• Radiation Oncology Journal
• /
• v.24 no.4
• /
• pp.237-242
• /
• 2006

$\underline{Purpose}$: We evaluated retrospectively the outcome of locally advanced non-small cell lung cancer patients treated with definitive radiotherapy to find out prognostic factros affecting survival. $\underline{Materials\;and\;Methods}$: 216 cases of stage IIIB non-small cell lung cancer were with treated radiotherapy at our Hospital between 1991 to 2002 and reviewed retrospectively. Cases were classified by mode of treatment and response to treatment. Patients showing complete response or partial response to treatment were included in the "response group", while those showing stable or progressive cancer were included in the "non-response group". $\underline{Results}$: 30 patients completed the planned radiotherapy treatments and 39 patients completed combined treatments or chemoradiotherapy. Median survival was 4.6 months for patients treated with radiotherapy and 9.9 months for those undergoing combined radiotherapy and chemotherapy. Survival rates for the first year were 13.3% with radiotherapy and 35.9% with chemoradiotherapy. In the second year, 3.3% of the radiotherapy patients survived and 20.5% of the patients receiving chemoradiotherapy survived. By the third year, 15.4% of the patients receiving the combined treatments survived. None of the patients treated with radiotherapy alone lived to the third year, however. Overall survival was significantly different between the radiotherapy patients and the combined chemoradiotherapy patients (p<0.001). In the response group, median survival was 7.2 months with radiotherapy and 16.5 months with combined therapy. In the non-response group, median survival was 4.4 months with radiotherapy and 6.7 months with combined treatments. Severe acute complications (grade 3) occurred in 2 cases using radiotherapy, and in 7 cases using combined therapy. $\underline{Conclusion}$: When the patients with stage IIIB non-small cell lung cancer received chemoradiotherapy, treatment response rate and overall survival was greater than with radiation alone.

• Korean Journal of Clinical Laboratory Science
• /
• v.49 no.4
• /
• pp.460-469
• /
• 2017

Heat shock proteins (HSPs) are induced as a self-defense mechanism of cells when exposed to various external stresses, such as high fever, infection, free radicals, and heavy metals. They affect the prognosis in the process of tumor formation. HSP is classified into four families: HSP27, HSP60, HSP90, and HSP100, depending on molecular weight. Heat shock protein 90 (HSP90), a molecular chaperone, plays an important role in the cellular protection against various stressful stimuli and in the regulation of cell cycle progression and apoptosis. In the present study, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC), and the correlation of their expression levels with clinicopathologic factors and patient survival rates. The result of this study can be summarized as follows; $HSP90{\alpha}$ showed higher expression in patients with no lymphovascular invasion (p=0.014). $HSP90{\beta}$ showed a higher expression of squamous cell carcinoma (p=0.003), and an over expression of glucose-related protein (GRP94) was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed a significant association with the survival status in patients with NSCLC. This study also indicates that $HSP90{\alpha}$ might contribute more to the carcinogenesis of NSCLC than $HSP90{\beta}$, and GRP94 and isoform selectivity should be considered when HSP90 inhibitors are studied or utilized in the treatment of NSCLC.

• Journal of Chest Surgery
• /
• v.40 no.8
• /
• pp.529-535
• /
• 2007

Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.

• Tuberculosis and Respiratory Diseases
• /
• v.64 no.1
• /
• pp.15-21
• /
• 2008

Background: The melanoma antigen-encoding (MAGE) genes are known to be expressed in various cancer cells, including non-small cell lung cancer (NSCLC), and are silent in all normal tissues except for the testis. In patients with peripheral NSCLC, bronchial washing fluid can be used to detect the MAGE genes, suggesting a diagnosis of lung cancer. In order to evaluate the diagnostic utility of the MAGE test in patients with peripheral NSCLC, bronchial washing fluid was investigated in patients with peripheral pulmonary nodules, which were invisible as detected by bronchoscopy. Methods: Bronchial washing fluid from 37 patients was used for cytological examinations and MAGE gene detection, using RT-nested-PCR of common A1-A6 mRNA. Results were compared to a final diagnosis of patients as confirmed by pathology. Results: Among the 37 subjects, NSCLC was diagnosed in 21 patients, and benign pulmonary diseases were diagnosed in 16 patients. MAGE mRNA was detected in 10 of 21 (47.6%) NSCLC patients, while conventional cytology examinations were positive for MAGE expression in 2 of 21 (9.5%) cases. MAGE expression was observed in 4 of 16 (25%) benign pulmonary disease patients. Conclusion: The MAGE test of bronchial washing fluid can be used as a sensitive predictor of peripheral NSCLC patients.

• Korean Journal of Clinical Laboratory Science
• /
• v.55 no.1
• /
• pp.16-28
• /
• 2023

Lung adenocarcinoma accounts for about 40% of all lung cancers. With the recent development of gene profiling technology, studies on mutations in oncogenes and tumor suppressor genes, which are important for the development and growth of tumors, have been actively conducted. Companion diagnosis using next-generation sequencing helps improve survival with targeted therapy. In this study, formalin-fixed paraffin-embedded tissues of non-small cell lung cancer patients were subjected to hematoxylin and eosin staining for detecting genetic mutations that induce lung adenocarcinoma in Koreans. Immunohistochemical staining was also performed to accurately classify lung adenocarcinoma tissues. Based on the results, next-generation sequencing was applied to analyze the types and patterns of genetic mutations, and the association with smoking was established as the most representative cause of lung cancer. Results of next-generation sequencing analysis confirmed the single nucleotide variations, copy number variations, and gene rearrangements. In order to validate the reliability of next-generation sequencing, we additionally performed the existing genetic testing methods (polymerase chain reaction-epidermal growth factor receptor, immunohistochemistry-anaplastic lymphoma kinase (D5F3), and fluorescence in situ hybridiation-receptor tyrosine kinase 1 tests) to confirm the concordance rates with the next-generation sequencing test results. This study demonstrates that next-generation sequencing of lung adenocarcinoma patients simultaneously identifies mutation.

• Radiation Oncology Journal
• /
• v.29 no.1
• /
• pp.28-35
• /
• 2011

Purpose: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. Materials and Methods: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. Results: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage 1, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 $Gy_{10}$. Among 20 lesions that received above 100 $Gy_{10}$, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. Conclusion: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 $Gy_{10}$ for peripheral T1 stage patients with NSCLC is recommended.

• Radiation Oncology Journal
• /
• v.22 no.1
• /
• pp.1-10
• /
• 2004

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

• Korean Journal of Clinical Laboratory Science
• /
• v.51 no.2
• /
• pp.221-234
• /
• 2019

Cancer is genetically, metabolically and infectiously induced life threatening disorder showing aggressive growing pattern with invasive tendency. In order to prevent this global menace from jeopardizing human life, enormous studies on carcinogenesis and treatment for chemotherapy resistance have been intensively researched. Hinokitiol (${\beta}$-thujaplicin) extracted from heart wood of cupressaceous is a well-known bioactive compound demonstrating anti-inflammation, anti-bacteria and anti-cancer effects on several cancer types via apoptosis and autophagy. This study proposed that hinokitiol activates transcription factor EB (TFEB) nuclear translocation for autophagy and lysosomal biogenesis regardless of nutrient condition in cancer cells. Mitophagy and ${\beta}$-catenin translocation into the nucleus under treatment of hinokitiol on non-small cell lung cancer (NSCLC) cells and HeLa cells were investigated. Hinokitiol exerted cytotoxicity on HeLa and HCC827 cells; moreover, artificially induced autophagy by overexpression of TFEB granted imperfect sustainability onto HeLa cells. Taken together, hinokitiol is the prominent autophagy inducer and activator of TFEB nuclear translocation. Alternative cancer therapy via autophagy is pros and cons since the autophagy in cancer cells is related to prevention and survival mechanism depending on nutrition. To avoid paradox of autophagy in cancer therapy, fine-tuned regulation and application of hinokitiol in due course for successful suppressing cancer cells are recommended.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.3
• /
• pp.339-346
• /
• 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.

• Journal of Chest Surgery
• /
• v.39 no.5 s.262
• /
• pp.376-381
• /
• 2006

Background: The Ki-67 protein is a biomarker associated with cell proliferation and a valuable negative prognostic factor in non-small cell lung cancer. We investigated the Ki-67 protein expression in resected non-small cell lung cancer to evaluate the impact on clinicopathological characteristics and postoperative prognosis. Material and Method: Using monoclonal antibody Ki-67, we immunohistochemically examined 38 surgically resected non-small ceil lung cancers to determine Ki-67 Labeling Index (LI). We analysed the differences of clinicopathological characteristics and postoperative recurrence and survival between High Ki-67 Group $(LI{\ge}20%)$ and Low Ki-67 Group (LI<20%). Result: The Ki-67 LIs were heterogenous and a mean values was $20.0{\pm}20.05%$. There were no significant differences in age, sex, smoking, TNM stage, and vascular invasion between High Ki-67 Group and Low Ki-67 Group. A High Ki-67 Group was significantly associated with squamous cell type, poor differentiation, and lymphatic invasion $(p{\le}0.05)$. High Ki-67 Group showed a trend of lower survival (median 47.2 vs. 90.5 months, p=0.312) and lower disease-free survival (median 18.2 vs. 72.3 months, p=0.327) than Low Ki-67 Group. Conclusion: These results indicate that increased Ki-67 protein expression may be a negative prognostic factor and showed a trend of shortened survival and disease-free survival. To evaluate the pivotal role of Ki-67 protein expression, a long-term follow-up and further study are required.