• Tuberculosis and Respiratory Diseases
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• 제75권3호
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• pp.95-103
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• 2013

Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

• Journal of Yeungnam Medical Science
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• 제31권2호
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• pp.82-88
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• 2014

Background: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. Methods: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan $60mg/m^2$, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. Results: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. Conclusion: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

• 대한한방내과학회지
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• 제40권4호
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• pp.709-722
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• 2019

Objective: The purpose of this study was to report the effect of traditional Korean medicine (TKM) in alleviating the side effects of lung cancer patient undergoing immunotherapy. Method: A 43-year-old man, who was diagnosed with non-small cell lung cancer, received pembrolizumab treatments. The patient was treated with acupuncture and herbal medicine (Geoeoyangpye-tang) to control various uncomfortable symptoms. The degree of pain was measured by the numeric rating scale (NRS). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and the EORTC 13-item lung cancer-specific module (EORTC LC-13 questionnaire) were used to assess the change in the quality of life. Results: After the TKM treatment, the flank pain and arthralgia based on the NRS were significantly improved. Various uncomfortable symptoms such as fatigue, dyspnea, insomnia, and loss of appetite were also significantly improved, based on the EORTC QLQ-C30 and EORTC QLQ-LC13. The size of the primary tumor was decreased during treatment. The disease status was stable radiologically after two months from discharge.

• Journal of Chest Surgery
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• 제57권4호
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• pp.351-359
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• 2024

Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis. Conclusion: In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5819-5823
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• 2014

Purpose: To investigate the expression of hypoxia-inducible factor prolyl hydroxylase 3 (HIFPH3) in non-small cell lung cancer (NSCLC) and explore the correlation of HIFPH3 expression with lymph node metastasis and microvessel density (MVD). Materials and Methods: A total of 73 cases of NSCLC specimens, 24 cases of para-cancerous tissues, and 20 normal pulmonary tissues were collected for HIFPH3 and CD31 immunohistochmical (IHC) study. Microvessel density (MVD) of the NSCLC tissues was also determined based on the expression of CD31. Results: The expression of HIFPH3 in carcinoma tissue was statistically higher than para-cancerous and normal pulmonary tissues (${\chi}^2=48.806$, p<0.05). Compared withthe negative lymph node metastasis group, the lymph node metastasis group showed significantly higher HIFPH3 expression (${\chi}^2=6.300$, p<0.05). The strong HIFPH3+group displayed a significantly higher MVD than weak HIFPH3+ and HIFPH3- groups (p<0.05). No differences in positive HIFPH3 expression were noted regarding the tumor diameter, age, smoking status, gender of NSCLC patients, tumor size, histopathology, or differentiation. Conclusions: HIFPH3 expression in human NSCLC lesions is significantly higher than that in para-cancerous and normal lung tissues and is positively associated with lymph node metastasis and MVD.

• Genomics & Informatics
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• 제21권3호
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• pp.38.1-38.8
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• 2023

Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DEmiRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co- expression network. Next, four modules were selected based on the Z_summary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.

• Tuberculosis and Respiratory Diseases
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• 제43권1호
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• pp.54-62
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• 1996

연구배경: $^{99m}Tc$ MIBI은 지용성 양이온으로 심근혈류에 따라 심근에 섭취되는 방사성 동위원소로써 Thallium-201과 함께 성근 관류 스캔에 사용되어 왔다. Thallium-201이 암세포에도 섭취된다는 것은 이미 잘 알려져 있으며, 최근 $^{99m}Tc$ MIBI도 심근 세포이외에 폐와 종격동의 암세포에도 섭취된다는 보고가 있다. 저지들은 $^{99m}Tc$ MIBI가 폐암의 진단이나 암세포의 임파절의 전이 유무의 확인에 어느 정도 효과적으로 사용될 수 있는지 알아보고자 하며 동시에 폐렴이나 폐결핵 등과 같은 양성 폐질환과의 감별진단에도 효과적으로 사용될 수 있을지에 관하여 알아보았다. 방법: 대상은 영남대학교 의과대학 부속병원 내과에서 원발성 폐암으로 확진된 환자 34예와 조직 검사나 객담 검사를 통하여 양성 폐질환으로 진단된 10예의 환자를 대상으로 하였다. 대상환자 모두에서 $^{99m}Tc$ MIBI lung SPECT를 시행하였으며 비슷한 시기에 시행한 흉부 단층 촬영소견과 비교하였다. $^{99m}Tc$ MIBI SPECT는 먼저 특별한 전처치없이 $^{99m}Tc$ MIBI 740MBq(20mCi)을 정맥 주사하고, 한시간 후에 고해상력 조준기를 장착한 회전 감마카메라(Prism-2000, Picker)를 이용하여 360도 회전시키면서 45개의 투사 영상을 얻었다. 각 영상은 감마 카메라에 연결된 컴퓨터에 수록되었고 Metz filter을 이용하여 여과후 역투사를 시행하였고 횡단면, 시상(矢狀, saggital)면과 coronal view를 얻었다. 각 상에서 폐암 병소, 심장 그리고 정상적인 폐 부위의 방사능을 측정하여 정상 폐에 대한 폐 병소의 섭취율(lung lesion/normal area; HT/NL), 정상 폐에 대한 심장의 섭취율(heart/normal area; HT/NL) 및 폐병소에 대한 심장의 섭취율(heart/lung lesion; HT/TR) 등의 비를 구하여 각 단면상에서의 $^{99m}Tc$ MIBI 섭취율을 비교하였다. 곁과: 원발성 폐암 34예 오해서 암병소에 $^{99m}Tc$ MIBI의 섭취가 증가되었으며 종격동 및 기관지 주변 임파절 전이부위에도 섭취가 증가되었다. 원발성 폐암과 양성 폐질환에서 병소와 정상 폐간의 섭취율의 각각 $3.79{\pm}1.82$, $1.67{\pm}0.63$로 두군간에 유의한 차이가 있었다(p<0.001). 원발성 폐암의 경우 각 조직형에 따른 병소와 정상 폐간의 섭취율의 비는 편평 상피 세포암의 경우 $3.64{\pm}1.66$, 소세포암의 경우 $3.57{\pm}0.72$, 선암의 경우 $4.31{\pm}2.28$로써 각 조직형에 따른 통계적인 차이는 없었다. 결론: $^{99m}Tc$ MIBI lung SPECT는 원발성 폐암의 진단 및 임파절 전이의 유무 확인은 물론 양성 폐질환과의 감별진단에도 도움이 될 것으로 생각된다.

• Radiation Oncology Journal
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• 제12권2호
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• pp.165-173
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• 1994

목적 : 폐암환자에 있어서 뇌전이는 심각한 문제이며 또한 장기간 생존을 기대할 수가 없다. 종양억제효과를 증가시키는 동시에 만발 장애를 감소시켜 전체 치료기간을 가능한 단축시키기 위하여 비소세포성 폐암화자의 뇌전이에 대한 다분할 조사법인 급속분할조사법을 시행하였다. 재료 및 방법 : 1991년부터 1993년까지 비소세포성 폐암으로 확진되어 뇌전이가 발생한 24명의 환자에게 6시간 간격으로 2Gy씩 하루 2회로 총 48Gy를 전뇌에 조사하였다. 단일 병소는 전뇌에 40Gy 조사후 치료범위를 축소하여 8Gy를 추가하였다. 총 26예증 신경증상이 점차 진행되는 양상을 보인 2명은 방사선치료를 중단하였다. 결과 : 방사선치료 도중에 3명은 급성 방사선효과로 오심과 구토를 호소하였으나, 방사선량 증가로 인한 심각한 부작용은 없었다. 통상적인 치료방법인 2주에 30Gy를 조사한 경우(4.5개월)보다 48Gy의 급속분할조사에 의한 방사선치료법이 중간생존기간을 향상시켰으나(7개월)통계학적 의의는 없었다(p>0.05). 뇌에 국한된 전이 환자와 활동수행 상태가 양호한 군이 다발성 전이나 활동수행상태가 불량한 군보다 중간생존기간과 반년생존율에 있어서 유의한 증가를 나타내었다(p<0.01). 결론 : 뇌전이 단독소견과 양호한 활동수행능력 상태등 양호한 예후인자를 가진 환자는 생존기간 향상이 기대된다. 본 연구결과로 환자의 quaility of life를 고려하여 하후 1회 치료법과 2또는 3회치료법을 비교하는 다자간의 전향적인 연구가 필요하리라 생각된다.

• Archives of Pharmacal Research
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• 제29권6호
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• pp.497-502
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• 2006

A new natural C-benzylated chalcone, $2',4'-dihydroxy-3'-(2-hydroxybenzyl)-6{\c}-methoxychalcone$ (2), along with two other flavonoids, tiliroside and kaempferol 3-O-rutinoside, and an oxoaporphine alkaloid, lanuginosine were isolated from the aerial parts of Ellipeiopsis cherrevensis (Annonaceae). Two known polyoxygenated cyclohexene derivatives, ferrudiol and zeylenol, and a new analog, ellipeiopsol D, were also isolated. The chalcone 2 exhibited cytotoxic activity against human small-cell lung-cancer (NCl-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines with $IC_{50}$ values of 1.40, 5.31 and $13.92\;{\mu}g/mL$, respectively. This compound also showed antimalarial activity against Plasmodium falciparum with an $IC_{50}$ value of $7.1\;{\mu}g/mL$ as well as antimicrobacterial activity against Mycobacterium tuberculosis with a MIC of 25 mg/mL.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.354.2-354.2
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• 2002

Fifty of 3.4-diaryl-2(5H)-furanone derivatives were synthesized and evaluated for their cytotoxicity in a small panel of cancer cell lines. Eleven compounds in this series, were found to have significant cytotoxic activities with ED$_{50}$ values of less than 1 4{\mu}$M in most of the cell lines tested. Compound RTMSI, 3-(3.4, 5-trimethoxyphenyl)-4-(3-amino-4-methylamino)-2(5H)-furanone exhibited the most potent cytotoxic activity with ED$_{50}$ value of 0.003 4{\mu}$M and antitumor activity on BDF1 mice bearing Lewis lung carcinoma cells with inhibition ratio of 72 %.%.