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)

The principles of cancer chemotherapy applied to adult patients today have been substantially derived from experience of cancer in children. Studies of pediatric solid tumors also provided the first evidence that chemotherapy combined with surgery and/or radiotherapy could markedly enhance the curative potential of these local modalities. Conceptual advances in cancer chemotherapy revealed the superiority of intermittent chemotherapy over continuous low-dose therapy with respect to tumor cell kill and the recovery of normal cells. Childrens' Cancer and Leukemia Study Group of Japan applied intensive intermittent chemotherapy for maintenance therapy for leukemia, malignant lymphoma and to adjuvant chemotherapy for solid tumors. Event-free survival rate in treatment of childhood cancer by the Department of Pediatrics, Aichi Medical University, has markedly improved: ALL, 70%; malignant lymphoma, 50%; ANLL, 33%; hepato-blastoma, 100%; osteosarcoma, 65%; neuroblastoma, 54%; and rhabdomyosarcoma, 51%. The 14% rate for brain tumors was the only exception. Current Phase I and II trials based on pharmacokinetics and pharmacodynamics in children were reviewed.
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PMID:[Current status in treatment of childhood cancer]. 766 60

Survival rates for childhood cancers were analyzed with a total of 2,209 cases who were registered in a population-based cancer registry in Osaka, Japan in 1975-1984. These cases were reclassified according to Birch's classification and the survival rate of each diagnostic group was calculated by Kaplan-Meier methods. Death certificate-only cases, which amounted to 3.9% of all incidence, were excluded from the calculation. The five-year cumulative survival rate for both sexes was 46% for all cancer children. Among 12 major diagnostic groups, the most favorable survival was seen in retinoblastoma (87.5%), followed by renal tumors, epithelial neoplasms, and gonadal and germ-cell tumors. The outcome was unfavorable in leukemias, sympathetic nervous system tumors, hepatic tumors and malignant bone tumors. Comparing the survival in 1975-1979 with that in 1980-1984, the rate for all childhood cancer rose from 41% to 51%. Improvement in survival was also observed in 4 groups; acute lymphocytic leukemia, acute non-lymphocytic leukemia, non-Hodgkin's lymphoma and osteosarcoma. One attributable factor for the rise of survival was proved to be improvement of medical treatment by Cox's hazard model analysis. Comparison of survival rates in Osaka with those in England and the U.S. revealed that the prognosis for acute lymphocytic leukemia and acute non-lymphocytic leukemia was less favorable in Osaka than in England and the U.S.
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PMID:Survival rates of childhood cancer patients in Osaka, Japan, 1975-1984. 773 5

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

The surveillance, epidemiology, and end-results (SEER) data on 5-year relative survival rates (1973-1987) for the most common pediatric tumors (ages 0-14) were analyzed. The SEER data are population based, so the observed progress in survival from childhood cancer represents the real impact that development in cancer treatment had on the population followed by the registry. The greatest increase in survival rate from 1973 until 1987 has been achieved in hematopoietic tumors such as acute lymphocytic leukemia (ALL), in which survival increased from 47.6% (1973-1977) to 60.8% (1983-1987), and Burkitt's lymphoma in which survival increased from 27.6% (1973-1977) to 68.7% (1983-1987). Solid tumors showed a less steep, but steady increase in survival rates. Flattening in the survival rates since 1978-1982 has been observed for acute leukemia, astrocytoma, medulloblastoma, and osteosarcoma. Females have better survival rates for most pediatric tumors, except Hodgkin's disease. Analysis of race of childhood leukemia confirmed that black children have worse survival than white. When solid tumors were analyzed by stage at presentation, there was no indication that diagnosis in earlier stages of disease accounted for the improved survival. Observed flattening in the survival rates since 1978-1982 of leukemia and some solid tumors warrants further follow-up.
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PMID:U.S. childhood cancer survival, 1973-1987. 793 74

Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.
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PMID:Serum intercellular adhesion molecule-1 in childhood malignancy. 810 31

As little is known about the aetiology of cancer in children, analysis of time trends may be useful. Recent data on time trends for paediatric cancers are very limited. We report here on trends in the incidence of 15 categories of cancer in children under 15 years of age from 1970 to 1989, using data from the Greater Delaware Valley Pediatric Tumor Registry in the US. Total cancer incidence increased 1% per year (P < 0.001). Neither acute lymphocytic leukaemia, acute myelocytic leukaemia, nor total leukaemia incidence changed significantly. In contrast, the incidence of central nervous system (CNS) tumours rose 2.7% per year (P < 0.001). All three subgroups of this category, glioma, primitive neuroectodermal tumor (PNET)/medulloblastoma, and other CNS tumours, showed increases. For glioma and PNET/medulloblastoma, trends differed by age, race, and/or gender. Among the other childhood cancers, significant increases were observed for non-Hodgkin lymphoma and neuroblastoma. For osteosarcoma and retinoblastoma, no overall change in incidence was observed, although decreases were observed in some age and race subgroups. The rise in CNS tumour incidence confirms previous reports from the US and Great Britain. The lack of change for acute lymphocytic leukaemia conflicts with other data from the US, but diagnostic changes appear to explain at least part of the discrepancy. The increase in neuroblastoma has also been observed in Great Britain. In contrast to our finding, investigators in the US and Great Britain have reported no rise in non-Hodgkin lymphoma. Analyses for more of the childhood cancers from other registries would aid in detecting and interpreting incidence trends in recent years.
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PMID:Increasing incidence of childhood cancer: report of 20 years experience from the greater Delaware Valley Pediatric Tumor Registry. 882 74

Methotrexate (MTX) is a clinically important antifolate that has been used in combination with other chemotherapeutic agents in the treatment of malignancies including acute lymphocytic leukemia, osteosarcoma, carcinomas of the breast, head and neck, choriocarcinoma and non-Hodgkin's lymphoma. The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. Understanding of MTX action has revealed how cells acquire resistance to this drug. The four known mechanisms of MTX resistance are a decrease in the uptake of the drug, a decrease in the retention of the drug due to defective polyglutamylation or an increase in polyglutamate breakdown, an increase in the enzyme activity and a decrease in the binding of MTX to DHFR. The molecular basis for some of these mechanisms has been elucidated in MTX resistant cell lines; in particular the occurrence of gene amplification resulting in increased DHFR and point mutations resulting in altered DHFR with reduced affinity for MTX. Cloning of the human folylpolyglutamate synthase gene and the reduced folate transport gene have been reported recently and should facilitate the identification of the molecular basis of these resistant phenotypes. DHFR protein has been shown to regulate its synthesis by exerting an inhibitory influence on its own translation. Addition of MTX relieves this inhibition thus providing a possible molecular explanation for the rapid rise in DHFR activity noted in some cells after MTX administration. Alterations in genes involved in regulating the cell cycle such as cyclin D1 and the retinoblastoma (Rb) gene have also been shown to influence cellular response to MTX. Overexpression of cyclin D1 in HT1080, a human fibrosarcoma cell line, results in decreased MTX sensitivity. The molecular basis of this observation is under investigation. Abnormalities in the Rb gene may also have profound effects on MTX sensitivity. Rb interacts with the family of transcription factors called E2F reducing transcription of genes that contain E2F binding sites in the promoter regions e.g. DHFR. When Rb is deleted or rendered nonfunctional levels of "free" or unbound E2F are high resulting in enhanced transcription of genes such as DHFR. This results in increased DHFR protein and may lead to MTX resistance. As the knowledge regarding mechanisms of resistance increases newer approaches to circumvent such resistance or to target resistant cells can be undertaken.
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PMID:Molecular mechanisms of resistance to antifolates, a review. 885 36

The met protooncogene was activated by a rearrangement involving the fusion of tpr (1q25) and met (7q21-31) gene sequence in a human osteosarcoma cell line (HOS) incubated in vitro with N-methyl-N-nitro-N-nitrosoguanidine (MNNG). We examined the expression of tpr-met mRNA by means of the reverse transcription-nested polymerase chain reaction (RT-nested PCR) in human two gastric cell lines (MKN-1 and MKN-45), T-cell acute lymphocytic leukemia cell line (MOLT-4), and in gastric tissue samples including normal mucosa, intestinal metaplasia and carcinoma from three surgical specimens. A DNA fragment of 88-bp was amplified in MKN-1 and MOLT-4, 96-bp in MKN-45 and of 58-bp in all nine tissue samples including gastric carcinomas. The amplified DNA sequences were not homologous with the rearranged tpr-met gene. Our study indicated that rearranged tpr-met mRNA is not expressed either in human gastric carcinoma cell lines or in gastric mucosa and carcinoma.
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PMID:Lack of rearranged Tpr-met mRNA expression in human gastric cancer cell lines and gastric mucosa and carcinoma. 891 2

Loss of the p16INK4A gene by homozygous deletions or point mutations is attributed to the development of many types of cancers including leukemia. T cell acute lymphoblastic leukemias (T-ALLs) and B-cell ALLs show a remarkable rate of 75 and 20% homozygous deletion of this gene, respectively. Restoration of p16 expression in p16-deficient solid tumor cell lines results in a dramatic reduction of growth and maligant phenotype. To test the hypothesis that p16INK4A suppresses the growth of p16-deficient leukemias, we utilized a retroviral system to restore wild-type (wt) or mutant p16 protein expression. We tested the efficacy of our system by expressing the wt or mutant p16 genes in the osteosarcoma cell line, U20S, which lacks p16 and retains functional retinoblastoma protein (pRb). The wt p16 protein formed complexes with both cyclin-dependent kinases (CDK) 4 and 6 and inhibited U20S growth by 30-fold. The p16 mutants E120K and R144C formed complexes with CDK4 and CDK6 in cells and inhibited cell growth as effectively as wt p16 (20-fold) while the mutant proteins that did not complex with detectable levels of CDK4 or CDK6 only inhibited growth 0.25- and five-fold (G101W and D141, respectively) or not at all (H83Y and DA4). The COOH-terminal 'tail' of the wt p16 protein (amino acid residues 141-156), missing in mutant D141, enhanced the growth suppressive capability of p16. The amino acid substitutions in mutants G101W and H83Y not only disrupted CDK4 and CDK6 binding, but decreased the protein half-lives by two- and three-fold, respectively, compared to wt p16. The wt, but not mutant p16 genes, effectively inhibited the growth of T cell acute lymphoblastic (CEM) and myeloid leukemia (NB-4 and K562) cell lines that lacked the p16 gene, but retained functional pRb. Growth of the T-ALL cell line, HSB-2, which lacked both p16 and pRb, was not inhibited, indicating the growth suppression involved the pRb pathway. These results define regions critical for the function of p16 and demonstrate that restoration of wt p16 expression in p16-deficient leukemias significantly reverted their transformed phenotype and inhibited their growth.
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PMID:Inhibition of growth of human leukemia cell lines by retrovirally expressed wild-type p16INK4A. 932 88

Second malignancy after childhood neoplasms is a well-known complication. However, frequency differs considerably according to the types of primary neoplasm and the specifics of therapy. Ten patients with a second malignancy after being cured of the primary tumor are described. There were 2 patients with acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma developed osteosarcomas in the irradiation field after a latent period of 7 and 14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor. One patient with acute lymphoblastic leukemia developed a secondary AML 10 years after achieving initial remission, and a meningioma was diagnosed in another patient with cured acute lymphoblastic leukemia. One patient died of peritoneal sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid leukemia. All patients received radiotherapy for the primary neoplasms. Secondary neoplasms in other patients were probably missed because they occurred in adulthood when the patients were transferred to other medical centres. It is impossible to trace these patients because central registration of patients with neoplasms is lacking. It is therefore important to establish a central cancer registry for the whole of Switzerland. Second malignancy after childhood cancer is not a rare event and requires long-term follow-up of patients with neoplasms.
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PMID:[Insufficient understanding of second tumors after childhood neoplasms in Switzerland]. 958 99


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