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Article: 1α-Hydroxyvitamin D 2 inhibits growth of human neuroblastoma

Title1α-Hydroxyvitamin D 2 inhibits growth of human neuroblastoma
Authors
KeywordsDoxercalciferol
Neuroblastoma
Serum calcium
Vitamin D analog
Xenograft model
Issue Date2007
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-594X
Citation
Journal Of Neuro-Oncology, 2007, v. 85 n. 3, p. 255-262 How to Cite?
AbstractNeuroblastoma is the most common extracranial solid tumor in childhood. The poor outcomes of patients with high-risk neuroblastoma have encouraged the search for new therapies. In the current study, the effect of the vitamin D analog 1α-hydroxyvitamin D 2 (1α-OH-D 2, doxercalciferol) was assessed in a mouse xenograft model of human neuroblastoma. Vitamin D receptor (VDR) expression levels in seven neuroblastoma cell lines were compared using real-time PCR. SK-N-AS cells, which express relatively high levels of VDR, were injected into the flanks of 60 mice. The mice were treated daily via oral gavage for 5 weeks with vehicle (control), 0.15 μg, or 0.3 μg of 1α-OH-D 2. The animals were then euthanized, and tumors, sera, and kidneys were collected and analyzed. End tumor volumes were significantly smaller in both the 0.15 μg group (712.07 mm 3, P = 0.0121) and 0.3 μg group (772.97 mm 3, P = 0.0209) when compared to controls (1,681.75 mm 3). In terms of toxicity, serum calcium levels were increased but mortality was minimal in both treatment groups. These results were similar to those previously described in the transgenic (LHβ-Tag) and human xenograft (Y-79) models of retinoblastoma, a related tumor. In vitro cell viability studies of SK-N-AS and NGP cells, which represent two major human neuroblastoma subtypes that differ in their genetic abnormalities as well as their VDR expression levels, show that both are sensitive to calcitriol, the active metabolite of vitamin D 3. In conclusion, the present study shows that 1α-OH-D 2 can inhibit human neuroblastoma growth in vivo with relatively low toxicity. The safety of 1α-OH-D 2 has been extensively studied; the drug is FDA-approved for the treatment of adult kidney patients, and Phase I/II trials have been conducted in adult oncology patients. There should not be major obstacles to starting Phase I and II clinical trials with this drug in pediatric patients with high-risk neuroblastoma. © Springer Science+Business Media, LLC 2007.
Persistent Identifierhttp://hdl.handle.net/10722/92826
ISSN
2015 Impact Factor: 2.754
2015 SCImago Journal Rankings: 1.274
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorvan Ginkel, PRen_HK
dc.contributor.authorYang, Wen_HK
dc.contributor.authorMarcet, MMen_HK
dc.contributor.authorChow, CCen_HK
dc.contributor.authorKulkarni, ADen_HK
dc.contributor.authorDarjatmoko, Sen_HK
dc.contributor.authorLindstrom, MJen_HK
dc.contributor.authorLokken, Jen_HK
dc.contributor.authorBhattacharya, Sen_HK
dc.contributor.authorAlbert, DMen_HK
dc.date.accessioned2010-09-17T10:58:31Z-
dc.date.available2010-09-17T10:58:31Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Neuro-Oncology, 2007, v. 85 n. 3, p. 255-262en_HK
dc.identifier.issn0167-594Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/92826-
dc.description.abstractNeuroblastoma is the most common extracranial solid tumor in childhood. The poor outcomes of patients with high-risk neuroblastoma have encouraged the search for new therapies. In the current study, the effect of the vitamin D analog 1α-hydroxyvitamin D 2 (1α-OH-D 2, doxercalciferol) was assessed in a mouse xenograft model of human neuroblastoma. Vitamin D receptor (VDR) expression levels in seven neuroblastoma cell lines were compared using real-time PCR. SK-N-AS cells, which express relatively high levels of VDR, were injected into the flanks of 60 mice. The mice were treated daily via oral gavage for 5 weeks with vehicle (control), 0.15 μg, or 0.3 μg of 1α-OH-D 2. The animals were then euthanized, and tumors, sera, and kidneys were collected and analyzed. End tumor volumes were significantly smaller in both the 0.15 μg group (712.07 mm 3, P = 0.0121) and 0.3 μg group (772.97 mm 3, P = 0.0209) when compared to controls (1,681.75 mm 3). In terms of toxicity, serum calcium levels were increased but mortality was minimal in both treatment groups. These results were similar to those previously described in the transgenic (LHβ-Tag) and human xenograft (Y-79) models of retinoblastoma, a related tumor. In vitro cell viability studies of SK-N-AS and NGP cells, which represent two major human neuroblastoma subtypes that differ in their genetic abnormalities as well as their VDR expression levels, show that both are sensitive to calcitriol, the active metabolite of vitamin D 3. In conclusion, the present study shows that 1α-OH-D 2 can inhibit human neuroblastoma growth in vivo with relatively low toxicity. The safety of 1α-OH-D 2 has been extensively studied; the drug is FDA-approved for the treatment of adult kidney patients, and Phase I/II trials have been conducted in adult oncology patients. There should not be major obstacles to starting Phase I and II clinical trials with this drug in pediatric patients with high-risk neuroblastoma. © Springer Science+Business Media, LLC 2007.en_HK
dc.languageengen_HK
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-594Xen_HK
dc.relation.ispartofJournal of Neuro-Oncologyen_HK
dc.subjectDoxercalciferolen_HK
dc.subjectNeuroblastomaen_HK
dc.subjectSerum calciumen_HK
dc.subjectVitamin D analogen_HK
dc.subjectXenograft modelen_HK
dc.title1α-Hydroxyvitamin D 2 inhibits growth of human neuroblastomaen_HK
dc.typeArticleen_HK
dc.identifier.emailMarcet, MM: marcet@hku.hken_HK
dc.identifier.authorityMarcet, MM=rp01363en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s11060-007-9418-zen_HK
dc.identifier.pmid17603751-
dc.identifier.scopuseid_2-s2.0-36348994279en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36348994279&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume85en_HK
dc.identifier.issue3en_HK
dc.identifier.spage255en_HK
dc.identifier.epage262en_HK
dc.identifier.eissn1573-7373-
dc.identifier.isiWOS:000250920000004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridvan Ginkel, PR=6505834031en_HK
dc.identifier.scopusauthoridYang, W=19838753600en_HK
dc.identifier.scopusauthoridMarcet, MM=8891087900en_HK
dc.identifier.scopusauthoridChow, CC=7402578414en_HK
dc.identifier.scopusauthoridKulkarni, AD=20433998000en_HK
dc.identifier.scopusauthoridDarjatmoko, S=35554693400en_HK
dc.identifier.scopusauthoridLindstrom, MJ=34571495000en_HK
dc.identifier.scopusauthoridLokken, J=6508329781en_HK
dc.identifier.scopusauthoridBhattacharya, S=7404284681en_HK
dc.identifier.scopusauthoridAlbert, DM=36044032300en_HK

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