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Sei-Hoon Yang,Mi-Seong Kim,양세훈,김민석 대한결핵및호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2
Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drugresistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear.Methods: Afatinib-mediated changes in the level of store-operated Ca2+ entry (SOCE)-related proteins and intracellular Ca2+ level in non–small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation.Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca2+ ATPase [SERCA2]) decreased after afatinib treatment in non–small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinibresistant non–small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR ). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca2+. Moreover, extracellular Ca2+ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca2+.Conclusion: Extracellular Ca2+ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca2+ is essential for determining anti-cancer drug efficacy.
원발성 폐암에서 p53 의 발현과 S - Phase Fraction 및 예후와의 관계
정은택(Eun Taik Jeong),양세훈(Sei Hoon Yang),김학렬(Hak Ryul Kim),정병학(Byung Hak Jeong),문형배(Hyung Bae Moon) 대한내과학회 1996 대한내과학회지 Vol.51 No.5
N/A Objectives: The p53 has been implicated in the control of cell cycle, DNA repair and programmed cell death especially, arrest of the cell cycle at G1 phase during DNA damage and repair. It is now widely accepted that mutations of p53 are among the most common changes that occur during malignant progression of diverse types of cancer. Based on this information, it seems reasonable to expect that there may be clinical prognostic significance of p53 changes in primary lung cancer. But its prognostic significance is controversial. Methods: To investigate the role of p53 mutation in lung cancer, we performed immunohistochemical stain of p53 on 57 resected primary non-small cell lung cancer specimens, thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between p53 expression, S-phase fraction and survival. Results: 1) p53 was detected in 70% of total 57 patients (according to histologic type, squamous carcinoma 74%, adenocarcinoma 69%, large Cell carcinoma 33%). p53 was positive in 71% of stage 1, 76% of stage 2, 63% of stage 3a, 67% of stage 3b (statistic insignificance). 2) Using the flow cytometric cell cycle analysis, mean S-phase fraction of p53(+) and (-) group are 21.3 (±7.4)%, 16.5 (±6.4)% (p<0.05) and mean G1 phase fraction of p53(+) and (-) group are 67.9 (±9.8)%, 75.4 (±10.5)% (p<0.05). 3) The median survival time of mt p53(+) and (-) group are 29.3 months, 39.5 months, but this could not reach the statistic significance. Conclusion: p53 was detected in 70% of primary non-small cell lung cancers. The S-phase fraction of p53(+) group was longer than (-) group (p<0.05). But, p53 could not be a prognostic factor.