Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular methylation imbalance is associated with tumor progression, hepatic cancer, and cardiovascular disease. S-Adenosylhomocysteine (SAH) is an inhibitor of cellular methyltransferases, and increasing evidence suggests that SAH rather than homocysteine (Hcy) plays a crucial role in mediating these disorders related to methylation imbalance. The anti-metastatic gene nm23-H1 was recently identified in murine and human cancer lines, and the expressions of nm23-H1 mRNA and protein have been shown to be useful tumor invasion markers. We investigated the relationships of tumor cell invasion activities with the intracellular levels of SAH and Hcy and the level of DNA methylation (measured as the cellular content of 5-methyldeoxycytidine, 5-mdc) in four hepatocarcinoma cell lines (Sk-Hep1, J5, Hep-G2, Hep-3B) and one normal liver cell line (Chang's liver cells) with different invasion activities (Sk-Hep1 > J5 > Hep-G2 = Hep-3B > Chang's liver cells). We found that the intracellular level of SAH was the highest in SK-Hep1 cells and was correlated with the invasion activities (r = 0.75, P = 0.008), whereas the level of intracellular Hcy was the highest in Chang's liver cells and was not significantly correlated with the invasion activities of these cell lines (r = 0.24, P = 0.38). The levels of 5-mdc increased with decreasing invasion activities of these cell lines (r = 0.82, P = 0.002), that is, the order of DNA hypomethylation in these cell lines was Sk-Hep1 > J5 > Hep-G2 = Hep-3B > Chang's liver cells, because the lower levels of 5-mdc% represent the higher DNA hypomethylation. Thus, our results demonstrate that SAH rather than Hcy is associated with invasion activities of hepatoma cells, and they suggest that SAH may play an important role in the invasion activities through DNA hypomethylation.
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PMID:Intracellular levels of S-adenosylhomocysteine but not homocysteine are highly correlated to the expression of nm23-H1 and the level of 5-methyldeoxycytidine in human hepatoma cells with different invasion activities. 1704 78

Based on the data reported to the OPTN/UNOS Liver Transplant Registry between 1987-2005, we found: 1. The number of deceased-donor liver transplantations increased slowly each year, with most of the increase being in adult recipients. The number of LD transplants, on the other hand, decreased sharply after 2002, following 3 years of rapid increase from 1998-2001 in both pediatric and adult recipients. 2. The number of DD liver recipients with non-cholestatic liver diseases increased very quickly during the past 18 years. Malignant disease as a cause of end-stage liver disease increased after implementation of MELD in 2002. Among LD liver recipients, non-cholestatic disease increased sharply from 1998-2001, but decreased from 2002. Malignant diseases as a cause for LD transplants decreased after 2002. 3. Among pediatric recipients, LD transplants provided better 5-year graft survival rates than transplants from deceased donors; in contrast, LD transplants in adults had poorer graft survival rates than those from deceased donors. 4. The use of marginal donors, including older donors, HCV (+) donors, donation after cardiac death donors, and diabetic donors, increased in the past 18 years. HCV(+) livers transplanted into HCV(+) cirrhosis recipients had similar graft survival when compared with HCV(-) donor livers, whereas when they were transplanted into non-HCV cirrhosis patients, they had poorer graft survival (60% vs. 70% at 5 years, respectively). When livers from diabetic donors were transplanted into diabetic recipients, they had much poorer graft survival than transplants from non-diabetic donors (54% vs. 77% at 5 years, respectively). 5. Split and partial liver transplants had poorer 5-year graft survival rates (58% and 57%, respectively) than whole liver transplants (62%), but the difference was mainly due to poorer outcomes during the first posttransplant year. 6. PELD allocation has resulted in improved one- and 3-year graft survival rates among pediatric liver recipients. Among adults MELD-based allocation has resulted in better one-year survival rates. When comparing the different original diseases, only HCC patients showed better one- and 3-year graft survival rates after MELD. 7. Within one year after transplantation, primary non-function and infection were the major causes of graft failure. These decreased after 1996, but recurrent hepatitis has increased as a cause of graft failure. After one year, chronic rejection and infection had decreased, while hepatitis recurrence still increased. 8. Cardiovascular deaths and deaths from multiorgan failure that occurred within the first year after transplantation have increased since 1996, while deaths due to infections have decreased. After the first year, deaths from graft failure increased, while CVD and infections decreased.
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PMID:Liver transplantation in the United States. 1742 22

Analysis of the human genome indicates that a large fraction of the genome sequences are RNAs that do not encode any proteins, also known as non-coding RNAs. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules 20-22 nucleotides (nt) in length that are predicted to control the activity of approximately 30% of all protein-coding genes in mammals. miRNAs play important roles in many diseases, including cancer, cardiovascular disease, and immune disorders. The expression of miRNAs can be regulated by epigenetic modification, DNA copy number change, and genetic mutations. miRNAs can serve as a valuable therapeutic target for a large number of diseases. For miRNAs with oncogenic capabilities, potential therapies include miRNA silencing, antisense blocking, and miRNA modifications. For miRNAs with tumor suppression functions, overexpression of those miRNAs might be a useful strategy to inhibit tumor growth. In this review, we discuss the current progress of miRNA research, regulation of miRNA expression, prediction of miRNA targets, and regulatory role of miRNAs in human physiology and diseases, with a specific focus on miRNAs in pancreatic cancer, liver cancer, colorectal cancer, cardiovascular disease, the immune system, and infectious disease. This review provides valuable information for clinicians and researchers who want to recognize the newest advances in this new field and identify possible lines of investigation in miRNAs as important mediators in human physiology and diseases.
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PMID:MicroRNAs: control and loss of control in human physiology and disease. 1903 Sep 26

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximately 75-92% and in the pediatric population at approximately 13-14%. The progressive form of NAFLD, nonalcoholic steatohepatitis, is estimated at approximately 3-5%, with approximately 3-5% of these having progressed to cirrhosis. Thus, the numbers of individuals at risk for end-stage liver disease and development of primary liver cancer is large. NAFLD is an independent risk factor for cardiovascular disease, leads to increased all-cause mortality, and to increased liver-related mortality. This review focuses on recent advances in our understanding of the NAFLD disease spectrum, including etiology, diagnosis, treatment, and genetic and environmental risk factors and suggests future directions for research in this important area.
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PMID:Nonalcoholic fatty liver disease. 1907 70

Overall life expectancy and quality of life among persons with haemophilia have increased in recent years, primarily because of the advances in factor replacement therapy and better treatment of infectious diseases. Older haemophilic patients now face aging co-morbidities that are common in the general male population, such as cardiovascular or metabolic diseases, prostate hypertrophy and hepatic, prostate and other cancers. The prevalence of cardiovascular disease and incidence of vascular events among older haemophilic patients can be expected to increase and haemophilic patients may become prone to some cardiovascular risk factors, warranting preventative measures. The treatment of long-term complications of hepatitis C virus infection such as liver cirrhosis and hepatic cancer can be expected to be required in a large portion of the older haemophilia population for some years to come. Appropriate antiviral treatment and close monitoring for possible disease advancement will constitute an important part of routine medical care, and special considerations may be appropriate in conjunction with invasive procedures, chemo- or radiotherapy. At the moment, hard data on which to base the management of these conditions are largely lacking, but can be expected to increase dramatically in the coming decades. In the meantime, the ageing population of haemophilia patients should be offered the same comprehensive health care offered to the general population, which may require a restructuring of health care delivery.
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PMID:Challenges and controversies in haemophilia care in adulthood. 1912 37

The impact of metabolic factors, which are major risk factors for cardiovascular disease, on total cancer risk has not been clarified. We prospectively examined whether metabolic factors and their aggregates predict the subsequent occurrence of total and major sites of cancer in the Japan Public Health Center-based Prospective Study. A total of 27 724 participants (9548 men and 18 176 women) aged 40-69 years participating in a questionnaire and health checkup survey in 1993-1995 were followed for total cancer incidence through 2004. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for metabolic factors and for two criteria of their aggregates (three or more than three factors and two or more than two additional factors in addition to being overweight) with a Cox proportional hazards model to control for potential confounding factors. In both sexes, the presence of metabolic factors in the aggregate did not predict subsequent occurrence of cancer as a whole. By site, a significant increase in risk was observed for male liver cancer [HR = 1.73, CI = 1.03-2.91 (three or more than three factors); HR = 1.99, CI = 1.11-3.58 (two or more than two additional factors in addition to being overweight)], and female pancreatic cancer [HR = 1.99, CI = 1.00-3.96 (two or more than two additional factors in addition to being overweight)]. For other sites, positive associations were observed only for specific metabolic factors, that is, high triglycerides and male colon cancer (HR = 1.71, CI = 1.11-2.62), and obesity and female breast cancer (HR = 1.75, CI = 1.21-2.55). Metabolic factors in the aggregate may have little impact on total cancer risk in the Japanese population, although the association between specific components and specific cancers suggests an etiologic link between them.
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PMID:Impact of metabolic factors on subsequent cancer risk: results from a large-scale population-based cohort study in Japan. 1949 12

An inverse association between serum total cholesterol and cancer mortality cast a controversy for cause or result of low cholesterol on cancer risk. Therefore, we examined a total of 33,368 Japanese men and women aged 40-69 years, who were free of prior diagnosis of cancer and cardiovascular disease, undertook serum total cholesterol measurement and completed a food frequency questionnaire between 1990 and 1994. They were followed to ascertain incident total and major sites of cancer until the end of 2004 to examine sex-specific associations between cholesterol and cancer risk by incident time, stage and virus infection. After 412,714 person-years of follow-up, 2,728 incident cancers were documented. Serum total cholesterol levels were inversely associated with risk of total cancer in men, with strong inverse associations with stomach cancer in men and liver cancer in both sexes. After exclusion for first 3-year incident cases and advanced cases with metastasis, the inverse association diminished for total and stomach cancers but remained for liver cancer. The multivariable hazard ratios (95% CI) for serum total cholesterol <4.14 mmol/l versus 4.65-5.16 mmol/l were 1.15(0.92-1.43); p-trend across the overall cholesterol categories = 0.25 for total cancer and 1.18(0.79-1.75), p-trend = 0.04 for stomach cancer and 5.12(1.65-15.9), p-trend = 0.0011 for liver cancer in men, and 5.73(1.57-20.9), p-trend = 0.0007 for liver cancer in women. The sustained excess risk of liver cancer associated with low cholesterol was observed regardless of hepatitis-C-virus infection and drinking habits. Although the inverse association for liver cancer remained to be examined further, our findings do not support that low serum total cholesterol levels increase risks of total cancer and other major sites.
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PMID:Serum cholesterol levels in relation to the incidence of cancer: the JPHC study cohorts. 1954 28

Hypertension, atherosclerosis, and resultant chronic heart failure (HF) reach epidemic proportions among older persons, and the clinical manifestations and the prognoses of these worsen with increasing age. Thus, age per se is the major risk factor for cardiovascular disease. Changes in cardiac cell phenotype that occur with normal aging, as well as in HF associated with aging, include deficits in ss-adrenergic receptor (ss-AR) signaling, increased generation of reactive oxygen species (ROS), and altered excitation-contraction (EC) coupling that involves prolongation of the action potential (AP), intracellular Ca(2+) (Ca(i)(2+)) transient and contraction, and blunted force- and relaxation-frequency responses. Evidence suggests that altered sarcoplasmic reticulum (SR) Ca(2+) uptake, storage, and release play central role in these changes, which also involve sarcolemmal L-type Ca(2+) channel (LCC), Na(+)-Ca(2+) exchanger (NCX), and K(+) channels. We review the age-associated changes in the expression and function of Ca(2+) transporting proteins, and functional consequences of these changes at the cardiac myocyte and organ levels. We also review sexual dimorphism and self-renewal of the heart in the context of cardiac aging and HF.
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PMID:Modulation of sarcoplasmic reticulum Ca(2+) cycling in systolic and diastolic heart failure associated with aging. 2041 45

The Baby Boomer generation is composed of 78 million Americans who are just beginning to reach their retirement years. Most Boomers have at least one chronic health problem, and these significantly increase the expense of providing medical care. Liver disease is the 12th most common cause of death in the United States, representing a relatively small portion of overall healthcare costs compared with cardiovascular disease and malignancy. Nonetheless, hepatitis C and fatty liver disease are more common in the Boomers and may play a more dominant role as they age. As a consequence, primary liver cancer is likely to become more prevalent. As with most chronic illnesses, prevention rather than disease management is likely to have the greatest impact. For those already afflicted by chronic liver disease, recognition and treatment can reduce the incidence of late complications, as was clearly demonstrated with chronic hepatitis B and C. Perhaps obesity is the greatest threat to our future health, and fatty liver disease, although likely preventable, will probably become the disease that fills the waiting rooms of future hepatologists.
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PMID:The healthcare burden imposed by liver disease in aging Baby Boomers. 2042 78

To determine wether there were connections among hepatocyte nuclear factor-1 alfa (HNF-1a), liver receptor homolog-1 (LRH-1), apolipoprotein M (apoM) and to investigate the effects of HNF-1a in HepG2 on the expressions of apoM, apolipoprotein A-I (apoA-I) and the key enzymes in cholesterol metabolism and biotransformation. The mRNA expressions of apoM, LRH-1 and HNF-1a were detected by RT-PCR. HNF-1a was interfered and RT-PCR was used to detect the changes of apo M, apo A-I, Cyp7A1, farnesoid X receptor (FXR) and small heterodimer partner-1 (SHP-1). Western blot was used to detect the change of apo M protein. The expressions of apoM, LRH-1 and HNF-1amRNA were obviously higher in HCC tissue than that in para-cancer tissue (the vaule of t is -7.167, -7.075, -8.803, P less than 0.01 respectively). HNF-1a and LRH-1 positively correlated with the expression of apoM (r=0.353, P less than 0.01; r=0.523, P less than 0.01 respectively); RT-PCR and western blot results showed that the expressions of apoM, FXR and SHP-1 mRNA, could be obviously suppressed by HNF-1a interfering as compared to the negative controls by 47.4%, 47.9%and 65.2% (P less than 0.01) respectively, and the expression of apoM protein also decreased by 54.3% (F = 43.482, P less than 0.01). The expressions of HMGCR and CYP7A mRNA increased by 101.1% and 138.5% (P less than 0.01) respectively as compared to the negative control. But there is no effect on expression of apoA-I mRNA (F = 0.170, P more than 0.05). HNF-1a could promote cholesterol biotransformation by increasing the expression of apoM and the key enzymes in cholesterol metabolism and decreasing inhibiting factor. So HNF-1a provided protection against cardiovascular disease.
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PMID:[Effect of interfering hepatocyte nuclear factor-1 alfa in HepG2 on the expressions of apoM, apoA-I and the correlative key enzyme of cholesterol metabolism]. 2149 16


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