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Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

World Journal of Gastroenterology 2007年第3期13卷 414-420页

作者： Kiminori Uka Hiroshi Aikata Shintaro Takaki Hiroo Shirakawa Soo Cheol Jeong Keitaro Yamashina Akira Hiramatsu Hideaki Kodama Shoichi Takahashi Kazuaki Chayama Department of Medicine and Molecular Science Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences Hiroshima University Hiroshima Japan

AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients. METHODS: After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features, prognosis, and treatment strategies. RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%). The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure. CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatictumor stage (T0-T2), and are free of portal venous invasion may improve survival.

关键词： Hepatocellular carcinoma Extrahepatic metastases Prognosis Causes of death

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Prediction of promiscuous T-cell epitopes in the Zika virus polyprotein:An in silico approach

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Asian Pacific Journal of Tropical Medicine 2016年第9期9卷 822-828页

作者： Hamza Dar Tahreem Zaheer Muhammad Talha Rehman Amjad Ali Aneela Javed Gohar Ayub Khan Mustafeez Mujtaba Babar Yasir Waheed Atta-ur-Rahman school of Applied biosciences(ASAB) National University of Sciences and Technology Shifa College of Pharmaceutical sciences Shifa Tameer-e-Millat University Foundation University medical College Foundation University Islamabad

Objective:To predict immunogenic promiscuous T-cell epitopes from the polyprotein of the Zika virus using a range of bioinformatics *** date,no epitope data are available for the Zika virus in the IEDB ***:We retrieved nearly 54 full length polyprotein sequences of the Zika virus from the NCBI database belonging to different outbreaks.A consensus sequence was then used to predict the promiscuous T cell epitopes that bind MHC 1 and MHC II alleles using Propred1 and Propred immunoinformatic algorithms *** antigencity predicted score was also calculated for each predicted epitope using the Vaxi Jen 2.0 ***:By using Pro Pred1,23 antigenic epitopes for HLA class I and 48 antigenic epitopes for HLA class II were predicted from the consensus polyprotein sequence of Zika *** greatest number of MHC class I binding epitopes were projected within the NS5(21%),followed by Envelope(17%).For MHC class II,greatest number of predicted epitopes were in NS5(19%) followed by the Envelope,NS1 and NS2(17% each).A variety of epitopes with good binding affinity,promiscuity and antigenicity were predicted for both the HLA ***:The predicted conserved promiscuous T-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates,which will be able to induce a broad range of immune responses in a heterogeneous HLA ***,our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.

关键词： Zika Virus B-Cell Epitopes T-Cell Epitopes Vaccine Antigenicity

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Hepatitis C: From inflammatory pathogenesis to antiinflammatory/hepatoprotective therapy

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World Journal of Gastroenterology 2018年第47期24卷 5297-5311页

作者： Hu Li Meng-Hao Huang Jian-Dong Jiang Zong-Gen Peng Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

Hepatitis C virus(HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals(DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with antiinflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanismsof HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

关键词： Hepatitis C virus infection Liver disease Inflammatory pathogenesis Anti-inflammatory and hepatoprotective therapy

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Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy

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World Journal of Gastroenterology 2015年第42期21卷 12150-12156页

作者： Shogo Ohkoshi Masahiko Yano Yasunobu Matsuda Department of Internal Medicine School of Life Dentistry at Niigata The Nippon Dental University division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

A well-known tumor suppressor, p21, acts parado-xically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma(HCC) therapy. Chromosome region maintenance 1(CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention.

关键词： p21 Tumor suppressors Oncogene Subcellular localiz

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Advances in Space Medicine Applied to Pandemics on Earth

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Space(Science & Technology) 2021年第1期2021卷 271-273页

作者： Ilaria Cinelli Thais Russomano Aerospace Human Factors Association Aerospace Medical AssociationUSA InnovaSpace Ltd&Centre for Human and Applied Physiological sciences School of Basic&Medical BiosciencesFaculty of Life Sciences and MedicineKing’s College LondonUK

Preparation and planning are critical when facing an epidemic or *** solutions must be incorporated in addition to existing guidelines in the case of a fast-spreading *** in space health have been driven by the need to preserve human health in an austere environment,in which medical assistance or resupply from the ground is not *** paper speculates on the similarities between human spaceflight and epidemics,extended to pandemics,identifying implementable solutions for immediate use by healthcare personnel and healthcare *** believe aerospace medical research can be seen as a resource to improve terrestrial medical care and the management of patients on Earth.

关键词： preserve incorporated addition

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Human papillomavirus in upper digestive tract tumors from three countries

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World Journal of Gastroenterology 2011年第48期17卷 5295-5304页

作者： Andres Castillo Chihaya Koriyama Michiyo Higashi Muhammad Anwar Mulazim Hussain Bukhari Edwin Carrascal Lida Mancilla Hiroshi Okumura Masataka Matsumoto Kazumasa Sugihara Shoji Natsugoe Yoshito Eizuru Suminori Akiba Department of Epidemiology and Preventive Medicine Kagoshima University Graduate School of Medicaland Dental Sciences Department of Human Pathology Kagoshima University Graduate School of Medical and Dental Sciences King Edward medical University Department of Pathology Universidad del Valle Universidad Santiago de Cali Department of Surgical Oncology and Digestive Surgery Ka-goshima University Graduate School of Medical and Dental Sci-ences Department of Maxillofacial Diagnostic and Surgical Science Kagoshima University Graduate School of Medical and Dental Sciences Department of Surgical Oncology and Digestive Surgery Ka-goshima University Graduate School of Medical and Dental Sciences division of Oncogenic and Persistent Viruses Kagoshima University Graduate School of Medical and Dental Sciences

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and-negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

关键词： Human papillomavirus Viral load Physical sta-tus E6 p53 p16^INK4a

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Natural regression of fibrosis in chronic hepatitis B

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World Journal of Gastroenterology 2016年第24期22卷 5459-5466页

作者： Shogo Ohkoshi Haruka Hirono Kazuhiko Watanabe Katsuhiko Hasegawa Kenya Kamimura Masahiko Yano Department of Internal Medicine School of Life Dentistry at Niigata The Nippon Dental University division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B(CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBe Ag seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma(HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been(pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosisinduced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue.

关键词： Chronic hepatitis B Cirrhosis Spontaneous remission Regression of fibrosis Occult hepatitis B infection Hepatocellular carcinoma surveillance of hepatitis B virus

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Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 73-81,I0006-I0009页

作者： Tiasha Dasgupta Venkatraman Manickam Department of Biomedical sciences School of Biosciences and TechnologyVellore Institute of TechnologyVellore 632014Tamil NaduIndia

Objective:To evaluate the protective effect of benzydamine hydrochloride against ethanol-induced oxidative stress and inflammation in RAW 264.7 ***:RAW 264.7 macrophages were treated with ethanol(100 mM)and benzydamine hydrochloride(7.5μM).The imflammatory status was confirmed by measuring pro-(TNF-αand IL-6)and anti-inflammatory(IL-10)cytokines through ELISA and RT-PCR *** oxygen species generation and mitochondrial membrane potential were investigated to study the protective role of benzydamine hydrochloride against ethanol-induced oxidative *** detection was also investigated using flow cytometry and acridine orange/ethidium bromide ***:Benzydamine hydrochloride significantly decreased the secretion of TNF-αand IL-6,as well as the generation of reactive oxygen species inside the cells,thereby stabilizing the mitochondrial membrane potential and reducing DNA *** ethanol-induced cellular necrosis was also reversed by the administration of benzydamine ***:Benzydamine hydrochloride ameliorates ethanol-induced cell apoptosis and inflammation in RAW macrophages.

关键词： Alcohol Benzydamine hydrochloride Inflammation Oxidative stress Apoptosis

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Massive low-grade myxoid liposarcoma of the floor of the mouth:A case report and review of literature

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World Journal of Clinical Cases 2022年第34期10卷 12742-12749页

作者： Takuma Kugimoto Yuko Yamagata Toshimitsu Ohsako Hideaki Hirai Naoto Nishii Kou Kayamori Tohru Ikeda Hiroyuki Harada Department of Oral and Maxillofacial Surgical Oncology Division of Oral Health ScienceGraduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8549TokyoJapan Department of Oral Pathology Division of Oral Health ScienceGraduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8549TokyoJapan

BACKGROUND Oral liposarcoma is an extremely rare lesion that is often clinically misdiagnosed as a benign tumor due to its asymptomatic and indolent clinical ***,we report a case of massive low-grade myxoid liposarcoma(MLS)of the floor of the *** SUMMARY A 71-year-old man presented with a huge mass in the left floor of the mouth.A biopsy was performed,and a diagnosis of a myxoid tumor suspicious for lowgrade MLS or myxoma was ***-enhanced T1-weighted magnetic resonance imaging showed an intensely enhanced tumor lesion that occupies the left sublingual space and extends to the submandibular *** dissection,tumor resection,and reconstruction with a radial forearm flap were *** surgical specimen exhibited histologically low-grade *** in sarcoma(FUS,also known as TLS)and DNA damage-inducible transcript 3(DDIT3,also known as CHOP)break-apart was not detected in the fluorescence in situ hybridization *** tumor was completely encapsulated and did not require additional ***,no recurrence was reported 40 mo after *** We experienced an extremely rare,massive,low-grade MLS emerging from the floor of the ***,an MLS of the floor of the mouth lacks significant clinical findings and is often *** no FUS-DDIT3 fusion gene was detected,a low-grade MLS was ultimately diagnosed based on the histological findings.

关键词： Myxoid liposarcoma Floor of mouth Surgery Fluorescence in situ hybridization Sublingual space Case report

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Narrow portion of the terminal choledochus is a cause of upstream biliary dilatation in patients with anomalous union of the pancreatic and biliary ducts

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World Journal of Gastroenterology 2005年第41期11卷 6503-6507页

作者： Tatsuya Nomura Yoshio Shirai Toshifumi Wakai Naoyuki Yokoyama Jun Sakata Katsuyoshi Hatakeyama division of Digestive and General Surgery Niigata University Graduate school of medical and Dental sciences 1 Asahimachi-doriNiigata951-8510Japan

AIM: To clarify the pathogenesis of biliary dilatation associated with anomalous union of the pancreatic and biliary ducts (AUPBD).METHODS: Direct cholangiopancreatograms of 350 adult patients with or with suspicion of hepatobiliary or pancreatic disorders were reviewed. AUPBD was diagnosed cholangiopancreatographically, when the pancreaticobiliary ductal union was located above the narrow distal segment of the bile duct, which represents the action of the sphincter of Oddi. The narrow portion of the terminal choledochus was defined as symmetrical stricture of the common bile duct just above the pancreaticobiliary ductal ***: AUPBD was found in 36 patients. Among cholangiopancreatographic features, the narrow portion of the terminal choledochus was the most pathognomonic for AUPBD (accuracy, 98%); it was present in 29 (81%)patients with AUPBD, but was not found in any patients without AUPBD. Among patients with AUPBD, biliary dilatation (＞10 mm) was more frequent in those with the narrow portion of the terminal choledochus (23/29)than in those without (2/7; P = 0.018) AUPBD. Among the patients with both AUPBD and the narrow portion of the terminal choledochus, there was a strong negative correlation between the minimum diameter of the narrow portion and the maximum diameter of the choledochus (r = -0.78, P＜0.001), suggesting that the degree of biliary narrowing at the narrow portion correlates with that of upstream biliary ***: The narrow portion of the terminal choledochus, a pathognomonic radiologic feature of AUPBD, may be a cause of biliary dilatation in patients with AUPBD.

关键词： Anomalous Biliary dilatation Congenital biliary dilatation Congenital choledochal cyst Terminal choledochus Cholangiopancreatography

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