DNA-Topoisomerase I, a new target for the treatment of neuroblastoma

Vassal, Gilles; Pondarré, Corinne; Cappelli, Carlo; Mj, Terrier-Lacombe; Boland, I; Morizet, Jackie; Bénard, Jean; Vénuat, AM; Ardouin, P; Hartmann, Olivier; Gouyette, Alain

doi:10.1016/s0959-8049(97)00296-7

Cited by 38 publications

(32 citation statements)

References 11 publications

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“…Similarly, Thompson et al (1997b) showed that oral CPT-11 was active against a panel of six NB xenografts. Similar effects have been reported for the topoisomerase I inhibitor topotecan, which induced tumour regression and a significant tumour growth delay (TGD) in animals bearing NB xenografts (Vassal et al, 1997). CPT-11 is currently evaluated in children with NB using several doses and schedules, such as 600 mg m À2 every 3 weeks, 50 mg m À2 day À1 Â 5 every 3 week or 20 mg m À2 day À1 Â 5 weekly for 2 weeks in a row every 3 weeks (Furman et al, 1999;Blaney et al, 2001;Vassal et al, 2003a).…”

supporting

confidence: 75%

“…Conversely, IGR-NB8-R and IGR-NB8 failed to respond to etoposide, a DNA-topoisomerase II inhibitor. However, IGR-NB8-R was significantly less sensitive to the DNA-topoisomerase I inhibitor topotecan (TGD, 13 days) than the parental IGR-NB8 (TGD, 26 days at 2.7 mg kg À1 ) (Vassal et al, 1997). Thus, IGR-NB8-R exhibited cross-resistance to topoisomerase I inhibitors, but not to DNA-damaging agents.…”

Section: Cross-resistancementioning

confidence: 97%

“…The MDR1 gene was overexpressed. IGR-NB8 proved to be sensitive in vivo to CPT-11, topotecan, cyclophosphamide and cisplatin, but refractory to etoposide (VP16) (Vassal et al, 1996(Vassal et al, , 1997.…”

Section: Nb Xenograftmentioning

confidence: 99%

“…on days 0 and 4 at a dose of 10 mg kg À1 day À1 . Topotecan, cisplatin and etoposide were given at the highest nontoxic dose and cyclophosphamide was given at 90% of the historical LD10 dose, as previously evaluated in athymic mice (Vassal et al, 1996(Vassal et al, , 1997.…”

Section: Tumour Transplantationmentioning

confidence: 99%

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No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecan

et al. 2004

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CPT-11 (irinotecan) is a DNA-topoisomerase I inhibitor with preclinical activity against neuroblastoma (NB) xenografts. The aim was to establish in vivo an NB xenograft resistant to CPT-11 in order to study the resistance mechanisms acquired in a therapeutic setting. IGR-NB8 is an immature NB xenograft with MYCN amplification and 1p deletion, which is sensitive to CPT-11. Athymic mice bearing advanced-stage subcutaneous tumours were treated with CPT-11 (27 mg kg À1 day À1 Â 5) every 21 days (1 cycle) for a maximum of four cycles. After tumour regrowth, a new in vivo passage was performed and the CPT-11 treatment was repeated. After the third passage, a resistant xenograft was obtained (IGRNB8-R). The tumour growth delay (TGD) was reduced from 115 at passage 1 to 40 at passage 4 and no complete or partial regression was observed. After further exposure to the drug, up to 28 passages, the resistant xenograft was definitively established with a TGD from 17 at passage 28. Resistant tumours reverted to sensitive tumours after 15 passages without treatment. IGR-NB8-R remained sensitive to cyclophosphamide and cisplatin and cross-resistance was observed with the topoisomerase I inhibitor topotecan. No quantitative or qualitative topoisomerase I modifications were observed. The level of expression of multidrug resistance 1 (MDR1), MDR-associated protein 1 (MRP1) and, breast cancer resistance protein, three members of the ATP-binding cassette transporter family was not modified over passages. Our results suggest a novel resistance mechanism, probably not involving the mechanisms usually observed in vitro.

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supporting

confidence: 75%

Section: Cross-resistancementioning

confidence: 97%

Section: Nb Xenograftmentioning

confidence: 99%

Section: Tumour Transplantationmentioning

confidence: 99%

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No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecan

et al. 2004

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“…The S-type neuroblastoma cells SH-EP and SH-EP FADD-DN (Hopkins-Donaldson et al, 2002) and N-type NB cells IGR-N91 (Vassal et al, 1997) were grown in RPMI medium supplemented with 10% of FCS, 200 mg/ml gentamicin (Essex Chemie AG). Cells were incubated with 100 ng/ml of soluble recombinant TRAIL (a gift from J Tschopp) and 1 mg/ml of crosslinking mouse anti-Flag Ab M2 (Sigma).…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

Drug-mediated sensitization to TRAIL-induced apoptosis in caspase-8-complemented neuroblastoma cells proceeds via activation of intrinsic and extrinsic pathways and caspase-dependent cleavage of XIAP, Bcl-xL and RIP

Mühlethaler-Mottet¹,

Bourloud²,

Auderset³

et al. 2004

Oncogene

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Neuroblastoma (NB) is a childhood neoplasm which heterogeneous behavior can be explained by differential regulation of apoptosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces rapid apoptosis in most tumor cells and thus represents a promising anticancer agent. We have reported silencing of caspase-8 expression in highly malignant NB cells as a possible mechanism of resistance to TRAIL-induced apoptosis. To explore the particular contribution of caspase-8 in such resistance, retroviral-mediated stable caspase-8 expression was induced in the IGR-N91 cells. As a result, sensitivity to TRAIL was fully restored in the caspase-8-complemented cells. TRAIL-induced cell death could be further enhanced by cotreatment of IGR-N91-C8 and SH-EP cells with cycloheximide or subtoxic concentrations of chemotherapeutic drugs in a caspase-dependent manner. Sensitization to TRAIL involved enhanced death receptor DR5 expression, activation of Bid and the complete caspases cascade. Interestingly, combined treatments also enhanced the cleavage-mediated inactivation of antiapoptotic molecules, XIAP, Bcl-x L and RIP. Our results show that restoration of active caspase-8 expression in a caspase-8-deficient NB cell line is necessary and sufficient to fully restore TRAIL sensitivity. Moreover, the synergistic effect of drugs and TRAIL results from activation of the caspase cascade via a mitochondrial pathway-mediated amplification loop and from the inactivation of apoptosis inhibitors.

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Successful clinical response to irinotecan in desmoplastic round blue cell tumor

Rosoff

Bayliff

1999

Med. Pediatr. Oncol.

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DNA-Topoisomerase I, a new target for the treatment of neuroblastoma

Cited by 38 publications

References 11 publications

No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecan

No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecan

Drug-mediated sensitization to TRAIL-induced apoptosis in caspase-8-complemented neuroblastoma cells proceeds via activation of intrinsic and extrinsic pathways and caspase-dependent cleavage of XIAP, Bcl-xL and RIP

Successful clinical response to irinotecan in desmoplastic round blue cell tumor

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