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)

In cancer chemotherapy, routine monitoring of drug concentrations has been practical only for methotrexate (MTX). The primary setting for pharmacokinetic monitoring of MTX is its use in high doses (HDMTX) for adjuvant therapy of osteosarcoma, for single-agent treatment of intracranial lymphomas, and in combination therapy of childhood leukemia as well as adult and pediatric non-Hodgkin lymphomas. Typically, HDMTX is infused in doses of 3-15 g/m2 over a period of 6-24 h. Precautions must be taken to ensure a high urine flow and an alkaline urine pH, so as to prevent precipitation of MTX in urine. Patients with decreased renal function, advanced in age, and taking nonsteroidal anti-inflammatory drugs or nephrotoxic agents are at increased risk of developing renal dysfunction during MTX infusion, thus being placed at high risk for toxicity. At the end of HDMTX infusion, and periodically thereafter for 24-48 h, drug concentrations are measured to assure that the disappearance rate of MTX from plasma is occurring at a normal rate. Also, at the end of HDMTX infusion, the patient is given leucovorin (5-formyl-tetrahydrofolic acid; LV), which replenishes intracellular stores of reduced folate and attenuates the toxicity secondary to HDMTX. In the presence of inappropriately high concentrations of MTX, routine doses of LV will be ineffective; the dose of LV required must be increased in proportion to the MTX concentration it faces in plasma. In practice, routine monitoring of plasma MTX concentrations allows early detection of abnormal clearance, as well as institution of early and effective countermeasures, including the use of increased and prolonged LV rescue.
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PMID:Concepts in use of high-dose methotrexate therapy. 869 6

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

Staging systems are used in staging most pediatric solid tumors outside the central nervous system. Common solid, nonneurologic pediatric tumors include liver tumors, Hodgkin disease, non-Hodgkin lymphoma, Wilms tumor, rhabdomyosarcoma, neuroblastoma, Ewing sarcoma, and osteosarcoma. Traditional staging of pediatric tumors depends on the anatomic distribution of the malignant disease. Almost all staging systems are based on the spread of the local primary tumor, metastasis to regional lymph nodes, and distant blood-borne metastatic spread. There is some variability as to how tumor spread is assessed. Such assessment may be performed before or after surgery. There are many potential problems with tumor staging systems. The systems vary in complexity and clinical usefulness, and there is some variation in the criteria used in the different systems. It is important for radiologists to have a sound working knowledge of staging systems to facilitate accurate staging. Imaging is an important aspect of every staging system.
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PMID:Visual presentation of the staging of pediatric solid tumors. 889 21

In the framework of the ITACARE project, a cooperative investigation conducted on the data from the Italian population-based cancer registries, survival of patients with childhood malignant neoplasms was studied. The study included 1,768 cases diagnosed at age 0-14 plus 29 osteosarcoma cases diagnosed at age 15-19. Cases were collected over the period 1978-1989, or more limited periods for some participating registries. A total of 1,138 cases were from the Childhood Cancer Registry of Piedmont and 659 from the registries operating in the provinces of Varese, Parma, Modena, Forli and Ravenna, Florence, Latina, Ragusa and in the cities of Genova and Torino (the last contributed only for bone neoplasm diagnosed at age 15-19). Overall 5-year survival was 54% for malignancies diagnosed in 1978-1981, 60% for the period 1982-1985; and 69% for the period 1986-1989. The range among registries of 5-year survival for cases diagnosed in 1986-1989 was 55-78%. Most diagnostic categories presented an improved prognosis for the cases diagnosed more recently. For cases diagnosed in 1986-1989, 5-year survival was: 74% for acute lymphatic leukaemia, 40% for acute non-lymphatic leukaemia, 65% for central nervous system neoplasms (76% for astrocytoma, 75% for ependymoma and 85% for medulloblastoma), 66% for osteosarcoma, 55% for Ewing's sarcoma, 87% for Hodgkin's disease, 64% for non-Hodgkin's lymphoma, 74% for rhabdomyosarcoma, 64% for neuroblastoma, 78% for nephroblastoma and 100% for retinoblastoma. Italian survival was similar to that observed in other population-based surveys in the UK and USA.
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PMID:Survival of childhood cancer patients in Italy, 1978-1989. ITACARE Working Group. 915 68

This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.
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PMID:Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. 922 42

The four national paediatric cancer clinical trials organisations in the United States--the Children's Cancer Group, the National Wilms' Tumor Study Group, the Intergroup Rhabdomyosarcoma Study Group and the Pediatric Oncology Group--were formed in 1955, 1969, 1972 and 1979, respectively. Together, the Children's Cancer Group and Pediatric Oncology Group serve as a national registry of nearly all childhood cancers in the United States, provide a national network of communication for researchers, care providers and families of paediatric patients with malignant disease and conduct laboratory investigations and clinical trials of new treatments of cancers in infants, children, adolescents and young adults. Nearly 95% of patients with cancer in the United States who are below 15 years of age are registered by the Children's Cancer Group and the Pediatric Oncology Group and more than half of American children with cancer are entered into at least one trial by a paediatric group. Improved survival of children receiving treatment according to well-defined protocols in specialised children's centres, in contrast to children who received treatment outside of these centres, has been shown for those with acute lymphoblastic leukaemia, lymphoma, Wilms' tumour, medulloblastoma, rhabdomyosarcoma and Ewing's sarcoma. By the year 2000, the overall cure rate for United States children and adolescents with cancer should exceed 85%. To reach this goal, the way forward will depend on international collaboration, implementation of global harmonisation, prevention of the erosion of biomedical research and clinical trials by the managed health care industry, increased public and private financial support and continued recruitment into paediatric oncology of brilliant and dedicated young investigators. The specific challenges ahead include: (1) transferring the knowledge, methodologies and technologies to countries that are less fortunate; (2) conducting multinational clinical trials in conjunction with paediatric cooperative groups in other countries; (3) accessing older adolescent patients who currently do not participate in cooperative group trials; (4) merging clinical trials by adult collaborative groups that overlap with the paediatric groups, as in acute lymphoblastic leukaemia, acute myelogenous leukaemia, Hodgkin's disease, osteosarcoma and germ cell tumours; (5) establishing a stable source of funding for national and international cooperative paediatric cancer clinical trials; (6) creating an informatics system that can link paediatric cooperative group operation centres around the world, and the institutions within each collaborative group; and (7) securing the support of the insurance industry and government in covering clinical trials.
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PMID:The U.S. pediatric cancer clinical trials programmes: international implications and the way forward. 933 87

Solid malignant tumours (n = 263) excluding brain and spinal cord tumours in children up to 14 years of age were studied. Retinoblastoma (27%) constituted the largest group followed by Wilms' tumour (14.1%) and lymphoma (13.7%). Most patients (55%) were of less than 5 years age and maximum incidence of embryonal tumours was found in this age group; other tumours were more frequent in higher age. A male preponderance was noted (male to female ratio as 1.6:1). Amongst lymphoma, 61% were non-Hodgkin's lymphoma and rest were Hodgkin's disease; 2 cases of Burkitt's lymphoma were found. Other notable tumours encountered in the study were embryonal rhabdomyosarcoma (n = 14), hepatoblastoma (n = 9), neuroblastoma (n = 7), Ewing's sarcoma (n = 21), osteogenic sarcoma (n = 19) and germ cell tumours (n = 14).
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PMID:Pattern of solid malignant tumours in children--a ten-year study. 935 72

A retrospective analysis of 515 pediatric cancer cases diagnosed over 18 years, 1973-1990, showed an annual incidence of pediatric solid tumors in northern Israel of 77.1 per million, somewhat lower than previously reported. Lymphomas predominated over central nervous system (CNS) neoplasms, suggesting an Afro-Asian rather than a Western pattern. Jewish and non-Jewish children were at approximately equal risk (1:07:1.0) for the nonleukemic cancer. However, there was a notably higher frequency in males than females (1:42:1.0) and in Ashkenasi Jews as compared to either Sephardi Jews (1.25:1.00) or non-Jews (1.23:1.0). Ethnic, age, and sex predispositions for particular types of malignancy were also noted. Non-Jews tended to have lymphomas or retinoblastomas and Sephardi Jews were predisposed to soft tissue sarcomas. Ashkenasi Jews tended to manifest CNS tumors, retinoblastoma, and osteosarcoma. Children under 5 years showed Burkitt's lymphoma and neuroblastoma, whereas the older group tended to have Hodgkin's lymphoma. Boys were more vulnerable to non-Hodgkin's lymphoma, medulloblastoma, neuroblastoma, and rhabdomyosarcoma, and girls were subject to higher incidences of bone, gonadal, germ cell, and epithelial tumors, as well as to astrocytoma. The implications for genetic or environmental contributions to several cancers are considered in conjunction with ethnic or gender predisposition to those cancers.
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PMID:Patterns of childhood solid tumor incidence in northern Israel, 1973-1990. 938 5

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

Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage previously described most frequently after breast cancer and Hodgkin disease treatment with radio and/or chemotherapy. We report two cases of classical osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive loco-regional irradiation in the second case.
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PMID:[Secondary head and neck osteosarcoma following treatment of undifferentiated nasopharyngeal neoplasms (UCNT)]. 958 63


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