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)

Most cancers rely disproportionately on glycolysis for energy even in the presence of adequate oxygen supply, a condition known as "aerobic glycolysis", or the Warburg effect. Pharmacological reversal of the Warburg effect has been shown to cause selective apoptosis of tumor cells, presumably by stimulating mitochondrial respiratory chain activity and production of reactive oxygen species that, in turn, induce a caspase-mediated series of reactions leading to cell death. We reasoned that a similar effect on tumor cells might result from up-regulation of the E1alpha subunit gene (pda1) of the pyruvate dehydrogenase complex (PDC) that catalyzes the rate-limiting step in aerobic glucose oxidation and thus plays a major role in the control of oxidative phosphorylation. To test this postulate, we employed a self-complementary adeno-associated virus (scAAV)-based delivery and expression system for targeting pda1 to the mitochondria of primary cultures of human hepatoblastoma (HB) and hepatocellular carcinoma (HCC) cells. Serotypes 1-10 scAAV vectors that included enhanced green fluorescent (egfp) reporter gene driven by either cytomegalovirus (CMV) or chicken beta-actin (CBA) promoters were analyzed for transduction ability of HB (Huh-6) and HCC (Huh-7 and HepG2) cell lines and primary cultures of normal human hepatocytes. Serotype 3 scAAV-egfp (scAAV3-egfp) vector was the most efficient and transduced up to 90% of cells. We limited the transgene expression primarily to liver cancer cells by generating scAAV3 vectors that contained the human alpha-fetoprotein promoter (AFP)-driven reporter gene (scAAV3.AFP-egfp) and the potentially therapeutic gene scAAV3.AFP-pda1. Infection of Huh-6 cells by the scAAV3.AFP-pda1 vector increased protein expression of E1alpha, PDC catalytic activity, and late-stage apoptotic cell death. Apoptosis was also associated with increased protein expression of Bcl-X/S, an early marker of apoptosis, and release of cytochrome c into the cytosol of infected HB cells. These data indicate that molecular targeting of mitochondrial oxidative metabolism in liver cancer cells by AAV3-mediated delivery of pda1 holds promise as a novel and effective therapeutic approach for human hepatic tumors.
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PMID:AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells. 1958 87

Hepatitis B and C viruses (HBV and HCV, respectively) are different and distinct viruses, but there are striking similarities in their disease potential. Infection by either virus can cause chronic hepatitis, liver cirrhosis, and ultimately, liver cancer, despite the fact that no pathogenetic mechanisms are known which are shared by the two viruses. Our recent studies have suggested that replication of either of these viruses upregulates a cellular protein called serine protease inhibitor Kazal (SPIK). Furthermore, the data have shown that cells containing HBV and HCV are more resistant to serine protease-dependent apoptotic death. Since our previous studies have shown that SPIK is an inhibitor of serine protease-dependent apoptosis, it is hypothesized that the upregulation of SPIK caused by HBV and HCV replication leads to cell resistance to apoptosis. The evasion of apoptotic death by infected cells results in persistent viral replication and constant liver inflammation, which leads to gradual accumulation of genetic changes and eventual development of cancer. These findings suggest a possibility by which HBV and HCV, two very different viruses, can share a common mechanism in provoking liver disease and cancer.
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PMID:Hepatitis B and hepatitis C virus replication upregulates serine protease inhibitor Kazal, resulting in cellular resistance to serine protease-dependent apoptosis. 1986 83

Hepatitis C virus is estimated to affect 170 million people worldwide. Infection can lead to cirrhosis, liver failure, or liver cancer. Hepatitis C is unique among chronic illnesses, in that potentially curative treatment is available. Therapy is of prolonged duration and associated with multiple physiological and psychological side effects. These side effects have the potential to impact not only the individual receiving therapy but also their family and the day-to-day functioning of the family unit.This paper describes data and findings obtained from a family impact study instigated to explore the repercussions of interferon treatment for chronic hepatitis C on family life, from both the perspectives of individuals who had received treatment and their family members. An exploratory study was conducted using semi-structured focus groups.Findings reveal the treatment impacted on physical, emotional, relational, and financial domains. The major themes identified were resilience, loss, hardship, anger and irritability, and secrecy. The side-effect profile of therapy exerted significant and previously unforeseen impacts on family relationships, both negatively and positively. Treatment receivers tended to view their experiences as having more adverse impact, while family members, although affected, demonstrated considerable resilience and coping.
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PMID:Interferon treatment for chronic hepatitis C: a family impact study. 2001 Feb 28

Infection with the human liver fluke, Opisthorchis viverrini, is a serious public health problem in Thailand, Laos and nearby locations in Southeast Asia. Both experimental and epidemiological evidence strongly implicate liver fluke infection in the etiology of one of the liver cancer subtypes, cholangiocarcinoma (CCA). To identify parasite proteins critical for liver fluke survival and the etiology of CCA, OFFGEL electrophoresis and multiple reaction monitoring were employed to characterize 300 parasite proteins from the O. viverrini excretory/secretory products and, utilizing selective labeling and sequential solubilization, from the host-exposed tegument. The excretory/secretory included a complex mixture of proteins that have been associated with cancers, including proteases of different mechanistic classes and orthologues of mammalian growth factors and anti-apoptotic proteins. Also identified was a cysteine protease inhibitor which, in other helminth pathogens, induces nitric oxide production by macrophages, and, hence may contribute to malignant transformation of inflamed cells. More than 160 tegumental proteins were identified using sequential solubilization of isolated teguments, and a subset of these was localized to the surface membrane of the tegument by labeling living flukes with biotin and confirming surface localization with fluorescence microscopy. These included annexins, which are potential immuno-modulators, and orthologues of the schistosomiasis vaccine antigens Sm29 and tetraspanin-2. Novel roles in pathogenesis were suggested for the tegument-host interface since more than ten surface proteins had no homologues in the public databases. The O. viverrini proteins identified here provide an extensive catalogue of novel leads for research on the pathogenesis of opisthorchiasis and the development of novel interventions for this disease and CCA, as well as providing a scaffold for sequencing the genome of this fluke.
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PMID:The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini. 2004 60

Infection by hepatitis B virus (HBV) and exposure to dietary aflatoxin B-1 (AFB(1)) have both been implicated by epidemiological studies to be important risk factors in the development of hepatocellular carcinoma (HCC). Our ability to derive transgenic mice which develop liver cancer as a consequence of the expression of a single gene from HBV, the HBx gene, provides an opportunity to use this animal model to test whether AFB(1) can induce p53 mutations, particularly at codon 249, which are frequently detected in HCC and, as a result, act synergistically with HBV to accelerate the manifestation of disease. While AFB(1) significantly shortened the latency of tumor development in the HBx transgenic mice, the tumors did not have p53 mutations. As in tumors from the untreated transgenic mice, the p53 tumor suppressor protein is found bound to the HBx protein and sequestered in the cytoplasmic compartment of the tumor cell. Despite the frequent involvement of ras mutations in mouse tumors, we also have not detected activation of the ms p21 protein in the tumors from the AFB(1)-treated mice. We conclude that although AFB(1) can act as a co-factor with HBx to induce HCC in mice, its mode of action in vivo remains obscure.
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PMID:Synergism between the hbx gene and aflatoxin B-1 in the development of murine liver-cancer. 2155 96

In an era of limited healthcare budgets, mathematical models can be useful tools to identify cost-effective programs and to support policymakers in informed decision making. This paper reports results of our work carried out over several years with the Asian Liver Center at Stanford University, a nonprofit outreach and advocacy organization that is an international leader in the fight against hepatitis B and liver cancer. Hepatitis B is a vaccine-preventable viral disease that, if untreated, can lead to death from cirrhosis and liver cancer. Infection with hepatitis B is a major public health problem, particularly in Asian populations. We used new combinations of decision analysis and Markov models to analyze the cost-effectiveness of several interventions to combat hepatitis B in the United States and China. The results of our OR-based analyses have helped change United States public health policy on hepatitis B screening for millions of people and have helped encourage policymakers in China to enact legislation to provide free catch-up vaccination for hundreds of millions of children. These policies are an important step in eliminating health disparities, reducing discrimination, and ensuring that millions of people who need it can now receive hepatitis B vaccination or lifesaving treatment.
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PMID:Doing Good with Good OR: Supporting Cost-effective Hepatitis B Interventions. 2176 Jun 50

Hepatocellular carcinoma is the most common primary liver malignancy and is an international public health concern, constituting one of the most deadly cancers worldwide. Infection with hepatitis B virus and hepatitis C virus is a major risk factor for HCC in developed countries. Emerging evidence indicates that there are other important lifestyle factors that contribute to the international burden of HCC, such as alcohol consumption, diabetes, obesity, and the intake of aflotoxin-contaminated food. Obesity and diabetes are also likely to be risk factors for HCC, the most frequent subtype of liver cancer. The chief pathway by which obesity increases risk involves the association between obesity and nonalcoholic fatty liver disease (NAFLD). Coffee consumption has been studied extensively and appears to have a favorable effect on the prevention of liver diseases, including HCC. One hypothesis suggests that coffee intake lowers serum levels of gamma-glutamyltransferase (GGT), which is associated with a lower incidence of HCC. It is estimated that more than 80% of HCC cases are attributable to four principal causes that are avoidable. It is difficult to make dietary recommendations, because it is unknown whether consuming higher amounts of specific antioxidants will decrease the risk of developing hepatocellular carcinoma. A diet rich that is in polyunsaturated fatty acids and, possibly, B-carotene could reduce the risk of HCC, and high dietary GL is associated with an increased risk independently of cirrhosis or diabetes.
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PMID:HCC, diet and metabolic factors: Diet and HCC. 2208 37

Worldwide, 130-170 million persons are living with chronic hepatitis C virus (HCV) infection, which, if left untreated, can result in cirrhosis and liver cancer. Egypt has the largest burden of HCV infection in the world, with a 10% prevalence of chronic HCV infection among persons aged 15-59 years. HCV transmission in Egypt is associated primarily with inadequate infection control during medical and dental care procedures. In response, the Egyptian Ministry of Health and Population (MOHP) in 2001 implemented a program to reduce health-care-associated HCV transmission and in 2008 launched a program to provide care and treatment. This report describes the progress of these programs, identifies deficiencies, and recommends enhancements, including the establishment of a comprehensive national viral hepatitis control program. Infection control programs implemented in 2001 at MOHP facilities resulted in improvements in infection control practices and a decrease in the annual incidence of HCV infection among dialysis patients from 28% to 6%. Through June 2012, a total of 23 hepatitis treatment facilities had been established in Egypt, providing care and treatment to nearly 190,000 persons with chronic HCV infection. Despite these programs, Egypt continues to face an ongoing hepatitis C epidemic. A comprehensive plan is needed to prevent and control hepatitis C in Egypt. This plan should address increasing community awareness and education, preventing of HCV infection in health-care settings, ensuring a safe blood supply, establishing surveillance and monitoring to track the effectiveness of control programs, and providing care and treatment.
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PMID:Progress toward prevention and control of hepatitis C virus infection--Egypt, 2001-2012. 2283 35

The reframed paradigm of cervical cancer prevention will include strategic combinations of at least four major components: 1) routine introduction of human papillomavirus (HPV) vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. On a global scale, vaccination of newborns and infants is well established and has developed a successful working infrastructure. The hepatitis B virus (HBV) vaccination programs offer a model for HPV introduction in which newborn and infant immunization achieves a rapid reduction in the prevalence of the HBV carrier rates in immunized cohorts of children, and of liver cirrhosis and liver cancer decades later. In contrast, screening for cervical pre-cancer is largely restricted to industrialized populations and upper social classes in developing countries. The expertise gained by vaccination programs worldwide needs to be coordinated with the traditional cervical cancer prevention community of gynecologists and pathologists. Significant political and advocacy efforts at the Global level (World Health Organization, other United Nations agencies and The GAVI Alliance) need to be organized and reinforced to achieve a meaningful reduction in HPV transmission and its related health conditions and cancers. This desirable goal is now scientifically and technologically attainable, and great progress is being made in obtaining financing for global HPV immunization. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
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PMID:Reframing cervical cancer prevention. Expanding the field towards prevention of human papillomavirus infections and related diseases. 2319 51

Although primary liver cancer is rare, its incidence rate has been rising quickly in Canada, more than tripling since the early 1980s. This cancer is more common in men than women, and the age-specific incidence rates in men have been increasing significantly in all age groups from 40 years of age onward. The death rate has followed a similar upward trajectory, in part because of the low 5-year survival rate of 18% in both sexes. Infection with the hepatitis B or C virus continues to be the most common risk factor, but other factors may also play a role. Risk reduction strategies, such as viral hepatitis screening, have been recommended in other countries and warrant consideration in Canada as part of a coordinated strategy of disease prevention and control.
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PMID:Canadian trends in liver cancer: a brief clinical and epidemiologic overview. 2344 30


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