Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The microbiome exerts essential functions in health and disease, modulating key processes in metabolism, inflammation and immunity. Recent evidence has revealed a key role of the microbiome in carcinogenesis as well as anti-cancer immune responses in mouse models and patients. Herein, we will review functions of the gut microbiome in hepatocellular carcinoma (HCC), the third leading cause of worldwide cancer mortality. The majority of HCC develops in patients with chronic liver disease, caused by viral hepatitis, non-alcoholic fatty liver disease (NAFLD) and alcohol-related fatty liver disease. In this review, we will discuss mechanisms by which the gut-liver axis promotes the development of HCC in mouse models and patients, including dysbiosis, the leaky gut and bacterial metabolites, with a particular focus on NAFLD as the fastest growing cause of HCC development. Moreover, we will review recent progress in harnessing the gut microbiome as a potential diagnostic tool and novel therapeutic target in patients with HCC, in particular in the setting of immunotherapy.
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PMID:Gut microbiome in HCC - Mechanisms, diagnosis and therapy. 3195 88

Precise hepatocellular carcinoma (HCC) risk prediction will play increasingly important roles with the contemporary HCC etiologies, that is, non-alcoholic fatty liver disease and resolved hepatitis C virus infection. Because the HCC incidence rate in this emerging patient population is relatively low (~1% per year), identification of a subset of patients at the highest risk is critical to concentrate the effort and resources of regular HCC screening to those who most need it. Omics profiling has been derived using several candidate HCC risk biomarkers, which could refine HCC screening by enabling individual risk-based personalized or risk-stratified patient management. Various types of biomolecules have been explored as sources of information to predict HCC risk at various time horizons. Germline DNA polymorphisms likely reflect race/ethnicity- and/or etiology-specific susceptibility to HCC development or chronic liver disease progression toward carcinogenesis. Transcriptomic dysregulations in the diseased liver capture functional molecular status supporting oncogenesis such as inflammatory pathway and myofibroblast activation. Circulating nucleic acids, proteins, and metabolites could serve as less-invasive measures of molecular HCC risk. Characterization of gut microbiota could also inform HCC risk estimation. Each biomarker could have its niche of clinical application depending on logistics of use, performance, and costs with a goal to eventually improve patient prognosis as a part of the whole algorithm of chronic liver disease management.
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PMID:Omics-derived hepatocellular carcinoma risk biomarkers for precision care of chronic liver diseases. 3232 26

Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients' disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.
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PMID:Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma. 3248 52

While metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.
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PMID:Combined alcoholic and non-alcoholic steatohepatitis. 3251 97

Chronic hepatitis B is mainly responsible for the morbidity and mortality from hepatitis B virus (HBV) related complications, including hepatocellular carcinoma and decompensated cirrhosis. Hepatocellular carcinoma remains the main challenge in the management of not only undiagnosed and/or untreated but also diagnosed and treated patients with chronic HBV infection, as its incidence decreases but is not eliminated even after many years of effective anti-HBV therapy. The exact mechanisms used by HBV to cause malignant transformation remain uncertain, although much of the available data are in favor of a pathogenetic role of HBx protein. Senescence is a cellular state, in which cells lose their ability to proliferate. This biological mechanism may function in a dual mode, namely being both cancer-protective due to reduced cellular proliferation, but also cancer-enhancing due to modulation of the tissular microenvironment by immune cells during persistent accumulation of senescent cells. Protein X of HBV protein exhibits many similarities in terms of the implemented mechanisms of action and pathways related to the biological process of cellular senescence. Concurrently, insufficient clearance of both senescent and pre-cancerous hepatocytes combined with inadequate immune surveillance due to immunosenescence caused by chronic HBV infection may lead to hepatocarcinogenesis. Thus, the effect of HBV seems to be critical as a connecting link between cellular senescence and development of hepatocellular carcinoma. An ongoing research is underway towards identifying and validating markers of hepatocyte senescence, which could improve the landscape for evaluation of chronic liver disease, thereby providing valuable information in terms of HBV related carcinogenesis.
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PMID:Cellular senescence and hepatitis b related hepatocellular carcinoma: an intriguing link. 3289 Apr 39

Hepatocellular carcinoma (HCC) is one of the major complications of chronic liver disease, mostly of liver cirrhosis. Liver diseases from different causes differ in the risks of HCC development. Different mechanisms of carcinogenesis are involved in HCC development in different liver diseases as well. Generally, two main pathways are distinguished: the cause of liver disease itself (e.g. viral infections, accumulation of heavy metals etc.) and chronic liver inflammation and fibrogenesis, including mechanisms of oxidative stress. Rare cases of HCC in liver without underlying cirrhosis are likely the consequences of the mechanisms directly linked with particular etiological factor (e.g. protein X in chronic hepatitis B virus (HBV) infection). The key approach which can lead to significantly better results of any treatment used in HCC cases is HCC screening and surveillance. The appropriate method of HCC surveillance is abdominal ultrasonography in 6-month intervals. There is still one question to be solved: the correct definition of target population which should undergo this method of surveillance. Currently, the target population in the developed world is defined as all patients with liver cirrhosis. Unfortunately, the only method of primary prevention of HCC is available: universal HBV vaccination. Antiviral treatment of hepatitis B or C is considered as a method of secondary prevention. Adjuvant therapy of HCC after its primary therapy (antiviral therapy after HCC resection etc.) and other measures able to reduce HCC recurrence risk are usually mentioned as tertiary prevention approach. The BCLC staging system is the most common system used in Europe for the classification of HCC at the dia-gnosis. This classification combines the stage of HCC itself with other parameters, such as liver disease severity (Child - Pugh classification), portal hypertension etc. BCLC is a system which guides the physicians to optimal treatment options in every HCC stage. The only potentially curable approaches are surgical resection or liver transplantation. These options may be used in 1/3 of all HCC patients. Unfortunately, the vast majority of HCC patients can be treated only by palliative treatment options with transarterial chemoembolisation being the most common one.
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PMID:Hepatocellular carcinoma from the view of gastroenterologist/hepatologist. 3321 64

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease. Various epidemiological and experimental studies have identified candidates for secondary prevention-both etiology-specific and generic prevention strategies-including statins, aspirin, and anti-diabetic drugs. The introduction of multi-cell based omics analysis along with better characterization of the hepatic microenvironment will further facilitate the identification of targets for prevention. In this review, we will summarize HCC risk factors, pathogenesis, and discuss strategies of HCC prevention. We will focus on secondary prevention and also discuss current challenges in translating experimental work into clinical practice.
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PMID:Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges. 3325 94


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