Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported marked biologic activity with the epipodophyllotoxins in phase I/II studies of childhood cancer conducted in the 1970s. We have since extensively used the combination of teniposide and ara-C in the treatment of acute lymphoblastic leukemia (ALL). Initially we treated patients with refractory disease and found that the combination lacked clinical cross-resistance with standard antileukemic drugs. This formed a rationale to move teniposide and/or etoposide to front-line therapy of childhood ALL. The superior results projected for our last trial, an overall cure rate of about 75%, are attributable in part to early use of epipodophyllotoxins. This class of agents is also used extensively in the treatment of newly diagnosed childhood solid tumors, including neuroblastoma, medulloblastoma, rhabdomyosarcoma, and germ-cell tumors. Secondary leukemias following treatment with epipodophyllotoxins have been reported in a small subset of patients. Current data show that the most important risk factor is the schedule of drug delivery, which has led to appropriate protocol modifications.
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PMID:Epipodophyllotoxins in the treatment of childhood cancer. 807 34

In the study of international childhood cancer incidence coordinated by the International Agency for Research on cancer, soft-tissue sarcomas comprised between 4 and 8% of all cancers between 0 and 14 years of age. Among predominantly white populations, the age-standardised annual incidence rate (ASR) for all soft-tissue sarcomas was between 5 and 9 per million. The most common histological subtypes were rhabdomyosarcoma (ASR 4-7 per million) and fibrosarcoma, including other malignant fibromatous tumours (ASR 1-2 per million). In the United States the incidence of rhabdomyosarcoma for black girls was only half that for white girls, while the rates for boys were similar in the two ethnic groups; fibrosarcoma had a higher incidence among black people than white people for both sexes. Throughout most of Asia, soft-tissue sarcomas almost invariably had a total ASR below 6 per million, rhabdomyosarcoma and fibrosarcoma again being the most common histological types. In Africa, incidence rates could not generally be calculated, but there were substantial numbers of registrations for rhabdomyosarcoma and fibrosarcoma. The majority of cases of Kaposi's sarcoma were in African children, and in eastern and southern Africa where Kaposi's sarcoma is endemic among adult men it comprised 25-50% of soft-tissue sarcomas and 2-10% of all childhood cancers; the sex ratio (M/F) was 2.2:1, in contrast to the overwhelming male predominance among adults. Variations between ethnic groups in the incidence of rhabdomyosarcoma and fibrosarcoma, together with their occurrence in a number of heritable syndromes, suggest that genetic predisposition is important in their aetiology. There was little evidence for an environmental aetiology in rhabdomyosarcoma and fibrosarcoma but an infectious agent may be responsible for childhood Kaposi's sarcoma.
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PMID:International variations in the incidence of childhood soft-tissue sarcomas. 815 13

Although the t(2;13)(q35;q14) translocation has been found in most cases of the pediatric cancer alveolar rhabdomyosarcoma, several cases have been reported with a variant t(1;13)(p36;q14) translocation. Our findings indicate that this t(1;13) rearranges PAX7 on chromosome 1 and fuses it to FKHR on chromosome 13. This fusion results in a chimeric transcript consisting of 5' PAX7 and 3' FKHR regions, which is similar to the 5' PAX3-3' FKHR transcript formed by the t(2;13). The 5' PAX3 and PAX7 regions encode related DNA binding domains, and therefore we postulate that these translocations create similar chimeric transcription factors that alter expression of a common group of target genes.
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PMID:Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. 818 70

While the incidence of cancer is increasing among both children and adults, mortality rates have decreased for children, while they have increased for adults. Of children diagnosed with cancer today, 80% are predicted to be long-term survivors. Although there are differences between children and adults with respect to the tumor types, biology, and outcome, there are common lessons which we can learn from our children regarding the genetics of cancer, its management and treatment, and the importance of longitudinal studies of the survivors. Specific pediatric cancers, such as retinoblastoma, have led to the recognition of tumor suppressor genes, now also observed among adult tumors including sarcomas, breast, lung, and bladder cancer. The presence of the tumor suppressor gene provides an understanding for the incidence of second malignant tumors among patients with heritable diseases. Furthermore, cancer prone families, such as those with the Li-Fraumeni syndrome, also carry the p 53 tumor suppressor gene; the presence of which greatly increases the risk of developing invasive cancer. Childhood cancer is rare; it represents only 1% of the total US cancer problem. However, 53% of all children with cancer, but only 2% of all adults, are studied via the NCI cooperative group mechanism. For some specific childhood tumors such as rhabdomyosarcoma and Wilms' tumor, as many as 70-85% of all cases are managed via NCI sponsored trials. Essentially all pediatric cancer is treated by interdigitating radiation with surgical resection and systemic chemotherapy. This approach has contributed to high cure rates. Finally, our understanding of the late effects of being a cancer survivor have come from longitudinal studies of children. The most severe long-term effects related to radiation in childhood pertain to growth and development, infertility, and second malignant tumor induction. Here the children treated for Hodgkin's disease have taught us the dose and volume effects on axial skeletal and soft tissue growth. Infertility issues are also treatment-related and may often be obviated by using gonadal shielding. The risk of secondary leukemia is related to dose and class of specific chemotherapeutic agents administered; it is 5.5% among children receiving 6 cycles of MOPP. There is a 22-fold risk at 30 years of age of solid tumor induction following radiotherapy for children with Hodgkin's disease. These serious concerns have been offset by current therapeutic approaches of using lower doses and smaller volumes of radiation with fewer cycles of less toxic chemotherapeutic agents. Childhood cancer ranks high among number of person-years of potential life saved annually.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lessons from our children. 834 41

To assess the proportion of children with cancer who have been managed by mainstream pediatric cancer programs, population-based cancer incidence data for Los Angeles County (LAC) children (under 20 years of age) for the years 1972 through 1987 were linked with patient records of children registered with the two national cooperative pediatric oncology groups, Children's Cancer Study Group and Pediatric Oncology Group. The proportion of children with cancer who were registered by cooperative groups increased markedly over time: 9% of LAC children younger than 15 years of age who were diagnosed with cancer in 1972 were registered with cooperative groups, compared to 52% of those diagnosed in 1980 and 62% of those diagnosed in 1987. Registration rates decreased with increasing age at cancer diagnosis. In the most recent time period, 1984-1987, 66% of LAC children diagnosed with cancer under age 5 years were registered with cooperative groups compared to 62% of those who were 5 to 9 years old and 49% of those who were 10 to 14 years old; although they were frequently diagnosed with tumors considered to be childhood cancers, only 19% of older adolescents (aged 15-19 years) were registered. In LAC, there was no apparent bias in registration rates with regard to gender or racial-ethnic background. Among patients diagnosed in the period 1984-1987, children in the highest of five socioeconomic status categories were underrepresented among registrants. Registration rates were highest (70% or greater) for patients with acute lymphocytic and acute nonlymphocytic leukemia, medulloblastoma, hepatoblastoma, Wilms tumor, and rhabdomyosarcoma. Fewer than 50% of patients with other brain and central nervous system tumors, retinoblastoma, other soft tissue sarcomas, and bone tumors were registered with the cooperative groups.
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PMID:Trends in patterns of treatment of childhood cancer in Los Angeles County. 849 Aug 58

There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood.
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PMID:Melanocytic naevi and melanoma in survivors of childhood cancer. 849 98

Neutropenic pediatric patients with solid tumors and malignant lymphomas were treated with recombinant granulocyte-macrophage colony stimulating factor (rh-GM-CSF). Eleven patients, including seven lympho-reticular malignancies, two Ewing's sarcoma and one patient in each group with the diagnosis of nasopharyngeal rhabdomyosarcoma, malignant mesenchymal tumor, entered the study. Six were females and five were males, the mean age was 10.4 yr, the range was 4 to 21 years. rh-GM-CSF was given at the dose of 5 micrograms/kg s.c. daily, starting either on the day following the last day of cytotoxic chemotherapy or when ANC < 1000/ml was determined. All patients received rh-GM-CSF for a total of seven days. Hematopoietic recovery occurred in all children except one. The response to rh-GM-CSF was achieved in a mean time of 7.4 days. Tolerance to rh-GM-CSF treatment was good. Adverse events were documented as fever, nausea, vomiting, fatigue, chills and itching. Sagittal sinus thrombosis developed in one patient 5 days following the completion of chemotherapy and rh-GM-CSF cycle. In conclusion, rh-GM-CSF can be applied during the intensive chemotherapy schedules of pediatric cancer patients.
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PMID:Granulocyte-macrophage colony stimulating factor (rh-GM-CSF) in the treatment of chemotherapy-induced neutropenia. 859 35

In the pediatric cancer alveolar rhabdomyosarcoma, characteristic t(2;13)(q35;q14) or variant t(1;13)(p36;q14) chromosomal translocations generate PAX3-FKHR or PAX7-FKHR fusion genes. Using fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction and quantitative Southern blot analyses, we demonstrate that these fusion genes are amplified in 20% of fusion-positive tumors. In particular, we found in vivo amplification of these fusions in one of 22 PAX3-FKHR-positive cases and five of seven PAX7-FKHR-positive cases. These findings indicate that translocation and amplification can occur sequentially in a cancer to alter both the structure and copy number of a gene and thereby activate oncogenic activity by complementary mechanisms.
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PMID:In vivo amplification of the PAX3-FKHR and PAX7-FKHR fusion genes in alveolar rhabdomyosarcoma. 878 35

Currently, approximately 67% of children diagnosed with cancer can be expected to survive more than 5 years. Among the most significant late effects of cancer therapy is the development of second malignant neoplasm (SMN). This study was performed to identify the factors associated with the development of second malignant neoplasms after treatment for soft tissue sarcomas in childhood. Retrospectively the charts of 20 children who developed second malignant neoplasms after treatment for primary childhood soft tissue sarcoma were reviewed. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment, family histories (when available), and outcome were recorded. The mean age of the patients (10 boys, 10 girls) was 8.5 years of age (range, 1 to 20 years). Most primary tumors were rhabdomyosarcoma (14/20) and occurred in an extremity (10/20). Ninety percent of the patients (18/20) had a complete response to treatment of the primary cancer. Eleven out of 20 received combined chemotherapy and radiation therapy. The most common secondary malignancy was a bone sarcoma (6/20), followed by brain tumors (n = 3), leukemia (n = 2), and other sarcomas (n = 2). Four of the bone sarcomas developed in the field of radiation treatment. Median follow-up was 16 years (range, 1 to 26 years). The median time to development of a SMN was 11.4 years (range, 1.5 to 21 years). Survival after a second malignancy was only 30%. Two patients developed a third malignant neoplasm. The occurrence of a secondary malignancy represents a serious complication of childhood cancer. Certain tumors are related directly to treatment such as osteosarcoma within irradiated fields and secondary leukemias or lymphomas after certain chemotherapy regimens. Combined radiotherapy and chemotherapy may play an additive role in the development of second malignant neoplasms. Genetic factors may predispose affected patients to the development of both primary and secondary malignancies. Close surveillance of children previously treated for childhood cancers is warranted.
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PMID:Second malignant neoplasms in children after treatment of soft tissue sarcoma. 904 56

The aim of this study was to identify patients treated in Great Britain for childhood cancer and subsequently referred for cardiopulmonary transplantation in order to assess diagnosis, cancer treatment, management and outcome. Computerised record linkage between the National Registry of Childhood Tumours and the national transplant database held and maintained by the United Kingdom Transplant Support Service Authority (UKTSSA) was used to identify patients. Verification and clinical details were then obtained from the oncology and transplant centres. 16 patients were identified from the 31992 cases of childhood malignancy diagnosed in Britain since 1970. These comprised 13 heart transplants, 2 heart/lung transplants and 1 patient who died while on the heart transplantation waiting list. All 14 potential heart transplant patients had cardiomyopathy presumed secondary to anthracycline therapy. The original diagnoses were acute myeloblastic leukaemia (3), Wilms' tumour (4), rhabdomyosarcoma (2) and one each of five different solid tumours. Median age at diagnosis was 44 months (range 4-165 months). Median anthracycline dose was 413 mg/m2 (range 240-680 mg/m2). 13 of the 14 potential cardiac transplantation patients were more than 2 years from end of their cancer treatment before requiring transplantation and the transplantation was performed 2-126 months after onset of cardiac failure at a median age of 163 months. Five year actuarial survival from transplantation was 74%. There was no recurrence of the original malignancy in any of these patients. Both heart/lung patients died, 3 and 11 months after the transplant. These heart transplantation data suggest that, in Britain, survival compares favourably with that of patients whose heart transplant was required for other causes of cardiomyopathy. This indicates that patients successfully treated for childhood cancer should not be excluded from transplant programmes.
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PMID:Cardiac transplantation in childhood cancer survivors in Great Britain. 908 61


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