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)

High-dose methotrexate is an important element of treatment protocols in childhood acute lymphocytic leukemia or osteosarcoma. A capillary electrophoretic method has been developed to measure peak levels and the metabolite pattern in patients with delayed methotrexate elimination. It serves to determine plasma levels of methotrexate, leucovorin and their metabolites, 7-hydroxymethotrexate, 2,4-diamino-N10 -methylpteroic acid and 5-methyltetrahydrofolic acid. For the determination of high concentrations (>10 microM) protein precipitation by acetonitrile will suffice for sample preparation. All other samples undergo solid-phase extraction and upgrading on C18 columns. Aminopterin, a therapeutic antecedent of methotrexate, serves as internal standard. Detection is done on a UV detector with a 300 nm filter. Five hundred microl of serum are needed to determine 0.2 microM of a specified substance (0.5 microM 5-methylterahydrofolic acid) with good precision and accuracy. For peak levels, 20 microl of capillary serum are sufficient.
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PMID:Capillary electrophoretic drug monitoring of methotrexate and leucovorin and their metabolites. 983 74

Seasonal trends in month of diagnosis have been reported for childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). This seasonal variation has been suggested to represent an underlying viral aetiology for these malignancies. Some studies have shown the highest frequency of diagnoses in the summer months, although this has been inconsistent. Data from the Children's Cancer Group and the Pediatric Oncology Group were analysed for seasonal incidence patterns. A total of 20,949 incident cancer cases diagnosed in the USA from 1 January 1989 through 31 December 1991 were available for analyses. Diagnosis-specific malignancies available for evaluation included ALL, acute myeloid leukaemia (AML), Hodgkin's disease, NHL, rhabdomyosarcoma, neuroblastoma, retinoblastoma, osteosarcoma, Wilms' tumour, retinoblastoma, Ewings' sarcoma, central nervous system (CNS) tumours and hepatoblastoma. Overall, there was no statistically significant seasonal variation in the month of diagnosis for all childhood cancers combined. For diagnosis-specific malignancies, there was a statistically significant seasonal variation for ALL (P = 0.01; peak in summer), rhabdomyosarcoma (P = 0.03; spring/summer) and hepatoblastoma (P = 0.01; summer); there was no seasonal variation in the diagnosis of NHL. When cases were restricted to latitudes greater than 40 degrees ('north'), seasonal patterns were apparent only for ALL and hepatoblastoma. Notably, 33% of hepatoblastoma cases were diagnosed in the summer months. In contrast, for latitudes less than 40 degrees ('south'), only CNS tumours demonstrated a seasonal pattern (P = 0.002; winter). Although these data provide modest support for a summer peak in the diagnosis of childhood ALL, any underlying biological mechanisms that account for these seasonal patterns are likely complex and in need of more definitive studies.
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PMID:Seasonal variations in the diagnosis of childhood cancer in the United States. 1094 15

Neurotoxicity after the administration of methotrexate continues to worry physicians. However, inadequate folinic acid rescue is often not considered as a cause of this complication. To clarify whether adequate folinic acid rescue prevents methotrexate-induced neurotoxicity without reducing the cure rate in childhood ALL, published evidence that supported or refuted this claim was investigated. A literature search was conducted and the authors of the relevant studies were contacted. The published data supported the contention that neurotoxicity can be prevented by adequate folinic acid rescue even after very high doses of methotrexate. The safe minimum dose of folinic acid can be defined in terms of the dose of methotrexate given; the time to start of rescue is probably less important. There was no evidence that higher doses of folinic acid, such as those used after methotrexate in the treatment of osteosarcoma, rescue leukemia cells. No change in cure rate was found in relation to changes in scheduling or clinically relevant doses of folinic acid rescue. The accumulation of folinic acid in the cerebrospinal fluid did not seem to be of clinical relevance. No studies indicate that doses of folinic acid after high-dose methotrexate administration interfere with the killing of leukemia cells, nor that delaying the start of rescue beyond a certain point increases the antileukemic effect; neurotoxicity will, however, be increased. Review of current protocols that use low-dose folinic acid rescue and are associated with neurotoxicity is highly recommended.
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PMID:Defining the appropriate dosage of folinic acid after high-dose methotrexate for childhood acute lymphatic leukemia that will prevent neurotoxicity without rescuing malignant cells in the central nervous system. 1516 44

The aim of this study was to investigate seasonal variation in the incidence of cancer in children aged 0-14 years. Details of 2959 primary malignant cases (1659 males, 1300 females), diagnosed during the period 1968-2005, were extracted from a specialist registry (the Northern Region Young Persons' Malignant Disease Registry). Seasonal variation was analysed with respect to month of birth and diagnosis. The chi-squared heterogeneity test was used to test for non-uniform variation. Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using month of birth and month of diagnosis, respectively, as covariates in separate models. There was significant sinusoidal variation based on month of birth for acute lymphoblastic leukaemia (ALL) aged 1-6 years (P = 0.04; peak in March). For 0- to 14-year-old boys, there was statistically significant sinusoidal variation in month of birth for acute non-lymphocytic leukaemia (P = 0.04; peak in September) and astrocytoma (P = 0.03; peak in October). Based on month of diagnosis, there was statistically significant sinusoidal variation in girls for all lymphomas (P = 0.048; peak in March) and Hodgkin lymphoma (HL) (P = 0.005; peak in January), and in boys for osteosarcoma (P = 0.049; peak in October). This study confirms previous findings of seasonal variation around the month of birth for childhood ALL (at the peak ages) and provides further evidence of seasonal variation around month of birth for astrocytoma and around month of diagnosis for HL. The results are consistent with a role for environmental factors in the aetiology of these diagnostic groups. Further studies are needed to examine putative candidate agents.
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PMID:Season of birth and diagnosis for childhood cancer in Northern England, 1968-2005. 2041 61

A peculiar feature of several types of childhood cancer is that loss-of-function mutations of the TP53 (p53) tumor suppressor gene are uncommon, in contrast to many adult tumors. As p53 needs to be inactivated in order for tumor cells to survive and thrive, pediatric tumors typically make use of other mechanisms to keep p53 in check. One of the critical negative regulators of p53 is the MDM2 oncoprotein. Many anticancer drug development efforts in the past decade have therefore been devoted to the discovery and optimization of small molecules that selectively disrupt the interaction between MDM2 and p53, which could provide, in principle, a potent means to restore p53 function in tumor cells with wild-type p53. The nutlins are the class of selective inhibitors of the p53-MDM2 interaction that are currently most advanced in their clinical development. We review here the preclinical data that support the potential therapeutic use of nutlin drugs in the treatment of various pediatric tumors, including neuroblastoma, retinoblastoma, osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, medulloblastoma, and childhood acute lymphoblastic leukemia.
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PMID:Pharmacologic activation of wild-type p53 by nutlin therapy in childhood cancer. 2426 62

Anthracyclines (doxorubicin, daunorubicin, epirubicin, and idarubicin) are among the most potent chemotherapeutic agents and have truly revolutionized the management of childhood cancer. They form the backbone of chemotherapy regimens used to treat childhood acute lymphoblastic leukemia, acute myeloid leukemia, Hodgkin lymphoma, Ewing sarcoma, osteosarcoma, and neuroblastoma. More than 50% of children with cancer are treated with anthracyclines. The clinical utility of anthracyclines is compromised by dose-dependent cardiotoxicity, manifesting initially as asymptomatic cardiac dysfunction and evolving irreversibly to congestive heart failure. Childhood cancer survivors are at a five- to 15-fold increased risk for congestive heart failure compared with the general population. Once diagnosed with congestive heart failure, the 5-year survival rate is less than 50%. Prediction models have been developed for childhood cancer survivors (i.e., after exposure to anthracyclines) to identify those at increased risk for cardiotoxicity. Studies are currently under way to test risk-reducing strategies. There remains a critical need to identify patients with childhood cancer at diagnosis (i.e., prior to anthracycline exposure) such that noncardiotoxic therapies can be contemplated.
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PMID:Predicting and Preventing Anthracycline-Related Cardiotoxicity. 3023 96