Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In populations with non-HIV immunodeficiency, non-Hodgkin lymphoma and soft tissue sarcoma, especially Kaposi's sarcoma, are the most prominent tumours, but Hodgkin's disease, gastric carcinoma, squamous cell skin cancer, malignant melanoma, hepatoma, myeloid leukaemia and/or colorectal carcinoma have been linked in various studies. Population based cancer registries and cohort studies of HIV infected persons have generally failed to detect HIV related increases in total cancer incidence or in specific tumours other than non-Hodgkin lymphoma and Kaposi's sarcoma; however, associations with anal carcinoma, hepatoma and Hodgkin's disease have been suggested by some studies. Although not indicating increased risk, HIV induced immunosuppression has been linked to an acceleration of cervical and anal neoplasia and to increased aggressiveness of Hodgkin's disease with a relative excess of the mixed cellularity type. Advances in treatment for HIV infection will delay progression to AIDS and may allow an altered natural history to emerge, including the occurrence of excesses of additional cancer types.
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PMID:HIV infection and cancers other than non-Hodgkin lymphoma and Kaposi's sarcoma. 182 20

In a case of epidermodysplasia verruciformis with impaired cell-mediated immunity and multiple skin cancers human papillomavirus type 5 (HPV5) DNA sequences were demonstrated in a cutaneous squamous cell carcinoma. HPV5 and HPV8 were detected in the benign disseminated skin lesions together with three newly characterized HPVs: HPV17, HPV19 and HPV24. A chronic infection with hepatitis B virus resulting in macronodular cirrhosis associated with a primary hepatocellular carcinoma was also acquired by this patient. This case provides an example of the circumstantial evidence which suggests that certain types of HPV are potentially oncogenic and stresses the importance of immune surveillance in the protection against virus-associated tumors.
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PMID:Epidermodysplasia verruciformis. Skin carcinoma containing human papillomavirus type 5 DNA sequences and primary hepatocellular carcinoma associated with chronic hepatitis B virus infection in a patient. 242

Archival tissues are a bountiful resource for various studies. Polymerase chain reaction permits the use of such tissues for molecular biological analyses of disease causation. However, a comprehensive study using a large number of decades-old samples (20 or more years) for molecular oncology/epidemiology has never been shown to be feasible. We have relied upon the unique tumor registry of atomic bomb survivors to show that such studies are possible using 275 hepatocellular carcinoma and 41 skin cancer cases. We used 23 relatively recent thyroid papillary carcinoma cases from persons living in the vicinity of the Chernobyl nuclear reactor accident for comparison. Degradation of DNA is severe in autopsy hepatocellular carcinoma samples but can be compensated for by decreasing the polymerase chain reaction product size. Increasing the amount of DNA that is used by a factor of 8 improved amplification efficiency from approximately 60 to 80%. Age of the samples was not as great a problem as was the source of procurement. The extracted DNA can be used for all types of assays that require polymerase chain reaction amplification, such as restriction fragment length polymorphism, single-strand conformation polymorphism, and direct sequencing.
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PMID:Feasibility of using decades-old archival tissues in molecular oncology/epidemiology. 870 80

In a series of 10151 organ allograft recipients who developed 10813 de novo malignancies after transplantation, 755 involved the hepato-biliary-pancreatico-duodenal (HBPD) area. If nonmelanoma skin cancers and in situ carcinomas of the uterine cervix were excluded (as they are from most cancer statistics), then the HBPD area was affected by 10% of neoplasms. Many of the tumors encountered were uncommon in the general population. The largest group of neoplasms was 474 lymphomas, which comprised 63% of the total. Other major malignancies were hepatocellular carcinomas (HCC; 15%), pancreatic carcinomas (11%), cholangiocarcinomas (3%), Kaposi's sarcomas (3%), and other sarcomas (1%). Lymphomas occurred at a younger age than other tumors (average, 39 versus 50 years), appeared earlier after transplantation (average, 24 versus 77 months), and were more frequently associated with immunosuppressive therapy with the antilymphocytic agents (ALG/ATG) and/or (OKT3) (59% versus 28%). Lymphomas were localized to the HBPD area in only 18% of patients, whereas in 82% there was involvement of other organs or sites. The liver was involved in 95% of lymphomas. Lymphomas frequently involved allografts, the liver in 84%, and the pancreas in 59%. Of 292 patients treated for lymphomas 67 (23%) had complete remissions lasting 6 months or more. HCC was frequently associated with hepatitis B or C infection. Kaposi's sarcomas were rarely confined to the HBPD area, and in 25% of cases there were no associated skin lesions. An unusual subset of tumors were leiomyosarcomas involving hepatic allografts of pediatric patients. The poor prognosis of most tumors in this series may be related to delays or problems in making the diagnosis in these immunosuppressed patients and, perhaps, it may also be related to the unusually aggressive behavior of some tumors.
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PMID:Primary malignancies of the hepato-biliary-pancreatic system in organ allograft recipients. 974 82

Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.
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PMID:Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. 976 49

Curcumin has been widely used as a spice and coloring agent in foods. Recently, curcumin was found to possess chemopreventive effects against skin cancer, forestomach cancer, colon cancer and oral cancer in mice. Clinical trials of curcumin for prevention of human cancers are currently ongoing. In this study, we examine the chemopreventive effect of curcumin on murine hepatocarcinogenesis. C3H/HeN mice were injected i.p. with N-diethylnitrosamine (DEN) at the age of 5 weeks. The curcumin group started eating 0.2% curcumin-containing diet 4 days before DEN injection until death. The mice were then serially killed at the scheduled times to examine the development of hepatocellular carcinoma (HCC) and changes in intermediate biological markers. At the age of 42 weeks, the curcumin group, as compared with the control group (DEN alone), had an 81% reduction in multiplicity (0.5 versus 2.57) and a 62% reduction in incidence (38 versus 100%) of development of HCC. A series of intermediate biological markers were examined by western blot. While hepatic tissues obtained from the DEN-treated mice showed a remarkable increase in the levels of p21(ras), PCNA and CDC2 proteins, eating a curcumin-containing diet reversed the levels to normal values. These results indicate that curcumin effectively inhibits DEN-induced hepatocarcinogenesis in the mouse. The underlying mechanisms of the phenomenon and the feasibility of using curcumin in the chemoprevention of human HCC should be further explored.
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PMID:Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. 1065 78

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons, p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in the p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer.
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PMID:Mutation analysis of P73 and TP53 in Merkel cell carcinoma. 1073 53

Mutations of the p53 tumor suppressor gene are found in about 50% of all human cancers. The p53 mutation spectra in these cancers are providing clues to the etiology and molecular pathogenesis of cancer. Recent studies indicate that the p53 protein is involved in several vital cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence and programmed cell death. Mutations in the p53 gene can abrogate these functions and may contribute to genomic instability and progression to cancer. Characteristic p53 mutation spectra have been associated with dietary aflatoxin B(1) (AFB(1)) exposure and hepatocellular carcinoma (HCC); sunlight exposure and skin cancer; and cigarette smoking and lung cancer. The mutation spectrum also reveals those p53 mutants that provide cells with a selective clonal expansion advantage during the multistep process of carcinogenesis. Although a number of different exogenous carcinogens have been shown to selectively target p53, pieces of evidence supporting the endogenous insult of p53 are accumulating. Furthermore, analysis of a characteristic p53 mutation load in nontumorous human tissue can indicate previous carcinogen exposure and may identify individuals at an increased cancer risk.
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PMID:Molecular epidemiology and carcinogenesis: endogenous and exogenous carcinogens. 1076 41

Liver transplant recipients are at greater risk for de novo neoplasia, especially lymphoma and nonmelanoma skin cancer; however, risk factors for this complication have not been well studied. Clinical and pathological records of 137 consecutive liver transplant recipients who had survived for at least 1 year were reviewed to register de novo neoplasia. Ten variables were analyzed for their association with the development of de novo malignancies by means of a log-rank test and stepwise selection in a multivariate analysis using the Cox proportional hazard model. Thirty de novo neoplasias appeared in 22 of 137 transplant recipients between 12 and 104 months after orthotopic liver transplantation (OLT; median follow-up, 69 months): 14 patients had 21 skin cancers, 6 patients had solid-organ cancer, and 3 patients developed a lymphoproliferative disease. Probabilities of de novo neoplasia were 13% at 5 years post-OLT and 26% at 8 years post-OLT. The only associated risk factor for any neoplasia was age. Age and hepatocarcinoma were independent risk factors associated with skin cancer. That hepatocarcinoma in the explanted liver is an independent risk factor for skin cancer suggests there is individual susceptibility to both neoplasias.
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PMID:Risk factors for development of de novo neoplasia after liver transplantation. 1169 33

The p53 tumor suppressor gene is mutated in about half of all human cancer cases. The p53 protein modulates multiple cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence, and apoptosis. Mutations in the p53 gene can abrogate these functions and may lead to genetic instability and progress to cancer. The molecular archeology of the p53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of cancer. The spectrum of somatic mutations in the p53 gene implicates environmental carcinogens and endogenous processes in the etiology of human cancer. The presence of a characteristic p53 mutation also can manifest a molecular link between exposure to a particular carcinogen and a specific type of human cancer, e.g. aflatoxin B1 (AFB1) exposure and codon 249ser mutations in hepatocellular carcinoma, ultraviolet (UV) exposure and CC to TT tandem mutations in skin cancer, and cigarette smoke and the prevalence of G to T transversions in lung cancer. Although several different exogenous carcinogens have been shown to selectively target p53, evidence supporting the endogenous insult of p53 from oxyradical and nitrogen-oxyradicals is accumulating. p53 mutations can be a biomarker of carcinogen effect. Determining the characteristic p53 mutation load in nontumorous tissue, with a highly sensitive mutation assay, can indicate a specific carcinogen exposure and also may help in identifying individuals at an increased risk of cancer.
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PMID:Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology and human risk assessment. 1172 Jul 36


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