386예의 전폐 절제술을 시행하였으며 좌측 238예, 우측 148예였으며 표준술식 207예, 확장술식 179예였다. 이중 115예의 합병증($28.5\%$)이 발생하였고, 12예에서 사망하여 $3.1\%$의 수술 사망률을 보였다. 이는 같은 기간에 시행된 폐엽 절제술의 수술사망률($2.1\%$)과 비슷하였다. 사망 예를 좌우로 구분해보면 좌측2예($0.5\%$), 우측 10예($2.6\%$)였다. 합병증을 증상별로 분류하면 애성 42예, 폐렴 및 급성호흡부전 17예(9예), 농흉 8예, 기관지-늑막루 5예(1예), 재수술을 요하는 출혈 5예(1예), 부정맥 5예, 폐 부종 1예(1예), 기타 25예이었다(괄호 안은 그 합병증에 의한 사망예). 수술사망에 영향을 미치는 요인으로는 먼저 확장 술식 6예($3.3\%$), 표준 술식 6예($2.9\%$)의 수술 사망을 보여 두 군간의 유의 있는 차이는 보이지 않았다(p=0.812). 그리고 60세 미만군(n=204)에서 2예($1.0\%$), 60세 이상 군(n=182)에서 10예($5.5\%$)가 사망하여 의미 있는 차이를 보였으며(p=0.016), 좌우를 비교했을 때 우측의 사망률이 5배정도 높았으며 통계적으로도 의미 있는 차이를 보였다(p=0.002). 호흡기계 합병증에 영향을 미치는 요인을 보면 60세 이상 군에서 20예($11.0\%$)와 60세 미만 군에서 7예($3.4\%$)로 60세 이상 군에서 의미 있는 차이를 보였으며(p=0.005), 좌측 전폐 절제술 군에서 10예($4.2\%$)와 우측 전폐 절제술 군에서 17예($11.5\%$)로 우측에서 의미 있는 차이를 보였다(p=0.008). 결론: 본 연구에서 전폐절제술의 수술사망과 호흡기계합병증은 60세 이상의 고령과 우측 전폐절제술 시 높아진다. 따라서 고 위험군의 수술 시에 수술대상환자의 선별과 수슬전 후 환자관리가 중요할 것으로 생각한다. 그러나 전폐절제술의 수술 사망률은 폐엽 절제술과 비슷하므로 폐암의 완전절제를 위해서는 전폐절제술은 안전하게 시행될 수 있는 술식으로 생각한다.

• Tuberculosis and Respiratory Diseases
• /
• 제58권2호
• /
• pp.135-141
• /
• 2005

배경 및 목적 : Multidrug Resistance-1 (MDR1) 유전자는 다약제내성에 관여하는 P-glycoprotein을 암호화한다. MDR1 유전자의 다형성은 P-glycoprotein의 발현과 기능의 차이를 일으켜 항암화학요법 반응에 영향을 미칠 수 있을 것이다. 저자들은 소세포폐암 환자에서 MDR1 유전자의 다형성과 일배체형에 따른 항암화학요법에 대한 반응을 조사하였다. 대상 및 방법 : 경북대학병원에서 병리적으로 소세포폐암으로 진단받고 etoposide-cisplatin 항암화학요법을 받은 54명을 대상으로 하였다. 전혈 5cc에서 DNA를 추출하고 PCR-RFLP법을 통해 MDR1 유전자 엑손 21의 2677G>T 다형성과, 엑손 26의 3435C>T 다형성을 조사하고 다형성과 일배체형에 따른 항암화학요법의 반응을 조사하였다. 결 과 : 2677G>T 유전자형에 따른 항암화학요법의 반응은 유의한 차이가 없었다. 3435 CC 유전자형은 3435 CT+TT 형에 비해 치료 반응율이 유의하게 높았다 (P = 0.025). 유전자형 분석 결과와 일치되게 2677G/3435C 일배체형은 다른 일배체형에 비해 치료반응을 보이는 경우가 유의하게 많았다 (P = 0.015). 결 론 : 소세포폐암에서 MDR1 유전자의 2677G>T와 3435C>T 다형성 및 이들 다형성의 일배체형은 etoposide-cisplatin 항암화학요법의 반응을 예측할 수 있는 지표로 사용될 수 있을 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권20호
• /
• pp.8911-8916
• /
• 2014

Background: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. Materials and Methods: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel ($20mg/m^2$) and cisplatin ($20mg/m^2$). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. Results: Median overall survival was $16{\pm}2.73$ (11.55-20.46) months for low expression vs $7{\pm}1.79$ months (7.92-16.08) months for high expression (p=0.039), while median local control was $13{\pm}2.31$ (8.48-17.5) months for low expression vs $6{\pm}0.85$ (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was $10{\pm}2.31$ (5.48-14.5) months for low expression vs $6{\pm}1.10$ (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. Conclusions: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5691-5696
• /
• 2014

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.