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

The outlook for children with rhabdomyosarcoma has change significantly in these last years. With an adeguate combined modality therapy more than 50% of these children may be cured. The results of the IRS-I indicate that the 3 year relapse-free survival rates are 85% for patients in group I 70% for those in group II, 45% for those in group III and 15% for those in group IV. In addition to the clinical group other significant prognostic factors are histologic cell type (alveolar, unfavorable) and primary site (disease in extremities and in retroperitoneal area, unfavorable). The chemiotherapy must be used in all patients for 12-24 months. The effective drugs are VCR, ACT-D, CTX, ADR combined in different schedules. It has been demonstrated that the effective doses of radiotherapy range from 4000 to 5000 rad and that radiotherapy may be omitted in patients in group I. Now a less aggressive surgical procedures may be employed, and patients with primary tumor in the orbit or in the pelvic organs may be cured saving the eye, or the bladder, the vagina and the uterus.
 ...
PMID:[Rhabdomyosarcoma: therapeutic results and prospectives]. 654 8

The determinants of intrinsic sensitivity to Vinca alkaloids in vivo were examined in 3 pediatric rhabdomyosarcoma xenografts maintained s.c. in immune-deprived mice. The three lines differed in their sensitivity to VCR and VLB: two lines (Rh12 and Rh28) were extremely sensitive to VCR, whereas Rh18 tumors were less sensitive. Rh28 tumors were also very responsive to VLB, which demonstrated only marginal activity in the other two lines. After administration of equimolar doses (3 mg/kg) of [3H]-VCR and [3H]VLB to tumor-bearing mice, [3H]VCR reached concentrations approaching 1.5 microM in cell water of each tumor line within 4 hr, at which time greater than 93% of the drug was cell-associated. The drug was subsequently retained at this level for at least 72 hr studied. [3H]VLB accumulated to lower maximal concentrations (approximately equal to 1 microM) within 8 hr, but was not retained and, by 72 hr, reached concentrations that were 3- to 4-fold lower than those of [3H]VCR. The extent of drug retention correlated with the antitumor activity except in Rh28 tumors, which were sensitive to VLB, but did not retain the drug. The threshold level for achieving cytotoxicity may, thus, be very low in this line. In normal tissues, maximal concentrations of both [3H]VCR and [3H]VLB were achieved within 1 hr of administration i.p. to tumor-bearing mice. In ileum, liver, and kidney, these were approximately 10-fold higher than the peak levels achieved within tumors or plasma, but declined rapidly to parallel the decrease in plasma reaching concentrations greater than 5-fold lower than the concentration of [3H]VCR in tumors at 72 hr after treatment. Drug concentrations in skeletal muscle also declined rapidly, whereas neither [3H] VCR nor [3H]VLB accumulated to any great extent in brain. The blood volumes of ileum, kidney, and liver were greater than for tumor tissues. Hence, the extent of drug delivery did not necessarily influence therapeutic selectivity. In the case of [3H]VLB, concentrations in tumors approached those of normal tissues at 72 hr after injection. At 24 hr after treatment, 86 to 99% of [3H] VCR and 78 to 90% of [3H]VLB were present in tumors as the parent compound, which also predominated in normal tissues. Metabolites or in vivo degradation products were also identified. Selective retention in tumors appears to be the mechanism by which therapeutic selectivity is achieved with VCR in rhabdomyosarcoma xenografts.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Determinants of intrinsic sensitivity to Vinca alkaloids in xenografts of pediatric rhabdomyosarcomas. 669 63

Rhabdomyosarcoma is a highly malignant, small blue cell tumor characterized by muscle differentiation. With modern treatment, more than 70% of children and adolescents with this disease are cured. Adequate biopsy to obtain sufficient tissue for accurate diagnosis and molecular characterization is critical. Patients must be assessed for tumor extent; the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and Staging system is universally applied in North America. Multidisciplinary therapy is necessary to maximize cure rates. Local control relies on complete surgical excision when possible; those whose tumors are not completely excised and those with alveolar histology tumors require local irradiation to maximize local control. In North America, vincristine (Oncovin); Eli Lilly and Company, Indianapolis, http://www.lilly.com), dactinomycin (Cosmegen); Merck & Co., Inc., Whitehouse Station, NJ, http://www.merck.com), and cyclophosphamide are the standard chemotherapy agents. The IRS has used therapeutic window studies to confirm the predictive nature of preclinical xenograft models and to identify several new single agents and combinations of agents with activity in high-risk patient groups. Despite these efforts, the outcome for these high-risk patients remains poor. The next generation of Children's Oncology Group studies will evaluate the efficacy of topoisomerase-I inhibitors and dose-compression therapy approaches. New advances in molecular characterization of tumors, including gene-expression analysis, may identify new therapeutic targets that can be exploited by expanded preclinical drug discovery efforts, and hold the promise of revolutionizing risk-based therapies.
 ...
PMID:Rhabdomyosarcoma: new windows of opportunity. 1607 19

Purpose. Post-operative radiotherapy (RT) is routinely applied in the treatment of several human tumours. The aim of the present study was to investigate the value of post-operative RT in a rat model.Methods. Experiments were performed using the rhabdomyosarcoma R1H of the WAG/Rij rat. Animals were randomized to different treatment schedules: surgery, RT or a combination of both. Tumours were excised at different sizes (0.1-4.5 g) aiming for complete macroscopic resection. RT (60 Gy in 30 daily fractions over 6 weeks) was applied either primarily or to the former turnout site from the third post-operative day. Tumour growth delay, time to recurrence and local tumour control were used as endpoints.Results. Pre-operative tumour size determined the time and rate of recurrence. The larger the tumour, the shorter the time to relapse and the higher the recurrence rate. The 50% local control rate (LCR(50)) for surgery was found in tumours with a mass of 0.8 g. For post-operative RT a LCR(50) was achieved for tumours with a mass of 1.1 g. For larger turnouts (> 1.1 g), however, the rate and time course of relapse were similar for both the group receiving RT alone and the group receiving post-operative RT.Discussion. In this model the tumour mass at excision governs the prognosis. Relatively small R1H turnouts may recur despite complete macroscopical resection. With regard to the LCR, the outcome for larger tumours is improved with post-operative RT (60 Gy/6 weeks) than compared with surgery alone. The factor is 1.3. Within a certain range of tumour sizes, combined treatment (surgery + RT) can improve the outcome considerably.
 ...
PMID:Post-Operative Radiotherapy of the Rhabdomyosarcoma R1H of the Rat. 1852 Dec 16