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)

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

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.
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PMID:[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study]. 780 68

A dose-intensive regimen of cyclophosphamide (140 mg/kg over 2 days), doxorubicin (Adriamycin, 75 mg/m2 over 3 days), and vincristine (1 mg/m2 on days 1, 2, and 3 and 1.5 mg/m2 on day 9) was tested in 18 children and adolescents with poor-prognosis recurrent or refractory solid tumors. Nine were affected by neuroblastoma, 3 by Ewing's tumors, 2 by rhabdomyosarcoma, 2 by synovial sarcoma, 1 by hepatocellular carcinoma, and 1 by osteogenic sarcoma. All enrolled patients were heavily pretreated, including 2 patients after bone marrow transplantation. Forty courses were applied (median, 2). The overall response rate was 33% (2 complete remissions and 4 partial remissions). Responses were obtained in children with neuroblastoma, Ewing's tumors, and hepatocellular carcinoma. Myelosuppression [World Health Organization (WHO) grade IV after all courses] and cardiac toxicity (3 WHO grade I, 5 WHO grade III, and 3 WHO grade IV) were the main side effects. Nephrotoxicity and hepatoxicity were not observed. With further therapy consisting of surgery, radiotherapy, and high-dose chemotherapy [cisplatin, carboplatin/etoposide (VP16), or ifosfamide/VP16 with or without autologous stem cell reinfusion after conditioning with melphalan/VP16/carboplatin], 3 complete remissions and 5 very good partial remissions were obtained. Ten of 18 patients are alive after a median follow-up of 16 months.
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PMID:High-dose cyclophosphamide, adriamycin, and vincristine (HD-CAV) in children with recurrent solid tumor. 785 84

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

Sixty-seven childhood tumors were studied immunohistochemically for the extracellular matrix element type IV collagen, laminin, and fibronectin. Tumors included Ewing's sarcoma, primitive neuroectodermal tumor, small cell osteosarcoma, neuroblastoma or ganglioneuroblastoma, rhabdomyosarcoma, and lymphoma. It was found that small cell osteosarcoma was often positive for fibronectin but not type IV collagen or laminin, a new observation. In the lymphomas, matrix proteins were rarely found. Ewing's sarcoma was variably positive for type IV collagen and laminin, but fibronectin was absent. Extracellular laminin and fibronectin were found in one of two cases of primitive neuroectodermal tumor. In neuroblastoma and ganglioneuroblastoma, the matrix components were rarely found. These results, discrepant with findings in cultured cells, may reflect the altered capacity of tumors to produce these proteins in vitro, which suggests that caution should be exercised in drawing conclusions regarding the nature or histogenesis of tumors from data obtained with cultured tumor cells. Embryonal rhabdomyosarcoma frequently contained all matrix elements in the extracellular space and in a dotlike pattern in the cytoplasm; alveolar rhabdomyosarcoma rarely contained these proteins and never exhibited the dotlike pattern. The frequent finding of matrix proteins in embryonal rhabdomyosarcoma but only rarely in alveolar rhabdomyosarcoma and the unique immunostaining pattern in embryonal rhabdomyosarcoma may prove to be a useful adjunct in the diagnosis of childhood tumors.
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PMID:Extracellular matrix of small round cell tumors of childhood: an immunohistochemical study of 67 cases. 815 9

Lactacystin, a microbial natural product, induces neurite outgrowth in Neuro 2A mouse neuroblastoma cells and inhibits progression of synchronized Neuro 2A cells and MG-63 human osteosarcoma cells beyond the G1 phase of the cell cycle. A related beta-lactone, clasto-lactacystin beta-lactone, formally the product of elimination of N-acetylcysteine from lactacystin, is also active, whereas the corresponding clastolactacystin dihydroxy acid is completely inactive. Structural analogs of lactacystin altered only in the N-acetylcysteine moiety are active, while structural or stereochemical modifications of the gamma-lactam ring or the hydroxyisobutyl group lead to partial or complete loss of activity. The inactive compounds do not antagonize the effects of lactacystin in either neurite outgrowth or cell cycle progression assays. The response to lactacystin involves induction of a predominantly bipolar morphology that is maximal 16-32 h after treatment and is distinct from the response to several other treatments that result in morphological differentiation. Neurite outgrowth in response to lactacystin appears to be dependent upon microtubule assembly, actin polymerization, and de novo protein synthesis. The observed structure-activity relationships suggest that lactacystin and its related beta-lactone may act via acylation of one or more relevant target molecule(s) in the cell.
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PMID:A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line. 815 52

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy. 826 99

Uncontrolled cell growth is at the basis of neoplastic proliferation and arteriosclerotic lesions. In vitro proliferation of vascular smooth muscle cells, Balb c/3T3 fibroblasts, retinal neuroepithelial cells and neuroblastoma cells is inhibited by d-alpha-tocopherol. On the contrary Chinese hamster ovary cells, osteosarcoma cells and macrophages are not sensitive. PDGF-BB activated proliferation is highly d-alpha-tocopherol sensitive while lysophosphatidic acid induced growth is poorly inhibited. d-beta-Tocopherol, an analogue of d-alpha-tocopherol, with similar antioxidant properties, does not inhibit proliferation. Protein kinase C activity is inhibited by d-alpha-tocopherol but not by d-beta-tocopherol, suggesting a central role of this enzyme in the control of cell proliferation by d-alpha-tocopherol. Activation of the transcription activation complex AP-1 (but not NFKB) is prevented by d-alpha-tocopherol and not by d-beta-tocopherol.
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PMID:d-alpha-tocopherol control of cell proliferation. 826 42

Choline acetyltransferase (ChAT) is specifically expressed in cholinergic neurons. To identify control mechanisms regulating the cell-specific expression of the gene encoding ChAT, transient expression of the luciferase gene driven by human ChAT gene 5'flanking sequences was compared in cholinergic and noncholinergic cell lines. Analysis of the gene indicated the presence of two regulatory elements with selective silencing activity. These elements, located between nucleotides -2043 to -3347 and nucleotides -3347 to -6550, act cooperatively to repress promoter activity > 10-fold in a human adrenergic neuroblastoma cell line, SHSY5Y, and a human osteosarcoma cell line, 143 TK-, while exhibiting less than a two-fold effect in cholinergic cell lines. Deletion of either nucleotides -2043 to -3347 or nucleotides -3348 to -6550 reduced cell-specific repression by approximately half. Such differential repression appears to be responsible for the selective expression of the ChAT component of the cholinergic phenotype.
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PMID:Cholinergic neuron-specific expression of the human choline acetyltransferase gene is controlled by silencer elements. 833 50

The human fibroblast activation protein (FAP), defined by monoclonal antibody F19, is expressed in vivo in reactive stromal fibroblasts of epithelial cancers, subsets of bone and soft tissue sarcomas, and granulation tissue of healing wounds. FAP is generally absent from the stroma of benign epithelial tumors and normal adult tissues. In vitro FAP induction is observed in proliferating cultured fibroblasts and in melanocytes grown with fibroblast growth factor and phorbol ester. In the present study, we show that fibroblast and melanocyte FAP is a cell surface protein comprising noncovalently linked M(r) 95,000 (p95) and M(r) 105,000 (p105) subunits. In contrast, cultured sarcoma and melanoma cell lines express only p95 or are FAP negative. Immunoblot experiments show that p95, but not p105, carries the epitope defined by monoclonal antibody F19. Furthermore, peptide maps of purified p95 and p105 differ, suggesting that they may be distinct gene products. Loss of FAP or a change from p95/p105 to p95 expression accompanies the acquisition of growth factor independence and tumorigenicity in several in vitro test systems, including simian virus 40 transformation of normal fibroblasts, Ha-ras transformation of normal melanocytes, supertransformation of osteosarcoma cells, and enhanced N-MYC expression in variant neuroblastoma cells, whereas serum-starved normal fibroblasts continue to express p95/p105. Thus, fAP expression appears to be linked to the growth factor-dependent proliferative capacity of normal cells and is not merely a secondary event in proliferating cells; furthermore, FAP expression is inversely correlated with growth factor independence and tumorigenicity in transformed cell lines. This distribution pattern is consistent with a role for p95/p105 in mediating extrinsic, growth regulatory signals in normal cells, possibly as a heteromeric cell surface receptor. Such a physiological function may be obviated when oncogenes with cytoplasmic or nuclear sites of action are activated, reducing extrinsic growth factor dependence and permitting down-regulation of FAP in certain transformed cells.
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PMID:Regulation and heteromeric structure of the fibroblast activation protein in normal and transformed cells of mesenchymal and neuroectodermal origin. 839 23


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