Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sufficient quantities of human leukocyte interferon have become available for small-scale clinical studies during the past years. The present status of the interferon treatment of respiratory infections, herpes keratitis, hepatitis B, osteogenic sarcoma, and some other tumours is surveyed. The pharmaco-kinetic and toxicological data obtained are summarized. The first clinical experiments with human fibroblast interferon have also been started. The prospects for mass production of human interferons for clinical use are discussed briefly.
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PMID:Prospects for the clinical use of exogenous interferon. 19 14

Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas from southern Africa and Qidong in China. To test this hypothesis, nine tumors induced by aflatoxin B1 in nonhuman primates were analyzed for mutations in the p53 gene. These included four hepatocellular carcinomas, two cholangiocarcinomas, a spindle cell carcinoma of the bile duct, a hemangioendothelial sarcoma of the liver, and an osteogenic sarcoma of the tibia. None of the tumors showed changes at the third position of codon 249 by cleavage analysis of the HaeIII enzyme site at codon 249. A point mutation was identified in one hepatocellular carcinoma at the second position of codon 175 (G to T transversion) by sequencing analysis of the four conserved domains (II to V) in the p53 gene. These data suggest that mutations in the p53 gene are not necessary in aflatoxin B1 induced hepatocarcinogenesis in nonhuman primates. The occurrence of mutation in codon 249 of the p53 gene in selective samples of human hepatocellular cancers may indicate involvement of environmental carcinogens other than aflatoxin B1 or that hepatitis B virus-related hepatitis is a prerequisite for aflatoxin B1 induction of G to T transversion in codon 249.
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PMID:Low frequency of p53 gene mutation in tumors induced by aflatoxin B1 in nonhuman primates. 131 Jun 37

Clinical trials of the antiviral action of interferon have shown an effect on the replication of several viruses including varicella zoster, herpes simplex, cytomegalovirus and hepatitis B. These studies indicate that administration early in the course of infection, or in some clinical circumstances, prophylactic administration, is likely to result in viral inhibition. The studies of interferon efficacy in topical application, as in prevention of recurrent herpes simplex keratitis, have shown limited efficacy except with very high doses. These studies are being pursued with more concentrated preparations of interferon. The evaluation of interferon in human malignancy is just beginning, but some encouraging results have been obtained in open trials of the drug in patients with non-Hodgkin's lymphoma, melanoma, osteogenic sarcoma, and other diseases. With newer methods for the production of interferon, it may be possible to evaluate its antiviral and anti-tumor effects in carefully controlled studies with larger numbers of subjects.
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PMID:Interferon as an antiviral and anti-tumor therapeutic agent. 616 51

A mutation in the tumor suppressor p53 gene resulting in an Arg-->Ser substitution in position 249 is found frequently in human hepatocellular carcinomas associated with hepatitis B infection and with aflatoxin exposure. To determine the significance of this mutation in an in vivo experimental model using transgenic mice, we introduced a two-nucleotide change in the mouse p53 gene at amino-acid position 246, which is equivalent to position 249 in human p53, by the recombinant polymerase chain reaction mismatched primer method. This p53 mutation resulted in the same change, an Arg-->Ser substitution, as in the human p53 gene at position 249. We now report that the protein product of this mutant mouse p53ser246 had properties similar to those of the wild-type protein when tested by binding to (i) monoclonal antibodies PAb246 and PAb240, ii) simian virus 40 large T antigen, and (iii) heat-shock protein. However, it had mutant-type transforming properties when tested for colony formation with an osteosarcoma cell line. It was not active, as is wild-type p53, in transcription activation of the muscle creatine kinase promoter. These properties are the same as those found in the p53trp248 product of the p53 mutation associated with the Li-Fraumeni syndrome. Although less is known about the human p53ser249 product associated with hepatocellular carcinoma, the mutant murine p53ser246 protein shares the known properties of the human gene product.
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PMID:Characterization of a murine p53ser246 mutant equivalent to the human p53ser249 associated with hepatocellular carcinoma and aflatoxin exposure. 760 78

Hepatitis B virus infection is primarily mediated by the interaction of the preS region of the viral envelope protein with its still unknown cellular receptor. Using recombinantly expressed preS proteins, the distribution of preS-binding receptors on cell lines from extrahepatic origins was determined by immunofluorescence and flow cytometry. In contrast to human liver cell lines, most cell lines from extrahepatic origins did not bind preS proteins. Nevertheless, exceptions were found in the bone marrow-derived cell line, KG-1, and the osteogenic sarcoma cell line SaOS-2, as well as in the previously reported EBV-transformed B-cell line, Wa. To determine the biochemical nature of these receptors, Wa-cells were cell surface biotinylated and the preS-binding receptors were isolated by immunoprecipitation. A specific band with a molecular weight of approximately 30 kDa was identified in a SDS-polyacrylamide gel, which further characterization is expected to provide clues regarding the infection mechanism of HBV in hepatic- and extra-hepatic cells.
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PMID:Detection of cellular receptors specific for the hepatitis B virus preS surface protein on cell lines of extrahepatic origin. 1102 70

The fragility of the evidence for SV40 association with human cancer is seen in studies of NHL. A publication in 1999 stated that SV40 is rarely present in NHL. In 2002, two laboratories reported SV40 sequences in 42% to 43% of cases of NHL . One of these laboratories also detected SV40 sequences in small proportions of pediatric tumors (e.g., Wilm's tumor, hepatoblastoma, rhabdomyosarcoma, medulloblastoma, osteosarcoma, and retinoblastoma) and adult carcinomas (e.g., lung, colon, breast, and prostate) These positive results were not confirmed in subsequent studies published in 2003. Capello et al and Mackenzie et al failed to detect SV40 sequences in NHL tissues. Sanjose et al examined sera from patients with NHL and from controls for antibodies reactive to SV40 VLPs, and they detected no significant differences between the two groups. The association of SV40 with NHL is in doubt. An etiologic link between a virus and a cancer becomes plausible when evidence from different lines of enquiry (e.g., epidemiology, pathogenesis, and molecular mechanisms) is mutually reinforcing and together provides a coherent picture that can connect the biology the virus to the characteristics of the disease. The associations of human papillomaviruses with cervical cancer and hepatitis B and C viruses with hepatocellular carcinoma are examples in which the etiologic link is clear. With SV40 and mesothelioma, the data on viral sequences in tumors is inconsistent and disputed, and serologic evidence does not support any association. The epidemiologic data do not show that documented exposures tt SV40 increase the risk of mesothelioma. It seems improbable that a single virus (which cannot be conclusively demonstrated to be present in the community) contributes to the development of such a wide variety of tumors, spanning all age groups and histologic types. The weaknesses in the evidence linking SV40 with mesothelioma are summarized in Box 11 It seems unlikely that infection with SV40 contributes to the development of human mesothelioma or any other human cancer.
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PMID:Causality of mesothelioma: SV40 question. 1555 56

Cancer therapy and supportive measures entail the risk of infection with hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV). The objective of this analysis was to establish the incidence of infections with these viruses during antineoplastic treatment in our paediatric sarcoma patients, who are being followed-up within the Late Effects Surveillance System (LESS), which prospectively registers sequelae of therapy for Ewing's-, soft tissue- and osteosarcoma in patients treated in Germany, Austria and Switzerland within the trials EICESS-92/EURO-E.W.I.N.G.-99, CWS-96/CWS-2002P and COSS-96. We studied 264 eligible relapse-free paediatric patients [median age at diagnosis 14.3 (IQR 11.1-16.4) years], treated from January 7, 1998 until April 24, 2004. According to the LESS protocol, serological examinations for HBV, HCV and HIV were scheduled 4 weeks and 6 months after cessation of antineoplastic treatment. The median follow-up was 20.6 (IQR 12.4-26) months. None of the patients was reported to have acquired HBV, HCV or HIV during antineoplastic treatment. Blood donor screening and prophylactic measures employed in Germany, Austria and Switzerland to prevent infections of cancer patients with HBV, HCV and HIV seem to be very effective, having fully prevented new infections in this large cohort of paediatric sarcoma patients.
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PMID:Prospective evaluation of hepatitis B, C and HIV infections as possible sequelae of antineoplastic treatment in paediatric sarcoma patients: a report from the Late Effects Surveillance System. 1646 31

T-cell immunoglobulin and mucin domain-containing-3 (TIM-3) performs a critical function in immune tolerance by suppressing the activation and proliferation of T cells. TIM-3 serves an important role in tumor progression in a number of carcinomas, including non-small cell lung cancer, hepatitis B virus-associated hepatocellular carcinoma, Langerhans cell sarcoma, head and neck cancer and follicular B cell non-Hodgkin lymphoma. The aim of the present study was to evaluate the possible association of TIM-3 with the prognosis of osteosarcoma. TIM-3 expression was assessed by immunohistochemical analysis in osteosarcoma tissues. The association between TIM-3 expression and prognosis was examined. To assess the association between TIM-3 expression levels and clinicopathological features, a Fisher's exact test was used. TIM-3 overexpression was indicated to be associated with surgical treatment and survival. Kaplan-Meier analysis indicated that TIM-3 is an independent predictor of overall survival, and its overexpression was indicated to be associated with poor prognosis in patients with osteosarcoma. Additionally, reverse transcription-quantitative polymerase chain reaction and western blot analysis were carried out to evaluate TIM-3 expression levels in fresh tumor tissue samples, adjacent-tissue samples, osteosarcoma cell lines, and in an osteoblastic cell line. TIM-3 was indicated to be overexpressed in fresh osteosarcoma tissue samples and in osteosarcoma cell lines. In conclusion, TIM-3 overexpression is associated with poor survival among patients with osteosarcoma and may be a possible therapeutic target in these types of tumors.
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PMID:TIM-3 expression and its association with overall survival in primary osteosarcoma. 3161 39