• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.909-914
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• 2012

Background: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. Methods: We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250mg/day, gefitinib group) or with concomitant WBRT (40Gy/20f/4w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. Results: The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease control rate of BM was 71.1% in gefitinib-WBRT group and 42.2% in gefitinib group (P=0.006). The median time to progression of BM was 10.6 months in gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median overall survival(OS) of gefitinib-WBRT and gefitinib alone group was 23.40 months and 14.83 months, respectively (HR, 0.432, P=0.002). Conclusion: Gefitinib plus concomitant WBRT had higher response rate of BM and significant improvement in OS compared with gefitinib alone in treatment of BM from NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.657-662
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• 2014

Background: The epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors. Materials and Methods: One hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively. Results: There were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:$3.66{\pm}4.53$) in positron emission tomography-computed tomography of mutant LC was significantly lower than that ($8.26{\pm}6.11$) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148). Conclusions: Mutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.409-417
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• 2018

Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe hypertension and increased risks of foetal and maternal mortality. The aetiology of PE not completely understood; however, maternal nutrition and oxidative stress play important roles in the development of hypertension. The treatment options for PE are currently limited to anti-hypertensive drugs. Punicalagin, a polyphenol present in pomegranate juice, has a range of bioactive properties. The effects of supplementation with punicalagin on angiogenesis and oxidative stress in pregnant rats with induced hypertension were investigated. The pregnant rats were randomly divided into five experimental groups (n=12 per group). Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on days 14-19 of pregnancy. Punicalagin (25, 50 or 100 mg/kg) was given orally on days 14-21 of pregnancy. Punicalagin treatment at the tested doses significantly reduced diastolic, systolic, and mean arterial blood pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic balance by increasing the expression of vascular endothelial growth factor and downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1. Punicalagin, significantly increased the placental nitric oxide levels as compared to PE group. The increased levels of oxidative stress in rats with PE were markedly decreased by treatment with punicalagin. Punicalagin at the tested doses markedly (p<0.05) enhanced the placental antioxidant capacity in L-NAME-treated rats. The raised catalase activity observed following L-NAME induction was significantly (p<0.05) and restored to normal activity levels in punicalagin treatment. Further, 100 mg dose of punicalagin exhibited higher protective effects as compared to lower doses of 25 and 50 mg. This study shows that supplementation with punicalagin decreased blood pressure and oxidative stress and restored angiogenic balance in pregnant rats with induced PE.

• 대한두경부종양학회지
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• 제19권2호
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• pp.121-126
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• 2003

Objectives: The c-kit gene encodes a transmembrane receptor-type tyrosine kinase, which is known to have a significant role in the normal migration and development of germ cells and melanocytes. In the previous studies of c-kit gene, c-kit expressions showed only in adenoid cystic carcinomas, lymphoepithelioma-like carcinomas and myoepithelial carcinomas, but not in others and mutation was not found in any types of salivary carcinoma. We investigate the c-kit expression which may be useful to differentiating adenoid cystic carcinomas from others, and mutation of the gene which may not be exist nor the mechanism of c-kit activation in salivary carcinomas. Material and Methods: The archival tissue samples from 42 salivary carcinomas of major and minor salivary glands were studied for c-kit expression by immunohistochemistry and gene mutation by polymerase chain reaction amplification and single strand conformational polymorphism. Results: The c-kit expressions were noted in 22/24 adenoid cystic carcinomas, 7/9 mucoepidermoid carcinomas, 2/3 acinic cell carcinomas, 3/4 malignant mixed tumors, and one undifferentiated carcinoma. The mutation of c-kit gene was found in 3/24 adenoid cystic carcinomas, 3/8 mucoepidermoid carcinomas, one acinic cell carcinoma, and 2/4 malignant mixed tumors. Conclusion: c-kit protein overexpression is seen in a variety of salivary gland carcinomas, and the mutation of the gene may be the mechanism of c-kit activation in these neoplasms.

• Tuberculosis and Respiratory Diseases
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• 제72권1호
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• pp.15-23
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• 2012

Background: The survival of non-small cell lung cancer (NSCLC) patients with brain metastases is reported to be 3~6 months even with aggressive treatment. Some patients have very short survival after aggressive treatment and reliable prognostic scoring systems for patients with cancer have a strong correlation with outcome, often supporting decision making and treatment recommendations. Methods: A total of one hundred twenty two NSCLC patients with brain metastases who received gamma knife radiosurgery (GKRS) were analyzed. Survival analysis was calculated in all patients for thirteen available prognostic factors and four prognostic scoring systems: score index for radiosurgery (SIR), recursive partitioning analysis (RPA), graded prognostic assessment (GPA), and basic score for brain metastases (BSBM). Results: Age, Karnofsky performance status, largest brain lesion volume, systemic chemotherapy, primary tumor control, and medication of epidermal growth factor receptor tyrosine kinase inhibitor were statistically independent prognostic factors for survival. A multivariate model of SIR and RPA identified significant differences between each group of scores. We found that three-tiered indices such as SIR and RPA are more useful than four-tiered scoring systems (GPA and BSBM). Conclusion: There is little value of RPA class III (most unfavorable group) for the same results of 6-month and 1-year survival rate. Thus, SIR is the most useful index to sort out patients with poorer prognosis. Further prospective trials should be performed to develop a new molecular- and gene-based prognostic index model.

• Tuberculosis and Respiratory Diseases
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• 제58권5호
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• pp.473-479
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• 2005

연구 배경 : Gefitinib은 경구용 상피세포 성장인자 수용체 억제제로서 주로 동양인, 여성, 비흡연가, 선암 세포형의 폐암 환자에서 반응율이 좋은 것으로 되어 있으나 그 정확한 기전에 대해 밝혀진 것을 없다. 최근 몇몇 보고에 의하면 병기가 진행된 폐암 세포에서 PTEN 발현이 감소되어 있었으며, 또한 PTEN 발현이 감소된 폐암 세포주에서 EGFR tyrosine kinase inhibitor의 반응율이 감소되었음을 보고한 논문들이 있다. 이에 저자들은 본원에서 비소세포 폐암으로 진단받고 표준 항암화학요법에 실패한 이후 gefitinib으로 치료받은 환자군의 폐조직을 대상으로 PTEN의 발현 정도를 조사하였으며, PTEN의 발현 정도와 임상병기, 치료반응율과의 상관관계에 대해 분석하였다. 대상 및 방법 : 2002년 1월부터 2004년 8월까지 본원에 내원하여 원발성 비소세포성 폐암 진단 받은 후 표준 항암 화학요법에 실패하고 gefitinib을 복용한 환자 38명 중 2개월 이상을 투여 받아 반응 정도를 평가가 가능한 환자로서 폐조직에 대해 PTEN 면역조직화학 염색 및 정량화를 시행할 수 있었던 22명의 환자들에 대해 환자들의 약제 반응율과 PTEN의 발현양상과의 관계에 대해 후향적으로 조사하였다. 결 과 : 평균 연령은 62세, 남녀의 비는 6.3:1이었으며, 조직 병리학적 분류는 편평상피암 32%, 선암 59%, 대세포암 등 기타가 9%였다. 병기는 I 병기 1례, II 병기 1례, III 병기 9례, IV 병기가 11례였다. ECOG performance status는 grade 0-1이 9명, 2가 11명, 3이 2명이었다. 조직 병리학적 분류에 따른 PTEN 발현의 유의한 차이는 없었다. 또한 TNM 병기 상승에 따른 PTEN 발현율과는 서로 통계적으로 유의한 차이가 없었다. 그 러나, 약제 반응을 보인 군에서 약제 반응을 보이지 않은 군보다 PTEN 발현율이 통계적으로 유의하게 높게 나타났다(p=0.039). 결 론 : 표준 항암 화학 요법에 실패하고 gefitinib을 복용한 비소세포 폐암 환자의 약제 반응율과 종양 억제 단백질인 PTEN의 발현율과 서로 상관관계가 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7367-7369
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• 2013

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

• Tuberculosis and Respiratory Diseases
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• 제57권2호
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• pp.160-168
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• 2004

배 경 : 비소세포폐암에서 2차 항암화학요법에 대한 치료반응과 역할은 아직 정립되어 있지 못한 실정이다. 한편, 최근 개발된 ZD1839는 상피세포성장인자 수용체 억제제로서 악성 고형 종양, 특히 비소세포폐암에서 항종양효과를 보이는 것으로 알려져 있다. 저자들은 기존의 표준 항암화학요법에 실패한 진행성 비소세포폐암 환자들을 대상으로 ZD1839를 투여하여 그 반응 및 안전성을 평가하고자 하였다. 대상 및 방법 : 원자력병원에서 비소세포폐암으로 조직학적 진단을 받고 임상 병기 IIIB 이상인 환자들 중에서 1차 이상의 항암화학요법을 시행 받은 후 치료실패로 판정된 환자들을 대상으로 2002년 1월부터 2003년 9월까지 ZD1839를 투여 하였다. 투여 용량은 하루 250 mg이었고, 반응 및 부작용을 평가하기 위해 1개월 간격으로 흉부 방사선 검사 및 외래 추적 검사를 실시하였다. 이 환자들 중 반응 및 독성의 평가가 가능하였던, 1개월 이상 투여 받은 83명의 환자들을 대상으로 하였다. 환자들의 중앙 연령은 59(33-76)세였고, 임상 병기는 IIIB가 12명, IV가 71명이었으며, ECOG 전신수행상태는 0-1이 10명, 2는 42명, 3은 31명이었다. ZD1839 투여일수는 중앙값이 90일이었다. 결 과 : ZD1839 투여 후 부분 반응은 12명(14.5%), 불변은 31명(37.3%), 진행은 40명(48.2%)이었고, 전체 생존기간과 병의 진행까지 기간의 중앙값은 각각 9.2 개월과 3.1 개월이었다. ZD1839의 부작용으로는 피부 발진을 보인 환자가 25명(25.8%)으로 가장 많았으며, 구토 및 설사를 보인 환자가 15(15.5%), 비정상적 간효소수치 상승 및 혈소판 감소를 보인 환자가 각각 1명(1.03%)이었다. Performance status 0, 1인 전신 상태와 선암종을 가진 환자군에서 반응률 및 생존률이 통계적으로 유의한 증가를 보였다. 결 론 : 기존의 항암화학요법에 실패한 일부 진행성 비소세포폐암 환자들에서 ZD1839 투여는 비교적 높은 반응률을 보였으며 부작용은 비교적 경미하였다. 향후 보다 대규모의 연구 결과에 대한 추시가 필요할 것으로 생각된다.