AMI Podcast
November 13, 2017 episode
2017 World Hepatitis Summit
Hepatitis C in Canada
Dr. Jordan Feld from the Toronto Centre for Liver Disease discuss what it will take for hepatitis C to be cured in Canada.
Of all infectious disease in Canada the one disease that causes most years of life lost is hepatitis C.
Listen here......
Wednesday, November 15, 2017
Listen: With Stricter Guidelines, Do You Have High Blood Pressure Now?
November 14, 201712:56 PM ET
Heard on All Things Considered
You may not have had high blood pressure Sunday, but you may have it today. Even if your blood pressure hasn't changed a smidge. What's up?
The rules shifted Monday. It used to be that we encouraged people to adopt healthy behavior to keep their blood pressure down but didn't label someone as having hypertension until systolic blood pressure (the top number) exceeded 140 millimeters of mercury and/or the diastolic blood pressure (the bottom number) exceeded 90 mm Hg. Lots of people watch those numbers closely.
Now the American College of Cardiology and the American Heart Association have updated blood pressure guidelines that move the goal post for many people.
Continue reading......
NIH blood pressure study supports important part of new AHA/ACC hypertension guidelines
Today the AHA and the ACC issued the first comprehensive new high blood pressure guidelines in more than a decade that indicate high blood pressure should be treated earlier with lifestyle changes and in some patients with medication – at 130/80 mm Hg rather than 140/90. An important component of these guidelines was informed by the results of the Systolic Blood Pressure Intervention Trial (SPRINT), a clinical study sponsored in part by the NHLBI and designed to determine the best way to treat blood pressure in adults with hypertension, 50 years or older, who are at high risk for heart disease.
SPRINT, which began in the fall of 2009, included more than 9,300 participants, recruited from about 100 medical centers and clinical practices throughout the United States. It remains the largest study of its kind to date to examine how maintaining systolic blood pressure at a lower than previously recommended level would impact cardiovascular and kidney diseases.
http://hepatitiscnewdrugs.blogspot.com/2017/11/nih-blood-pressure-study-supports.html
Heard on All Things Considered
You may not have had high blood pressure Sunday, but you may have it today. Even if your blood pressure hasn't changed a smidge. What's up?
The rules shifted Monday. It used to be that we encouraged people to adopt healthy behavior to keep their blood pressure down but didn't label someone as having hypertension until systolic blood pressure (the top number) exceeded 140 millimeters of mercury and/or the diastolic blood pressure (the bottom number) exceeded 90 mm Hg. Lots of people watch those numbers closely.
Now the American College of Cardiology and the American Heart Association have updated blood pressure guidelines that move the goal post for many people.
Continue reading......
NIH blood pressure study supports important part of new AHA/ACC hypertension guidelines
Today the AHA and the ACC issued the first comprehensive new high blood pressure guidelines in more than a decade that indicate high blood pressure should be treated earlier with lifestyle changes and in some patients with medication – at 130/80 mm Hg rather than 140/90. An important component of these guidelines was informed by the results of the Systolic Blood Pressure Intervention Trial (SPRINT), a clinical study sponsored in part by the NHLBI and designed to determine the best way to treat blood pressure in adults with hypertension, 50 years or older, who are at high risk for heart disease.
SPRINT, which began in the fall of 2009, included more than 9,300 participants, recruited from about 100 medical centers and clinical practices throughout the United States. It remains the largest study of its kind to date to examine how maintaining systolic blood pressure at a lower than previously recommended level would impact cardiovascular and kidney diseases.
http://hepatitiscnewdrugs.blogspot.com/2017/11/nih-blood-pressure-study-supports.html
Tuesday, November 14, 2017
Current and emerging pharmacological therapy for non-alcoholic fatty liver disease
Editorial
World J Gastroenterol. Nov 14, 2017; 23(42): 7495-7504
Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7495
Full Text Article Available Online
https://www.wjgnet.com/1007-9327/full/v23/i42/7495.htm
Current and emerging pharmacological therapy for non-alcoholic fatty liver disease
The main treatment of patients with non-alcoholic fatty liver disease (NAFLD) is life style modification including weight reduction and dietary regimen. Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis (NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an anti-oxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.
Core tip: Non-alcoholic fatty liver disease (NAFLD) is an increasing liver disease worldwide. However, most of patients are treated with life style modification including weight loss and dietary regimen. Pharmacologic therapy may be indicated in a group of patients with non-alcoholic steatohepatitis. Here in, the current and emerging medications for treatment of NAFLD was reviewed briefly with regard of their beneficial effects on histological outcomes.
Full Text: https://www.wjgnet.com/1007-9327/full/v23/i42/7495.htm
World J Gastroenterol. Nov 14, 2017; 23(42): 7495-7504
Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7495
Full Text Article Available Online
https://www.wjgnet.com/1007-9327/full/v23/i42/7495.htm
Current and emerging pharmacological therapy for non-alcoholic fatty liver disease
The main treatment of patients with non-alcoholic fatty liver disease (NAFLD) is life style modification including weight reduction and dietary regimen. Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis (NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an anti-oxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.
Core tip: Non-alcoholic fatty liver disease (NAFLD) is an increasing liver disease worldwide. However, most of patients are treated with life style modification including weight loss and dietary regimen. Pharmacologic therapy may be indicated in a group of patients with non-alcoholic steatohepatitis. Here in, the current and emerging medications for treatment of NAFLD was reviewed briefly with regard of their beneficial effects on histological outcomes.
Full Text: https://www.wjgnet.com/1007-9327/full/v23/i42/7495.htm
The negative impact of HBV/HCV coinfection on cirrhosis and its consequences
Alimentary Pharmacology & Therapeutics
The negative impact of HBV/HCV coinfection on cirrhosis and its consequences
The negative impact of HBV/HCV coinfection on cirrhosis and its consequences
Summary Source - http://www.gastrohep.com/news/news.asp?id=112892
Full Text Article
Alimentary Pharmacology & Therapeutics| Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. Dr Pol and colleagues from France compared the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. Of the 20,936 included patients, 95 had HBV/HCV coinfection, and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. F3-F4 fibrosis was more frequent in coinfected patients than in HBV-, but similar in HCV-monoinfected patients. Decompensated cirrhosis was more frequent in coinfected patients than in HBV- or HCV- monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients than in HBV, but similar in HCV monoinfected patients. The researchers found that coinfected patients had a higher proportion with arterial hypertension than HBV- or HCV-monoinfected patients. The research team confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients, and the association between decompensated cirrhosis and coinfection in HBV infected or HCV infected patients. Dr Pol's team concludes, "HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients." "HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients." Continue to full text - http://onlinelibrary.wiley.com/doi/10.1111/apt.14352/full |
FDA warns of ‘deadly risks’ of the herb kratom, citing 36 deaths
FDA warns of ‘deadly risks’ of the herb kratom, citing 36 deaths
Nonalcoholic fatty liver disease increases risk of liver, colorectal, and breast cancers
Public Release: 13-Nov-2017
Nonalcoholic fatty liver disease increases risk of liver, colorectal, and breast cancers
NAFLD is not only linked to hepatocellular carcinoma, but also to cancers outside the liver, report investigators in the Journal of Hepatology
Amsterdam, November 14, 2017 - Nonalcoholic fatty liver disease (NAFLD) is one of the more common chronic liver diseases worldwide. It is associated with metabolic syndrome (i.e. insulin resistance and diabetes) and predisposes to cardiovascular disease. In a new study published in the Journal of Hepatology, researchers identified links not only between NAFLD and hepatocellular carcinoma (HCC), which have been well established, but also to cancers outside the liver, including colorectal and breast cancer.
"NAFLD is a very important multisystem disease to which much attention should be paid," explained lead author Gi-Ae Kim, of the Health Screening and Promotion Center, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea. "Despite its strong relationship with HCC development, little attention has been paid to the association of NAFLD with the development of other extrahepatic cancers. Our study presents statistical evidence that NAFLD is associated with extrahepatic cancers. We hope this study will raise awareness of the increased cancer potential that NAFLD might have."
This retrospective study evaluated the records of almost 26,000 Korean individuals who underwent health checkups from September 2004 through December 2005, who had no cancer diagnosis within one year of the checkup, and were followed for an average of 7.5 years.
Data revealed that 8,721 (33.6%) of individuals in the study were diagnosed with NAFLD, and cancer incidence in that group was 32% higher than in the non-NAFLD group. Once the data were adjusted for demographic and metabolic factors, significant risks for specific cancers became evident. Specifically, patients with NAFLD were 16.73 times more likely to develop HCC, twice as likely to develop colorectal cancer (men), and almost twice as likely to develop breast cancer (women).
High scores on two measurements of liver fibrosis, the NAFLD fibrosis score (NFS) and the FIB-4 score, were also associated with a higher risk for all cancers, and especially HCC. A high NFS score indicated an 87% increase in risk and high FIB-4 score a 74% increase in risk. These scores serve as a predictor of cancers and of HCC in particular.
Principal investigator Han Chu Lee, MD, of the Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, noted, "Our results suggest that patients with NAFLD require multidisciplinary evaluation with particular attention to the development of cancers. Further studies are needed to specify which high-risk groups among patients with NAFLD carry a greater risk of developing specific cancers, including HCC, colorectal cancer, and breast cancer and that we should pay more attention to the cancer potential of NAFLD in clinical practice."
In an accompanying editorial, Peter Jepsen, PhD, of the Department of Hepatology and Gastroenterology and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark, and co-authors add perspective. "NAFLD is likely to become the most prevalent liver disease in many countries, yet clinicians are struggling to determine exactly why they should care about NAFLD. Is it merely a bystander--a manifestation of the metabolic syndrome resulting in cardiovascular disease--or is it a liver disease in its own right?"
Dr. Jepsen concludes that despite a number of open issues, the Korean cohort study by Kim et al provides relevant and valid information on the association between NAFLD and cancer risk, and definite evidence on its strong association with HCC.
Nonalcoholic fatty liver disease increases risk of liver, colorectal, and breast cancers
NAFLD is not only linked to hepatocellular carcinoma, but also to cancers outside the liver, report investigators in the Journal of Hepatology
Amsterdam, November 14, 2017 - Nonalcoholic fatty liver disease (NAFLD) is one of the more common chronic liver diseases worldwide. It is associated with metabolic syndrome (i.e. insulin resistance and diabetes) and predisposes to cardiovascular disease. In a new study published in the Journal of Hepatology, researchers identified links not only between NAFLD and hepatocellular carcinoma (HCC), which have been well established, but also to cancers outside the liver, including colorectal and breast cancer.
"NAFLD is a very important multisystem disease to which much attention should be paid," explained lead author Gi-Ae Kim, of the Health Screening and Promotion Center, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea. "Despite its strong relationship with HCC development, little attention has been paid to the association of NAFLD with the development of other extrahepatic cancers. Our study presents statistical evidence that NAFLD is associated with extrahepatic cancers. We hope this study will raise awareness of the increased cancer potential that NAFLD might have."
This retrospective study evaluated the records of almost 26,000 Korean individuals who underwent health checkups from September 2004 through December 2005, who had no cancer diagnosis within one year of the checkup, and were followed for an average of 7.5 years.
Data revealed that 8,721 (33.6%) of individuals in the study were diagnosed with NAFLD, and cancer incidence in that group was 32% higher than in the non-NAFLD group. Once the data were adjusted for demographic and metabolic factors, significant risks for specific cancers became evident. Specifically, patients with NAFLD were 16.73 times more likely to develop HCC, twice as likely to develop colorectal cancer (men), and almost twice as likely to develop breast cancer (women).
High scores on two measurements of liver fibrosis, the NAFLD fibrosis score (NFS) and the FIB-4 score, were also associated with a higher risk for all cancers, and especially HCC. A high NFS score indicated an 87% increase in risk and high FIB-4 score a 74% increase in risk. These scores serve as a predictor of cancers and of HCC in particular.
Principal investigator Han Chu Lee, MD, of the Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, noted, "Our results suggest that patients with NAFLD require multidisciplinary evaluation with particular attention to the development of cancers. Further studies are needed to specify which high-risk groups among patients with NAFLD carry a greater risk of developing specific cancers, including HCC, colorectal cancer, and breast cancer and that we should pay more attention to the cancer potential of NAFLD in clinical practice."
In an accompanying editorial, Peter Jepsen, PhD, of the Department of Hepatology and Gastroenterology and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark, and co-authors add perspective. "NAFLD is likely to become the most prevalent liver disease in many countries, yet clinicians are struggling to determine exactly why they should care about NAFLD. Is it merely a bystander--a manifestation of the metabolic syndrome resulting in cardiovascular disease--or is it a liver disease in its own right?"
Dr. Jepsen concludes that despite a number of open issues, the Korean cohort study by Kim et al provides relevant and valid information on the association between NAFLD and cancer risk, and definite evidence on its strong association with HCC.
'Mini liver tumors' created in a dish for the first time
Public Release: 13-Nov-2017
'Mini liver tumors' created in a dish for the first time
Wellcome Trust
Scientists have created mini biological models of human primary liver cancers, known as organoids, in the lab for the first time. In a paper published today in Nature Medicine, the tiny laboratory models of tumours were used to identify a new drug that could potentially treat certain types of liver cancer.
Primary liver cancer is the second most lethal cancer worldwide. To better understand the biology of the disease and develop potential treatments, researchers need models that can grow in the lab and accurately reflect how the tumours behave in patients. Previously, cultures of cells had been used but these are hard to maintain and fail to recreate the 3D structure and tissue architecture of human tumours.
The researchers created the mini tumours (up to 0.5mm) - termed tumouroids - to mimic the three most common forms of primary liver cancer. The tumour cells were surgically removed from eight patients and grown in a solution containing specific nutrients and substances which prevent healthy cells out-competing the tumour cells. The team, from the Wellcome/Cancer Research UK Gurdon Institute in Cambridge, used the tumouroids to test the efficacy of 29 different drugs, including those currently used in treatment and drugs in development. One compound, a type of protein inhibitor, was found to inhibit the activation of a protein called ERK in two of the three types of tumouroids, a crucial step in the development of liver cancer.
The researchers then tested this compound in vivo, transplanting two types of tumouroids into mice and treating them with the drug. A marked reduction in tumour growth was seen in mice treated with the drug, identifying a potential novel treatment for some types of primary liver cancer.
The tumouroids were able to preserve tissue structure as well as the gene expression patterns of the original human tumours from which they were derived. The individual subtypes of three different types of liver cancer, as well as the different tumour tissues which they came from, were all still distinguishable even after they had been grown in a dish for a long time. As the tumouroids retain the biological features of their parent tumour, they could play an important role in developing personalised medicine for patients.
The creation of biologically accurate models of tumours will also reduce the number of animals needed in certain experiments. Animal studies will still be required to validate findings, but the tumouroids will allow scientists to explore key questions about the biology of liver cancer in cultures rather than mice.
Lead researcher Dr Meritxell Huch, a Wellcome Sir Henry Dale Fellow from the Gurdon Institute, said: "We had previously created organoids from healthy liver tissue, but the creation of liver tumouroids is a big step forward for cancer research. They will allow us to understand much more about the biology of liver cancer and, with further work, could be used to test drugs for individual patients to create personalised treatment plans."
Dr Andrew Chisholm, Head of Cellular and Developmental Sciences at Wellcome said: "This work shows the power of organoid cultures to model human cancers. It is impressive to see just how well the organoids are able to mimic the biology of different liver tumour types, giving researchers a new way of investigating this disease. These models are vital for the next generation of cancer research, and should allow scientists to minimise the numbers of animals used in research."
Dr Vicky Robinson, Chief Executive of the NC3Rs which partially funded the work, said: "We are pleased to see that the funds from our annual 3Rs prize, sponsored by GlaxoSmithKline, have furthered Dr Huch's research. Each year the prize recognises exceptional science which furthers the 3Rs, and the work being conducted by Meri and her team is continuing to make progress in this area. This new breakthrough involving liver cancer organoids has the potential to reduce the number of animals required in the early stages of liver cancer research, and provide more biologically accurate models of human tumours."
###
This work was funded by a National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) research prize, Wellcome and Cancer Research UK Cambridge Centre.
The paper Human primary liver cancer-derived organoid cultures for disease modelling and drug screening is published in Nature Medicine http://dx.doi.org/10.1038/nm.4438 (URL will go live after embargo lifts)
About the Wellcome/Cancer Research UK Gurdon Institute
Named after its co-founder, Nobel Laureate Sir John Gurdon, the Gurdon Institute is a world-leading centre for research into the fundamental processes of biology and development, and how these go wrong in diseases such as cancer. More than 240 scientists work in the Institute's purpose-built laboratories on projects ranging from breast cancer and brain development to liver regeneration and leukaemia. Many have made pioneering contributions to the fields of basic cell biology, cellular reprogramming, epigenetics and DNA repair. Institute scientists use a range of model systems such as yeast, nematode worms, fruit flies, frogs, mammalian cells and organoids to study development and disease at the level of molecules, cells and tissues. Research conducted at the Institute has so far led to 11 spin-out companies (including Abcam, CellCentric, MISSION Therapeutics and Gen2 Neuroscience) and several candidate therapeutics have entered clinical trials. One of these, olaparib (Lynparza), has been approved in the UK, Europe and the USA for use against ovarian cancers. http://www.gurdon.cam.ac.uk
About the NC3Rs
The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is a leading independent scientific organisation dedicated to replacing, refining and reducing the use of animals in research and testing (the 3Rs). It supports the UK science base by driving and funding innovation and technological developments that minimise the need for animals in research and testing, and lead to improvements in welfare where animals continue to be used. It funds research, supports training and development, and stimulates changes in regulations and practice. Primarily funded by Government, the NC3Rs is also supported by the charitable and private sectors. It works with scientists in universities and industry in the UK and internationally. http://www.nc3rs.org.uk
About Cancer Research UK Cambridge Centre
The Cancer Research UK Cambridge Centre is a dynamic collaboration of over 600 academic researchers, clinicians, and scientists in the pharmaceutical and biotech industries, based in the Cambridge area. The Centre combines world-class science and technology with excellent patient care to pioneer new ways to prevent, detect, diagnose and treat cancer. By working together across different disciplines, the Centre is breaking down the barriers between the laboratory and the clinic, enabling patients to benefit from the latest innovations in cancer science faster. The formal partners of the Cancer Research UK Cambridge Centre are Cancer Research UK, the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust. http://www.crukcambridgecentre.org.uk
About Wellcome
Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. Wellcome.ac.uk
'Mini liver tumors' created in a dish for the first time
Wellcome Trust
Scientists have created mini biological models of human primary liver cancers, known as organoids, in the lab for the first time. In a paper published today in Nature Medicine, the tiny laboratory models of tumours were used to identify a new drug that could potentially treat certain types of liver cancer.
Primary liver cancer is the second most lethal cancer worldwide. To better understand the biology of the disease and develop potential treatments, researchers need models that can grow in the lab and accurately reflect how the tumours behave in patients. Previously, cultures of cells had been used but these are hard to maintain and fail to recreate the 3D structure and tissue architecture of human tumours.
The researchers created the mini tumours (up to 0.5mm) - termed tumouroids - to mimic the three most common forms of primary liver cancer. The tumour cells were surgically removed from eight patients and grown in a solution containing specific nutrients and substances which prevent healthy cells out-competing the tumour cells. The team, from the Wellcome/Cancer Research UK Gurdon Institute in Cambridge, used the tumouroids to test the efficacy of 29 different drugs, including those currently used in treatment and drugs in development. One compound, a type of protein inhibitor, was found to inhibit the activation of a protein called ERK in two of the three types of tumouroids, a crucial step in the development of liver cancer.
The researchers then tested this compound in vivo, transplanting two types of tumouroids into mice and treating them with the drug. A marked reduction in tumour growth was seen in mice treated with the drug, identifying a potential novel treatment for some types of primary liver cancer.
The tumouroids were able to preserve tissue structure as well as the gene expression patterns of the original human tumours from which they were derived. The individual subtypes of three different types of liver cancer, as well as the different tumour tissues which they came from, were all still distinguishable even after they had been grown in a dish for a long time. As the tumouroids retain the biological features of their parent tumour, they could play an important role in developing personalised medicine for patients.
The creation of biologically accurate models of tumours will also reduce the number of animals needed in certain experiments. Animal studies will still be required to validate findings, but the tumouroids will allow scientists to explore key questions about the biology of liver cancer in cultures rather than mice.
Lead researcher Dr Meritxell Huch, a Wellcome Sir Henry Dale Fellow from the Gurdon Institute, said: "We had previously created organoids from healthy liver tissue, but the creation of liver tumouroids is a big step forward for cancer research. They will allow us to understand much more about the biology of liver cancer and, with further work, could be used to test drugs for individual patients to create personalised treatment plans."
Dr Andrew Chisholm, Head of Cellular and Developmental Sciences at Wellcome said: "This work shows the power of organoid cultures to model human cancers. It is impressive to see just how well the organoids are able to mimic the biology of different liver tumour types, giving researchers a new way of investigating this disease. These models are vital for the next generation of cancer research, and should allow scientists to minimise the numbers of animals used in research."
Dr Vicky Robinson, Chief Executive of the NC3Rs which partially funded the work, said: "We are pleased to see that the funds from our annual 3Rs prize, sponsored by GlaxoSmithKline, have furthered Dr Huch's research. Each year the prize recognises exceptional science which furthers the 3Rs, and the work being conducted by Meri and her team is continuing to make progress in this area. This new breakthrough involving liver cancer organoids has the potential to reduce the number of animals required in the early stages of liver cancer research, and provide more biologically accurate models of human tumours."
###
This work was funded by a National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) research prize, Wellcome and Cancer Research UK Cambridge Centre.
The paper Human primary liver cancer-derived organoid cultures for disease modelling and drug screening is published in Nature Medicine http://dx.doi.org/10.1038/nm.4438 (URL will go live after embargo lifts)
About the Wellcome/Cancer Research UK Gurdon Institute
Named after its co-founder, Nobel Laureate Sir John Gurdon, the Gurdon Institute is a world-leading centre for research into the fundamental processes of biology and development, and how these go wrong in diseases such as cancer. More than 240 scientists work in the Institute's purpose-built laboratories on projects ranging from breast cancer and brain development to liver regeneration and leukaemia. Many have made pioneering contributions to the fields of basic cell biology, cellular reprogramming, epigenetics and DNA repair. Institute scientists use a range of model systems such as yeast, nematode worms, fruit flies, frogs, mammalian cells and organoids to study development and disease at the level of molecules, cells and tissues. Research conducted at the Institute has so far led to 11 spin-out companies (including Abcam, CellCentric, MISSION Therapeutics and Gen2 Neuroscience) and several candidate therapeutics have entered clinical trials. One of these, olaparib (Lynparza), has been approved in the UK, Europe and the USA for use against ovarian cancers. http://www.gurdon.cam.ac.uk
About the NC3Rs
The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is a leading independent scientific organisation dedicated to replacing, refining and reducing the use of animals in research and testing (the 3Rs). It supports the UK science base by driving and funding innovation and technological developments that minimise the need for animals in research and testing, and lead to improvements in welfare where animals continue to be used. It funds research, supports training and development, and stimulates changes in regulations and practice. Primarily funded by Government, the NC3Rs is also supported by the charitable and private sectors. It works with scientists in universities and industry in the UK and internationally. http://www.nc3rs.org.uk
About Cancer Research UK Cambridge Centre
The Cancer Research UK Cambridge Centre is a dynamic collaboration of over 600 academic researchers, clinicians, and scientists in the pharmaceutical and biotech industries, based in the Cambridge area. The Centre combines world-class science and technology with excellent patient care to pioneer new ways to prevent, detect, diagnose and treat cancer. By working together across different disciplines, the Centre is breaking down the barriers between the laboratory and the clinic, enabling patients to benefit from the latest innovations in cancer science faster. The formal partners of the Cancer Research UK Cambridge Centre are Cancer Research UK, the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust. http://www.crukcambridgecentre.org.uk
About Wellcome
Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. Wellcome.ac.uk
A new strategy for prevention of liver cancer development
Public Release:
A new strategy for prevention of liver cancer development
A synthetic double-stranded RNA has potential for use as an anti-liver cancer vaccine
University of California - San Diego
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective treatments or drugs. However, an unexpected finding made by a team of University of California San Diego School of Medicine researchers sheds light on the development of a new strategy for prevention of liver cancer.
While studying the pathogenic mechanisms of liver cancer, the researchers discovered that a commonly used synthetic double-stranded RNA (dsRNA) strongly boosts a variety of anti-tumor innate immune functions. They suggest it may have the potential to be administered as a vaccine to prevent cancer in individuals at high-risk of developing liver cancer.
"The liver has unique immune tolerance, which is why existing treatments, including immunotherapy, have little to no lasting effects on liver cancer," said Gen-Sheng Feng, PhD, professor of pathology and molecular biology at UC San Diego and senior author on the paper. "We were initially performing gene deletion to investigate how different types of cells communicate in the liver to promote or suppress cancer development when we found that this synthetic double-stranded RNA prevented liver cancer from initiating by harnessing the body's own innate immune system."
In the findings, published online on November 14 in Cell Reports, researchers describe how dsRNA polyinosinic-polycytidylic acid (pIC) prevented primary liver cancer from occurring in mouse models when it was injected into the body cavity during the pre-cancer stage. Primary liver cancer is cancer that begins in the liver; metastatic liver cancer starts elsewhere in the body and spreads to the liver.
The study showed that the formation of tumors -- or tumorigenesis -- was suppressed by reprogramming macrophages (specialized immune cells that destroy targeted cells) and activation of natural killer cells and dendritic cells that kill tumor cells directly or boost adaptive immunity.
Mouse models with tumors induced either by chemical carcinogen or fatty liver diseases were injected with pIC at different stages. Tumor inhibition was successful in all models that received the dsRNA before tumor formation. The greatest decrease in tumor numbers and size was seen when pIC was administered at one month. At three months the impact was reduced but still significant. At five months, when tumors had already began to form, there was little inhibitory effect observed when comparing tumor numbers or sizes to control groups.
Future studies will look at dosages and timing of pIC as a vaccine, said Feng. In addition, the researchers will evaluate the use of pIC in combination with other agents to stop tumor growth when cancer has already initiated.
"The findings suggest that the drug may prevent liver cancer. We have more work to do, but we could make a real impact at a time when liver cancer rates are increasing," said Feng, also a researcher with UC San Diego Moores Cancer Center. "There is a large population living with chronic liver disease who are at high risk of developing cancer. If we can develop a vaccine that prevents tumor formation or a therapeutic combination that stops existing cancer from growing, we could reduce the rapid increase of liver cancer rates."
Liver cancer in adults is among the leading causes of cancer mortality in the world, with more than 780,000 new cases and 740,000 deaths each year. More than 40,000 new cases are diagnosed and 29,000 deaths are reported in the United States annually.
Co-authors include: Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M. Varki, Wenxian Fu, UC San Diego; Shuang-Jian Qiu, Fudan University; and Bing Ren, Ludwig Cancer Research Institute and UC San Diego.
A synthetic double-stranded RNA has potential for use as an anti-liver cancer vaccine
University of California - San Diego
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective treatments or drugs. However, an unexpected finding made by a team of University of California San Diego School of Medicine researchers sheds light on the development of a new strategy for prevention of liver cancer.
While studying the pathogenic mechanisms of liver cancer, the researchers discovered that a commonly used synthetic double-stranded RNA (dsRNA) strongly boosts a variety of anti-tumor innate immune functions. They suggest it may have the potential to be administered as a vaccine to prevent cancer in individuals at high-risk of developing liver cancer.
"The liver has unique immune tolerance, which is why existing treatments, including immunotherapy, have little to no lasting effects on liver cancer," said Gen-Sheng Feng, PhD, professor of pathology and molecular biology at UC San Diego and senior author on the paper. "We were initially performing gene deletion to investigate how different types of cells communicate in the liver to promote or suppress cancer development when we found that this synthetic double-stranded RNA prevented liver cancer from initiating by harnessing the body's own innate immune system."
In the findings, published online on November 14 in Cell Reports, researchers describe how dsRNA polyinosinic-polycytidylic acid (pIC) prevented primary liver cancer from occurring in mouse models when it was injected into the body cavity during the pre-cancer stage. Primary liver cancer is cancer that begins in the liver; metastatic liver cancer starts elsewhere in the body and spreads to the liver.
The study showed that the formation of tumors -- or tumorigenesis -- was suppressed by reprogramming macrophages (specialized immune cells that destroy targeted cells) and activation of natural killer cells and dendritic cells that kill tumor cells directly or boost adaptive immunity.
Mouse models with tumors induced either by chemical carcinogen or fatty liver diseases were injected with pIC at different stages. Tumor inhibition was successful in all models that received the dsRNA before tumor formation. The greatest decrease in tumor numbers and size was seen when pIC was administered at one month. At three months the impact was reduced but still significant. At five months, when tumors had already began to form, there was little inhibitory effect observed when comparing tumor numbers or sizes to control groups.
Future studies will look at dosages and timing of pIC as a vaccine, said Feng. In addition, the researchers will evaluate the use of pIC in combination with other agents to stop tumor growth when cancer has already initiated.
"The findings suggest that the drug may prevent liver cancer. We have more work to do, but we could make a real impact at a time when liver cancer rates are increasing," said Feng, also a researcher with UC San Diego Moores Cancer Center. "There is a large population living with chronic liver disease who are at high risk of developing cancer. If we can develop a vaccine that prevents tumor formation or a therapeutic combination that stops existing cancer from growing, we could reduce the rapid increase of liver cancer rates."
Liver cancer in adults is among the leading causes of cancer mortality in the world, with more than 780,000 new cases and 740,000 deaths each year. More than 40,000 new cases are diagnosed and 29,000 deaths are reported in the United States annually.
Co-authors include: Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M. Varki, Wenxian Fu, UC San Diego; Shuang-Jian Qiu, Fudan University; and Bing Ren, Ludwig Cancer Research Institute and UC San Diego.
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