咳嗽病毒杀死肝癌细胞和肝炎病毒

StephenW

Public Release: 15-Nov-2016
Cough virus kills liver cancer cells and hepatitis virus

Reovirus stimulates the body's own immune system to kill off the cancerous cells

University of Leeds

A virus that causes childhood coughs and colds could help in the fight against primary liver cancer, according to a study.

Reovirus stimulates the body's own immune system to kill off the cancerous cells, the researchers at the University of Leeds found.

In addition, Reovirus is able to kill off the hepatitis C virus - a common cause of primary liver cancer - at the same time, the team discovered.

These early-stage findings are important because primary liver cancer is the third highest cause of cancer deaths worldwide and, if surgery is not an option, the prognosis is poor.

Study co-leader Dr Stephen Griffin, Associate Professor of Viral Oncology at the University of Leeds, said: "Ultimately we hope that by simultaneously treating the tumour, and the hepatitis virus that is driving the growth of the tumour, we may provide a more effective therapy and improve the outcomes for patients.

"Current treatments for liver cancer that can't be removed by surgery are mainly palliative - with chemotherapy only tending to prolong life, rather than cure - and it can have significant side effects."

Reovirus can cause respiratory illnesses and stomach upsets in children but by adulthood most people have been exposed to it and therefore it does not cause illness.

The University of Leeds team, whose study is published today in the journal Gut, found that Reovirus was successful in treating both liver cancer cells grown in the laboratory and those taken directly from patients undergoing surgery.

When introduced into the body, Reovirus stimulates an immune system factor known as interferon, which in turn causes the activation of a specific white blood cell called a Natural Killer cell.

These Natural Killer cells then kill both the tumour, and cells infected with the hepatitis C virus.

Stimulating the immune system to kill cancer cells is known as immunotherapy. It differs from chemotherapy, in which the actual drugs kill the cancer cells.

The researchers are now hoping to start the first in-human clinical trials.

Study co-leader Professor Alan Melcher, now Professor of Translational Immunotherapy at the Institute of Cancer Research, London, said:

"Our study establishes a completely new type of viral immunotherapy for the most common primary liver cancer type, hepatocellular carcinoma, which has a very poor prognosis in its advanced form.

"Using a mixture of experiments in human cancer samples and mice, our research showed that the Reovirus therapy switches on the host immune system to attack cancer cells - as well as suppressing the replication of hepatitis C virus, which is linked to many hepatocellular cancers.

"We also showed that Reovirus therapy could be used to treat a range of other cancer types associated with viral infection, including Epstein Barr Virus-associated lymphoma."

Primary liver cancer is cancer that starts in the liver. It is a separate condition from secondary liver cancer, where the cancer originally developed in another part of the body and then spread to the liver.

Most cases of primary liver cancer are associated with damage and scarring of the liver, most commonly from having a hepatitis B or hepatitis C viral infection. Less commonly it is caused by drinking excessive amounts of alcohol over many years.

At least 130 million people globally have chronic hepatitis C infection, according to the World Health Organisation, and a significant proportion of these will develop liver cancer.

Co-researcher Dr Adel Samson from the University of Leeds said: "It is becoming increasingly clear that one of the most powerful weapons available to treat cancer is our own immune system.

"However, as cancers are formed from our own cells, the immune system frequently struggles to identify the subtle differences that differentiate cancerous cells from normal cells, without help.

"Immunotherapy involves various strategies - such as a virus, as in our study - to kick-start our immune system to better identify and fight cancer.

"These 'oncolytic' viruses show great promise in clinical trials, and the first such virus has recently been licensed as a medicine for the treatment of skin cancer."

Dr Justine Alford, senior science information officer at Cancer Research UK which funded the research, said: "This study in cells and mice suggests the possibility of using a harmless oncolytic virus as an immune-boosting one-two punch against liver cancer and the cancer-causing hepatitis C virus.

"These early results also suggest this oncolytic virus could be used more widely in the treatment of virus-driven cancers.

"In these cancers, the viruses can represent a major hurdle for treatment, so we urgently need new and effective ways to tackle the root of the problem.

"The next step will be to see if this technique will work in patients."

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MORE INFORMATION

For a copy of the research paper, or to interview Dr Stephen Griffin, contact the University of Leeds press office on 0113 343 4031 or email [email protected]

To interview Professor Alan Melcher, contact the Institute of Cancer Research press office on 0207 153 5380.

StephenW

公开发布：2016年11月15日
咳嗽病毒杀死肝癌细胞和肝炎病毒

呼肠孤病毒刺激身体自身的免疫系统以杀死癌细胞

利兹大学

根据一项研究，导致儿童咳嗽和感冒的病毒可帮助对抗原发性肝癌。

呼吸道病毒刺激机体自身的免疫系统杀死癌细胞，利兹大学的研究人员发现。

此外，呼肠孤病毒能够杀死丙型肝炎病毒 - 这是原发性肝癌的常见原因，同时，研究小组发现。

这些早期发现是重要的，因为原发性肝癌是全世界癌症死亡的第三高原因，如果手术不是一种选择，预后很差。

研究共同领导者利兹大学病毒肿瘤学副教授Stephen Griffin博士说：“最终我们希望通过同时治疗肿瘤和推动肿瘤生长的肝炎病毒，我们可以提供更多有效治疗并改善患者的预后。

“目前治疗肝癌不能通过手术去除主要是姑息治疗 - 化疗只能延长寿命，而不是治愈，并且它可以有显着的副作用。

呼肠孤病毒可以引起儿童的呼吸道疾病和胃部不适，但是成年后大多数人已经暴露于其中，因此它不会引起疾病。

利兹大学的研究团队今天发表在期刊Gut上，发现呼肠孤病毒成功地治疗了实验室中生长的肝癌细胞和直接从接受手术的患者获得的肝癌细胞。

当引入体内时，呼吸道病毒刺激称为干扰素的免疫系统因子，其又导致称为自然杀伤细胞的特异性白细胞的活化。

这些自然杀伤细胞然后杀死肿瘤和感染了丙型肝炎病毒的细胞。

刺激免疫系统以杀死癌细胞被称为免疫治疗。它不同于化疗，其中实际的药物杀死癌细胞。

研究人员现在希望开始第一次人体临床试验。

研究共同领导者Alan Melcher教授，现为伦敦癌症研究所转化免疫治疗教授说：

“我们的研究建立了一种全新类型的病毒免疫治疗最常见的原发性肝癌类型，肝细胞癌，其先进形式的预后非常差。

“在人类癌症样本和小鼠中使用实验的混合物，我们的研究表明呼肠病毒治疗开启宿主免疫系统攻击癌细胞，以及抑制与许多肝细胞癌相关的丙型肝炎病毒的复制。

“我们还显示呼肠孤病毒治疗可用于治疗一系列与病毒感染相关的其他癌症类型，包括爱泼斯坦巴尔病毒相关淋巴瘤。

原发性肝癌是在肝脏中开始的癌症。它是与继发性肝癌不同的病症，其中癌症最初在身体的另一部分中发展，然后扩散到肝脏。

大多数原发性肝癌的病例与肝脏的损伤和瘢痕形成有关，最常见的是患有乙型肝炎或丙型肝炎病毒感染。较不常见的是多年来饮用过量的酒精引起的。

根据世界卫生组织的数据，全球至少有1.3亿人患有慢性丙型肝炎感染，其中很大一部分将发展成肝癌。

来自利兹大学的Adel Samson博士的合作研究员说：“越来越清楚，用于治疗癌症的最强大的武器之一是我们自己的免疫系统。

“然而，由于癌症是由我们自己的细胞形成的，免疫系统经常努力找出微小的差异，从而区分癌细胞与正常细胞，没有帮助。

“免疫疗法包括各种策略 - 例如病毒，如我们的研究 - 启动我们的免疫系统，以更好地识别和对抗癌症。

“这些”溶瘤病毒“病毒在临床试验中显示出巨大的希望，第一个这样的病毒最近已被许可作为治疗皮肤癌的药物。

“癌症研究英国癌症研究高级科学信息官Justine Alford博士说，”这项研究在细胞和小鼠中提示了使用无害的溶瘤病毒作为免疫促进一两对肝癌和癌症的可能性 - 引起的丙型肝炎病毒。

“这些早期结果也表明这种溶瘤病毒可以更广泛地用于治疗病毒驱动的癌症。

“在这些癌症中，病毒可能是治疗的主要障碍，因此我们迫切需要新的有效的方法来解决问题的根源。

“下一步将是看这种技术是否会在患者中工作。

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更多信息

有关研究论文的副本或采访Stephen Griffin博士，请联系利兹大学新闻办公室（电话：0113 343 4031）或发送电子邮件至[email protected]

要访问Alan Melcher教授，请联系癌症研究所新闻办公室0207 153 5380。

newchinabok

今天试了一下。咳嗽了一天，感觉肝脏是好多了

只一个衣

多了一份希望。

幸福来临

自从09年开始嗑药抗病毒，我这些年就没感冒过，这是好事儿还是坏事儿啊

StephenW

回复 幸福来临 的帖子

好事.三楼只是开玩笑.

东霸天

乙肝患者都不感冒  怎么办？  我大三   好几年不感冒  我都羡慕感冒的人？

StephenW

Gut doi:10.1136/gutjnl-2016-312009

    Hepatology

    Original article

Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer
Open Access

    Adel Samson1, Matthew J Bentham1, Karen Scott1, Gerard Nuovo2, Abigail Bloy1, Elizabeth Appleton1, Robert A Adair1, Rajiv Dave1, Adam Peckham-Cooper1, Giles Toogood1, Seishi Nagamori, Matthew Coffey3,4, Richard Vile1,5,6, Kevin Harrington6, Peter Selby1, Fiona Errington-Mais1, Alan Melcher6, Stephen Griffin1

    1Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James’ University Hospital, Leeds, UK
    2The Ohio State University, Comprehensive Cancer Centre, Columbus, Ohio, USA
    3Department of Virology II, National Institute of Infectious Diseases 1-23-1 Toyama, Tokyo, Japan
    4Oncolytics Biotech, Calgary, Alberta, Canada
    5Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
    6Department of Molecular Medicine, The Institute of Cancer Research, London, UK

    Correspondence to Dr Stephen Griffin and Prof Alan Melcher, Faculty of Medicine and Health, Leeds Institute of Cancer & Pathology, University of Leeds, Wellcome Trust Brenner Building, St James’ University Hospital, Leeds LS7 9TF, UK; s.d.c.griffin{at}leeds.ac.uk and a.a.melcher{at}leeds.ac.uk

    Received 6 April 2016
    Revised 26 September 2016
    Accepted 13 October 2016
    Published Online First 15 November 2016

Abstract

Objective Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer.

Design and results Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein–Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue.

Conclusions We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

StephenW

Gut doi：10.1136 / gutjnl-2016-312009

    肝脏病学

    原文

溶瘤呼肠孤病毒作为组合的抗病毒和抗肿瘤剂用于治疗肝癌
开放获取

    Adel Samson1，Matthew J Bentham1，Karen Scott1，Gerard Nuovo2，Abigail Bloy1，Elizabeth Appleton1，Robert A Adair1，Rajiv Dave1，Adam Peckham-Cooper1，Giles Toogood1，Seishi Nagamori，Matthew Coffey3,4，Richard Vile1,5,6，Kevin Harrington6，Peter Selby1，Fiona Errington-Mais1，Alan Melcher6，Stephen Griffin1

    1利兹癌症与病理学研究所（LICAP）和利兹癌症研究英国临床中心，利兹大学医学与健康学院，圣詹姆斯大学医院，英国利兹
    2俄亥俄州立大学，综合癌症中心，哥伦布，俄亥俄州，美国
    3Department of Virology II，National Institute of Infectious Diseases 1-23-1 Toyama，Tokyo，Japan
    4Oncolytics Biotech，Calgary，Alberta，Canada
    5，美国明尼苏达州罗切斯特市梅奥诊所免疫学部
    6分子医学，分子医学研究所，癌症研究所，伦敦，英国

    通讯作者：Stephen Griffin博士和Alan Melcher教授，利兹大学利兹癌症与病理学研究所医学与健康学院，Wellcome Trust Brenner大楼，圣詹姆斯大学医院，Leeds LS7 9TF，英国;斯里格斯·格里芬

    收到2016年4月6日
    2016年9月26日修订
    接受2016年10月13日
    在线发布首先2016年11月15日

抽象

目的溶瘤病毒（OV）代表有希望的促炎症癌症治疗。在这里，我们探讨OV诱导先天免疫反应是否可以同时抑制HCV而抑制肝细胞癌（HCC）。此外，我们将这个示例扩展到其他病毒相关癌症模型。

设计和结果临床级溶瘤性直肠病毒（Reo）在不存在细胞毒性且不依赖于病毒基因组复制的情况下在原代人肝组织内引发先天免疫激活。除了通过激活先天脱颗粒免疫细胞在HCC的临床前模型中实现治疗，Reo诱导的细胞因子应答有效抑制体外和体内的HCV复制。此外，Reo诱导的先天反应也有效对抗HBV相关HCC模型，以及爱泼斯坦 - 巴尔病毒相关淋巴瘤的替代内源性模型。有趣的是，Reo在其引起来自原发性肝组织的固有炎症反应的能力方面优于OV的大多数。

结论我们建议Reo和其他选择性促炎性OV可用于治疗与致癌病毒感染相关的多种癌症，同时减少病毒相关的致癌性驱动和肿瘤负荷。在HCV相关HCC（HCV-HCC）的情况下，Reo应该被认为是补充和支持当前HCV-HCC治疗的替代药剂，特别是在那些获得新的HCV抗病毒治疗可能有限的国家。

这是一个根据知识共享署名（CC BY 4.0）许可条款分发的开放获取文章，允许他人分发，重新混合，适应和构建这项工作，商业使用，只要原始的工作被正确引用。参见：http：//creativecommons.org/licenses/by/4.0/

hao2014

我昨天咳嗽了半小时


然后今天检查 ，惊奇的发现 ALT AST下降5.38%左右  抗原下降0.15log  抗体缓慢增多

不敢独享 给各位增添一点正能量