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)

Bleomycin sensitivity has been proven to be a useful biomarker for environmental carcinogenesis and tumor genetic instability. We have previously reported a significant increase in the chromosomal aberrations induced by chemotherapy regimens. This study aimed to test whether there is an inherent increased genetic instability in cancer patients at diagnosis, to determine the increase and time course of the chemotherapy-induced instability and to test whether bleomycin sensitivity can be used as a predictor of tumor evolution or relapse. The analysis included 99 pediatric cancer patients with four different tumor types (Ewing's sarcoma, osteosarcoma, lymphoma and CNS tumors) and 25 controls. Blood samples (n = 171) were obtained before and at the end of treatment, during clinical remission and at relapse and bleomycin tests on lymphocyte cultures were performed. We detected a significant increase (P = 0.004) in mutagen sensitivity in patients at the end of treatment compared with untreated patients, regardless of the tumor type. In both the longitudinal and cross-sectional analyses maximal and similar values of mutagen sensitivity were found in patients during treatment (1.84 +/- 0.82) and at relapse (1.78 +/- 0.52); minimum and similar values were found in controls (0.93 +/- 0.23), untreated patients (1.15 +/- 0.65) and in those who had fulfilled the chemotherapy protocols for at least 2 years before their sample was collected (1.09 +/- 0.53). From this preliminary data we can conclude that cytostatic drugs induce a transient increase in chromosomal instability in pediatric cancer patients that can be monitored by bleomycin-induced sensitivity tests and that the genetic instability indices should be further investigated as predictors of relapse.
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PMID:Measurement and analysis of the chemotherapy-induced genetic instability in pediatric cancer patients. 1188 May 47

Anemia is a hematologic abnormality commonly discussed during the treatment of childhood cancer, but its incidence has not been previously reported. As the basis for determining the incidence of anemia, this retrospective review of medical records combined databases containing the records of all patients 1 to 18 years of age with newly diagnosed neuroblastoma, rhabdomyosarcoma, Hodgkin disease, Ewing sarcoma, or osteosarcoma from two pediatric oncology centers. Data from 405 patients were included in the analysis of hemoglobin at the time of diagnosis. Across diagnoses, 51% to 74% of patients were anemic using the Centers for Disease Control and Prevention age- and sex-specific values to define anemia. The long-term complications of anemia in children with cancer are unknown. Further investigation of the clinical significance of anemia, including its impact on quality of life, is warranted.
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PMID:Incidence of anemia in children with solid tumors or Hodgkin disease. 1190 37

A certain number of pediatric cancer patients still succumb to relapse following conventional treatment of their malignancies. One of the mechanisms of relapse is escape from immunity. Adoptive cellular immunotherapy with effector cells has the potential to overcome this escape. In adults, the CD3+ CD56+ cell, a cytokine-induced killer (CIK) cell, appears to be a promising effector cell type with the greatest cytotoxicity. This effector cell type may work in children as well. No similar studies with children have been published. We speculated that expanded CD3+ CD56+ cells obtained from pediatric cancer patients during remission would act similarly against various pediatric tumor cell lines; therefore, we undertook the present study to find support for our speculation. This study was undertaken to generate and expand CD3+ CD56+ CIK cells from normal peripheral blood mononuclear cells (PBL) obtained from 6 children with cancer (2 with acute lymphoblastic leukemia, 2 with large cell lymphoma, and 2 with osteosarcoma) in remission after intensive chemotherapy and to study the cytotoxic activities of these cells against chronic myeloid leukemia cell line K562 t(9;22), 4 pediatric tumor cell lines [infant acute lymphoblastic leukemia RS4 t(4;11), TEL/AML acute lymphoblastic leukemia REH t(12;21), alveolar rhabdomyosarcoma Rh-Cr t(2;13), and Ewing sarcoma EW-Le t(11;22)], and 2 pediatric glioblastoma multiforme cultured cell lines (G74 and G77). CIK cells were generated and expanded in culture medium to which interferon gamma, monoclonal antibody against CD3, and interleukin 2 were added at appropriate times. Cells were counted by flow cytometry. Net lactate dehydrogenase release from target cells incubated with CIK cells was used as an index of CIK cell cytotoxicity against various pediatric tumor cell lines. The results show that after 21 days in culture CD3+ CD56+ CIK cells derived from the 6 pediatric patients accounted for a median of 28.3% of the entire culture (range, 10.7%-36.4%). Before expansion no such cells were found in any of the 6 children. Median lytic activity rates of CIK cells were 45.5% to 64.5%, rates that contrasted drastically to the lytic activity rates of PBL, which were only 8% to 12%. The findings of the present study are encouraging. They provide information for developing adoptive immunotherapy for future clinical trials with pediatric cancer patients, particularly those patients with minimal residual disease after intensive chemotherapy or stem cell transplantation (especially nonmyeloablative transplantation procedures).
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PMID:Generation of CD3+ CD56+ cytokine-induced killer cells and their in vitro cytotoxicity against pediatric cancer cells. 1262 54

To analyze the effect of cancer treatment on pregnancy, delivery and progeny of women survivors of childhood cancer, 18 of them (15 to 49 years of age) were interviewed, with diagnosis and treatment between july 1965 and December 1982 (15 from the Oncology Unit of the Children's Hospital of Buenos Aires and 3 from a private practice) and evaluated until December 2000. The following potential determinants to suffer adverse effects on pregnancy, delivery and descendence were considered: laparotomy, alkylating agents, doxorubicine, infradiaphragmatic radiotherapy. Diagnoses were: non-Hodgkin lymphoma 6, nephroblastoma 5, retinoblastoma 3, osteosarcoma 1, fibrosarcoma 1, Langerhans cell histiocytosis 2. Ten patients were laparotomized, 11 were treated with alkylating agents, 8 with doxorubicin and 7 with infradiaphragmatic radiotherapy. Twenty-eight offsprings were born. Congenital anomalies were not detected. Inherited cancer was observed in two siblings whose mother had suffered bilateral retinoblastoma. Additional follow-up from woman survivors of childhood cancer is necessary to determine the effect of cancer and its treatment on pregnancy, delivery and offspring.
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PMID:[Pregnancy of 18 women survivors of childhood cancer]. 1279 77

Our understanding of the clinical and cellular pharmacology of drugs commonly used in the treatment of childhood cancer have increased greatly over the past two decades. However, with the exception of childhood acute lymphoblastic leukaemia (ALL), our current knowledge of factors such as inter-patient pharmacokinetic variability and cellular determinants of chemosensitivity has not been utilized in the design of integrated clinical studies. Recent pre-clinical and clinical evaluation of the topoisomerase I inhibitors topotecan and irinotecan has highlighted the potential importance of pharmacological factors in their effectiveness as cytotoxics. In this review, the clinical and cellular pharmacology of vincristine, actinomycin D, doxorubicin, cyclophosphamide, ifosfamide, cisplatin, carboplatin and etoposide will be discussed in relation to the major paediatric solid tumours. For each disease type, knowledge of the clinical and cellular pharmacology of a candidate drug will be related to pharmacodynamic responses such as response, toxicity and prognosis. For diseases such as Wilms' tumour, osteogenic sarcoma and Ewing's tumour, histological response to initial induction chemotherapy is of prognostic significance, and the depth of response is increasingly recognised as an important determinant of prognosis for high-risk neuroblastoma. For several of these tumour types, the dose-intensity of chemotherapy may be an important variable in determining prognosis. However the relationship between pharmacokinetic variability, cellular pharmacology and the major determinants of chemosensitivity to those drugs employed in first line therapy is unknown. The study of these relationships, by means of up front window studies in children who present with high-risk disease, may be as important as the introduction of new agents. Indeed, the optimisation of current therapies may be required to allow a fully informed selection of those children for whom novel therapies are truly needed. Funding and international collaboration at the clinical and scientific level would be required to achieve these aims.
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PMID:Clinical and cellular pharmacology in relation to solid tumours of childhood. 1292 66

Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane. In a mouse model of osteosarcoma, a highly metastatic pediatric cancer, we found ezrin to be necessary for metastasis. By imaging metastatic cells in the lungs of mice, we showed that ezrin expression provided an early survival advantage for cancer cells that reached the lung. AKT and MAPK phosphorylation and activity were reduced when ezrin protein was suppressed. Ezrin-mediated early metastatic survival was partially dependent on activation of MAPK, but not AKT. To define the relevance of ezrin in the biology of metastasis, beyond the founding mouse model, we examined ezrin expression in dogs that naturally developed osteosarcoma. High ezrin expression in dog tumors was associated with early development of metastases. Consistent with this data, we found a significant association between high ezrin expression and poor outcome in pediatric osteosarcoma patients.
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PMID:The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. 1470 91

We reviewed the current status of our knowledge of pharmacokinetics and pharmacodynamics of some anti-neoplastic drugs, used in the treatment of childhood cancer. Extrapolation of data from pharmacokinetic studies in adults to the paediatric population is often not feasible. Specific studies in children are needed. Of all reviewed anti-neoplastic drugs methotrexate appears to be most extensively studied. Methotrexate pharmacokinetics is correlated with toxicity and response to therapy, and it has been shown that individualized adaptive dosing of methotrexate is correlated with a better response to therapy without increasing toxicity in children with ALL and osteosarcoma. Of most of the other reviewed anti-neoplastic drugs it is demonstrated that pharmacokinetics is correlated with toxicity, and of some drugs a relationship of pharmacokinetics with response to therapy is demonstrated as well. In case of cytarabine, etoposide, and teniposide, individualized dosing also appears to be feasible. However, there is no evidence that this strategy improves response to therapy. Specifically data on pharmacokinetic and pharmacodynamic correlations and effect of pharmacokinetically guided, individualized dosing are important for the design of optimal cancer chemotherapy for individual patients. Unfortunately for a considerable number of anti-neoplastic drugs these specific data are lacking in children and future research is needed.
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PMID:Pharmacokinetic studies in children with cancer. 1558 85

Constitutional molecular defects are known to play a role in oncogenesis, as shown by the increased incidence of embryonic cancers in children with Beckwith-Wiedemann syndrome (BWS) or of leukemia in children with Down syndrome. To establish the incidence and spectrum of malformation syndromes associated with childhood cancer we performed a clinical morphological examination on a series of 1,073 children with cancer. We diagnosed a syndrome in 42 patients (3.9%) and suspected the presence of a syndrome in another 35 patients (3.3%), for a total of 7.2%. This incidence of patients with a proven or suspected syndrome is high, and points to a possible association. We describe new syndrome-tumor associations in several entities: cleidocranial dysostosis (Wilms tumor), Bardet-Biedl syndrome (BBS) (acute lymphoblastic leukemia), Kabuki syndrome (neuroblastoma), LEOPARD syndrome (neuroblastoma), Poland anomaly (osteosarcoma; Hodgkin disease), and blepharophimosis epicanthus inversus syndrome (Burkitt lymphoma). Twenty of the 42 syndrome diagnoses were not recognized in the patients prior to this study, indicating that these diagnoses are commonly missed. We propose that all children with a malignancy should be examined by a clinical geneticist or a pediatrician skilled in clinical morphology to determine if the patients have a malformation syndrome.
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PMID:High incidence of malformation syndromes in a series of 1,073 children with cancer. 1653 61

To investigate the incidence and outcome of secondary neoplasms in pediatric patients treated for childhood cancer. Between December 1971 and January 2000, a total of 5859 patients younger than age 17 were diagnosed and treated for childhood cancers in our center. Of this group, 1511 (36%) patients were followed for more than 36 months. These long-term survivors were included in this analysis. Twenty-six patients developed a secondary malignancy with an overall risk of 1.7% in this cohort. The male:female ratio was 17:10, with a median age of 7.66 at diagnosis (range, 2 to 16 y). Four patients (14.8%) with Hodgkin lymphoma; 3 each (11.1%) with retinoblastoma and rhabdomyosarcoma; 2 each (7.4%) with Wilms tumor, Ewing sarcoma, medulloblastoma, ganglioneuroblastoma, and non-Hodgkin lymphoma; and 1 each (3.7%) with ependymoma, nasopharyngeal carcinoma, osteosarcoma, astrocytoma had a secondary malignant disease during the long-term follow-up period. Secondary malignant diseases were osteosarcoma in 6 patients, acute lymphoblastic leukemia in 2, acute myelogenous leukemia in 2, and rare malignant disease in others. Four patients with osteosarcoma developed disease within the radiation field. Osteosarcoma was the most frequently occurring secondary neoplasm. Less toxic treatment modalities should be used to decrease the risk of secondary malignant diseases.
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PMID:Second neoplasms in pediatric patients treated for cancer: a center's 30-year experience. 1679 6

Data on 5572 children and adolescents diagnosed with malignant bone tumours (International Classification of Childhood Cancer, Group VIII) before the age of 20 years during 1978-1997 in Europe were extracted from the Automated Childhood Cancer Information System (ACCIS) database. Age-standardised incidence among children during the period 1988-1997 was similar for boys and girls aged 0-14 years (5.5-5.6 per million). Among adolescents aged 15-19 years, males had higher incidence (19.3 per million) than females (10.7 per million). Among children, osteosarcoma accounted for 51% of registrations and Ewing's sarcoma for 41%. Among adolescents, 55% of registrations were osteosarcoma and 28% Ewing's sarcoma. Both tumours had their highest incidence in late childhood or early adolescence. There were no significant time trends in incidence during 1978-1997. Five-year survival estimates for patients diagnosed during 1988-1997 were, respectively, 59% and 51% among children and adolescents with osteosarcoma and 62% and 30% among children and adolescents with Ewing's sarcoma. Between 1978-1982 and 1993-1997, survival increased for both children and adolescents with osteosarcoma, and for children with Ewing's sarcoma.
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PMID:Bone tumours in European children and adolescents, 1978-1997. Report from the Automated Childhood Cancer Information System project. 1691 76


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