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Parents' use of cocaine and marijuana and increased risk of rhabdomyosarcoma in their children.

Parents' use of marijuana and cocaine was evaluated in a national (United States) case-control study of childhood rhabdomyosarcoma (RMS). Subjects were 322 RMS cases, aged 0-20 years, from the Intergroup Rhabdomyosarcoma Study, and 322 matched controls identified by random-digit telephone dialing. Parents of subjects were interviewed by telephone using a structured questionnaire. Mothers' marijuana use during the year before their child's birth was associated with a 3.0-fold increased risk of RMS in the child (95% confidence interval [CI] = 1.4-6.5) and maternal cocaine use was associated with a 5.1-fold increased risk (CI = 1.0-25.0). Risk was increased 3.1-fold (CI = 1.4-6.7) with use of any recreational drug. Fathers' marijuana use was associated with a 2.0-fold increased risk (CI = 1.3-3.3), cocaine use with a 2.1-fold increased risk (CI = 0.9-4.9), and use of any recreational drug with a 2.0-fold (CI = 1.3-3.3) increased risk. Case mothers' cocaine use and both parents' marijuana use were associated with their children being diagnosed at a significantly younger age. It was not possible to determine whether cocaine and marijuana have independent effects, since use of the two drugs was materially correlated. Similarly, mothers' and fathers' use of these drugs was highly correlated. In summary, parents' marijuana and cocaine use during the year preceding their child's birth may increase, by twofold to fivefold, the risk of RMS in their children.

Adolescent↗

Effects of glycosaminoglycans and extracellular matrix components on metastatic rat rhabdomyosarcoma tumor and myoblast cell proliferation.

Experiments were performed to determine the relative effects of glycosaminoglycans and extracellular matrix components alone or in association with various substrates, including extracellular matrix, on the proliferation of rat rhabdomyosarcoma (RMS) cell lines of different metastatic potential and nontumorigenic rat myoblast L6 cells. The assays used various substrates: tissue culture plastic, type I and IV collagen, fibronectin, laminin and extracellular matrix deposited by corneal endothelial cells. In control experiments, tumor cells grew faster on fibronectin and extracellular matrix than on the other substrates, and their proliferation rate was decreased slightly by laminin. Collagens were growth-inhibitory only for the highly metastatic line. The proliferation rate of L6 myoblasts was not greatly affected by the different substrates. The addition of exogenous glycosaminoglycans to the culture medium modified cell proliferation on the various substrates. Heparin inhibited the growth of all the cell lines tested, independent of the substrate. When cultured on laminin substrate the proliferation rates of the cell lines were depressed by addition of heparan sulfate to the medium, and this effect was more pronounced in the metastatic RMS lines. Chondroitin sulfate and dermatan sulfate enhanced the growth rates of the tumorigenic cells when cultured on collagen type I surfaces. Hydrocortisone, which induces myogenic differentiation, decreased the cell proliferation rates of all the cell lines tested and intensified the inhibitory effects of heparin when added simultaneously to the culture medium. The results showed that glycosaminoglycans and other matrix components can affect the proliferation rates of rhabdomyosarcoma cell lines.

Animals↗

Influence of dimethyl sulphoxide on intermediate filament proteins in human rhabdomyosarcoma cell lines: modulation at subcellular level.

The effects of dimethyl sulphoxide have been investigated on differentiation in human rhabdomyosarcoma cell lines obtained from typically malignant, poorly differentiated tumours. The expression of cell differentiation marker proteins (desmin and vimentin) was assessed in cell lines A-204, A-673 and RD, and the modifications in expression after 3, 8 and 24 h of induction with 1.25% dimethyl sulphoxide were recorded. Protein expression in both the cytoplasm and cytoskeleton was significantly altered by treatments lasting 8 and 24 h, the most noteworthy changes being increased desmin and decreased vimentin expression. The results clearly indicate that dimethyl sulphoxide induced changes typical of differentiation in rhabdomyosarcoma cell lines A-673 and RD; less marked changes were observed in line A-204.

Blotting, Western↗

Paratesticular rhabdomyosarcoma.

Even though rhabdomyosarcoma is the most common soft tissue sarcoma in children, accounting for 5-10% of all malignant disease in children under 15 years of age, so few cases are seen in a single institution that only the combined efforts of multicentre prospective trials made it possible fro adequate treatment schedules to be devised. Thank to this cooperation, survival rates have increased dramatically in recent decades; risk factors have been identified and treatment can now be adapted accordingly. This is especially true for the paratesticular rhabdomyosarcoma (PTRM), which now has a good prognosis in all stages. The striking similarity of tumor behavior and metastatic pathways to those in germ-cell tumors in young male adults can provide us with more extensive data derived from a much larger group of patients. Recent data are gathered and evaluated in this review. Only in this way will it be possible to eliminate all treatment modalities known to be followed by severe sequelae, thus avoiding exposure of the patients to a therapy that carries more risks than the primary tumor itself.

Child↗

A novel site of DNA amplification on chromosome 1p32-33 in a rhabdomyosarcoma revealed by comparative genomic hybridization.

Cytogenetic analysis of a human embryonal rhabdomyosarcoma revealed a near-diploid karyotype with structural chromosome aberrations not involving the typical rearrangements of rhabdomyosarcomas, plus a large number of double minutes. Comparative genomic hybridization revealed a previously undescribed site of DNA amplification on the short arm of chromosome 1 (band 1p32-33).

Child↗

Indium 111 antimyosin for the detection of leiomyosarcoma and rhabdomyosarcoma.

111In-antimyosin monoclonal antibody complex passes through damaged myocardial cell membranes and binds to the intracellular myosin. Normal myocardial and other muscle cells show no uptake. Rhabdomyosarcoma and Leiomyosarcoma cells also contain intracellular myosin and the cell membrane permeability is greater than normal. Significant uptake of 111In-antimyosin was observed in patients with Leiomyosarcoma and Rhabdomyosarcoma suggesting that the reagent has a potential for the in vivo detection of these tumour types. Tumour to background ratios of 10:1 were measured in one case and in view of the fact that the site of accumulation is intracellular, antimyosin may have a potential as a carrier for therapeutic agents.

Adult↗

Genetics of susceptibility in the platyfish/swordtail tumor system to develop fibrosarcoma and rhabdomyosarcoma following treatment with N-methyl-N-nitrosourea (MNU).

About 7000 animals of 65 different genotypes of the xiphophorine fish were treated with the direct acting chemical carcinogen N-methyl-N-nitrosourea (MNU; 10(-3)M; four times for 1 hour in two week intervals), in order to find out whether the susceptibility for development of fibrosarcomas and rhabdomyosarcomas is directly related to the genotype. A genotype specific susceptibility was found, ranging from zero to about nine percent. The highest susceptibles were found in certain backcross hybrids involving P.variatus/X.helleri-hybrids and X.helleri, as the recurrent parent. These genotypes were further analysed. Both P.variatus and X.helleri, as werr as their F1 proved to be insusceptible; while from the three backcrosses, which were tested, namely the BC1, BC4 and BC15, both the BC1, and the BC4, were susceptible, but the BC15 was insusceptible. The results are interpreted on the basis of the assumption that the differential susceptibility is a function of the type of control of a tumor gene (Tu-Fi-Rh) endogenous to P.variatus and involved in development of fibrosarcomas and rhabdomyosarcomas. Accordingly, in P.variatus and in the F1 the Tu-Fi-Rh is controlled by repressing genes (R-genes) linked as well as non-linked to Tu-Fi-Rh; because simultaneous mutation of both R-genes following treatment with MNU is an extremely unlikely event, these genotypes have an extremely low susceptibility. By contrast, in the BC1 and the BC4 the non-linked R-genes become eliminated and only the linked R-gene remains for repression of Tu-Fi-Rh; this condition confers a high degree of susceptibility, because one single mutation may lead to impairment of the R-gene and to Tu-Fi-Rh-mediated formulation of fibrosarcomas and rhabdomysarcomas. In the BC15, furthermore, also the Tu-Fi-Rh has become eliminated, resulting in a loss of the susceptibility. The results suggest that in the xiphophophorine fish the susceptibility for responding to MNU-treatment with the development of fibrosarcomas and rhabdomysarcomas is related directly to the genotype.

Age Factors↗

Rhabdomyosarcoma of the oesophagus. Light and electron microscopic study of a rare tumor.

A 61-year-old man was operated for a large tumor, 12 x 4 cm in size, in the lower third of the oesophagus. The tumor had the appearance of a pleomorphic rhabdomyosarcoma showing cross striations by light microscopy and typical sarcomeres by electron microscopy. This is the fifth undisputed oesophageal rhabdomyosarcoma described in the literature and the first examined using electron microscope.

Esophageal Neoplasms↗

Primary rhabdomyosarcoma combined with chronic paragonimiasis in the cerebrum: a necropsy case and review of the literature.

A necropsy case of a primary rhabdomyosarcoma with chronic paragonimiasis in the cerebrum of a 68-year-old man is reported. The clinical data showed a right hemiplegia and dysarthria which became lethal in 6 months even though operation and radiation therapy were performed. Computed tomography revealed a large low-density area associated with the peripheral enhancement in the left basal ganglia, and multiple conglomerated calcified masses in the left temporal and occipital lobes. Biopsied and necropsied materials of the tumor in the basal ganglia was reddish brown in color and histologically was composed of purely mesenchymal derivatives with both embryonal and mature striated muscle cells but neither neuronal nor glial elements. Some of the tumor cells with extending slender cytoplasms showed obvious cross striations at the light and electron microscope levels and immunohistochemical reactivity for myoglobin. All tumor cells were also positive for vimentin, but not for glial fibrillary acidic protein. The clinical and necropsy findings revealed no primary lesion anywhere but in the brain. In addition, numerous dead oval eggs of Paragonimus westermani were found in many cystoid lesions encapsulated by thick connective tissues with calcification and/or ossification. Clinicopathological features of 24 cases of primary rhabdomyosarcoma of the central nervous system reported in the literature are reviewed briefly. The histogenesis of this tumor are discussed together with comments on cerebral paragonimiasis.

Aged↗

Primary rhabdomyosarcoma of brain and cerebellum. Report of four cases in infants: an immunohistochemical study.

Tumors of the central nervous system (CNS) composed of pure mesenchymal derivatives with both embryonal and mature striated muscle cells devoid of neuroblastic elements should be considered rhabdomyosarcomas. Some 13 cases have been reported, and here we study four additional cases in infancy under 3 years of age which represent 0.82% of 483 intracranial tumors studied by us at the Children's Hospital in the last 12 years. Two cases were localized in the temporal lobes, and two were in the cerebellar vermis. All of them were typical embryonal rhabdomyosarcomas at various stages of differentiation including undifferentiated mesenchymal cells, embryonal cells, and rhabdomyoblasts. Tumor cells achieved a higher degree of differentiation in the cerebellum, as shown by readily detectable immature muscle fibers which were consistently absent in tumors involving the brain. Myoglobin [peroxidase-antiperoxidase (PAP) technique] was positive throughout in rhabdomyoblasts and in immature muscle cells, whereas glial fibrillary acidic protein was negative in all four tumors. In spite of the well differentiated appearance of the cerebellar tumors, their behavior was highly malignant with extensive infiltration of brainstem leptomeninges in one case, and all patients survived for only a short time after surgery. These tumors may be observed in the midline structures of the posterior fossa and in the brain, but we suspect their true incidence might be higher if immunohistochemical techniques were applied.

Brain Neoplasms↗

Ossification in a soft tissue embryonal rhabdomyosarcoma.

We describe the previously unreported finding of ossification within a rhabdomyosarcoma of the extremity in the absence of bone destruction. Rhabdomyosarcoma is a highly malignant tumor but could not be radiographically differentiated from benign or other malignant causes of soft-tissue masses containing calcium. Definitive diagnosis and thus appropriate therapy requires prompt pathologic examination.

Female↗

Replication of human cytomegalovirus in a rhabdomyosarcoma cell line depends on the state of differentiation of the cells.

The replication of human cytomegalovirus (HCMV) was investigated in a new human rhabdomyosarcoma cell line (KFR) with morphological and biochemical characteristics of fetal striated muscle precursors (rhabdomyoblasts). KFR cells exhibited the unique property for spontaneous morphological transformation from a poorly-differentiated state into well-differentiated (myotube-like) rhabdomyoblasts. The poorly-differentiated rhabdomyoblasts promoted both complete viral gene expression and the production of infectious virus. In contrast, in well-differentiated rhabdomyoblasts HCMV infection was abortive. The results showed that replication of HCMV in this human rhabdomyosarcoma cell line depended on the state of cellular differentiation.

Antigens, Viral↗

Rhabdomyosarcoma in the region of the sella turcica.

Intracranial extension of rhabdomyosarcoma from the face, nasopharynx or middle ear is rare. A 16-year-old boy presented with deterioration of vision and headache. CT scan revealed a soft tissue mass occupying the sphenoid and ethmoid sinuses, extending to the suprasellar fossa and impinging on the optic chiasm. The tumour, mimicking pituitary carcinoma, was removed by transsphenoidal craniotomy. Morphologic studies, including immunohistochemistry and electron microscopy, revealed that the tumour was a rhabdomyosarcoma. This case stresses the value of immunohistochemical and ultrastructural studies in the diagnosis of tumours occurring in the region of the sella turcica. The origin of this tumour was thought to be the sphenoid or ethmoid sinus. The pituitary gland appeared intact.

Adolescent↗

Modulation of proteoglycan metabolism by hydrocortisone and by growth factors in rhabdomyosarcoma cell lines of different metastatic potentials.

Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials, grown in the presence or in the absence of hydrocortisone and of growth factor (EDF and EDGF) were investigated comparatively. The newly formed [35S]sulphate and [3H]glucosamine-labelled glycosaminoglycans were analysed in the extra-, peri- and intra-cellular compartments of the following cell lines: the strongly metastatic and colonizing 9-4/0 parental line, the very weakly metastatic and weakly colonizing subline 8 and the very weakly metastatic but colonizing subline 13a2. The cell surface of the weakly metastatic 8 and 13a2 lines was richer at least 5 and 2 times respectively in sulphated glycosaminoglycan label than the surface of the strongly metastatic 9-4/0 parental line. Hydrocortisone provoked an approximately four-fold increase in the label of the sulphated cell surface glycosaminoglycans of the 9-4/0 line. The pattern of the labelled cell surface glycosaminoglycans of these cells become similar to that of cells from the very weakly invading subline 8. Hydrocortisone induced only minor changes in the distribution of the glycosaminoglycans in the 8 and 13a2 lines, and at the same time, their proliferation rate and differentiation state was only slightly affected by this drug. Conversely to hydrocortisone, EGF increases the proliferation of the 9-4/0 line and also increases the label in sulphated cell surface glycosaminoglycans. This increase is about 50 per cent of that obtained by hydrocortisone. Thus, the accumulation of the glycosaminoglycan label on the cell surface is not directly related to the cell growth in the case of these cells. The results suggest that sulphated cell surface glycosaminoglycans, especially chondroitin sulphate, are involved in the inhibition of metastasis formation of the rhabdomyosarcoma cell lines studied.

Animals↗

Rhabdomyosarcomas developing in association with mediastinal germ cell tumours.

Two mediastinal rhabdomyosarcomas that arose in association with germ cell tumours are reported. One presented as a small component of a mixed germ cell tumour with yolk sac and immature teratomatous elements. The other appeared as a large mass 4 months after diagnosis of a yolk sac carcinoma that had been treated with chemotherapy. The first patient was alive and free of disease 7 years later, whereas the second died of tumour 3 months post-operatively. The proportion of rhabdomyosarcoma within the germ cell tumours appears to have influenced the prognosis of these patients. This observation emphasizes the necessity of performing a thorough search for sarcomatous elements and quantifying their relative proportion in germ cell tumours of the mediastinum.

Adult↗

Rhabdomyosarcoma associated with familial adenomatous polyposis.

We report a case of a 16 year old girl with orbital rhabdomyosarcoma who during chemotherapy developed bloody diarrhoea. On investigation she was found to have multiple colonic polyps. Cytogenetic analysis has shown a pattern typical of familial adenomatous polyposis. We present a review of the literature concerning the associations of familial adenomatous polyposis. The association of familial adenomatous polyposis with rhabdomyosarcoma has not been previously reported.

Adenomatous Polyposis Coli↗

Cell necrosis and endocytosis (apoptosis) in an embryonal rhabdomyosarcoma of the orbit.

An orbital embryonal rhabdomyosarcoma, which was excised from the orbit of an 8-year-old girl, was studied by light microscopy and transmission electron microscopy. Cells within the tumour demonstrated by light microscopy diffuse areas of necrosis and isolated single-cell necrosis. There were many viable tumour cells with intracytoplasmic vacuolar structures which contained basophilic granules. Ultrastructural studies showed close apposition between well-preserved tumour rhabdomyoblasts and degenerate or necrotic tumour cells: degenerate cells and condensed cell fragments were observed within the cytoplasm of the well-preserved tumour cells. Some cells which showed degenerative changes had features which suggested that they had ingested more than one degenerate cell on separate occasions. This phenomenon may be regarded as a variant of selective individual cell death, currently referred to as apoptosis, which has not been previously reported in a case of embryonal rhabdomyosarcoma. The patient remains free of tumour recurrence four years following treatment with combined radiotherapy and chemotherapy.

Cell Survival↗

A common region of loss of heterozygosity in Wilms' tumor and embryonal rhabdomyosarcoma distal to the D11S988 locus on chromosome 11p15.5.

The development of Wilms' tumor has been associated with two genetic loci on chromosome 11: WT1 in 11p13 and WT2 in 11p15.5. Here, we have used loss of heterozygosity (LOH) in Wilms' tumors to narrow the WT2 locus distal to the D11S988 locus. A similar region was apparent for the clinically associated tumor, embryonal rhabdomyosarcoma. We have also demonstrated that a constitutional chromosome translocation breakpoint associated with Beckwith-Wiedemann syndrome and an acquired somatic chromosome translocation breakpoint in a rhabdoid tumor each occur in the same chromosomal interval as the smallest region of LOH in Wilms' tumors and embryonal rhabdomyosarcoma. Finally, we report the first Wilms' tumor without a cytogenetic deletion that shows targeted LOH for 11p15 and 11p13 while maintaining germline status for 11p14.

Base Sequence↗