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)

Immunodeficiency, be it congenital, therapeutic, or infectious in origin, increases the risk of certain, but not all, types of cancer. A common feature of these cancers is that specific infectious agents appear to be important in their etiology, not only in immunodeficient subjects but also in the general population. People with acquired immunodeficiency syndrome (AIDS) are at an increased risk of Kaposi's sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, squamous cell carcinoma of the conjunctiva, and childhood leiomyosarcoma. It is striking that most of these cancers have been associated with specific human herpesvirus (HHV) infections: HHV-8 with Kaposi's sarcoma and the closely related Epstein-Barr virus with non-Hodgkin's lymphoma, Hodgkin's disease, and possibly also with childhood leiomyosarcoma. Moreover, similar associations between these viruses and cancer have been found, albeit inconsistently, in people who are not immunosuppressed. Further research is needed to establish whether the risk of other cancers is also increased in people with AIDS, although, if so, the cancers are likely to be rare or to have comparatively small associated relative risks. Existing evidence suggests that there may be no marked increase in the risk of two common cancers that are known to be caused by infectious agents--hepatocellular carcinoma and invasive carcinoma of the uterine cervix. The apparent lack of an increase in invasive cervical cancer is unexpected and needs further investigation, especially since the prevalence of cervical infection with human papillomaviruses and of low-grade preneoplastic changes in the cervical epithelium is increased in women with AIDS. With the prospect of improved survival in people with AIDS, the effect of immunosuppression on cancer is likely to become an increasingly important issue.
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PMID:Overview of the epidemiology of immunodeficiency-associated cancers. 970 94

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

At present, there is no case report of HHV8- primary effusion lymphoma (PEL) with t(9;14)(p13;q32) involving both PAX-5 and immunoglobulin heavy chain gene rearrangement, which is a rare translocation in B-cell non-Hodgkin's lymphoma, in an HIV- patient. We examined an HIV-seronegative 63-year-old Japanese man with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma manifesting peritoneal lymphomatous effusion without tumor mass at any body site. The lymphoma cells were examined twice by light microscopy, immunohistochemistry, three-color flow cytometry, cytogenetics, and molecular analyses. The nuclear morphology of lymphoma cells was similar to that of large noncleaved cells, although the lymphoma cell size was a little smaller that of the usual large-cell lymphoma. Immunophenotyping of lymphoma cells in the ascitic fluid revealed a mature peripheral B-cell phenotype (CD5- CD10- CD19+ CD20+ CD22+ Ig G+ lambda+). Cytogenetics showed a clonal population: 45,X,-Y, der(2) t(2;6)(q31;p21.3), t(4;8)(q21;q11.2), der(6) t(2;6)(q31;p21.3) add(6)(q15), t(9;14)(p13;q32.3) [10]/47, idem, +der(6) t(2;6), +16[10]. Southern blot analysis revealed rearranged fragments with a probe for immunoglobulin heavy chain, some of which were a size similar to those with a PAX-5 gene probe. Polymorphism, not rearrangement, of the c-MYC gene, was also found. HHV8 and the Epstein-Barr virus were not detected by polymerase chain reaction. This case is the first report of an HHV8- PEL with t(9;14) involving a PAX-5 gene rearrangement in an HIV-seronegative patient. This primary effusion lymphoma manifested spontaneous regression without any therapy. These findings suggest that there may be an additional subcategory of primary effusion lymphoma that is not associated with HHV8 nor c-MYC(R) but is pathogenetically associated with the PAX-5 gene or hepatitis C virus.
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PMID:Herpes virus type 8-negative primary effusion lymphoma associated with PAX-5 gene rearrangement and hepatitis C virus: a case report and review of the literature. 1063 3

Extended schedules of oral etoposide have been evaluated in many types of advanced cancer. In addition to their use in the common solid tumours, extended schedules have been employed in Kaposi's sarcoma (both AIDS-related and endemic types), medulloblastoma, glioma, and hepatocellular carcinoma. Single agent activity was demonstrated in all of these tumour subtypes. For patients with carcinoma of unknown primary site, we have recently incorporated a 10-day oral etoposide schedule into a combination regimen that also includes paclitaxel and carboplatin. With this regimen we achieved a 47% response rate in a group of 53 evaluable patients, with a median survival of 13.4 months. Patients with adenocarcinoma and poorly differentiated carcinoma of unknown primary site had comparable response rates and survival. According to a large number of clinical trials and pharmacokinetic data, a daily oral etoposide dose of 50 mg/m2 consistently produces serum concentrations >1 mg/L for several hours each day. Lower doses fail to consistently produce this serum concentration, which is considered necessary for optimum tumoricidal activity. Optimal dose duration is 10 to 14 days, particularly when combination regimens are being employed. Oral etoposide has an established role as a single agent in patients with low grade non-Hodgkin's lymphoma, Kaposi's sarcoma, and testicular cancer (if residual carcinoma is resected after first-line treatment). The optimal use of extended-schedule etoposide in combination regimens is not defined but is being evaluated in a number of etoposide-sensitive malignancies.
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PMID:Extended-schedule oral etoposide in selected neoplasms and overview of administration and scheduling issues. 1071 42

Liver transplantation is the established therapy of choice for endstages of acute and chronic liver diseases of various aetiologies. The place of liver transplantation in the treatment of malignant liver disease, in particular hepatocellular carcinoma, remains, however, debated: liver transplantation for hepatocellular carcinoma achieves 5-year survival similar to that for other indications, and 5-year disease-free survival better than that following "curative" resection, provided certain criteria are fulfilled (one node max. 5 cm in diameter or max. 3 nodes each of max. 3 cm in diameter). This must be weighed against the uncertainties of preoperative staging and the shortage of donor organs. In contrast, cholangiocarcinoma has a poor prognosis after liver transplantation with 3- and 5-year survival rates below 20%. Only small, incidental, peripheral, intrahepatic cholangiocarcinomas in patients with primary sclerosing cholangitis seem to be an exception to this rule. Liver metastases indicate generalised tumour spread, and thus are not an indication for liver transplantation. Liver transplantation may be justified for liver metastases of neuroendocrine gastrointestinal tumours, provided the primary has been curatively resected and there is no extrahepatic spread. Finally, liver-transplanted (immunosuppressed) patients are at increased risk to develop malignant tumours. This includes in particular epithelial skin tumours, (EBV-associated lymphoproliferative diseases and (HHV8-induced) Kaposi's sarcoma.
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PMID:[Liver transplantation and tumors: risk and chance]. 1090 24

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) type 1 receptor antagonists have strong cytostatic properties on in vitro cultures of many normal and neoplastic cells. They are effective, in particular, in reducing the growth of human lung fibroblasts, renal canine epithelial cells, bovine adrenal endothelial cells, simian T lymphocytes, and of neoplastic cell lines derived from human neuroblastomas, a ductal pancreatic carcinoma of the Syrian hamsters, human salivary glands adenocarcinomas, and two lines of human breast adenocarcinomas. ACE inhibitors are also effective in protecting lungs, kidneys and bladders from the development of nephropathy, pneumopathy, cystitis, and eventually fibrosis in different models of organ-induced damage such as exposure to radiation, chronic hypoxia, administration of the alkaloid monocrotaline or bladder ligation. ACE inhibitors and AII type 1 receptor antagonists are also effective in reducing excessive vascular neoformation in a model of injury to the cornea of rats and rabbits, and in controlling the excessive angiogenesis observed in the Solt-Farber model of experimentally induced hepatoma, in methylcholantrene or radiation-induced fibrosarcomas, in radiation-induced squamous cell carcinomas and in the MA-16 viral-induced mammary carcinoma of the mouse. Captopril was, in addition, effective in controlling tumor growth in a case of Kaposi's sarcoma in humans. The inhibition of AII synthesis and/or its blockade by AII receptors is likely to be an important mechanism for this cytostatic action. The mitogenic effect of AII is well established and a reduction of AII synthesis may well explain cell and neoplasm delayed growth. Moreover, AII regulates and enhances the activity of several growth factors including transforming growth factor B (TGFB) and smooth muscle actin (SMA); and many of these factors are reduced in tissues of animals treated with ACE inhibitors and AII type 1 receptor antagonists. These processes seem to be particularly relevant in the control of fibroblast growth and in the control of the ensuing fibrosis. The ACE inhibitors containing a sulphydril (SH) or thiol radical in their moiety (Captopril and CL242817) seemed to be more effective in controlling fibrosis and the growth of some neoplastic cells than those ACE inhibitors without this thiol radical in their structure, even if the second group of these drugs show in vitro a stronger inhibitory effect on converting enzyme activity. Pharmacologically it is known that ACE inhibitors containing a thiol radical also have antioxidant properties and they are efficient in controlling metalloproteinase action. However, although these additional properties are pharmacologically relevant, the blockade of AII synthesis plays an essential role in the cytostatic activity of these two categories of drugs. These observations underline that in addition to the beneficial effect of these drugs on the cardiovascular system, new potential applications are opening for their wider deployment.
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PMID:Cytostatic properties of some angiotensin I converting enzyme inhibitors and of angiotensin II type I receptor antagonists. 1257 Jul 92

The immunotherapeutic treatment of cancers using antibodies (naked or conjugated to a drug, toxin, or radionuclide) relies upon the preferential expression of a targeted antigen on the cancer cell compared to normal tissues. Polyclonal antiferritin antisera have shown selective distribution and therapeutic efficacy when radiolabeled in Hodgkin's disease and hepatoma. In this immunohistochemical study, we investigated the distribution of ferritin in tumors from 6 patients with Kaposi's sarcoma, 12 patients with Hodkgin's disease, and 9 patients with hepatoma, as well as in selected normal tissues. We found that the monoclonal antiferritin antibody binds primarily to histiocytes in samples from Kaposi's sarcoma and Hodgkin's disease. One hepatocellular carcinoma showed diffuse cytoplasmic staining with ferritin. Deposition of the monoclonal antibody was not detectable in the remaining hepatocellular carcinoma samples.
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PMID:Distribution of monoclonal antiferritin antibody in Kaposi's sarcoma, Hodgkin's disease, and hepatocellular carcinoma. 1273 20

Patients with HIV infection are at increased risk for developing Kaposi's sarcoma, non-Hodgkin's lymphoma, and several other cancers. The relative risks for the most common epithelial cancers in the general population--lung, breast, colon/rectum, stomach, liver, and prostate--are not increased substantially in people with AIDS, however. Accumulating data suggest that HIV-infected patients also are at increased risk for developing Hodgkin's lymphoma, cervical carcinoma in situ (CIS), other anogenital neoplasms (invasive cancer and CIS), leiomyosarcoma, and conjunctival squamous cell carcinoma. There is inconclusive evidence, however, with regard to HIV infection being associated with invasive cervical cancer, testicular seminoma, or hepatocellular carcinoma. Notably, other viral infections have been implicated in the etiology of many of these conditions. The introduction of highly active antiretroviral therapy (HAART) has decreased the incidence of AIDS-associated cancers in Western countries, but less than 1% of AIDS patients are receiving HAART in the HIV epicenter of sub-Saharan Africa. Further therapeutic advances that extend survival with HIV infection with varying reconstitution of immune competence may lead to additional alterations in cancer risk.
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PMID:Epidemiology of AIDS-related malignancies an international perspective. 1285 50

The etiology of cancers appears to be complex and multifactorial. Peyton Rous and others demonstrated the process of co-carcinogenesis by exposing rabbits to a virus and tars. Epidemiologists have proposed virus-chemical interactions to cause several cancers. For example, one might propose that the etiology of cervical cancer results from a complex interplay between oncogenic viruses and cervical tar exposures through tar-based vaginal douching, cigarette smoking, and/or long-term cooking over wood-burning stoves in poorly ventilated kitchens. Hepatocellular carcinoma may result from the joint effects of viruses and hepatotoxic chemical carcinogens. Kaposi's sarcoma might happen following reciprocal actions of human herpes virus-8 infection, immunosuppression, and chemical exposures, such as nitrite radicals and alumino-silicates. Use of Koch's postulates will not help one prove or disprove a multifactorial causation of disease; new criteria are needed. Delineating the web of causation may lead to additional strategies for prevention and treatment of several cancers.
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PMID:Viruses, chemicals and co-carcinogenesis. 1532 20

Infectious agents, mainly viruses, are among the few known causes of cancer and contribute to a variety of malignancies worldwide. The agents and cancers considered here are human papillomaviruses (cervical carcinoma); human polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B and hepatitis C viruses (hepatocellular carcinoma); Human T-cell Leukemia Virus-1 (T-cell leukemias); and helicobacter pylori (gastric carcinoma), which account for up to 20% of malignancies around the globe. The criteria most often used in determining causality are consistency of the association, either epidemiologic or on the molecular level, and oncogenicity of the agent in animal models or cell cultures. However use of these generally applied criteria in deciding on causality is selective, and the criteria may be weighted differently. Whereas for most of the tumor viruses the viral genome persists in an integrated or episomal form with a subset of viral genes expressed in the tumor cells, some agents (HBV, HCV, helicobacter) are not inherently oncogenic, but infection leads to transformation of cells by indirect means. For some malignancies the viral agent appears to serve as a cofactor (Burkitt's lymphoma-EBV; mesothelioma - SV(40)). For others the association is inconsistent (Hodgkin's Disease, gastric carcinomas, breast cancer-EBV) and may either define subsets of these malignancies, or the virus may act to modify phenotype of an established tumor, contributing to tumor progression rather than causing the tumor. In these cases and for the human polyomaviruses the association with malignancy is less consistent or still emerging. In contrast despite the potent oncogenic properties of some strains of human adenovirus in tissue culture and animals the virus has not been linked with any human cancers. Finally it is likely that more agents, most likely viruses, both known and unidentified, have yet to be implicated in human cancer. In the meantime study of tumorigenic infectious agents will continue to illuminate molecular oncogenic processes.
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PMID:Infectious agents and cancer: criteria for a causal relation. 1548 39


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