Background: The role of sorafenib in patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been rarely studied. The aim of this study was to evaluate the efficacy of sorafenib in post-LT era. Methods: Consecutive patients with post-transplant HCC recurrence not eligible to resection or locoregional therapy were included. Patients receiving best supportive care (BSC) until 2007 were compared with those treated by sorafenib thereafter. Results: Of a total of 65 patients, 20 patients received BSC and 45 received sorafenib. Clinical characteristics were similar between two groups except that sorafenib group received tacrolimus and mammalian target-of-rapamycin inhibitors more frequently than BSC group. Treatment with sorafenib conferred a survival advantage as compared with BSC for survival after recurrence (median, 14.2 vs. 6.8 months; P = 0.01). In multivariate analyses, high serum ${\alpha}$-fetoprotein level, synchronous intrahepatic recurrence and distant metastasis at the time of recurrence, and BSC were independently associated with poorer survival after recurrence. Sorafenib treatment was associated with better survival after recurrence as compared with BSC (hazard ratio, 0.25; 95% confidence interval, 0.10-0.62; P = 0.002). In addition, sorafenib group showed tolerable toxicity in the post-transplant setting. Conclusion: Sorafenib may be beneficial in patients with post-transplant HCC recurrence.
Kim, Jeong Han;Choe, Won Hyeok;Kwon, So Young;Yoo, Byung-chul
Journal of Korean Medical Science
/
v.33
no.52
/
pp.335.1-335.17
/
2018
Background: Spontaneous bacterial peritonitis (SBP) is a serious infectious complication in patients with liver cirrhosis. However, information about prognosis of SBP in hepatocellular carcinoma (HCC) patients is limited. We investigated the clinical course of SBP in HCC patients. Methods: This study enrolled patients diagnosed with SBP between 2005 and 2017. Medical records of patients were reviewed and clinical course was compared between the non-HCC and HCC groups. Results: In total, 123 SBP cases including 49 HCC cases were enrolled. Men were predominant (48/74, 64.9% vs. 34/49, 69.4%; P = 0.697); median age was 58 years in both non-HCC and HCC groups (P = 0.887). The most common etiology was alcohol (32/74, 43.2%) in non-HCC group and hepatitis B (30/49, 61.2%) in HCC group (P = 0.009). Antibiotic resistance rate was higher in non-HCC than in HCC group (29.7% vs. 12.2%; P = 0.028); in-hospital mortality did not differ between the groups (25/74, 33.8% vs. 13/49, 26.5%; P = 0.431). Development rate of hepatorenal syndrome did not differ between non-HCC and HCC group (14/74, 18.9% vs. 10/49, 20.4%; P = 1.000), but hepatic encephalopathy was less common in HCC group (26/74, 35.2% vs. 9/49, 18.3%; P = 0.008). The most important predictor of in-hospital mortality in patients with HCC was white blood cell count above $11,570cells/mm^3$ (odds ratio, 6.629; 95% confidence interval, 1.652-26.590; P = 0.008). Conclusion: Prognosis of SBP in HCC patients is relatively less severe. This result may be related with reduced antibiotics resistance and lower development rates of other complications, such as hepatic encephalopathy. Degree of systemic inflammation may be the most important factor for in-hospital mortality.
Objective: To compare the therapeutic efficacy between conventional transarterial chemoembolization (cTACE) and combined therapy using cTACE and radiofrequency ablation (RFA) in ultrasound (US)-invisible early stage hepatocellular carcinoma (HCC). Materials and Methods: From January 2008 to June 2016, 167 patients with US-invisible early stage HCCs were treated with cTACE alone (cTACE group; n = 85) or cTACE followed by immediate fluoroscopy-guided RFA targeting intratumoral iodized oil retention (combined group; n = 82). Procedure-related complications, local tumor progression (LTP), time to progression (TTP), and overall survival (OS) were compared between the two groups. Multivariate analyses were performed to identify prognostic factors. Results: There was no major complication in either group. The cTACE group showed higher 1-, 3-, and 5-year LTP rates than the combined group; i.e., 12.5%, 31.7%, and 37.0%, respectively, in the cTACE group; compared to 7.3%, 16.5%, and 16.5%, respectively, in the combined group; p = 0.013. The median TTP was 18 months in the cTACE group and 24 months in the combined group (p = 0.037). Cumulative 1-, 3-, and 5-year OS rates were 100%, 93.2%, and 87.7%, respectively, in the cTACE group and 100%, 96.6%, and 87.4%, respectively, in the combined group (p = 0.686). Tumor diameter > 20 mm and cTACE monotherapy were independent risk factors for LTP and TTP. Conclusion: Combined therapy using cTACE followed by fluoroscopy-guided RFA is a safe and effective treatment in US-invisible early stage HCCs. It provides less LTP and longer TTP than cTACE alone.
Background: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells. Methods: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated. Results: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5. Conclusions: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.
Nattokinase (NK, E.C. 3.4.21.62) is a serine protease produced by Bacillus subtilis natto that shows promise for the treatment of thrombotic disease. In this study, we assessed the effects of NK on the development of hepatocellular carcinoma (HCC), a principal malignancy of the liver that causes morbidity and mortality worldwide. Crude extracts of NK (NCE) were isolated from fermentation medium by centrifugation and separated into three fractions (<10 K, 100~30 K and >30K). Orthotopic HCC mouse models were established and NCE was administered by oral gavage. H&E staining was performed to examine the pathology of HCC livers. Immunohistochemistry and immunofluorescence were used to evaluate FOXM1, CD31, CD44 and vimentin expression in the liver. Compared to PBS groups, NCE increased the survival rates of HCC-bearing mice to 31% and decreased ascites. Low-intensity ultrasound imaging showed that the hypoechoic mass area was lower in NCE-treated mice and that tumor growth significantly decreased. IHC staining showed that the expression of FOXM1 was inhibited by NCE treatment. Immunofluorescence results revealed lower levels of CD31, CD44 and vimentin in the NCE groups. Taken together, these data demonstrate that NCE from Bacillus subtilis natto improves survival and inhibits tumor growth in HCC mice.
Jung, Jong-myung;Chung, Chun Kee;Kim, Chi Heon;Yang, Seung Heon
Journal of Korean Neurosurgical Society
/
v.62
no.4
/
pp.467-475
/
2019
Objective : There is a lack of knowledge regarding whether decompression is necessary in treating patients with epidural spinal cord compression (ESCC) grade 2. The purpose of this study was to compare the outcomes of minimally invasive surgery (MIS) without decompression and conventional open surgery (palliative laminectomy) for patients with hepatocellular carcinoma (HCC) spinal metastasis of ESCC grade 2. Methods : Patients with HCC spinal metastasis requiring surgery were retrospectively reviewed. Patients with ESCC grade 2, medically intractable mechanical back pain, a Nurick grade better than 3, 3-6 months of life expectancy, Tomita score ${\geq}5$, and Spinal Instability Neoplastic Score ${\geq}7$ were included. Patients with neurological deficits, other systemic illnesses and less than 1 month of life expectancy were excluded. Thirty patients were included in the study, including 17 in the open surgery group (until 2008) and 13 in the MIS group (since 2009). Results : The MIS group had a significantly shorter operative time ($94.2{\pm}48.2minutes$ vs. $162.9{\pm}52.3minutes$, p=0.001), less blood loss ($140.0{\pm}182.9mL$ vs. $1534.4{\pm}1484.2mL$, p=0.002), and less post-operative intensive care unit transfer (one patient vs. eight patients, p=0.042) than the open surgery group. The visual analogue scale for back pain at 3 months post-operation was significantly improved in the MIS group than in the open surgery group ($3.0{\pm}1.2$ vs. $4.3{\pm}1.2$, p=0.042). The MIS group had longer ambulation time ($183{\pm}33days$ vs. $166{\pm}36days$) and survival time ($216{\pm}38days$ vs. $204{\pm}43days$) than the open surgery group without significant difference (p=0.814 and 0.959, respectively). Conclusion : MIS without decompression would be a good choice for patients with HCC spinal metastasis of ESCC grade 2, especially those with limited prognosis, mechanical instability and no neurologic deficit.
Currently speaking, it is noted that radiofrequency ablation (RFA) has been the most widely used treatment for hepatocellular carcinoma (HCC) occurring in patients. However, accumulating evidence has demonstrated that the incidence of insufficient RFA (IRFA) may result in the identified rapid progression of residual HCC in the patient, which can greatly hinder the effectiveness and patient reported benefits of utilizing this technique. Although many efforts have been proposed, the underlying mechanisms triggering the rapid progression of residual HCC after IRFA have not yet been fully clarified through current research literature reviews. It was shown in this study that cell proliferation, migration and invasion of residual HepG2 and SMMC7721 cells were significantly increased after the IRFA was simulated in vitro. In other words, it is noted that IRFA could do this by enhancing the image of autophagy of the residual HCC cell via the $HIF-1{\alpha}/BNIP3$ pathway. Consequently, the down-regulation of BNIP3 may result in the inhibition of the residual HCC cell progression and autophagy after IRFA. Our present study results suggest that IRFA could promote residual HCC cell progression in vitro by enhancing autophagy via the $HIF-1{\alpha}/BNIP3$ pathway. For this reason, it is noted that the targeting of the BNIP3 may be useful in preventing the rapid growth and metastasis of residual HCC after IRFA.
Background: With increasing economic evaluation studies on the treatment of or screening tools for liver diseases that cause hepatocellular carcinoma (HCC), interest in the analysis of the medical utilization and costs of HCC treatment is increasing. Therefore, we aimed to estimate the medical utilization and costs of HCC patients, and calculate the cost of main procedures for HCC treatment, including liver transplant (LT), hepatic resection (HR), radiofrequency ablation (RFA), and transarterial chemoembolization (TACE). Methods: We analyzed claim data from January to December 2018 from the Health Insurance and Review and Assessment Service-National Patient Sample (HIRA-NPS-2018) dataset, including data of patients diagnosed with HCC (Korean Standard Classification of Diseases code C22.0) who had at least one inpatient claim for HCC. Results: A total of 715 HCC patients were identified. In 2018, the yearly average medical cost per HCC patient was ₩18,460K (thousand), of which ₩14,870K was attributed to HCC. Among the total medical costs of HCC patients, the inpatient cost accounted for the largest portion of both the total medical and HCC-related costs. The major procedures of HCC treatment occurred most frequently in the order of TACE, RFA, HR, and LT. The average medical cost per treatment episode was the highest for LT (₩87,280K), followed by HR (₩10,026K), TACE (₩4,047K), and RFA (₩2,927K). Conclusion: By identifying the medical costs of HCC patients and the costs of the main procedures of HCC treatment, our results provide basic information that could be utilized for cost estimation in liver disease-related economic evaluation studies.
It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.
Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.