• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1457-1461
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• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• 생명과학회지
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• 제20권1호
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• pp.103-112
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• 2010

페메트렉시드(pemetrexed, $alimta^{(R)}$)는 중피종(mesothelioma)과 비소세포폐암 (non-small cell lung cancer)을 비롯한 다양한 암종에서 엽산(folate) 대사과정에 관여하는 대사물질의 활성을 억제하여 항암효능을 나타낸다. 다중표적 항암제 (multitargeted antifolate)인 pemetrexed는 엽산의 세포내 주요 이동통로인 reduced folate carrier(RFC)를 통해 세포 내로 유입된 후 folylpolyglutamate synthetase (FPGS)에 의해 폴리글루타민산염(polyglutamate) 유도체로 활성되고 thymidylate synthase (TS)와 dihydrofolate reductase (DHFR)를 표적하는 것으로 알려져 있다. 조직형이 서로 다른 비소세포폐암 세포주를 선정하여 pemetrexed의 대사과정에 관여하는 유전자들의 단일염기서열 다형성을 조사하고, mRNA와 단백질의 발현 정도를 비교하여 pemetrexed의 세포독성 효과와의 상관성을 분석하였다. 4개의 비소세포폐암 세포주인 A549, PC14, HCC-1588과 H226에서 RFC, FPGS, TS와 DHFR의 유전형을 조사하였다. Pemetrexed의 약물의 감수성을 알아보기 위해 real-time PCR과 Western blot 방법으로 mRNA 발현과 단백질 발현 정도를 비교하였고, SRB 법으로 약물에 대한 세포독성 효과를 측정했다. PC14 세포주와 H226 세포주에서는 약물처리 전 RFC와 FPGS의 mRNA 발현이 높은 것으로 나타났고, $IC_{50}$값이 각각 $0.08{\pm}0.01\;uM$과 $0.07{\pm}0.01\;uM$로 pemetrexed에 대한 감수성이 높은 것을 알 수 있었다. A549 세포주에서 TS의 유전형이 2R/2R일 때 mRNA발현이 증가하고 pemetrexed의 약물 저항성과 관련이 있었다. 반면, TS의 유전형이 3R/3R로 나타난 H226에서는 mRNA 발현이 낮은 것을 알 수 있었지만 pemetrexed의 높은 감수성과 관련이 있었다. 세포주 모두에서 pemetrexed 약물처리 후 DHFR의 mRNA 발현은 약물처리 전보다 낮아지는 경향을 보였지만 단백질 발현은 오히려 증가하는 상반된 결과를 보였다. 또한 DHFR 프로모터에 위치한 -1726C>T, -1188A>C SNP는 서로 연쇄 불평형 상태(linkage disequilibrium, LD)에 있었다. 연구결과에서 pemetrexed의 세포독성 효과는 약물 대사과정에 관여하는 여러 분자들의 유전형과 발현 정도에 의해 결정되는 것을 알 수 있었고, 다양한 분석결과를 토대로 항암효능을 평가하는 것이 필요하다고 생각된다.

• Radiation Oncology Journal
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• 제7권2호
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• pp.247-257
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• 1989

절제 불가능한 원발성 간암은 여러 가지 다양한 치료법의 시도에도 불구하고 그 예후는 극히 불량하다. 이에 본 저자들은 온열요법에 대한 축적된 경험을 바탕으로 1988년 4월부터 7월까지 본과에 내원한 30명 의 절제 불가능한 원발성 간암 환자들에 대하여 온열 및 방사선 병용요법을 시행하였다. 방사선치료는 일일 조사량 180 cGy씩 3. 5주에 3060 cGy를 조사하였고 온열요법은 8 MHz 유전형온열치료기 (Thermotron RF-8, Cancermia)를 사용하여 주 2회씩 총 5회 시행하되 순서는 방사선 치료를 먼저 한 후 30분 이내에 온열요법이 30~60분간 시행되었다. 그 결과 부분반응이 12예에서 관찰되었고(40%), 증상의 호전이 28예 중 22예에서 관찰되었다(78.6%), 종양의 반응을 예측할 수 있는 인자로서는 형태학적 유형이 가장 유의하게 나타났다(single massive: 10/14, 71.4%, diffuse infiltrative: 2/10, 20% : multinodular : 0/6, 0%, p<0.005). 치료로 인한 심각한 부작용은 관찰되지 않았다. 1년 생존율은 34%였고 정중앙 생존기 간은 6.5개월이었다. 부분반응을 보인 환자군의 생존율 및 정중앙 생존 기간은 각각 50%, 11개월로서 반응을 보이지 않은 환자군의 22%, 5개월과 비교해 볼 때 정중앙 생존기간의 차이가 통계적으로 유의하였다.(p<0.05). 결론적으로 온열 및 방사선 병용요법은 절제 불가능한 원발성 간암의 증상호전 및 국소적 치료에 효과가 있는 것으로 생각되며 생존율 및 부작용 등에 관해서는 앞으로 연구가 더 진행되어야 할 것으로 생각된다.

• BMB Reports
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• 제49권6호
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• pp.325-330
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• 2016

T-complex protein 10A homolog 2 (TCP10L) was previously demonstrated to be a potential tumor suppressor in human hepatocellular carcinoma (HCC). However, little is known about the molecular mechanism. MAX dimerization protein 1 (MAD1) is a key transcription suppressor that is involved in regulating cell cycle progression and Myc-mediated cell transformation. In this study, we identified MAD1 as a novel TCP10L-interacting protein. The interaction depends on the leucine zipper domain of both TCP10L and MAD1. TCP10L, but not the interaction-deficient TCP10L mutant, synergizes with MAD1 in transcriptional repression, cell cycle G1 arrest and cell growth suppression. Mechanistic exploration further revealed that TCP10L is able to stabilize intracellular MAD1 protein level. Consistently, the MAD1-interaction-deficient TCP10L mutant exerts no effect on stabilizing the MAD1 protein. Taken together, our results strongly indicate that TCP10L stabilizes MAD1 protein level through direct interaction, and they cooperatively regulate cell cycle progression.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.999-1003
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• 2014

Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.

• 대한방사선치료학회지
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• 제26권1호
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• pp.1-9
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• 2014

목 적 : 간암 치료 시 호흡으로 인한 움직임을 최소화하기 위해 환자 체위 변화에서 종양의 움직임과 용적 변화를 분석하고자 하였다. 대상 및 방법 : 간 세포암종(Hepatocellular Carcinoma) 환자 14명의 환자를 대상으로 시행하였다. 바로 누운 자세(Supine position)와 엎드린 자세(Prone position)에서 2가지 방법으로 환자 고정기구를 제작하고 영상을 획득하여 간 종양의 움직임과 용적 그리고 선량을 분석하였다. 결 과 : 바로 누운 자세(Supine position)와 엎드린 자세(Prone position) 에서 표적의 왼쪽-오른쪽(LR, Left-right) 움직임은 평균 $2.76{\pm}1.25mm$, $2.21{\pm}0.93mm$이고, 앞-뒤(AP, Anterior-posterior)와 상하(SI. Superior-inferior) 방향의 움직임은 각각 $4.02{\pm}1.63mm$, $11.56{\pm}3.08mm$, $3.36{\pm}1.17mm$, $7.45{\pm}1.96mm$이었다. 이를 이용한 엎드린 자세(Prone position)에서 치료 용적(Treatment volume)은 감소하였고, 이에 따라 정상간 용적은 증가 하였다. 결 론 : 호흡에 의한 간의 움직임을 최소화함으로써 치료 용적(Treatment volume)의 경계여유를 감소시킬 수 있었다. 즉 환자 자세 변화 특히 엎드린(Prone) 자세는 간의 움직임을 감소 시켜주고 정상 간의 용적을 증가 시킬 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8301-8310
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• 2014

Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materials and Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results: A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.

• 대한한방내과학회지
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• 제36권1호
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• pp.58-68
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• 2015

목 적: 소세포 폐암 및 전이성 폐암은 폐암 중에서도 가장 예후가 불량하고 생존율도 상대적으로 낮은 암으로 알려져 있다. 난치성 폐암 환자에 대해 한방치료가 생존 기간 연장 및 삶의 질 관리면에 있어서 효과가 있음을 보여주고자 한다. 연구방법 및 대상: 본원에서 입원 및 통원치료를 병행한 소세포폐암 환자 1명과 원발성 간암에서 폐로 전이된 전이성 폐암 환자 1명에 대하여 한방치료의 효과 및 임상경과를 후향적으로 조사하였다. 치료기간은 각각 2000년 1월-2009년 12월과 2004년 9월-2014년 2월이었으며 한약치료는 평균 1개월 간격으로 행해졌으며 입원기간 동안에는 한약치료를 포함한 침구치료를 추가로 시행하였다. 치료효과 및 경과 판정을 위해 흉부 방사선 검사 및 혈액검사를 평균 1개월 간격으로 시행하였으며 내원시마다 환자의 증상 및 상태를 확인하였다. 결 과: 2명의 폐암 환자 모두 꾸준한 한방치료를 받으며 진단시점부터 9년 이상의 상당히 오랜 기간 동안 비교적 좋은 삶의 질을 유지하면서 종양으로 인한 임상경과 또한 완만하게 진행이 되었다. 결 론: 본 증례는 한방치료가 불응성 폐암 환자에 대해 삶의 질을 양호하게 유지하고 증상 조절 및 종양의 진행양상을 완화시켜 주며 나아가 생존기간 연장에도 효과가 있음을 보여준다.

• Korean Journal of Radiology
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• 제24권8호
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• pp.761-771
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• 2023

Objective: To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP. Materials and Methods: In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed. Results: Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0-0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumor-puncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03-1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0-2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41-22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. Conclusion: ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.

• Korean Journal of Radiology
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• 제22권12호
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• pp.1974-1984
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• 2021

Objective: This study aimed to compare the efficacy between no-touch (NT) radiofrequency ablation (RFA) and conventional RFA using twin internally cooled wet (TICW) electrodes in the bipolar mode for the treatment of small hepatocellular carcinomas (HCC). Materials and Methods: In this single-center, two-arm, parallel-group, prospective randomized controlled study, we performed a 1:1 random allocation of eligible patients with HCCs to receive NT-RFA or conventional RFA between October 2016 and September 2018. The primary endpoint was the cumulative local tumor progression (LTP) rate after RFA. Secondary endpoints included technical conversion rates of NT-RFA, intrahepatic distance recurrence, extrahepatic metastasis, technical parameters, technical efficacy, and rates of complications. Cumulative LTP rates were analyzed using Kaplan-Meier analysis and the Cox proportional hazard regression model. Considering conversion cases from NT-RFA to conventional RFA, intention-to-treat and as-treated analyses were performed. Results: Enrolled patients were randomly assigned to the NT-RFA group (37 patients with 38 HCCs) or the conventional RFA group (36 patients with 38 HCCs). Among the NT-RFA group patients, conversion to conventional RFA occurred in four patients (10.8%, 4/37). According to intention-to-treat analysis, both 1- and 3-year cumulative LTP rates were 5.6%, in the NT-RFA group, and they were 11.8% and 21.3%, respectively, in the conventional RFA group (p = 0.073, log-rank). In the as-treated analysis, LTP rates at 1 year and 3 years were 0% and 0%, respectively, in the NT-RFA group sand 15.6% and 24.5%, respectively, in the conventional RFA group (p = 0.004, log-rank). In as-treated analysis using multivariable Cox regression analysis, RFA type was the only significant predictive factor for LTP (hazard ratio = 0.061 with conventional RFA as the reference, 95% confidence interval = 0.000-0.497; p = 0.004). There were no significant differences in the procedure characteristics between the two groups. No procedure-related deaths or major complications were observed. Conclusion: NT-RFA using TICW electrodes in bipolar mode demonstrated significantly lower cumulative LTP rates than conventional RFA for small HCCs, which warrants a larger study for further confirmation.