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1.

論文(リポジトリ)

論文(リポジトリ)
曽我, 憲二 ; 相川, 啓子 ; 豊島, 宗厚 ; 柴崎, 浩一
出版情報: 新潟医学会雑誌 — 新潟医学会雑誌.  111  pp.301-305,  1997-05.  新潟医学会
本文リンク: http://hdl.handle.net/10191/44854
概要: Hyperthermia with systemic chemotherapy as a adjuvant therapy for unresectable hepatocellular and biliary carcinoma was performed, and the therapeutic effects of hyperthermia were evaluated. Twenty eight patients with unresectable hepatocellular carcinoma(HCC)and 29 patients(11 patients with cancer of biliary tract, 3 with gallbladder cancer and 15 with pancreas cancer)were treated. The hyperthermia was applied for 40 minutes once a week, using of the equipment of radiofrequency of 13.56 MHz and during heating systemic chemotherapy such as MMC and 5-FU was injected simultaneously. Ten patients with HCC were performed transcatheter arterial embolization and 13 patients with biliary carcinoma were received radiation therapy before hyperthermia. The therapeutic effects of hyperthermia evaluated by imaging modalities were showed as follows. Four patients with HCC revealed partial reduction(PR)in tumor size. Four patients with PR were all of massive type HCC. Two patients with biliary carcinoma showed complete reduction and 5 patients PR. These results suggest that hyperthermia may be useful for massive type HCC and a part of patients with biliary carcinoma. 続きを見る
2.

論文(リポジトリ)

論文(リポジトリ)
加村, 毅
出版情報: 新潟医学会雑誌 — 新潟医学会雑誌.  122  pp.119-127,  2008-03.  新潟医学会
本文リンク: http://hdl.handle.net/10191/19601
概要: The current frontiers of diagnostic imagings on hepatocellular carcinoma (HCC) are as follows: first, the detection of well differentiated HCC (w-HCC), and second, the detection and confirmation of moderately or poorly differentiated HCC (mp-HCC) less than 10 mm in diameter. HCC nodules developed first as w-HCC, and then they become mp-HCC (de-differentiation). The w-HCC shows more favorite prognosis than and -HCC. The detection rates of w-HCC histologically proved with hepatic resection and percutaneous ultrasonography-guided biopsy are 63 % (17/29) with X-ray computed tomography (CT), and 68 % (18/29) with magnetic resonance imaging (MRI). However, we may miss a lot of w -HCCs, because most of the HCC nodules are found as mp -HCC. Most of the mp -HCCs larger than 1cm in diameter are detected and confirmed with CT and MRI. The smaller mp -HCC nodules are difficult to detect and confirm, and CT with intra -arterial administration of contrast materials may show more nodules. Intrahepatic arterio - portal shunts and some of hyperplastic hepatocellular nodules (mainly developed in Budd - Chiari syndrome and alcoholic liver cirrhosis) mimic mp -HCC, and to differentiate the latter, T2 - weighted images of MRI may be useful. 続きを見る
3.

学位論文(リポジトリ)

学位
Kobayashi, Takamasa
出版情報: pp.1-28,  2018-09-20.  新潟大学
本文リンク: http://hdl.handle.net/10191/50785
概要: Background: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. Patients and Methods: This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). Visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. Results: Among the body composition indexes, only SATI could significantly differentiate OS (P= .012). Multivariate analysis showed that SATI (low- vs. high-SATI; hazard ratio [HR], 2.065; 95% confidence interval [CI], 1.187-3.593; P= .010), serum albumin (<3.5 vs. ≥3.5 g/dL; HR, 2.007; 95% CI, 1.037-3.886; P= .039), serum alpha-fetoprotein (<20 vs. ≥20 ng/mL; HR, 0.311; 95% CI, 0.179-0.540; P< .001), and mRECIST assessment (complete response + partial response + stable disease vs. progressive disease; HR, 0.392; 95% CI, 0.221-0.696; P= .001) were indicated as independent prognostic factors for OS. Conclusions: High SAT volume is associated with better survival outcomes in HCC patients treated with transcatheter intra-arterial therapies. Elucidation of the mechanisms regulating SAT volume may offer new therapeutic strategy in these patients.<br />学位の種類: 博士(医学). 報告番号: 甲第4491号. 学位記番号: 新大院博(医)甲第828号. 学位授与年月日: 平成30年9月20日<br />Cancer Management and Research. 2018, 10, 2231-2239.<br />新大院博(医)甲第828号 続きを見る
4.

学位論文(リポジトリ)

学位
Seino, Satoshi
出版情報: 2018-09-20.  新潟大学
本文リンク: http://hdl.handle.net/10191/50771
概要: The high heterogeneity of hepatocellular carcinomas (HCCs) complicates stratification of HCC patients for treatment. The refore, it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC) markers epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), delta-like 1 homolog (DLK1), and cytokeratin 19 (CK19). Staining patterns were analysed for their prognostic association with relapse-free survival and overall survival. α-Fetoprotein (AFP), lectin-reactive α-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin (DCP) were assessed as indicators of HPC protein expression. Expression pattern of HPC markers correlated with tumour malignancy indicated by high AFP/AFP-L3 serum levels, more frequent vascular invasion, and poorer tumour differentiation. EpCAM expression, DCP ≥300 mAU/ml, age ≥60, and Child-Pugh score grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and serum levels of AFP/AFP-L3 correlated with the expression of HPC proteins. Our study paved the way for further elucidation of the association among HPC markers, serum tumour markers, and HCC clinical outcome for precision medicine.<br />学位の種類: 博士(医学). 報告番号: 甲第4492号. 学位記番号: 新大院博(医)甲第829号. 学位授与年月日: 平成30年9月20日<br />Oncotarget. 2018, 9(31), 21844-21860.<br />新大院博(医)甲第829号 続きを見る
5.

論文(リポジトリ)

論文(リポジトリ)
松田, 康伸 ; 若井, 俊文 ; 廣瀬, 雄己 ; 坂田, 純 ; 小林, 隆 ; 大澤, まみ ; 藤巻, 隼 ; 窪田, 正幸
出版情報: 新潟大学保健学雑誌 — 新潟大学保健学雑誌.  11  pp.51-56,  2014-03.  新潟大学医学部保健学科
本文リンク: http://hdl.handle.net/10191/38939
概要: 【目的】非アルコール性脂肪肝炎(NASH)は,近年急速に増加している原因不明の肝疾患である。本研究では,肝がん治療に有効とされる分子標的薬ラパマイシンの標的シグナルp70S6キナーゼが,NASH肝がんの病態に関与している可能性について検討し た。 【方法】根治的外科手術療法を施行したNASH肝がん22例の病変組織に対して,リン酸化型(活性型)p70S6キナーゼの免疫組織化学染色を行い,臨床因子・予後の比較検討を行った。 【結果】NASH肝がん22例中12例(54.5%)がリン酸化型p70S6キナーゼを高発現しており,組織未分化度と相関した(p = 0.047)。リン酸化型P70S6キナーゼ高発現群は,外科切除後3年以内再発率が有意に増加していた(p = 0.045)。 【総括】p70S6キナーゼを高発現しているNASH肝がんは,再発頻度が高い傾向がある。同シグナルを阻害する分子標的薬ラパマイシンは,本疾患の再発防止に有効である可能性が示唆された。<br />Objective: Non-alcoholic steatohepatitis(NASH)is a recently identified liver disease which causes hepatocellular carcinoma(HCC). In this study, we addressed whether p70S6 kinase(p70S6K), a main target of the anti-cancer agent rapamycin, is involved in the clinicopathological factors in NASH-related HCC. Methods: HCC tissue samples were obtained from 22 NASH patients with radical surgical treatment. Phosphorylation level of p70S6K was analyzed by immunohistochemical analysis, and the correlation with the clinicopathological factors were examined. Results: Phosphorylated p70S6K was detected in 54.5%(12/22)of NASH-related HCCs. The levels of phosphop70S6K were correlated with histological grade of HCC(p = 0.047), but not with clinical factors. Phosphorylation of p70S6K was correlated with increased cancer recurrence after 3 years of the treatment(p= 0.045). Conclusion: Phosphorylation level of p70S6K was correlated with cancer recurrence of NASH-related HCC. Rapamycin might be a useful agent for treating NASH-associated HCC. 続きを見る
6.

論文(リポジトリ)

論文(リポジトリ)
北澤, 幹男 ; 大西, 義久
出版情報: 新潟医学会雑誌 — 新潟医学会雑誌.  100  pp.751-755,  1986-12.  新潟医学会
本文リンク: http://hdl.handle.net/10191/35761
概要: One hundred and fourty seven cases of hepatocellular carcinoma, autopsied between 1964~1984, were clinicopathologically studied. The average age of the cases was 56 year-old, the male to female ratio was 5.13, and the average clinical course was 9.7 months. The positive cases for α-fetoprotein was 88.7%, and those for HBsAg was 43.5% of the examined cases. Macroscopically, the tumor, showing nodular type, predominantly located in the right lobe of the liver. Histopathologically, sinusoidal-trabecular type and well differentiated type of the tumor-cells were predominant. Frequency of the cases with distant metastasis was 78.2% of the total cases and that with metastasis to the lymph node was by no means low. The incidence of the tumor thrombosis into the portal vein was 76.1% and that into the hepatic vein was 44.3%. All cases of the hepatic cirrhosis combined with the hepatocellular carcinoma were posthepatitic type. The incidence of the distant metastasis was slightly higher in the cases without combination of the cirrhosis than those with combination of the cirrhosis. 続きを見る
7.

学位論文(リポジトリ)

学位
Niwa, Yusuke ; 丹羽, 佑輔
本文リンク: http://hdl.handle.net/10191/0002000824
概要: Background: Since CCNDBP1 is a cyclin D-binding dominantly-negative helix-loop-helix protein that is expressed in variou s tissues, it is considered a tumor suppressor, as it negatively regulates TGF-β signal-induced cell migration depending on the surrounding condition. When expressed in tumor cells, CCNDBP1 can contribute to the viability of cancer cells by rescuing them from chemotherapy-induced DNA damage. Therefore, this study focused on investigating the function of CCNDBP1, which is directly related to survival from DNA damage and chemoresistance in cancer cells. Methods: Molecular mechanisms of CCNDBP1 related to the recovery from DNA damage were examined in vitro and in vivo, using hepatocellular carcinoma (HCC) cells and tissues obtained from Ccndbp1 knockout mice. X-ray irradiation was then used to induce DNA damage. Subsequently, gene and protein expression changes associated with CCNDBP1's upregulation, downregulation, and irradiation were assessed. Results: As observed, CCNDBP1's overexpression in HCC cells stimulated cell growth and showed resistance to X-ray irradiation. Gene expression analyses of CCNDBP1-overexpressed cells and Ccndbp1 knockout mice revealed that Ccndbp1 inhibitory dependently controlled the expression of Ezh2. However, irradiation Ccndbp1-dependently decreased Ezh2's expression. Further analyses of DNA damage-related protein expressions in vitro and in vivo also showed that Ccndbp1 activated the Atm-Chk2 pathway through the inhibition of Ezh2 expression, thereby accounting the resistance to DNA damage. Conclusions: Our study, therefore, demonstrated that by inhibiting EZH2, CCNDBP1 contributed to the activation of the ATM-CHK2 pathway to alleviate DNA damage, leading to chemoresistance.<br />Journal of clinical medicine. 2022, 11(3), 851.<br />新大院博(医)第1038号 続きを見る
8.

論文(リポジトリ)

論文(リポジトリ)
小方, 則夫
出版情報: 新潟医学会雑誌 — 新潟医学会雑誌.  103  pp.466-471,  1989-06.  新潟医学会
本文リンク: http://hdl.handle.net/10191/41296
概要: We have previously described that 1) integration of hepatitis B virus (HBV) DNA into host chromosomes of hepatocytes occurs at a high frequency during the course of the viral carrier state, 2) hepatocytes containing the integrated viral DNA undergo multiclonal growth, and 3) all hepatocellular carcinomas (HCCs) develop clonally and some HCCs are of multiclonal origins even in a same liver. These findings indicate that HBV related HCC may be established through several steps of genetic alterations after the initial integration event of the viral DNA. To investigate the critical mode of HBV DNA integration for the transforming process of hepatocyte, we analyzed a HCC case for the structure of the integrants in both hepatocytes and hepatoma cell using molecular cloning technique. Characteristic features of the integrant found in the hepatoma cell were 1) the cohesive end region of HBV DNA along with flanking cellular DNA showed inverted repeat structure, and 2) the integration sites in host DNA was within human highly repetitive sequence, alpha satellite DNA. Results described were discussed from a viewpoint of a possible role of HBV in hepatocarcinogenesis. 続きを見る
9.

論文(リポジトリ)

論文(リポジトリ)
小黒, 仁
出版情報: 新潟医学会雑誌 — 新潟医学会雑誌.  106  pp.1055-1068,  1992-11.  新潟医学会
本文リンク: http://hdl.handle.net/10191/40072
概要: The plasma concentrations of PIVKA-II in samples from 155 patients with HCC and 298 with other liver diseases were deter mined. The serum concentrations and fucosylation index of alpha-fetoprotein (AFP), sialyl stage-specific embryonic antigen-1 (SLX), CA-50, and Dupan-2 were also determined in 60 patients with HCC, 70 with nonneoplastic liver diseases and 25 with carcinoma metastatic to the liver. In 16 HCC patients with positive reactions of both PIVKA-II and AFP longitudinal series of their plasma concentrations were measured in evaluating the effect of the treatment to HCC. Next, the reactivity of PIVKA-II, AFP, prothrombin, transferrin and alpha-1-antitrypsin with concanavalin A and Lens culinaris agglutinin was studied in 11 patients with HCC by crossed immunoaffinoelectrophoresis and affinity colomn chromatography. The results are as follow:1. The plasma concentrations of PIVKA-II in patients with HCC were higher than those with other liver diseases with statistical significance, and the sensitivity, specificity and total accuracy of the present analysis were 54, 98 and 85%, respectively. 2. The determinations of serum concentrations and fucosylation index of AFP and SLX were also useful for diagnosing HCC, and 88% of HCC was able to be diagnosed by the measurement of these markers together with PIVKA-II serologically. 3. Simultaneous determinations of PIVKA-II and AFP were recommended in the follow-up of patients with HCC since 5 HCC patients with the dissociation of the concentrations of PIVKA-II and AFP were observed. 4. Concanavalin A-nonreactive fraction of PLVKA-II was detected in serum from patient with HCC, suggesting an altered glycosylation of PIVKA-II. 続きを見る
10.

論文(リポジトリ)

論文(リポジトリ)
渡辺, 勇四郎 ; 宮村, 達男
出版情報: 新潟医学会雑誌 — 新潟医学会雑誌.  104  pp.998-1003,  1990-12.  新潟医学会
本文リンク: http://hdl.handle.net/10191/35153
概要: The agent that causes blood-borne non-A, non-B hepatitis has been identified by M.Houghton and his colleagues. A cDNA of this virus has been cloned and assay system of HCV-antibody has been established. By using this assay system, we have been accumulating new epidemiological and clinical findings. We also isolated HCVcDNA clones from the serum of a Japanese healthy HCV carrier. Nucleotide sequences of these cDNA clones showed high homology with the Houghton's clones. Amino acid homology in the non-structural region (NS3) is 93% between the two HCV isolates. 続きを見る