No abstract available.
Neuroblastoma*

No abstract available.
Neuroblastoma*

PURPOSE: Recent clinical studies have shown that arsenic trioxide(As2O3) at low concentrations induces complete remission without significant toxicity in patients with refractory acute promyelocytic leukemia(APL). Like APL cells, neuroblastoma(NB) cells are thought to be arrested at an early stage of differentiation, and can respond with retinoic acid treatment. Sulindac, a nonsteroidal antiinflammatory drug, was reported to induce antitumor activity against various tumors through induction of apoptosis and inhibition of angiogenesis. There was no data with the effect of sulindac on NB, and the concentration of sulindac for antitumor effect could not be safely used in the clinical field. Therefore, we at first focused the synergistic cytotoxicity of two drugs using CHLA-15, CHLA-20 NB cells with different resistance to anticancer drugs, and then studied the mechanism of synergistic cytotoxicity at a clinically safe concentration of two drugs. METHODS: CHLA-15 and CHLA-20 cells were cultured in IMDM and treated with As2O3 and/or sulindac. Cell viability was measured by methilthiazol-2-yl-2, 5-diphenyl, tetrazolium bromide(MTT) assay. Apoptosis was assessed by DNA fragmentation assay. Apoptotic machinaries including FAS, caspase-3, PARP[poly(ADP-ribose) polymerase] were determined by Western blot analysis. RESULTS: As2O3 caused significant cytotoxicity on both CHLA-15 and CHLA-20 cell lines in a dose dependent manner, whereas sulindac had no demonstrable cytotoxic effects. Both drugs in combination induced synergistic cytotoxicity on two cell lines. Especially on a clinically therapeutic level with 2micrometer of As2O3 and 10micrometer of sulindac in combination, the viability of CHLA-15 and CHLA-20 cells was decreased to 15%, 60% more than arsenic alone, respectively. The synergistic cytotoxicity occurred by apoptosis through up-regulation of the Fas receptor, activation of caspase-3 and cleavage of PARP, which was a central pathway of induction of apoptosis. CONCLUSION: As2O3 and sulindac induced synergistic cytotoxicity and apoptosis on NB through up- regulation of the FAS receptor, activation of caspase-3 and cleavage of PARP. Taken together, these results indicate that As2O3 and sulindac are therapeutic agent candidates for treatment of NB.
Neuroblastoma

No abstract available.
Neuroblastoma*

No abstract available.
Neuroblastoma*

No abstract available.
Neuroblastoma*

No abstract available.
Neuroblastoma*

No abstract available.
Neuroblastoma*

Neuroblastoma, ganglioneuroblastoma and ganglioneuroma are derived from primordial neural crest cells and can be conceptualized as three different maturational manifestations of a common neoplasm. To assess the validity of immunohistochemistry and DNA Ploidy in the diagnosis of neuroblastic tumor in terms of prognostication, histologic and immunohistochemical evaluation with NB-84, neuron specific enolase(NSE) and S-100 protein and flow Cytometric DNA analysis were done on 21 neuroblastomas and 19 ganglioneuromas. Thirteen of 21 neuroblastomas were undifferentiated and 8 differentiating in type. Eleven of the 19 ganglioneuromas were mature in type and 8 had immature foci. Eighty one percent of neuroblastomas were positive for NB-84, 100% for NSE and 67% for S-100 protein, respectively. All ganglioneuromas were positive for NSE and S-100 protein, in contrast, only immature foci in ganglioneuroma were positive for NB-84. B-84 reacted positively with undifferentiated and differentiating neuroblasts including neuropil but not with mature ganglion cells. In contrast, NSE reacted positively with all components of neuroblastic tumor and S-100 protein mainly with cells of Schwannian differentiation. Three of eight(37.5%) differentiating neuroblastomas were strongly positive for NB-84 in contrast with seven of thirteen(53.8%) undifferentiated tumors, reflecting that undifferentiated cells tended to be positive for NB-84 in neuroblastoma. Twenty two percent of neuroblastoma showed diploidy and 78% aneuploidy including 11% of near-diploidy. Seven of eight(87.5%) differentiating neuroblastomas in contrast with seven of ten(70%) undifferentiated tumors showed aneuploidy. By contrast, 53% of ganglioneuroma showed diploidy and 47% aneuploidy with DNA index ranged from 1.12 to 1.19. Three of nine(33.3%) mature ganglioneuromas in contrast with five of eight(62.5%) ganglioneuromas with immature foci showed aneupolidy. Differentiating neuroblastoma tended to be aneuploid and ganglioneuroma with immature foci tended to be near-diploid. In conclusion, immunohistochemistry for NB-84, NSE and S-100 protein is useful for confirming neuronal, both neuronal and Schwannian, and Schwannian differentiation, respectively. Immunohistochemistry together with flow cytometric DNA analysis would be helpful to confirm the immature foci in ganglioneuroma.
Neuroblastoma

Both Acanthopanax senticosus and Acorus gramineus Soland are typical Oriental herbs. They have been used as a tonic, anti-rheumatic, anti-inflammatory, anti-stress, anti-cancer agent. But, it is still unclear how they effectively regulate their various biological properties. Ceramide is emerging as a second messenger of apoptotic cell death and there is increasing evidence that ceramide is involved in neurodegenerative disease and the process of senescence. The present study investigated the different effects of A. senticosus and A. gramineus on ceramide-induced apoptosis in human neuroblastoma SK-N-SH cells. We showed that ceramide induced apoptosis through the mediation of reactive oxygen species(ROS) production and A. senticosus, as an effective antioxidant, significantly inhibited the increase of ROS generation, thereby preventing apoptosis. Furthermore, an increase of caspase activity (apoptosis executors) resulted from ceramide reduced by A. senticosus. But A. gramineus had almost no protective effects. These results implicate that ROS play on important roles in ceramide-induced apoptosis, also A. senticosus protects effectively via inhibition of ROS generation by ceramide through selective pathway.
Humans ; Neuroblastoma