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)

Rhabdomyosarcomas secrete high levels of insulin-like growth factor-II, suggesting this autocrine growth factor plays a major role in the unregulated growth of this childhood cancer. Treatment of Rh30 rhabdomyosarcoma cells with insulin-like growth factor binding protein-6 (IGFBP-6; 1000 ng/ml), which binds insulin-like growth factor-II with high affinity, inhibited growth in vitro (p < 0.001). Co-incubation of cells with rapamycin (1.56 ng/ml), an inhibitor of p70 S6 kinase, and IGFBP-6 (200 ng/ml) resulted in a significant reduction in Rh30 cell number compared to rapamycin or IGFBP-6 alone (p < 0.05 for both). Co-treatment of Rh30 cells with CCI-779 (5 and 50 ng/ml), an ester analogue of rapamycin, and IGFBP-6 (200 or 1000 ng/ml) also inhibited growth in vitro relative to CCI-779 alone (p < 0.01 and p < 0.001, respectively). In a nude mouse model, xenografts of Rh30 cells transfected with a recombinant vector encoding IGFBP-6 (phBP6-E3) showed delayed growth relative to vector control xenografts (27 days vs. 19 days to reach an average tumour volume of 0.5 cm (3); p < 0.001). Treatment with CCI-779 (10 mg/kg) of mice inoculated with vector control xenografts, also delayed growth (to 31 days; p = 0.0055) relative to untreated mice with vector control xenografts. Co-treatment with CCI-779 (10 mg/kg) reduced phBP6-E3 transfected xenograft growth even further (to 45 days) compared to vector control xenografts (p < 0.001, day 33). CCI-779 thus acts additively with IGFBP-6 to reduce rhabdomyosarcoma growth both in vitro and in vivo.
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PMID:Insulin-like growth factor binding protein-6 and CCI-779, an ester analogue of rapamycin, additively inhibit rhabdomyosarcoma growth. 1471 Mar 64

In the pediatric cancer alveolar rhabdomyosarcoma (ARMS), the 2;13 chromosomal translocation juxtaposes the PAX3 and FKHR genes to generate a chimeric transcription factor. To explore molecular pathways altered by this oncoprotein, we generated an inducible form by fusing PAX3-FKHR to a modified estrogen receptor ligand-binding domain and expressed this construct in the RD embryonal rhabdomyosarcoma cell line. This inducible system permits short-term evaluation of downstream expression targets of PAX3-FKHR and complements a panel of stable long-term RD subclones constitutively expressing PAX3-FKHR. Using these two sets of resources, we investigated several candidate PAX3-FKHR target genes. First, we demonstrated in both short-term and long-term systems that PAX3-FKHR upregulates expression of the gene encoding the chemokine receptor CXCR4. In addition, we found that expression of wild-type PAX3 is upregulated, whereas expression of wild-type PAX7 is downregulated by PAX3-FKHR. In the presence of cycloheximide, CXCR4 and PAX3 are still inducible, supporting the hypothesis that these genes are direct transcriptional targets of PAX3-FKHR. Finally, studies of ARMS tumors revealed CXCR4, PAX3, and PAX7 expression levels consistent with our cell culture results. These findings of genes regulated by PAX3-FKHR will direct future biological and clinical investigation to important pathways contributing to ARMS tumorigenesis and progression.
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PMID:Inducible short-term and stable long-term cell culture systems reveal that the PAX3-FKHR fusion oncoprotein regulates CXCR4, PAX3, and PAX7 expression. 1518 10

Multidisciplinary collaboration in therapeutic research in childhood cancer has been responsible for enormous improvements in outcomes. Many of the improvements have resulted from large clinical trials carried out in multisite settings through the Children's Oncology Group (COG) and its predecessors, the Children's Cancer Group, the Pediatric Oncology Group, the National Wilms' Tumor Study, and Intergroup Rhabdomyosarcoma Study Groups. Childhood acute lymphoblastic leukemia models the past success of 35 years of randomized clinical trials that resulted in survival rates of around 80%. However more can be done to improve both survival rates and the quality of survival. Areas that can benefit from a transdisciplinary model of research are discussed, as well as challenges to this form of collaboration.
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PMID:Pediatric cancer research from past successes through collaboration to future transdisciplinary research. 1529 38

Pleuropulmonary blastoma (PPB) was defined in 1988 by Manivel et al. in a series describing 11 intrathoracic pulmonary neoplasms in young children. The PPB is a unique peripheral pulmonary or pleural-based tumor of childhood that is characterized in its earliest form as a bland-appearing multiloculated cyst with small foci of tumor cells and in later forms as mixed and predominantly primitive, overtly malignant neoplasms. Prior to the introduction of the PPB as a distinct entity, this tumor had been reported in the literature as pulmonary blastoma, sarcoma arising in mesenchymal cystic hamartoma, embryonal sarcoma, malignant mesenchymoma, primary pulmonary rhabdomyosarcoma and rhabdomyosarcoma arising in congenital adenomatoid malformation or bronchogenic cyst. Over the past 15 years, PPB has come to be recognized in centers around the world. With the establishment of the Pleuropulmonary Blastoma Registry by Jack Priest, MD, and colleagues, there has been improved understanding of this rare pediatric neoplasm.
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PMID:USCAP Specialty Conference: case 1-type I pleuropulmonary blastoma. 1571 5

Infectious diseases represent one of the most important secondary problems related to the treatment of childhood cancer, being the leading cause of death in this population. They are predominantly of bacterial and fungal etiology. The association between tetanus, a bacterial vaccine-preventable disease, and cancer is virtually undescribed. The authors present the case of a previously nonimmunized child, due to his parents' choice, who developed severe tetanus with an ulcerated rhabdomyosarcoma as portal of entry. Due to an unfavorable evolution, the child underwent a hip disarticulation to provide tetanus control. The ulterior tumor management was successful: the child has been off therapy for more than 108 months with no evidence of disease.
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PMID:Ulcerated rhabdomyosarcoma as portal of entry for tetanus in a previously nonimmunized child. 1583 97

Cancer occurring in infants often has clinical and biological properties that are different from those of the same histologic type of cancer occurring in older children. The histologic distribution of cancers in infants and that in older children are also different. The aim of this study was to find these differences between infants and older children, and to compare the percent distribution of infant cancer subtypes with that reported by other countries. The authors collected infant cases diagnosed as having cancer from the database of the Cancer Registry in our Medical Center between 1995 and 2001. Subjects were selected subjects from inpatient logs, and their medical records were reviewed. Eighty-two infants (40 males and 42 females), including 12 neonates, were diagnosed with cancer over this 7-year period. Acute leukemia was diagnosed in 21 infants (25.6%; acute myeloid leukemia in 12, and acute lymphoblastic leukemia in 9), retinoblastoma in 14 (17.1%), neuroblastoma in 12 (14.6%), brain tumor in 9 (11.0%), germ cell tumor in 8 (9.8%), renal cancer in 8 (Wilms tumor 3, mesoblastic nephroma 1, renal sarcoma 1, rhabdoid tumor 3), hepatoblastoma in 5 (6.1%), and soft tissue sarcoma in 5 (rhabdomyosarcoma 1, fibrosarcoma 3, other sarcoma 1). The overall disease-free survival rate was 61.0% (50/82) with a median follow-up duration of 6.8 years for the survivors. The 4 most common types of cancer occurring in infants are the same in the present series and in most larger childhood cancer series reported by other countries; but rank differently. In this study there were more infants with acute leukemia and retinoblastoma, and less with neuroblastoma. The prognosis is poor for infant leukemia and rhabdoid tumor, while it is good for embryonal tumors and germ cell tumors occurring in infancy.
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PMID:Cancer in infants: a review of 82 cases. 1616 13

We previously demonstrated that constitutional BUB1B mutations cause mosaic variegated aneuploidy, a condition characterized by constitutional aneuploidies and childhood cancer predisposition. To further investigate the role of BUB1B in cancer predisposition we performed comparative genomic hybridization analysis in an embryonal rhabdomyosarcoma from an MVA case with biallelic BUB1B mutations, revealing aneuploidies typical of sporadic E-RMS, with gain of chromosomes 3, 8, 13 and loss of chromosomes 9, 14, X. To investigate whether somatic BUB1B mutations occur in sporadic childhood cancers we screened 30 Wilms tumours, 10 acute lymphoblastic leukemias, nine rhabdomyosarcomas and 11 rhabdomyosarcoma cell lines for BUB1B mutations. We identified seven exonic and six intronic variants. Six of the exonic variants were synonymous and one resulted in a non-synonymous conservative missense alteration that was also present in a control. These data suggest that the genetic progression in rhabdomyosarcoma from MVA and non-MVA cases may be similar, but that somatic BUB1B mutations are unlikely to be common in sporadic childhood cancers known to be associated with MVA.
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PMID:Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. 1618 41

Treatments for childhood cancer and consequent long-term survival rates continue to improve. As the success of these therapies advances, premature ovarian failure and sterility have become an increasingly evident long-term morbidity. Abdominal and pelvic radiation have been specifically shown to induce early menopause and decreased fertility. In order to minimize radiation injury, we utilized novel techniques to reposition ovaries in two girls with pelvic tumors prior to initiation of pelvic radiation. One girl with a sacral Ewing sarcoma underwent laparoscopic anterior suspension of the ovaries, using a simple and easily reversible technique. The second patient, who underwent hysterectomy for a recurrent uterine rhabdomyosarcoma, underwent widely lateral and cephalad repositioning of the ovaries. Both procedures were well tolerated, with no significant morbidity. In both cases the ovaries were moved well beyond the planned radiation field. We propose that open or laparoscopic ovarian repositioning in children is a simple, flexible, and reversible option to reduce radiation injury to the ovaries in pediatric cancer patients.
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PMID:Ovarian repositioning in pediatric cancer patients: Flexible techniques accommodate pelvic radiation fields. 1626 63

Parents asked to consent to a child's randomization in a pediatric cancer clinical trial are often unprepared to grasp the implications of this scientifically crucial but seemingly unfair process. Physicians must adopt specific communication skills to engage families in open dialogue from the outset in order to elicit truly shared informed consent. Starting from the case of a family with an only child affected by disseminated neuroblastoma, we wish to comment on the problems surfacing in the informed consent process for treatment and research in pediatric oncology that implicate an understanding of bioethical issues and psychological principles. Although the outcome of childhood cancer has improved dramatically over the last 30 years, with overall survival rates now exceeding 70%, there are regretfully still types and stages of cancer carrying a very high risk of death that urgently require new clinical strategies. The response to this need has been the design of experimental protocols that often entail randomized controlled trials (RCT). A large number of these trials concern stage IV neuroblastoma, acute leukemia, rhabdomyosarcoma, and other types of childhood cancers presenting great heterogeneity both in terms of localization and responsiveness to therapy. Most trials for disease relapses also include one or more randomizations. The scientific motivation justifying an RCT is the need to compare and evaluate an innovative protocol (or part thereof) with reference treatment modalities. Nevertheless, the process brings to bear the ethical dilemma of having to weigh the needs of the single afflicted child against the benefit which may ensue for a much larger patient community.
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PMID:Randomization, informed consent and physicians' communication skills in pediatric oncology: a delicate balance. 1639 46

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


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