폐선암조직에서 Neutral Ribonuclease의 분리와 성상에 관한 연구

김응수,고재경,지행옥 한양대학교 의과대학 1993 한양의대 학술지 Vol.13 No.1

Concentrations of nucleic acids and proteins were determined in adenocarcinoma tissue of the lung and were compared with those in the control lung tissue. Also studied were properties of the neutral RNase specific to the lung cancer to investigate the possible role of the RNase in process involved in carcinogenesis of adenocarcinoma of the lung. DNA and protein centents were unchanged, but RNA content was increased in adenocarcinoma tissue of the lung. Neutral RNase activity was unchanged in the cancer tissue, indicating that the RNase could not be used as a marker for the lung cancer. Proteins and neutral RNase in adenocarcinoma tissue of the lung were separated by a DEAE-cellulose column chromatography into 7peaks each, of which the peak I neutral RNase isozyme was not found in the control lung tissue. This indicated that the peak I neutral RNase was specific to the adenocarcinoma of the lung. The peak I neutral RNase isolated from the adenocarcinoma tissue of the lung did not hydrolyze single stranded (ss) polydeoxyribonucleotides and double stranded (ds) polynucleotides, but hydrolyzed ss polyribonucleotides. The enzyme was observed to be highly active toward poly C, poly U and RNA, indicating that the RNase appeared to be mixed type of secretory and nonseretory RNase. The peak I RNase was not active toward A-A and G-G linkages, but unusually highly active toward A-C and A-U linkages (4 to 6 fold as active as C-C linkage). These results indicated that the peak I neutral RNase isolated from the adenocarcinoma of the lung was (1)specific to the lung cancer. (2) mixed type of seretory and nonsecretory enzymes, (3) unusually highly active toward A-C and A-U linkages of ss polyribonucleotides and RNA, suggesting that the RNase might play roles in processes involved in carcinogenesis and suppression of cancer.

폐선암에 특이한 Ribonuclease Isozyme의 성상에 관한 연구

정종수,지행옥,고재경 한양대학교 의과대학 1995 한양의대 학술지 Vol.15 No.2

It has been reported that ribonucleases (RNases) are involed in carcinogenesis processes and play variable roles in metabolic events occuring cancer tissues. The present study was to investigate the mechanism of action of the RNase activated in and specific to adenocarcinoma of the lung. RNase isozyme V appeared to be specific to the adenocarcinoma was separated and purified by a DEAE cellulose column chromatography and high performance liquid chromatography (HPLC) and was analyzed for substrate specificity and mode of action. RNases in the adenocarcinoma tissue of the lung were separated by a DEAE cellulose column chromatography into 7 isozymes, of which four isozymes including RNase isozyme V activated and three isozymes specific to the cancer. The RNase isozyme V was further purified by 1200 folds by a HPLC. The purified RNase isozyme V was highly active toward poly ACU, AC, A and CU and less active toward RNA, poly A and U, indicating that the isozyme was secretory type of RNase. No activity was observed toward poly G, AG, GU, ACG and AGU. The substrate specificity for the RNase isozyme V in the lung cancer tissue appeared to be different from that in the control lung tissue, suggesting that the isozyme in the lung cancer tissue might be specific to the adenocarcinoma of the lung. Majority of hydrolytic products of poly C by the action of the RNase isozyme V from the lung cancer tissue was observed to be oligo-or poly-ribonucleotides with chain length between 5 and 20, indicating the isozyme as an endonuclease in nature. The RNase isozyme V isolated and purified from the adenocarcinoma tissue of the lung is activiated in and specific to the lung cancer, is the secretory type of RNase, is highly active toward poly A, AC, ACU and CU and is an endoribonclease in nature. The results suggest the possible role of the RNase isozyme V in the suppressive action of carcinogenesis processes in adenocarcinoma of the lung.

폐선암조직의 핵산분해 효소에 대한 연구

지행옥,유정훈,고재경 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.1

Activites of cid deoxyribonuclease(DNase), neutral ribonuclease(RNase) and RNase inhibitor were determined in adenocarcinoma tissue of the lung and were compare with those in control tissue of the lung. Also isolated and fractionated were RNases and RNase inhibitors by a DEAE-cellulose column chromatography from the adenocarcinoma tissue of the lung to find out the presence of the enzymes and the enzyme inhibitors specific to the lung cancer. Concentrations of DNA and protein were unchanged, but RNA content was significantly increased(47%) in adenocarcinoma tissue of the lung. Acid DNase activity was significantly increased(66%), but RNase and RNase ingibitor activities were unchanged. The positive rate of acid DNase ativity as a marker for the lung cancer was high, suggesting the acid DNase activity as a biochemical marker for the lung cancer. Neutral RNases in the adenocarcinoma tissue of the lung were separated by a DEAE-cellulose column chromatography into 7 isozymes, of which three(Ⅰ,Ⅵ and Ⅶ) isozymes were found to be specific to the lung cancer. RNase isozymes Ⅵ and Ⅶ were observed to be nonsecretory type of the enzyme and RNase isozyme I was found to be mixed type of the enzyme. The three RNase isozymes specific to the lung cancer exhibited relatively gigh RNase inhibitor activity. Observations that (1)RNase isozyme I was the isozyme specific to the lung cancer exhibiting the mixed type enzyme and that (2)RNase isozyme I exhibited high RNase ingibitor activity suggested that RNase isozyme I might play a role in carcinogenesis and suppression of the lung cancer.

Circulating Tumor Cell Number Is Associated with Primary Tumor Volume in Patients with Lung Adenocarcinoma

( Byung Ju Kang ),( Seung Won Ra ),( Kyusang Lee ),( Soyeoun Lim ),( So Hee Son ),( Jong-joon Ahn ),( Byung Chul Kim ) 대한결핵 및 호흡기학회 2020 Tuberculosis and Respiratory Diseases Vol.83 No.1

Background: Circulating tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma. Methods: We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients. Results: CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 cm³ and 64.8 cm³, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis). Conclusion: Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.

Solitary polypoid colonic metastasis from adenocarcinoma of the lung: A Case Report

강다현,김주옥,정성수,박희선,문재영,정재욱,박동일,이정은 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Introduction: Lung cancer usually spreads to lymph nodes, liver, brain, and bone. Colonic metastasis from lung cancer is very rare, most of which manifest as multiple lesions. Herein, we report a case of solitary colonic metastasis from primary lung adenocarcinoma, revealed by colonoscopy. Case: A 75-year-old female was diagnosed with primary lung adenocarcinoma with visceral pleura invasion and multiple lung metastases in August 2013. The patient have received the chemotherapy of pemetrexed/cisplatin for 4 cycles, and chest computed tomography (CT) followed up periodically, remained the stable disease status. 4 years later, the patient underwent colonoscopic examination, because the stool occult blood test for a routine check-up was positive. A polypoid lesion which had features of primary early colon cancer was revealed at cecum by colonoscopy, and polypectomy was performed. The pathological diagnosis of the polyp was compatible with metastatic adenocarcinoma originating from the lung, positive results for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7) with negative result for cytokeratin 20 (CK20) on immunohistochemistry (IHC) staining. Conclusion: We report an interesting case of solitary colonic metastasis from lung adenocarcinoma in polypoid form mimicking early colon cancer on gross examination. This case suggests that it is important to consider the metastatic lesion for the colon polyp in patients with history of primary lung cancer.

Down-regulation of Protease-activated Receptor 4 in Lung Adenocarcinoma is Associated with a More Aggressive Phenotype

Jiang, Ping,Yu, Guo-Yu,Zhang, Yong,Xiang, Yang,Hua, Hai-Rong,Bian, Li,Wang, Chun-Yan,Lee, Wen-Hui,Zhang, Yun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

The role of protease-activated receptors (PARs) in lung tumors is controversial. Although PAR4 is preferentially expressed in human lung tissues, its possible significance in lung cancer has not been defined. The studies reported herein used a combination of clinical observations and molecular methods. Surgically resected lung adenocarcinomas and associated adjacent normal lung tissues were collected and BEAS-2B and NCI-H157 cell lines were grown in tissue culture. PAR4 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and immunohistochemistry analysis. The results showed that PAR4 mRNA expression was generally decreased in lung adenocarcinoma tissues as compared with matched noncancerous tissues (67.7%) and was associated with poor differentiation (p=0.017) and metastasis (p=0.04). Western blotting and immunohistochemical analysis also showed that PAR4 protein levels were mostly decreased in lung adenocarcinoma tissues (61.3%), and were also associated with poor differentiation (p=0.035) and clinical stage (p=0.027). Moreover, PAR4 expression was decreased in NCI-H157 cells as compared with BEAS-2B cells. In conclusion, PAR4 expression is significantly decreased in lung adenocarcinoma, and down-regulation of PAR4 is associated with a more clinically aggressive phenotype. PAR4 may acts as a tumor suppressor in lung adenocarcinoma.

Loss of DBC2 Expression is an Early and Progressive Event in the Development of Lung Adenocarcinoma

Dong, Wei,Meng, Long,Shen, Hong-Chang,Du, Jia-Jun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Purpose: DBC2 (Deleted in Breast Cancer 2) has been indicated to be a tumor suppressor gene in many cancers including lung adenocarcinoma recently. In this study, we aimed to explore the expression status of DBC2 in different subtypes of lung adenocarcinoma (from pre-invasive to invasive lesions), and to determine if downregulation becomes more marked with pathological progression. Methods: We collected 172 tissue samples from different subtypes of lung adenocarcinoma and investigated the frequency of DBC2 loss by immunohistochemistry. Results: Our results indicated that DBC2 downregulation is a relatively frequent event in lung adenocarcinoma. Moreover, as the adenocarcinoma subtype turns to be more invasive, more downregulation occurred. Conclusion: We conclude that loss of DBC2 expression is an early and progressive event in the pathogenesis of lung adenocarcinoma. Positive DBC2 immunohistochemistry may become an indicator for early stage disease and better prognosis of lung adenocarcinomas.

Screening of Differentially Expressed Genes among Various TNM Stages of Lung Adenocarcinoma by Genomewide Gene Expression Profile Analysis

Liu, Ming,Pan, Hong,Zhang, Feng,Zhang, Yong-Biao,Zhang, Yang,Xia, Han,Zhu, Jing,Fu, Wei-Ling,Zhang, Xiao-Li Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: To further investigate the molecular basis of lung cancer development, we utilize a microarray to identify differentially expressed genes associated with various TNM stages of adenocarcinoma, a subtype with increasing incidence in recent years in China. Methods: A 35K oligo gene array, covering about 25,100 genes, was used to screen differentially expressed genes among 90 tumor samples of lung adenocarcinoma in various TNM stages. To verify the gene array data, three genes (Zimp7, GINS2 and NAG-1) were confirmed by real-time RT-PCR in a different set of samples from the gene array. Results: First, we obtained 640 differentially expressed genes in lung adenocarcinomas compared to the surrounding normal lung tissues. Then, from the 640 candidates we identified 10 differentially expressed genes among different TNM stages (Stage I, II and IIIA), of which Zimp7, GINS2 and NAG-1 genes were first reported to be present at a high level in lung adenocarcinoma. The results of qRT-PCR for the three genes were consistent with those from the gene array. Conclusions: We identified 10 candidate genes associated with different TNM stages in lung adenocarcinoma in the Chinese population, which should provide new insights into the molecular basis underlying the development of lung adenocarcinoma and may offer new targets for the diagnosis, therapy and prognosis prediction.

UBE2S promotes the proliferation and survival of human lung adenocarcinoma cells

( Zhi Liu ),( Lijun Xu ) 생화학분자생물학회 2018 BMB Reports Vol.51 No.12

Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitination process, is involved in development of various cancers. However, its role in lung adenocarcinoma, has not been well elucidated. In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes were regulated by UBE2S, and p53 signaling pathway may be critical, to the role of UBE2S in cancer development. Together, UBE2S could be a potential target for lung adenocarcinoma. [BMB Reports 2018; 51(12): 642-647]

P-88 Correlation between impaired lung function and PD-L1 expression in lung adenocarcinoma

조강원,강혜선,신아영,여창동,박찬권,김주상,김진우,김승준,이상학 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Purpose: The objective of the present study was to clarify whether the programmed death-ligand-1 (PD-L1) expression is associated with clinical characteristics including impaired lung function in lung adenocarcinoma. Patients and methods: This was a retrospective study performed between September 2016 and May 2017 in Seoul St. Mary’s Hospital, Bucheon St. Mary’s Hospital, Incheon St. Mary’s Hospital and Uijeongbu St. Mary’s Hospital, The Catholic University of Korea. A total of 140 patients with lung adenocarcinoma were analyzed for PD-L1 by immunohistochemistry using the clone 22C3 PharmDx kit and evaluated to determine the association between PD-L1 expression and pulmonary function test. Results: A PD-L1 tumor proportion score of at least ≥ 1% was seen in 60.0% of tumors. In a multivariate analysis, low diffusing capacity of the lung for carbon monoxide (DLCO) (Odds ration[OR]=5.829, 95% confidence intervals(CI)=1.337-25.42, P=0.019) and smoking pack-years (OR=1.051, 95% CI=1.016-1.088, P=0.005) were found to be associated with PD-L1 expression. However, chronic obstructive pulmonary disease or low forced expiratory volume 1 was not associated with PD-L1 expression. Conclusion: low DLCO was associated with PD-L1 expression in lung adenocarcinoma.