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

beta-Adrenergic receptors were demonstrated in membrane preparations from 6 human Ewing's sarcomas and compared to those from 46 other pediatric cancers with the use of the beta-adrenergic antagonist (-)-(3H)dihydroalprenolol [(-)[3H]DHA]. In contrast to the high numbers of receptor sites found in Ewing's sarcomas (55-640 fmol x mg-1 protein; dissociation constant Kd, 1-2 nM), other childhood cancers (neuroblastoma, rhabdomyosarcoma, brain tumors, lymphoma, osteosarcoma, hepatoblastoma, yolk sac, and Wilms' tumor) contained in general fewer beta-adrenergic receptor sites. Characteristics of (-)-[3H]DHA binding were therefore more fully characterized in the Ewing's tumors. Competition of (-)-[3H]DHA binding by classical catecholamine agonists, as well as by subtype selective agents metoprolol and zinterol, demonstrated the presence of a homogeneous population of beta 1-adrenergic sites in several Ewing's tumors. Adenylate cyclase activity in all Ewing's sarcomas was enhanced by GTP and NaF. However, in spite of high numbers of beta-adrenergic receptors, (-)-isoproterenol was not very effective in the activation of adenylate cyclase activity in several of the Ewing's tumors tested. Neither guanyl-5'-yl-imidophosphate nor GTP altered agonist potency for the receptor site in these catecholamine-insensitive tumors. Hill coefficients obtained from the competition experiments with (-)-isoproterenol (in the presence or absence of guanine nucleotide) were approximately 1.0. These uncoupled receptors were resistant to N-ethylmaleimide denaturation and were densensitized only 50% during culture in the presence of (-)-isoproterenol. Thus Ewing's sarcomas are relatively rich in beta-adrenergic sites, and several tumors appear to have a coupling lesion involving guanine nucleotide-dependent regulatory protein interaction with beta-adrenergic receptors and adenylate cyclase, similar in phenotype to that described in the (unc) variant of S49 mouse lymphoma.
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PMID:beta-Adrenergic receptors in pediatric tumors: uncoupled beta 1-adrenergic receptor in Ewing's sarcoma. 631 52

Sections from 21 tumours diagnosed as primary or metastatic rhabdomyosarcoma were stained for alpha and beta enolase. The cases were subdivided into embryonal and alveolar subtypes (38% and 62%, respectively). Positive cytoplasmic staining for alpha enolase was seen in all but one case, and cytoplasmic staining for beta enolase was seen in some cells in 18 of the 21 cases (86% of the total, 88% of the alveolar subgroup, and 85% of the embryonal subgroup). No cells stained positively for beta enolase in the control series of neuroblastomas, fibrosarcomas, Wilms' sarcomas, and an osteosarcoma. The results show that beta enolase is a sensitive marker of muscular differentiation in rhabdomyosarcoma.
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PMID:An investigation of beta enolase as a histological marker of rhabdomyosarcoma. 638 45

Few pathologists have given much thought to the problem of post-chemotherapeutic tumoral regression of upper respiratory and digestive tract carcinoma. In other oncological fields (pediatry: nephroblastoma, embryonic sarcoma, osteosarcoma; gynecology: mammary tumors...) pre- and post-chemotherapy tissue studies have led to histological grading of prognostic value (particularly well known is that of Rosen et al). Numerous specimens were examined following operations for cancer, including pelvimandibulectomy, buccopharyngectomy, facial resection... Possible tumoral changes were evaluated using a conventional scale of regression based on 6 histologic degrees, and findings were of prognostic significance when compared with the initial biopsy results. This evaluation scale may require modification in the near future since recently introduced chemotherapy, particularly cisplatinum, appears to have a more potent and more specific effect on histologie features.
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PMID:[Tumor regression following local chemotherapy in carcinomas of the upper respiratory and digestive tracts. The viewpoint of the pathologist]. 667 Aug 9

A total of 114 children with solid tumors refractory to conventional therapy were evaluated for response and/or toxic effects after receiving cisplatin at doses of 3.0-4.5 mg/kg with aggressive hydration and mannitol diuresis every 3 weeks; a minimum of two courses was required for evaluation of response (110 patients). Objective responses were noted in 18 patients: rhabdomyosarcoma (three), Wilm's tumor (three), osteogenic sarcoma (three). Ewing's sarcoma (two), neuroblastoma (one), undifferentiated sarcoma (one), hepatoblastoma (one), ovarian teratoma (one), hepatocellular carcinoma (one), embryonal carcinoma of the mediastinum (one), and thymoma (one). Twenty-six patients had some evidence of renal toxicity. Asymptomatic hearing loss was commonly found when audiometry was performed (eight of 18 patients tested). Eight additional patients had symptomatic hearing problems--tinnitus or hearing loss. Myelosuppression was mild. Hypomagnesemia and/or hypocalcemia were common but only one patient had symptoms. Cisplatin, administered at a dose of 3.0 mg/kg with aggressive hydration and mannitol diuresis, is reasonably well-tolerated. Its role in the therapy for those tumors against which it shows activity remains to be determined.
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PMID:Phase II trail cisplatin in refractory childhood cancer: Children's Cancer Study Group Report. 694 56

The incidence of childhood cancer in Queensland has been studied using the data of the population-based Queensland Childhood Malignancy Registry. During the 7-year period 1973-1979, 454 cases were registered, giving an annual age-specific incidence of 11.34/10(5) for the age group 0-14 years inclusive. There was a male/female ratio of 1.36. The commonest group of diseases was that of the leukaemias, followed by that of CNS tumours. The incidences of the various types of tumour in Queensland have been compared with those from other reported series. The incidence of leukaemia was midway between that of U.S. whites and that of Manchester, while the incidences of lymphoma and Wilms' tumour were much closer to those of the United States. Ewing's tumour was considerably commoner than osteosarcoma.
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PMID:Incidence of childhood tumours in Queensland. 731 68

The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in a subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing WT1 under an inducible tetracycline-regulated promoter. Induction of WT1 resulted in programmed cell death. This effect, which was differentially mediated by the alternative splicing variants of WT1, was independent of p53. WT1-mediated apoptosis was associated with reduced synthesis of the epidermal growth factor receptor (EGFR), but not of other postulated WT1-target genes, and it was abrogated by constitutive expression of EGFR. WT1 repressed transcription from the EGFR promoter, binding to two TC-rich repeat sequences. In the developing kidney, EGFR expression in renal precursor cells declined with the onset of WT1 expression. Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles.
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PMID:WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. 758 96

The Wilms' tumor-suppressor gene product WT1 coimmunoprecipitates with p53 from baby rat kidney (BRK) cells and Wilms' tumor specimens, and expression of WT1 in BRK cells is associated with increased levels of endogenous wild-type p53 protein. To study the effect of WT1 on p53 function, we cotransfected expression constructs into Saos-2 cells, an osteosarcoma cell line without endogenous expression of either gene. Expression of WT1 resulted in increased steady-state levels of p53, attributable to a prolongation in protein half-life, and associated with protection against papillomavirus E6-mediated degradation of p53. This effect mapped to zinc fingers 1 and 2 of WT1 and was not observed with the closely related EGR1 protein. The stabilized p53 demonstrated enhanced binding to its target DNA sequence and increased trans-activation of a promoter containing this RGC site, but reduced transcriptional repression of a TATA-containing promoter lacking this site. Expression of WT1 inhibited p53-mediated apoptosis triggered by UV irradiation or by expression of temperature-sensitive p53 in the wild-type conformation, but did not affect p53-mediated cell cycle arrest. We conclude that WT1 protein can stabilize p53, modulate its trans-activational properties, and inhibit its ability to induce apoptosis. This effect may contribute to the elevated levels of wild-type p53 protein that are observed in Wilms' tumors.
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PMID:The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis. 765 66

More aggressiveness in treatment of childhood malignancies has had an evident impact on survival and rate of cure but, it has also allowed us to discover long-term effects of these treatments, and second malignant tumors of them. Between 1970 and 1993, 472 cases of malignant tumors in childhood were diagnosed in our department. Six of them (1.27%) developed a second tumor (five malignant and one benign). Relationship between first and second tumors are: seven years old boy, cervical lymphosarcoma-thyroid carcinoma; eleven years old boy, osteogenic sarcoma-vesical carcinoma: two years and six months old boy, cerebellar astrocytoma-soft tissue osteogenic sarcoma; five years old girl. Wilm's tumor-scapular osteogenic chondroma; one year and a half old girl, abdominal neuroblastoma-granulocytic sarcoma (chloroma); twelve years old boy. Hodgkin's disease-acute myeloblastic leukemia. All of them were clearly related to concogenic effect of radiation or chemotherapy.
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PMID:[Second tumors in childhood]. 776 70

An analysis of seven hundred and ninety one children aged 0.2 to 14 years with confirmed malignant disease recorded by the Malawi National Cancer Registry over a period of 9 years is presented. Childhood cancer constituted 6.9% of all malignancies recorded during the study period. The top ten neoplasms in descending order of frequency were: non-Hodgkin's lymphoma 434 (54.9%), retinoblastoma 89 (11.3%), nephroblastoma 50 (6.3%), epithelial carcinoma 45 (5.7%), Hodgkin's disease 38 (4.8%), soft tissue sarcoma (excluding Kaposi): 34(4.3%), Kaposi's sarcoma 32 (4.0%), malignant tumours (not specified): 20 (2.5%), acute leukaemias 18(2.3%) and osteogenic sarcoma 16 (2.0%). Some differences noted in the pattern of neoplasms in this study from those of developed and developing African countries are discussed. The findings highlight the most common childhood malignancies in Malawi where intense research should be directed so that meaningful and cost effective therapeutic intervention programmes can be planned and developed.
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PMID:Spectrum of childhood cancers in Malawi 1985-1993. 778 51

Insulin-like growth factors are abnormally expressed in some pediatric solid tumors. In addition, tumors that do not show significant alterations in pattern of expression are responsive to and may be dependent upon insulin-like growth factors for proliferation. These can be produced by the tumor cells (autocrine), surrounding stromal cells (paracrine), or at a distance (endocrine). Insulin-like growth factor-II plays a role in Wilm's tumor, neuroblastoma, and rhabdomyosarcoma, either as a proliferation factor, a motility factor, or both. Insulin-like growth factor-I may regulate osteosarcoma and the Ewing's family of tumors (primitive neuroectodermal tumors). Understanding the biology of these growth factors and their receptors can lead to new therapeutic approaches.
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PMID:Diverse roles of insulin-like growth factors in pediatric solid tumors. 805 16


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