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 influence of all-trans-retinoic acid-beta-D-glucopyranosylester, all-trans-retinoic acid-beta-D-galactopyranosylester, methyl-(1-O-retinoyl-beta-D-glucopyranoside)uronate and all trans-retinyl-beta-D-glucuronide were investigated on the celle line BA-HAN-1C. This clonal cell line was derived from a dimethylbenzanthracene induced rhabdomyosarcoma in the rat. The tumor cells were incubated for 5 days with medium which was supplemented with various concentrations of the different compounds. The action of the retinoids were measured by comparing the cellular growth and the creatine kinase activity (as differentiation marker) with an supplemented cell line. The retinoids which are based on all-trans-retinoic acid (all-trans-retinoic acid-beta-D-glucopyranosylester, all-trans-retinoic acid-beta-D-galactopyranosylester, methyl-(1-O-retinoyl-beta-D-glucopyranoide)uronate and their chemical precursors) showed similar biological effects as all-trans-retinoic acid and could be used in higher concentrations than retinoic acid without the appearance of toxic effects. The all-trans-retinyl-beta-D-glucuronide derivatives did not show any influence on the cell growth and their creatinine kinase activity. With respect to the effects of the compounds two hypothesis about their function were possible: They act as a whole molecule, or: they are bound to a receptor where the really effective substance, all-trans-retinoic acid is released from the molecule by hydrolytic cleavage as required. Investigations with the carbohydrates D-glucose, D-galactose and D-uronic acid disproved the second theorie because these substances enormously support the growth of the tumor cells. The effectively of the free all-trans-retinoic acid would have been diminished by these components. However, this effect did not appear if hydrolysis is considered.
 ...
PMID:Effects of novel retinoids on growth and differentiation of a rhabdomyosarcoma cell line. 141 77

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. Both the induction of differentiation by retinoic acid (RA) and by sodium butyrate (NaBut), as well as the inhibition of proliferation by fetal calf serum (FCS)-depleted medium uniformly resulted in the same effects. There was a significant (p less than 0.001) inhibition of proliferation and induction of cellular differentiation, as evidenced by a significant (p less than 0.05) increase in creatine kinase activity. Furthermore, after exposure to RA-supplemented or FCS-depleted medium, a significant (p less than 0.001) increase in the number of myotube-like giant cells was observed. These effects were preceded by a uniform enhancement of c-raf mRNA expression, which became evident 6 h after exposure to RA, NaBut and FCS-depleted media. C-raf mRNA expression persisted at an elevated level throughout the observation period of 5 days after exposure to RA or NaBut, whereas the increased expression of c-raf mRNA observed after FCS-depletion declined near to the basal level after only 24 h. Furthermore, a transient c-fos mRNA expression was observed 15 and 30 min after exposure to RA-supplemented and FCS-depleted medium but not after exposure to NaBut. The present results suggest a possible role of c-raf in the regulation of differentiation and proliferation of this cell line. Since all our experiments with RA, NaBut and FCS-depletion resulted in an early peak of c-raf mRNA expression, it is suggested that this early peak may be sufficient to trigger events crucial for differentiation and proliferation of BA-HAN-1C tumor cells.
 ...
PMID:Uniform response of c-raf expression to differentiation induction and inhibition of proliferation in a rat rhabdomyosarcoma cell line. 198 May 57

BA-HAN-IC is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated post-mitotic myotubes. Exposure of BA-HAN-IC cells to retinoic acid (RA) or N-methylformamide (NMF) resulted in a significant inhibition of proliferation (p less than 0.001) and in cellular differentiation, as evidenced by a significant increase in the creatine kinase (CK) activity (p less than 0.05) and the number of terminally differentiated post-mitotic myotubes (p less than 0.001). Furthermore, between 5% (NMF) and 30% (RA) of the mononuclear tumor cells exhibited ultrastructural features of rhabdomyogenic differentiation, not observed in their mononuclear counterparts under standard growth conditions. Although BA-HAN-IC cells responded to both inducers of differentiation, differences in time course and magnitude of both increase of differentiation and growth inhibition were observed. These effects of RA and NMF were preceded by a marked enhancement of c-raf expression which became evident 6 and 12 hr after exposure to RA and NMF, respectively, and which persisted throughout the observation period of 5 days. Furthermore, a transient expression of c-fos could be observed 15 and 30 min after exposure to RA. Our results suggest that c-raf expression might be implicated in the differentiation process of BA-HAN-IC tumor cells.
 ...
PMID:Enhanced expression of the proto-oncogenes fos and raf in the rhabdomyosarcoma cell line BA-HAN-1C after differentiation induction with retinoic acid and N-methylformamide. 210 33

BA-HAN-1C is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotubelike giant cells. Exposure to retinoic acid resulted in an inhibition of proliferation and a marked increase in cellular differentiation. The number of myotubelike giant cells significantly increased, and about 30% of the mononuclear tumor cells exhibited morphological features of rhabdomyogenic differentiation which were not observed in the mononuclear cells of untreated cultures. Morphological differentiation was paralleled by an increase in total creatine kinase activity as a biochemical marker of differentiation. These effects of retinoic acid were preceded by an increased expression of proto-oncogene raf and transient expression of proto-oncogene fos. The maximum level of fos expression was observed at 15 min and of raf at 12 hr after exposure to retinoic acid. No expression of the proto-oncogenes src, myb, myc, ros, mos, erbA, and erbB was detected.
 ...
PMID:Morphological, biochemical, and molecular biological characterization of a rat rhabdomyosarcoma cell line during differentiation induction in vitro. 227 13

We report on the establishment of a model for differentiation induction in sarcomas, using the clonal rhabdomyosarcoma cell line BA-HAN-1C. This rhabdomyosarcoma cell line is composed of morphologically undifferentiated mononuclear stem cells, some of which spontaneously fuse to form terminally differentiated multinuclear myotube-like giant cells. The deprivation of fetal calf serum (FCS) or the exposure to retinoic acid, respectively, resulted in a significant inhibition of proliferation (P less than 0.001) and a marked increase in cellular differentiation as shown by a significant increase in the number of myotube-like giant cells (P less than 0.001) and in the creatine kinase activity (P less than 0.05) used as a biochemical marker of differentiation. Furthermore, after exposure to retinoic acid about 30% of the mononuclear tumour cells exhibited morphological features of rhabdomyogenic differentiation, such as bundles of thick and thin myofilaments, which had never been observed in the mononuclear cells of untreated cultures. These results confirm that the inverse linkage between proliferation and differentiation known from embryonic myogenesis is preserved in our rhabdomyosarcoma cell line. The failure to induce terminal differentiation by exposure to retinoic acid in all the cells of our clonal cell line indicates that some tumour cells might epigenetically be blocked from responding to retinoic acid. The temporary growth retardation observed after FCS-deprivation suggests that autocrine stimulation of proliferation may be operating in our cell line, too.
 ...
PMID:Fetal calf serum and retinoic acid affect proliferation and terminal differentiation of a rat rhabdomyosarcoma cell line (BA-HAN-1C). 275 24

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C was tested for its susceptibility to differentiation induction with different polar compounds. This cell line is composed of proliferating mononuclear tumour cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotube-like giant cells. Exposure of BA-HAN-1C cells to dimethylsulphoxide (DMSO), hexamethylene bisacetamide (HMBA), sodium butyrate (NaBut) and N-monomethylformamide (NMF) resulted in a significant inhibition of proliferation (P less than 0.001) and in a simultaneous increase in differentiation. The response was most pronounced after exposure to NMF as evidenced by a marked increase in the creatine kinase activity used as a biochemical marker of differentiation (P less than 0.05) and the number of terminally differentiated myotube-like giant cells (P less than 0.001). Furthermore, about 5% of the mononuclear cells exhibited thick and thin myofilaments which were never observed in the mononuclear cells of the control. In contrast, the effects of DMSO, HMBA and NaBut were exclusively confined to a significant increase in biochemical differentiation (P less than 0.05), whereas no increase in morphological differentiation was observed and the number of myotube-like giant cells even significantly (P less than 0.001) decreased. This heterogeneous response to differentiation induction with different polar compounds probably indicates different mechanisms of action and suggests that the induction of biochemical differentiation might be independently regulated from events leading to cell fusion and terminal differentiation.
 ...
PMID:Heterogeneous response to differentiation induction with different polar compounds in a clonal rat rhabdomyosarcoma cell line (BA-HAN-1C). 280 27

A permanent rat rhabdomyosarcoma cell line (BA-HAN-1C) has been established, the phenotype of which is characterized by the coexistence of undifferentiated mononuclear cells and differentiated multinuclear myotube-like giant cells. The failure of attempts to separate these two cell types by repeated recloning procedures indicates their close histogenetic relationship and suggests that differentiation in this tumor proceeds in a similar manner to that in normal striated muscle where postmitotic myotubes arise from mononuclear myoblasts by fusion. The morphologically undifferentiated mononuclear tumor cells were shown to be actively proliferating and to incorporate thymidine methyl-3H(3H-TdR). The myotube-like giant cells neither incorporated 3H-TdR nor underwent mitosis or exhibited any clonogenic potential. After retransplantation into syngenic rats, tumor growth was markedly retarded when the tumor cell inoculum contained a high percentage of myotube-like giant cells. These data show that proliferative activity in this rhabdomyosarcoma cell line is confined to the mononuclear tumor cell compartment, the multinuclear myotube-like giant cells having withdrawn from the cell cycle and represent terminally differentiated postmitotic cells. This cell line should provide a valuable tool for further investigation of coherent aspects of proliferation and differentiation using various differentiation inducers.
 ...
PMID:Terminally differentiated postmitotic tumor cells in a rat rhabdomyosarcoma cell line. 290 Nov 65

BA-HAN-1C is a clonal rat rhabdomyosarcoma cell line composed of proliferating mononuclear cells, which partly fuse to terminally differentiated postmitotic myotube-like giant cells. The exposure to retinoic acid in vitro resulted in time- and dose-dependent changes of both cell differentiation and cell growth. The mononuclear cells revealed bundles of newly formed thick and thin myofilaments, never observed in untreated cultures, and exhibited signs of contact inhibition. In addition, there was a statistically significant increase (P less than 0.001) in the number of terminally differentiated postmitotic myotube-like giant cells and in the creatine kinase activity (P less than 0.05) which was used as a biochemical differentiation marker. At the same time cell growth was significantly inhibited (P less than 0.001) in vitro and a decrease in plating efficiency, as well as in saturation density, was observed. These data demonstrate that retinoic acid can suppress cell growth and simultaneously initiate differentiation in a malignant mesenchymal tumor cell line. However, despite the clonal nature of BA-HAN-1C, the complete status of terminal differentiation was not achieved by all tumor cells. The reason why not all tumor cells responded to retinoic acid is unknown at the present time and will have to be the subject of further studies.
 ...
PMID:Terminal differentiation and growth inhibition of a rat rhabdomyosarcoma cell line (BA-HAN-1C) in vitro after exposure to retinoic acid. 340 49

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. This cell line has been shown to be susceptible to differentiation induction with all-trans retinoic acid (RA). Since it is still unknown whether exclusively all-trans RA itself or also its metabolites can act as inductive compounds in our cell line, we exposed BA-HAN-1C cells to the metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA. Exposure to these RA metabolites resulted in a significant inhibition of proliferation (P < 0.001) and induction of cellular differentiation, as evidenced by a significant increase in the number of myotube-like giant cells (P < 0.05) and a significant increase in creatine kinase activity (P < 0.05). However, differences in the inductive potency of these RA metabolites became apparent. Furthermore, RA metabolites exhibited a significantly weaker (P < 0.05) inductive activity when compared to all-trans RA. Summarizing our results we could demonstrate that the endogenous metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA are not merely deactivated cellular excretion products of all-trans RA, but potent inducers of differentiation and inhibitors of proliferation, possibly contributing to the complex physiological actions of retinoic acid.
 ...
PMID:Effects of retinoic acid metabolites on proliferation and differentiation of the clonal rhabdomyosarcoma cell line BA-HAN-1C. 798 40

Differentiation of a tumor plays an important role in terms of biological aggressiveness. The question arises as to whether this is reflected in differences in the metabolic and energetic status of solid tumors. The aim of this study was to analyze the influence of clonal tumor cell differentiation on the microenvironment of rat rhabdomyosarcomas. Two distinct lines of a rhabdomyosarcoma (BA-HAN-1) with different histomorphological properties were used (line F1, co-existence of mononuclear stellate cells and multinuclear myotube-like giant tumor cells; G8, polygonal, mononuclear tumor cells). Solid tumors were grown s.c. on the hind food dorsum of Lewis rats. Tumor oxygenation was measured using O2-sensitive needle electrodes. For determining tumor blood flow, the 133Xe clearance method was used. Global glucose and lactate concentrations were measured enzymatically, global ATP, ADP, and AMP were analyzed by HPLC. The regional distribution of metabolic and energetic parameters within the tumors was analyzed using quantitative bioluminescence and image analysis. Tumor growth rate was significantly different between the two lines. The volume doubling time was 2.5 days for the F1 and 3.0 days for G8 tumors. No differences in blood flow were seen between the two lines investigated, oxygenation was slightly poorer, glucose and ATP levels slightly higher, and lactate concentration somewhat lower in the F1 line as compared to the G8 line. From these differences - although marginal - it is concluded that the G8 line presumably relies on glycolysis whereas the F1 line seems to prefer oxidative glucose turnover. Despite these different metabolic profiles between the two tumor lines, the histopathology of the rhabdomyosarcomas seems to be only of limited significance for the tissue oxygenation status as already postulated for various tumors in the clinical setting.
 ...
PMID:Blood flow, oxygenation, metabolic and energetic status in different clonal subpopulations of a rat rhabdomyosarcoma. 966 12


1