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Circulating tumor DNA dynamics analysis in a xenograft mouse model with esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2021年第41期27卷 7134-7143页

作者： Hiroyuki Terasawa Hideaki Kinugasa kazuhiro nouso Shumpei Yamamoto Mami Hirai Takehiro Tanaka Akinobu Takaki Hiroyuki Okada Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan Department of Pathology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan

BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always *** use liquid biopsies clinically,it will be very important to address these *** To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA *** Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell *** of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA *** of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)*** Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week *** hTERT was detected at week 4,but it was detected at week ***,in four-site xenograft mice,hTERT was detected both at week 4 and week *** experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of *** resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after *** We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important *** also found that when the tumor was completely resected,ctDNA was absent after one or more days.

关键词： Liquid biopsy Circulating tumor DNA Xenograft Esophageal squamous cell carcinoma Dynamics of circulating tumor DNA

Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

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World Journal of Gastroenterology 2014年第15期20卷 4151-4159页

作者： Koji Miyahara kazuhiro nouso Kazuhide Yamamoto Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama-cityOkayama 700-8558Japan Department of Molecular Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama-cityOkayama 700-8558Japan

The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma(HCC).After development of sorafenib and its introduction as a therapeutic agent used in the clinic,several critical questions have been *** parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be *** it is difficult to know the responders in advance using conventional characteristics of patients,there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of *** and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet *** addition,effectiveness of the expanded application of sorafenib is still controversial,although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage ***,over 50 relevant drugs have been developed and are currently under *** efficacy of some of these drugs has been extensively examined,but none have demonstrated any superiority over sorafenib,so ***,there are several drugs that have shown efficacy for treatment after sorafenib failure,and these are proceeding to further *** address these issues and questions,we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib.

关键词： Biomarker Molecular targeted therapy Clinical tria

Regression of hepatocellular carcinoma during vitamin K administration

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World Journal of Gastroenterology 2005年第42期11卷 6722-6724页

作者： kazuhiro nouso Shuji Uematsu Kunihiro Shiraga Ryoichi Okamoto Ryo Harada Shoko Takayama Wakako Kawai Shigeru Kimura Toru Ueki Nobuaki Okano Masahiro Nakagawa Motowo Mizuno Yasuyuki Araki Yasushi Shiratori Department of Internal Medicine Hiroshima City Hospital Hiroshima 730-8518 Japan Department of Medicine and Medical Science Okayama University Graduate School of Medicine and Dentistry Okayama 700-8558 Japan

An 85-year-old man with HCV infection and diabetes mellitus was diagnosed as having hepatocellular carcinoma (HCC, 13 cm in diameter) based on high serum alpha-fetoprotein (AFP),AFP-L3,and des-γ-carboxy prothrombin levels as well as typical enhancement pattern on contrast-enhanced CT. The patient did not receive any interventional treatments because of advanced age and the advanced stage of *** chose to take vitamin K,which was reported to suppress the growth of HCC in vitro. Three months after starting vitamin K, all three tumor markers were normalized and HCC was markedly regressed, showing no enhancement in the early arterial phase on CT. Here we present the report describing the regression of HCC during the administration of vitamin K.

关键词：肝细胞癌维生素K 病理机制临床表现

Hepatocellular carcinoma recurrence in HCV patients treated with direct-acting antivirals after curative treatment

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Hepatoma Research 2019年第5期5卷 26-36页

作者： Shinichiro Nakamura kazuhiro nouso Hiroyuki Okada Hideki Onishi Shin-ichi Fujioka YasuyukiAraki Shouta Iwadou Takashi Kumada Hidenori Toyoda Kenta Motomura Kazuya Kariyama Haruhiko Kobashi Toshihiko Kaneyoshi Masaharu Ando Akio Moriya Hideaki Taniguchi YouichiMorimoto Hiroaki Hagihara Masatoshi Tanaka Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesOkayama 700-8558Japan Okayama Saiseikai General Hospital Okayama 700-8558Japan Hiroshima City Hiroshima Citizens Hospital Hiroshima 731-0293Japan Ogaki Municipal Hospital Gifu 503-8502Japan Iizuka Hospital Fukuoka 820-8505Japan Okayama City Hospital Okayama 700-8557Japan Okayama Red Cross General Hospital Okayama 700-8607Japan Fukuyama Medical Center Hiroshima 720-8520Japan Mitoyo General Hospital Kagawa 769-1695Japan Tottori Municipal Hospital Tottori 680-8501Japan Kurashiki Central Hospital Okayama 710-8602Japan Sumitomo Besshi Hospital Ehime 792-8543Japan Yokokura Hospital Fukuoka 839-0215Japan Japanese Red Cross Society Himeji Hospital Hyogo 670-8540Japan

Aim:The increased risk of hepatocellular carcinoma(HCC)recurrence in hepatitis C virus(HCV)-infected patients treated with direct-acting antivirals(DAAs)after curative treatment for HCC is *** purpose of this study was to examine the risk of HCC recurrence after DAA ***:We conducted a retrospective cohort study of 312 consecutive patients with HCV-related HCC who received DAA therapy in participating institutions between September 2014 and July *** patients received curative ;hepatectomy or radio-frequency *** calculated the annual incidence of HCC recurrence after DAA therapy and identified the risk factors for HCC recurrence using Cox regression ***:The median age was 74 years old,and a sustained virological response was achieved by 288 *** 3-year-overall survival rate was 95.4%in a median follow-up period of 855 *** recurred in 135 *** 1-,2-and 3-year recurrence rates were 18.3%,38.8%and 55.4%,respectively.A multivariate analysis revealed that the following factors were associated with HCC recurrence:multiple tumors at the first HCC treatment[hazard ratio(HR)=2.21;95%CI:1.41-3.49],a history of multiple treatments for HCC(HR=1.97;95%CI:1.28-3.02),andα-fetoprotein(AFP-L3)≥10%at the initiation of DAA therapy(HR=4.74;95%CI:2.10-10.7).Conclusion:Among patients treated with DAAs after the curative treatment of HCC,multiple tumors at the first HCC treatment,multiple prior HCC treatments and a high AFP-L3 level before DAA therapy were associated with recurrence,and the rate of recurrence was comparable to that before the DAA era.

关键词： Hepatocellular carcinoma hepatitis C virus direct-acting antiviral recurrence

雷莫芦单抗用于经乐伐替尼治疗后进展的不可切除肝细胞癌的治疗效果

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Gastroenterology Report 2021年第2期9卷 133-138,I0002页

作者： Atsushi Hiraoka Takashi Kumada Toshifumi Tada Chikara Ogawa Joji Tani Shinya Fukunishi Masanori Atsukawa Masashi Hirooka Kunihiko Tsuji Toru Ishikawa Koichi Takaguchi Kazuya Kariyama Ei Itobayashi Kazuto Tajiri Noritomo Shimada Hiroshi Shibata Hironori Ochi Kazuhito Kawata Hidenori Toyoda Hideko Ohama kazuhiro nouso Akemi Tsutsui Takuya Nagano Norio Itokawa Korenobu Hayama Taeang Arai Michitaka Imai Yohei Koizumi Shinichiro Nakamura Kojiro Michitaka Yoichi Hiasa Masatoshi Kudo Gastroenterology Center Ehime Prefectural Central HospitalEhimeJapan Department of Gastroenterology and Hepatology Ogaki Municipal HospitalGifuJapan Department of Internal Medicine Himeji Red Cross HospitalHyogoJapan Department of Gastroenterology and Hepatology Takamatsu Red Cross HospitalTakamatsuJapan Department of Gastroenterology and Hepatology Kagawa universityKagawaJapan Department of Gastroenterology Osaka Medical CollegeOsakaJapan Division of Gastroenterology and Hepatology Department of Internal MedicineNippon Medical SchoolTokyoJapan Department of Gastroenterology and Metabology Ehime University Graduate School of MedicineEhimeJapan Center of Gastroenterology Teine Keijinkai HospitalSapporoJapan Department of Gastroenterology Saiseikai Niigata HospitalNiigataJapan Department of Hepatology Kagawa Prefectural Central HospitalTakamatsuJapan Department of Gastroenterology Okayama City HospitalOkayamaJapan Department of Gastroenterology Asahi General HospitalAsahiJapan Department of Gastroenterology Toyama University HospitalToyamaJapan Division of Gastroenterology and Hepatology Otakanomori HospitalKashiwaJapan Department of Gastroenterology Tokushima Prefectural Central HospitalTokushimaJapan Hepato-biliary Center Matsuyama Red Cross HospitalMatsuyamaJapan Department of Hepatology Hamamatsu University School of MedicineHamamatsuJapan Department of Gastroenterology Kindai UniversityOsakaJapan

背景:在日本,乐伐替尼可用于不可切除原发性肝癌的一线、二线或三线治疗。本研究评估新近研发的雷莫芦单抗用于经乐伐替尼治疗后进展的不可切除的原发性肝癌的疗效。方法:2018年5月至2020年1月间在日本16家中心接受乐伐替尼治疗的385例... 详细信息

背景:在日本,乐伐替尼可用于不可切除原发性肝癌的一线、二线或三线治疗。本研究评估新近研发的雷莫芦单抗用于经乐伐替尼治疗后进展的不可切除的原发性肝癌的疗效。方法:2018年5月至2020年1月间在日本16家中心接受乐伐替尼治疗的385例不可切除原发性肝癌患者中,我们将其中接受雷莫芦单抗作为下一线治疗的28例患者纳入研究,对其治疗效果进行回顾性分析。结果:28例患者中位年龄70岁,中位白蛋白-胆红素(ALBI)评分为2.19。28例患者中,23例为男性;21例为Child-Pugh A级,7例为Child-Pugh B级;3例为BCLC B期,25例为BCLC C期。雷莫芦单抗用于二线、三线和四线治疗的病例分别为14例、9例和5例患者。26例患者获得疗效评估,客观缓解率为3.8%(1/26),疾病控制率为42.3%(11/26);中位疾病进展时间为2个月。未继续接受雷莫芦单抗治疗的原因包括16例出现疾病进展和2例出现3级不良反应(消化道出血和腹水)。结论:我们的初步研究显示,对于乐伐替尼治疗进展的不可切除原发性肝癌,雷莫芦单抗并没有获得预期的治疗效果。

关键词： hepatocellular carcinoma ramucirumab lenvatinib sorafenib

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development

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World Journal of Hepatology 2015年第19期7卷 2220-2228页

作者： Yasuto Takeuchi Fusao Ikeda Toshiya Osawa Yasuyuki Araki Kouichi Takaguchi Youichi Morimoto Noriaki Hashimoto Kousaku Sakaguchi Tatsuro Sakata Masaharu Ando Yasuhiro Makino Shuji Matsumura Hiroki Takayama Hiroyuki Seki Shintarou Nanba Yuki Moritou Tetsuya Yasunaka Hideki Ohnishi Akinobu Takaki kazuhiro nouso Yoshiaki Iwasaki Kazuhide Yamamoto Department of Gastroenterology and Hepatology Okayama University Graduate School of Medicine Dentistry and Pharma- ceutical Sciences Department of Molecular Hepatology Okayama University Graduate School of Medicine Dentistry and Pharma- ceutical Sciences Department of Internal Medicine Okayama Saiseikai General Hospital Department of Internal Medicine Hiroshima City Hospital Department of Internal Medicine Kagawa Prefectural Central Hospital Department of Internal Medicine Kurashiki Central Hospital Department of Internal Medicine Mihara Red Cross hospital Department of Internal Medicine Fukuyama City Hospital Department of Internal Medicine National Hospital Organization Fukuyama Clinical Center Department of Internal Medicine Mitoyo General Hospital Department of Gastroenterology National Hospital Organization Iwakuni Clinical Center Department of Internal Medicine Sumitomo Besshi Hospital Department of Gastroenterology Tsuyama Central Hospital Health Service Center Okayama University

AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m ***: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

关键词： Hepatitis C virus Interferon Hepatocellular carcin