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Surgery in rhabdomyosarcoma of the bladder, prostate and vagina.

The treatment of bladder and prostate rhabdomyosarcoma (RMS) is highly controversial. Aside from chemotherapy, treatment modalities include conservative surgery, radical surgery, and pre-, intra-, or postoperative irradiation. Between 1968 and 1993, 78 children with RMS were treated at our institution. In all, 22 tumors were located in the urogenital tract (bladder/prostate, 13; paratesticular, 5; vaginal, 2; others, 2). Altogether, 6 patients had stage II disease; 7, stage III disease; and 2, stage IV disease. All 15 patients with RMS of the bladder, prostate, or vagina received chemotherapy, and 4 had additional radiotherapy. Surgery was also done in 10 patients; parents refused an operation in 3 cases. In all, 3 patients in an advanced tumor stage died of their disease. All other children currently show no evidence of disease (mean follow-up, 6 years; range, from 2 months to 18 years). After chemotherapy, radical operative intervention with multiple biopsies (encircling the tumor)--in contrast to local tumor excision or partial resection--permits complete tumor resection followed by excellent long-term results. Following radiotherapy, often a consequence of organ-sparing therapy, many complications ensued (60%); therefore, irradiation should be restricted to highly selected cases.

Adolescent↗

[Primary pleomorphic rhabdomyosarcoma of the liver].

Two female adults with primary rhabdomyosarcoma of the liver were operated on in 1981 and 1987 in the Department of Surgery in the University Hospital of Hamburg-Eppendorf (Germany). In both cases a hemihepatectomy was performed. Postoperatively, the younger woman received adjuvant chemotherapy. Both patients are still alive. Both cases are reviewed with reference to the unusual findings in the liver combined with a really short history. In addition, the possibilities opened up by the diagnostic are measures discussed. Contrary to the literature, this rare malignant tumour seems to be curable if it is diagnosed early and treated while confined to the liver.

Adult↗

In vitro differentiation and proliferation in a newly established human rhabdomyosarcoma cell line.

A newly established cell line, designated NRS-1, was derived from an alveolar rhabdomyosarcoma that developed in the left forearm of a 7-year-old girl. The cell line had a t(2; 13) chromosomal translocation. Reverse transcription-polymerase chain reaction demonstrated that 5' PAX3-3' FKHR chimeric transcript was expressed in NRS-1 cells. NRS-1 cells showed myogenic differentiation without any particular stimulus in vitro and exhibited various kinds of muscle markers. All-trans retinoic acid promoted cell differentiation in the myogenic direction. Transforming growth factor-beta (TGF-beta) inhibited myogenic differentiation of those cells and promoted cell proliferation.

Base Sequence↗

Comparison of the rates of response to ifosfamide and cyclophosphamide in primary unresectable rhabdomyosarcomas.

In the 1981 cooperative soft-tissue sarcoma (CWS-81) study, a clear correlation between the degree of response to initial chemotherapy comprising vincristine, actinomycin D, cyclophosphamide, and Adriamycin (VACA) and the survival of patients with rhabdomyosarcoma was found. In the subsequent CWS-86 study, cyclophosphamide was replaced by ifosfamide (VAIA) in the expectation that the combination VAIA might be more effective than VACA. In both studies, the initial cytostatic response for primary unresectable tumors was evaluated after the first cycle of chemotherapy at weeks 7-9. The reduction in tumor volume was measured by computerized axial tomographic (CAT) scan or sonography, and the patients were categorized as complete responders, patients with a tumor regression of greater than 2/3 albeit incomplete, patients with a tumor regression of less than 2/3 but greater than 1/3, and nonresponders, who underwent either a tumor regression of less than 1/3 or tumor progression. We compared the response rate obtained with VACA chemotherapy and that resulting from VAIA chemotherapy. The preliminary data from this comparison show a tendency for a higher rate of good responders (complete and less than 2/3 tumor regression) to be induced by VAIA therapy (71%) than that obtained using the VACA combination (55%). From the response-prognosis relationship, we confidently expect that the final outcome for patients in the present study will be better than that in the previous study.

Antineoplastic Combined Chemotherapy Protocols↗

Autoradiographic distribution of [14C]-labelled pimonidazole in rhabdomyosarcoma-bearing rats and pigmented mice.

The hypoxic cell radiosensitizer [2-14C] pimonidazole (2-nitro-alpha-(piperidinomethyl)-l-imidazole ethanol) was injected i.p. into pigmented mice and rats bearing transplanted rhabdomyosarcoma. The injected dose level was 200 mg/kg, and the delivered activity was 96 microCi/kg. Whole-body autoradiography was carried out on all animals. We noted an extensive whole-body distribution of radioactivity. At short intervals, the autoradiograms were characterized by an accumulation of radioactivity in the metabolic and excretory organs (liver, kidney, urinary tract, and intestinal content) as well as in lymphomyeloid tissues (thyroid gland, suprarenal gland, and hypophysis) and salivary glands. In pigmented mice, the uveal and biliary tracts were the highest labelled. The liver and particularly the renal medulla were identified as sites of retention of radioactivity. In the tumor the radioactivity was detected only in peripheral regions, with higher uptake in viable zones than in necrotic islets.

Animals↗

Uptake, metabolism, and cytotoxicity of doxorubicin in human Ewing's sarcoma and rhabdomyosarcoma cells.

Uptake, metabolism, and cytotoxicity of doxorubicin (DOX) in human Ewing's sarcoma (ES) and rhabdomyosarcoma (RS) cells were examined. Cellular uptake of DOX was determined by liquid scintillation spectrometry, and intracellular metabolism was examined by high performance liquid chromatography. The cytotoxicity of DOX was assessed by two different methods: an extracellular matrix detachment assay (ECM-D) and 3H-thymidine incorporation. The uptake of DOX by ES cells was 1.5-3.0 times greater than RS cells, even though both cell types achieved intracellular steady-state though both cell types achieved intracellular steady-state concentrations between 6-8 h. No significant intracellular metabolism ( less than 5%) was seen after 8-h incubations with the drug. The cytotoxic effects of DOX in both cell lines were concentration-dependent, with the RS cells being more sensitive. Measurement of 14C-DOX appears to be a reliable method for quantitating intracellular DOX. In addition, the ECM-D and 3H-thymidine assays used for assessing cytotoxicity produced similar results, showing that the ECM-D can be reliable and easily performed test of cell death.

Cell Line↗

Imaging of pelvic rhabdomyosarcoma by bone scintigraphy.

Urinary tract distortion caused by pelvic rhabdomyosarcoma was imaged during 99mTc-oxidronate bone scintigraphy for suspected metastatic disease. This appearance correlated well with the anatomy defined on other imaging modalities. Bone scanning also proved valuable in detecting an otherwise occult osseous metastasis from this unusual tumor.

Adolescent↗

Primary intracranial rhabdomyosarcoma: report of two cases.

Primary intracranial rhabdomyosarcoma (RMS) is a rare tumor in infancy and childhood that is found in various locations in the central nervous system. The clinical course worsens rapidly, and the final outcome is poor, with a median survival time of 8-10 months. Invasion of the meninges, spontaneous intratumoral bleeding, spinal leptomeningeal CSF spreading of tumor cells, and early recurrence of the mass are the distinctive features of RMS. Diagnosis of RMS may be missed: immunohistochemical staining using specific markers (myoglobin, myosin, desmin, vimentin, enolase), along with ultrastructural studies, provide the basis for making the final diagnosis. Treatment of RMS includes surgical excision, craniospinal radiation therapy, and chemotherapy. We report two cases of primary RMS in the CNS located in the posterior fossa and frontotemporal area. Both children underwent total surgical removal of the mass. Early recurrence of the tumor mass was noticed in both patients 2 months after surgery. Both children died shortly thereafter.

Adolescent↗

Evaluation of 3-(p-fluorophenyl)-L-alanyl-3-[m-bis-(2-chloroethyl) aminophenyl]-L-alanyl-L-methionine ethyl ester HCl (PTT.119) against xenografts of human rhabdomyosarcoma.

PTT.119 [p-F-phe-m-bis(2-chloroethyl)amino-L-phe-met ethoxy HCl], a synthetic tripeptide mustard, was evaluated for therapeutic efficacy against a spectrum of childhood rhabdomyosarcomas (RMS) maintained as xenografts in immune-deprived mice. These xenografts were established from previously untreated tumors, and sublines were selected in mice for resistance to L-phenylalanine mustard (L-PAM). PTT.119 caused regression of four of six RMS lines established from untreated tumors, and demonstrated activity similar to that of L-PAM in this model. Against tumors Rh18/L-PAM and Rh28/L-PAM, selected in situ for L-PAM resistance, PTT.119 had no significant activity. Rh28/L-PAM was cross-resistant also to oxazophosphorine mustards (ifosfamide, cyclophosphamide), and both tumors were cross-resistant to adriamycin and vincristine. PTT.119 caused hematologic toxicity similar to that of L-PAM, characterized by a marked decrease in white blood cells and thrombocytopenia.

Animals↗

Neurological manifestations of rhabdomyosarcomas in the head and neck in childhood. Neuroradiological study.

Two cases of rhabdomyosarcoma in the head and neck with neurological manifestations are presented. Brain scan demonstrated an apparent area of increased uptake of 99mTc in the tumor. Cerebral angiography revealed a sharply demarcated but rather faint tumor stain. The contributing vessels were hypertrophied branches of the external carotid artery, a dural branch of the internal carotid artery, and branches of the vetebrobasilar systes emphasized because the recent combination of chemotherapy in conjuction with surgery and irradiation seems to be encouraging.

Adolescent↗

The radiological manifestations of intracranial rhabdomyosarcoma.

Two cases of rhabdomyosarcoma, one arising in the parotid gland and the other within the middle ear cavity, are presented. Both cases developed neurological signs of intracranial extension, which, in one, were non-localizing. The angiographic characteristics of these two cases as well as those reported in the literature are discussed. Angiography delineated the extent of tumor involvement and influenced the treatment ports. Isolated reports of long term survivals and some promising preliminary results from more aggressive therapy warrant delineation of tumor extent. To this end angiography is helpful.

Adolescent↗

Myosin isoform expression in rat rhabdomyosarcoma induced by Moloney murine sarcoma virus.

Myosin isoform expression was analyzed in experimental rhabdomyosarcoma (RMS) using monoclonal antibodies (mAbs) and immunofluorescence techniques. Tumors induced by inoculating newborn rats with Moloney murine sarcoma virus (Mo-MSV) were examined 30-90 days after birth. Nine tumors and two lymph node metastases were studied by direct, indirect, and double immunofluorescence assays using a panel of five anti-myosin mAbs. The mAb BF-45 was specifically reactive with embryonic myosin heavy chain (MHC), mAb BF-34 was specific for a neonatal MHC epitope, mAb BF-B6 was directed against an epitope present in both embryonic and neonatal MHC, and mAbs BF-F3 and BF-32 detected epitopes present in adult MHC isoforms. Anti-desmin antibodies were also used for comparison. The results of this study show that: (1) the majority of neoplastic cells stained for desmin while only a minority of neoplastic cells were labeled by anti-myosin antibodies; (2) myosin positive tumor cells contained predominantly embryonic and neonatal MHC types but rare RMS cells reacted exclusively with anti-adult myosin antibodies; and (3) adult and embryonic MHC phenotypes were occasionally detected within the same tumor cell especially in RMS with the longest latencies. Together these results would suggest that the mechanism(s) regulating MHC gene expression in skeletal muscle cells can be altered by the transforming activity of Mo-MSV.

Animals↗

[Clinical picture and morphology of orbital rhabdomyosarcomas in children].

The clinical course of orbital rhabdomyosarcoma is described in seven male children. A survey of the literature on the subject is given. Particular attention is paid to certain diagnostic problems of this most frequent orbital malignant primary in childhood. An adequate combination therapy which results in cure in more than half of the patients should be employed provided that an exact morphological diagnosis is made; this still causes often great difficulty. Electron microscopy is of great value in distinguishing this type of tumor from other malignancies, including the so-called reticulosarcoma. In comparison with the case material of other authors, there was a relatively high rate of late deaths in our patients.

Child↗

Chromosome translocation (2;13)(q37;q14) in a disseminated alveolar rhabdomyosarcoma.

Chromosome analysis of tumour cells in the bone marrow of a 13.5-year-old girl (without a primary tumour) revealed a pseudo-diploid or pseudo-tetraploid karyotype with a translocation involving the long arms of chromosomes 2 and 13: t(2;13)(q37;q14). This finding enabled the diagnosis of a disseminated alveolar rhabdomyosarcoma (RMS) to be established. The patient was treated by cytotoxic chemotherapy, went into complete remission, but died of relapse 14 months after diagnosis. As several cases with this translocation have been described recently, this additional report confirms that t(2;13) is specific for the alveolar subtype of RMS.

Adolescent↗

Local therapy of rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma of children and adolescents.

Local control of the primary tumour is a fundamental requirement for clinical cure. Towards this aim, the primary tumour must be diagnosed early and identified histologically. The size, extension, and spread within the patient must be defined precisely. In planning effective local therapy, additional questions must be answered including resectability, mutilation, sensitivity to radio- and chemotherapy, anticipated morbidity from therapeutic measures, etc. For osteosarcoma there is no reasonable alternative to radical surgery. Because of the 20% local recurrence rate of Ewing's sarcoma following radiotherapy, radical surgical removal of the primary tumour should be attempted whenever possible. For rhabdomyosarcoma, particularly for its embryonal histology, non-radical removal of the primary sarcoma is still compatible with a cure, provided adequate radio- and chemotherapy is also administered. Primary irradiation is indicated in radiosensitive unresectable primary tumours and may convert these into an operable state. Chemotherapy is the domain of prevention and treatment of metastatic disease. It has, however, also a proved effect on primary tumours and, in several recent protocols, precedes local therapy.

Adolescent↗

Rhabdomyosarcoma of the temporal bone: clinical report.

Rhabdomyosarcoma is the most common soft tissue sarcoma of the head and neck in young children, but it is a rare entity in the temporal bone. We have detailed our experiences with two of our patients who had tumor in this site. Both were under the age of 2 years. One child had 6th and 7th nerve paralysis. The clinical features associated with these tumors and available treatment are reviewed.

Child, Preschool↗

Primary rhabdomyosarcoma of the central nervous system.

A case of primary rhabdomyosarcoma in the brain stem is described in an 8 year old girl. The clinical data showed a right side hemiplegia then a total paralysis of the left sixth cranial nerve and a paraplegia which became lethal in 3 months. The necrospy revealed a tumoral nodule in the left medulla oblongata and pons with diffuse subarachnoidal extension from the cranial nerves to the cauda equine roots. Histologically the tumor appeared to be polymorph with numerous rhabdomyoblasts which had a clear cross striation and which were sometimes less differentiated without any neuronal or glial elements. Perivascular tumoral cells and blood vessels were closely linked, the Virchow-Robin spaces were clearly involved. The electron microscopic study confirmed that the less differentiated cells were of a rhabdomyoblastic nature. A review of the litterature indicates that these malignant neoplasias are highly exceptional, and can be classified within the group of primary tumors of the neuraxis with muscular elements. The histogenetic origin of these tumors appears to be the ectomesenchyme of neural crests.

Brain Neoplasms↗

Gliomyosarcoma. Report of a case of rhabdomyosarcoma arising in a malignant glioma.

The development of sarcoma within a glioblastoma is a well recognised complication: in the majority of cases it is a fibro-sarcoma originating in the tissues of the proliferating hyperplastic blood vessels. In the case described here the tumour is a rhabdomyosarcoma, apparently derived from abnormal prolific vascular mesenchyme. Only one comparable example has been recorded previously.

Brain Neoplasms↗