Inhibition of proliferation of human cerebral meningioma cells by suramin: effects on cell growth, cell cycle phases, extracellular growth factors, and PDGF-BB autocrine growth loop

Schrell, U.; Gauer, Stefan; Kiesewetter, F.; Bickel, Andreas; Hren, Jürgen; Adams, Eric F.; Fahlbusch, Rudolf

doi:10.3171/jns.1995.82.4.0600

Cited by 43 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistently with involvement of ERK 1/2 in cisplatin toxicity, we found that PD98059, is a MEK inhibitor and suramin, a polysulphonated compound previously used as inhibitor of extracellular receptors for growth factors [Schrell et al, 1995;Li et al, 1999;Laubinger et al, 2003], not only inhibited ERK 1/2 activation but also reduced the extent of CDDP-induced cell death. These compounds, which can both block the upstream signaling to ERK 1/2, are also able to significantly reduce the Fig.…”

Section: Discussionsupporting

confidence: 55%

Cisplatin cytotoxicity in organ of corti‐derived immortalized cells

Previati¹,

Lanzoni²,

Astolfi³

et al. 2007

J of Cellular Biochemistry

View full text Add to dashboard Cite

Cisplatin is an anticancer drug currently used in the treatment of genital and head and neck tumors. Its use in these and other types of tumors is narrowed by onset of chemoresistance and severe undesired side effects, like as nephro- and ototoxicity, whose mechanisms of action are only partially understood. In the present study we investigated the effects of cisplatin (cis-dichlorodiaminoplatin, CDDP) on a cell line (OC-k3) developed from organs of Corti of transgenic mice. We observed at 48 h that cell death due to cisplatin was time and concentration-dependent. The cell death displayed some morphological hallmarks of apoptosis, including nuclear fragmentation into several large nuclear fragments, surrounded by a rearranged and thickened actin cytoskeleton. No DNA laddering was detected, suggesting absence of endonuclease activity, nor annexin V positivity, suggesting absence of phosphatidylserine externalization. Several molecules protected the cells against CDDP induced cytotoxicity, including methionine, suramin and PD98059. Methionine reduced CDDP-uptake, while suramin, a polycathionic compound a specifically binding external proteins, did not. This finding suggested that suramin could exert its protective effect by acting on an intracellular transduction pathway. We tested this hypothesis by studying the effect of suramin and PD98059, a MEK inhibitor, on the mitogen activated protein kinase (MAPK) cascade. After CDDP treatment, we found an increase of phosphorylation of extracellular regulated kinases (ERK)1/2, that could be inhibited by PD98059 and suramin. These data suggest that ERK pathways can play a role in mediating the cell death induction in presence of a CDDP challenge.

show abstract

Section: Discussionsupporting

confidence: 55%

Cisplatin cytotoxicity in organ of corti‐derived immortalized cells

Previati¹,

Lanzoni²,

Astolfi³

et al. 2007

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…23A2 myoblasts cultured in naive DM which has been boiled identically had no a ect on their abiity to express MHC or fuse (d.n.s.). The actions of many peptide growth factors are abrogated by the non-speci®c antagonist, suramin (Schrell et al, 1995). 23A2 myoblasts cultured in DM supplemented with suramin express MHC to the same level as cells cultured without suramin (Figure 4b).…”

Section: Mhcmentioning

confidence: 99%

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

Weyman

Wolfman

1997

Oncogene

View full text Add to dashboard Cite

Expression of oncogenic H-Ras in 23A2 myoblasts (A2:H-Ras cells) is su cient to induce both a transformed phenotype and a di erentiation-defective phenotype. Because oncogenic Ras is known to induce the secretion of several di erent growth factors involved in maintaining the transformed phenotype of both ®broblast and epithelial cells, we explored the possibility that expression of oncogenic Ras in 23A2 myoblasts might lead to the secretion of a factor which inhibits di erentiation. The di erentiation of 23A2 myoblasts was inhibited (i) by coculture with an equal number of A2:H-Ras cells, (ii) by culture with an equal number of A2:H-Ras cells in the same tissue culture medium on an insert which allowed equilibration of molecules smaller than 1 micron, and (iii) by culture in media previously conditioned by A2:H-Ras cells. Similar results were obtained when 23A2 myoblasts expressing oncogenic NRas were substituted for A2:H-Ras cells in each assay. No inhibition of di erentiation was observed, however, when di erentiation-defective E1A-expressing 23A2 cells or C3H10T1/2 ®broblasts were substituted for A2:HRas cells. The di erentiation inhibitor(s) in media conditioned by A2:H-Ras cells is heat stable, larger than 3 kD, and sensitive to the non-speci®c growth factor antagonist, suramin. Western analyses failed to detect either FGF-2 or TGFb (the known inhibitors of myoblast di erentiation) in media conditioned by A2:H-Ras cells. Furthermore, while FGF-2 is a potent activator of MAP kinase and TGFb is a potent inhibitor of mink lung epithelial cell (CCL64) growth, conditioned media from A2:H-Ras cells does not activate MAP kinase and does not inhibit the growth of CCL64 cells. These results indicate that expression of oncogenic Ras induces the secretion of a novel inhibitor of skeletal myoblast di erentiation. Furthermore, these results are the ®rst to implicate an autocrine/paracrine mechanism in the inhibition of di erentiation by oncogenic Ras.

show abstract

“…Esses fatores de crescimento ligam-se a receptores celulares específicos, os receptores tirosina-quinase. Vários estudos demonstram a expressão de diversos fatores de crescimento como o fator de crescimento epidérmico (EGF), o fator de crescimento derivado das plaquetas (PDGF) e o VEGF pelas células tumorais de meningiomas in vitro e in vivo 3,24 . Esses fatores de crescimento têm provavelmente uma atividade de estimulação autócrina de proliferação das células neoplásicas.…”

Section: Incidência Deunclassified

“…Esses fatores de crescimento têm provavelmente uma atividade de estimulação autócrina de proliferação das células neoplásicas. A suramina, droga que se liga a uma série de fatores de crescimento como o EGF, o PDGF, o fator de crescimento de fibroblastos (FGF-b), entre outros, inibe a proliferação de células de meningiomas em cultura 24 . Os efeitos de estimulação parácrina dos fatores de crescimento expressos nas células dos meningiomas permanecem em investigação.…”

Section: Incidência Deunclassified

Edema cerebral em meningiomas: aspectos radiológicos e histopatológicos

Souto

Chimelli

Takya

et al. 2002

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

RESUMO -Diversos fatores têm sido associados ao desenvolvimento de edema peritumoral nos meningiomas. Foram estudados os aspectos radiológicos e anátomo-patológicos de 51 meningiomas intracranianos operados no Hospital Universitário Clementino Fraga Filho (HUCFF). Dois terços dos meningiomas apresentavam edema perilesional. O tamanho dos meningiomas correlacionou-se com a presença de edema, sendo mais frequente nos meningiomas grandes (>4cm). A localização parece, também, influenciar no desenvolvimento do edema peritumoral, sendo mais acentuado nos meningiomas da asa do esfenóide e incomum nos meningiomas do tubérculo selar. Os subtipos histológicos de meningioma não se correlacionaram com a intensidade do edema peritumoral. Dos diversos mediadores químicos descritos na literatura recente relacionados ao desenvolvimento de edema peritumoral em tumores intracranianos, destaca-se o fator de crescimento do endotélio vascular (VEGF). A expressão nos meningiomas do VEGF e de seu receptor flk-1 foi estudada com técnica imunohistoquímica, demonstrando a sua expressão nas células tumorais.PALAVRAS-CHAVE: edema cerebral, meningioma, imuno-histoquímica, tomografia computadorizada, ressonância magnética. Brain edema in meningiomas: radiological and histological factorsABSTRACT -Many factors have been associated to the development of peritumoral edema in meningiomas. We studied the radiological and pathological features of 51 intracranial meningiomas surgically treated in the University Hospital of the Federal University of Rio de Janeiro. Two thirds of the meningiomas in our series had peritumoral edema. The size of the meningioma was probably related to the development of edema. Peritumoral edema was found frequently in the large meningiomas. The location of the meningioma was also associated with the frequency of peritumoral edema. Sphenoid wing meningiomas had significantly more peritumoral edema. In contrast, tuberculum sellae meningiomas were almost never associated with cerebral edema. There is growing evidence in the literature that vascular endothelial growth factor (VEGF) is a key factor in the pathogenesis of peritumoral edema. We studied by immunohistochemical techniques the expression of VEGF and its receptor flk-1 in meningiomas. Os meningiomas na sua maioria têm grande implantação dural e apresentam plano de clivagem bem definido com o parênquima cerebral adjacente, que geralmente está deslocado e comprimido. Boa parte das lesões tem crescimento lento, podendo alcançar tamanho considerável de forma assintomática, especialmente em algumas localizações, como os meningiomas originários da goteira olfativa. O comportamento biológico de cada meningioma é, entretanto, variável, principalmente quanto à capacidade de invasão dos tecidos adjacentes e produção de edema perilesional.Edema vasogênico, como definido por Klatzo (1967) 1 , é causado por aumento da permeabilidade capilar. Esse tipo de edema ocorre no tecido cerebral adjacente a uma série de neoplasias intracranianas, principalmente metástases, gliomas malign...

show abstract

Inhibition of proliferation of human cerebral meningioma cells by suramin: effects on cell growth, cell cycle phases, extracellular growth factors, and PDGF-BB autocrine growth loop

Cited by 43 publications

References 36 publications

Cisplatin cytotoxicity in organ of corti‐derived immortalized cells

Cisplatin cytotoxicity in organ of corti‐derived immortalized cells

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

Edema cerebral em meningiomas: aspectos radiológicos e histopatológicos

Contact Info

Product

Resources

About