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)

The purpose of this study was to determine the toxicity, maximum tolerated dose, and pharmacokinetics of a 21-day continuous infusion of topotecan in children with relapsed solid tumors. Fifteen patients received 40 courses of continuous ambulatory infusions of topotecan every 28 days or when there was resolution of hematological toxicity and any grade 2 or greater nonhematological toxicity. The starting dose was 0.4 mg/m2/day. Total topotecan levels were measured on days 1, 7, 14, and 21. Three of four patients who received a starting dose of 0.4 mg/m2/day experienced dose-limiting myelosuppression. At the reduced dose of 0.3 mg/ m2/day, only two of the seven patients experienced dose-limiting myelosuppression. Subsequently, four patients with more limited prior therapy were treated with 0.4 mg/m2/ day; three had dose-limiting myelosuppression. Two patients with a dose-limiting toxicity at 0.4 mg/m2/day tolerated additional courses at 0.3 mg/m2/day. An equal number of patients had grade 4 neutropenia or thrombocytopenia. Other adverse events were rare. Two patients with ependymoma, one with rhabdomyosarcoma, and one with retinoblastoma metastatic to the brain had objective responses. The steady state plasma concentration and clearance of topotecan (Css) was achieved by day 1. Css in six patients with complete data were 1.44 +/- 0.50 and 2.13 +/- 0.83 ng/ml at 0.3 and 0.4 mg/m2/day, respectively. Thus, a 21-day topotecan infusion was well-tolerated at 0.3 mg/m2/day. Myelo-suppression was the dose-limiting toxicity at 0.4 mg/m2/day. The steady state and clearance of topotecan in this study are similar to those reported in adult patients.
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PMID:Phase I study of topotecan administered as a 21-day continous infusion in children with recurrent solid tumors: a report from the Children's Cancer Group. 1063 25

Hereditary retinoblastoma is different from non-hereditary retinoblastoma in the following ways. It has a germinal mutation of Rb gene located in 13q14. Its inheritance is autosomally dominant with 80% penetrance. Retinal tumors are present usually multiply (average number is three) in both eyes. The patients are found at a younger age than those non-hereditary retinoblastoma. About 5% of them are accompanied by a pineal tumor or paracellular neuroectodermal tumor, in such cases they are called trilateral retinoblastoma. Secondary malignancies such as osteosarcoma and rhabdomyosarcoma are more frequent, and they are the main causes of death of patients with hereditary retinoblastoma. Considering these facts, education of patients and their family members and development of new modalities of treatment for preserving eyeballs without inducing secondary malignancies are important.
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PMID:[Retinoblastoma]. 1092 15

High-dose chemotherapy followed by autologous haematopoietic rescue is widely used in the treatment of patients with paediatric malignancies. It is now well established as a major component for the treatment of children with metastatic neuroblastoma over the age of one at diagnosis. Its place for other tumours, such as metastatic Ewing and rhabdomyosarcoma, needs to be better established. In the future, high-dose chemotherapy may replace cranio-spinal irradiation in the treatment of medulloblastoma in young children and represent a major tool for retrieval therapy in relapsing Wilm's and retinoblastoma. More co-operative studies are needed in order to clarify the population of patients who may most benefit from this approach and to determine the optimal chemotherapy regimen needed for each disease.
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PMID:Autologous haematopoietic stem cell transplantation for paediatric solid tumours. 1100 Sep 97

In the present study, DNA flow cytometry (FCM) and immunocytochemistry (ICC) with a selected panel of antibodies were performed on 51 cases of malignant tumors which were referred for fine-needle aspiration biopsy (FNAB) to our Department of Cytology for the last 2 yr. Twelve cases were diagnosed as neuroblastoma, 16 as Ewing's sarcoma, 2 as retinoblastoma, 5 as non-Hodgkin's lymphoma (NHL), 5 as rhabdomyosarcoma, 2 as peripheral neuroectodermal tumors (PNETs), and 8 as Wilms' tumor. Eleven of 12 neuroblastomas were diploid by FCM, and 1 was aneuploid, with an S-phase fraction (SPF) of 8.3%. Neuron-specific enolase (NSE) was negative in 3 and positive in 8 cases of neuroblastoma, whereas neuroblastoma marker was positive in 3/11. Sixteen of 17 Ewing's sarcomas were diploid, and 1 showed tetraploid aneuploidy, with an SPF of 10.06%. Eight of 13 Ewing's sarcomas were positive for Mic-2 gene product (Ewing's marker). All 5 NHL were positive for leukocyte-common antigen (LCA). Three of 5 rhabdomyosarcomas were diploid, and 2 cases showed aneuploidy. Rhabdomyosarcoma showed muscle-specific actin positivity in 4 and desmin positivity in 3 cases. All 3 cases of PNET were diploid and positive for the Mic-2 gene product, whereas NSE and vimentin were positive in 2 cases. Both cases of retinoblastoma were diploid. Immunostaining was noncontributory in 1 case, and the other showed positivity for the retinoblastoma gene product, NSE, and chromogranin. Seven of 8 Wilms' tumors were diploid, and 1 showed aneuploid, with an SPF of 11.13%. Seven of 8 Wilms' tumors were positive for cytokeratin (CK), 5 were positive for NSE, 6 were positive for epithelial membrane antigen (EMA), and 5 were positive for vimentin. FNAB diagnosis of malignant round-cell tumors is difficult only by light microscopy. Due to the availability of specific markers for subgrouping tumors, ICC has proved to be more useful these days, while DNA FCM has little diagnostic value, as most of them are diploid. Further ancillary studies, e.g., electron microscopy, image analysis, and other molecular investigations, are required to further categorize these tumors more precisely for better clinical management of these cases.
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PMID:Role of immunocytochemistry and DNA flow cytometry in the fine-needle aspiration diagnosis of malignant small round-cell tumors. 1128 17

Exploiting the lytic life cycle of viruses has gained recent attention as an anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)-mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad gene transduction and infection. RMS cells were variably transduced by Ad. Compared with control cells, RMS cells were less sensitive or even resistant to oncolysis by wild-type virus. RMS cells expressed the Ad internalization receptors, alpha(v) integrins, but had low or undetectable expression of the major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells seen with a wild-type vector, suggesting that residual or heterogeneous CAR expression mediated the little transduction that was detectable. Immunohistochemical analysis of archived clinical specimens showed little detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable transduction of the cDNA for CAR enabled both efficient Ad gene transfer and oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression is the limiting feature. Gene transfer to RMS cells was increased >2 logs using Ads engineered with modified fiber knobs containing either an integrin-binding RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus, the development of replication-competent vectors targeted to cell surface receptors other than CAR is critical to advance the use of Ad for treating RMS.
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PMID:Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells. 1130 73

Nuclear medicine is important in the diagnosis, staging, and long-term surveillance of a number of pediatric cancers. Skeletal scintigraphy is used to evaluate primary skeletal cancers, such as osteosarcoma and Ewing sarcoma, and nonskeletal cancers such as neuroblastoma, lymphoma, medulloblastoma, rhabdomyosarcoma, and retinoblastoma. Metaiodobenzylguanidine scintigraphy is valuable in examinations of children with neuroblastoma. The therapeutic response of primary bone and brain tumors can be assessed using Tl-201 and Tc-99m MIBI scintigraphy. Imaging strategies for staging and monitoring the therapeutic response of Hodgkin's lymphoma include Ga-67 citrate scintigraphy. Pediatric oncologic applications of positron emission tomography are being investigated extensively.
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PMID:Applications of nuclear medicine in pediatric oncology. 1178 42

Aberrant promoter methylation of tumor suppressor genes has not been fully investigated in pediatric tumors. Therefore, we examined the methylation status of nine genes (p16(INK4A), MGMT, GSTP1, RASSF1A, APC, DAPK, RARbeta, CDH1 and CDH13) in 175 primary pediatric tumors and 23 tumor cell lines using methylation-specific PCR. We studied the major forms of pediatric tumors--Wilms' tumor, neuroblastoma, hepatoblastoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma, retinoblastoma and acute leukemia. The most frequently methylated gene in both primary tumors and cell lines was RASSF1A (40, 86%, respectively). However, the rates of RASSF1A methylation in individual tumor types varied from 0 to 88%. RASSF1A methylation was tumor specific and was absent in adjacent non-malignant tissues. Methylation of the other genes was relatively rare in tumors and non-malignant tissues (less than 5%). Neuroblastoma patients with methylation of RASSF1A were significantly older than patients without methylation (P=0.008). There was no relationship between methylation status and other clinico-pathologic parameters. We treated six cell lines lacking RASSF1A mRNA with 5-aza-2'deoxycytidine to examine the relationship between methylation and transcriptional silencing. In five of six cell lines, restoration of RASSF1A mRNA was confirmed by RT-PCR. Our findings indicate that aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many different forms of pediatric tumors.
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PMID:Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines. 1208 24

We report an unusual case of a leiomyosarcoma of the urinary bladder after chemotherapy for retinoblastoma and the results of a review of the published reports of bladder sarcomas. A 22-year-old man presented with hematuria and was found to have a mass in his urinary bladder on computed tomography. Transurethral resection of the mass revealed a leiomyosarcoma. The patient underwent radical cystectomy and an ileal conduit was created. The final pathologic examination confirmed high-grade leiomyosarcoma. Prospective randomized combination trials similar to the Intergroup Rhabdomyosarcoma Study in the pediatric population are necessary to better understand and manage these potentially curable sarcomas.
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PMID:Leiomyosarcoma in urinary bladder after cyclophosphamide therapy for retinoblastoma and review of bladder sarcomas. 1210 Sep 53

The antitumor efficacy of the synthetic benzamide derivative MS-27-275 (MS-275), an inhibitor of histone deacetylation [T. Suzuki et al., J. Med. Chem., 42: 3001-3003, 1999], was evaluated in a series of pediatric solid tumor cell lines, including neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma (EWS), retinoblastoma, medulloblastoma, undifferentiated sarcoma (US), osteosarcoma, and malignant rhabdoid tumors. Treatment with MS-275 results in an increase in acetylation of histones within 4 h of drug exposure. The cell lines were treated with various concentrations of MS-275 for 3 days and incubated with [(3)H]thymidine for 20 h before cell harvest. MS-275 inhibited [(3)H]thymidine uptake in a dose-dependent manner in all tumor cell lines examined. The IC(50) ranged from 50 nm in the D283 medulloblastoma cell line to 1.3 micro M in the US. A common feature of MS-275 treatment of pediatric tumor cell lines was induction of p21mRNA. However, the effects on cell cycle were diverse because in some cases MS-275 induced an increase in G(1) or G(2), whereas in others, there was an induction of apoptosis. In EWS, the EWS/fli chimeric transcription factor created by the t(11;22) suppresses transforming growth factor (TGF) betaRII transcription, however, MS-275 was able to induce an increase in TGF-betaRII mRNA and restore TGF-beta signaling. Using xenograft orthotopic models of US, EWS, and neuroblastoma, we find that the growth of established tumors is inhibited in mice treated with MS-275.
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PMID:MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors. 1241 35

From 1972 to 2000, 123 patients with solid tumors whose complaints had started in the first 28 days of life were retrospectively evaluated. Fifty-five patients were diagnosed in the first 28 days and 68 patients were diagnosed after 28 days. In the former group, 85.5% of patients had symptoms in the first day of life. In the latter group, 77.9% had the onset of symptoms in the first day. Tumor subgroups in the neonatal period included teratoma (34), neuroblastoma (11), rhabdomyosarcoma (3), Wilms tumor (1), and retinoblastoma (3), and the others (3). Three patients had other, less common tumors. In the second group the numbers were the following: for teratoma (32), neuroblastoma (15), germ cell tumors other than teratomas (8), rhabdomyosarcomas (4), the other soft tissue sarcomas (3), Wilms tumor (1), retinoblastoma (1), and other, rare tumors (4). There were 22 malignant tumors in the first group, and 44 in the second group. Fourteen patients in the first group died in the early postoperative period or with progressive disease. Nineteen of 44 patients died in the second group. Overall survival rates were 24.9% and 51.6% in first and second groups, respectively (p = 0.015). Event-free survival rates were 14.7% and 47.7% in these groups, respectively (p = 0.0063). This is the first report comparing clinical features and prognosis of tumors diagnosed in the first 28 days of the life with those diagnosed after 28 days. The prognosis was worse in infants diagnosed in the first 28 days of life.
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PMID:Solid tumors in the neonatal period. 1263 79


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