uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Differentiated expression of somatostatin receptor subtypes in experimental models and clinical neuroblastoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. (Barnonkologisk forskning/Pfeifer)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
Department of Womeńs and Childreńs Health, Astrid Lindgren Childreńs Hospital, Karolinska Institute, Stockholm, Sweden.
Show others and affiliations
2011 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 56, no 4, p. 584-589Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Neuroblastoma (NB) is a solid tumor of childhood originating from the adrenal medulla or sympathetic nervous system. Somatostatin (SS) is an important regulator of neural and neuroendocrine function, its actions being mediated through five specific membrane receptors. The aim of this study was to investigate the expression of the different somatostatin receptors (SSTRs) in NB tumor cells that may form targets for future therapeutic development.

PROCEDURE:

Tumor specimens from 11 children with stage II-IV disease were collected before and/or after chemotherapy. Experimental tumors derived from five human NB cell lines were grown subcutaneously in nude mice. Expression of SSRTs, the neuroendocrine marker chromogranin A (CgA) and SS was detected by immunohistochemistry using specific antibodies.

RESULTS:

SSTR2 was detected in 90%, SSTR5 in 79%, SSTR1 in 74%, SSTR3 in 68% whereas SSTR4 was expressed in 21% of the clinical tumors. The experimental tumors expressed SSTRs in a high but variable frequency. All clinical tumors showed immunoreactivity for CgA but not for SS.

CONCLUSION:

The frequent expression of SSTRs indicates that treatment with unlabeled or radiolabeled SS analogs should be further explored in NB.

Place, publisher, year, edition, pages
2011. Vol. 56, no 4, p. 584-589
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-140509DOI: 10.1002/pbc.22913ISI: 000287986700013PubMedID: 21120894OAI: oai:DiVA.org:uu-140509DiVA, id: diva2:383724
Available from: 2011-01-05 Created: 2011-01-05 Last updated: 2018-10-31
In thesis
1. On the Diagnostics of Neuroblastoma: Clinical and Experimental Studies
Open this publication in new window or tab >>On the Diagnostics of Neuroblastoma: Clinical and Experimental Studies
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neuroblastoma (NB) is one of the most common childhood cancers. Patients with low stage tumor have high survival rate, while those with advanced stage and/or unfavorable molecular biology have poor prognosis. A correct histopathological diagnosis, clinical stage, and identified genetic aberrations are crucial for treatment stratification according to current protocol. The tumor sample is obtained either by fine needle aspiration, cutting needle biopsy or open biopsy. NB exhibits neuroendocrine differentiation by showing immunoreactivity for chromogranin A (CgA), synaptophysin (syn), and neuron specific enolase (NSE) and 90% of the patients have increased levels of urine catecholamine metabolites.

Experimental and clinical NB tumor samples were immunostained for somatostatin receptors (SSTRs) 1-5, somatostatin and CgA. Clinical tumor samples were also immunostained for syn, synaptic vesicle protein 2 (SV2), and vesicle monoamine transporter 1 (VMAT1) and 2 (VMAT 2). Blood samples from 92 patients were analyzed for level of CgA, NSE, and chromogranin B and compared with control groups. The urinary excretion of catecholamine metabolites was analyzed in samples collected at diagnosis. Clinical and laboratory data were extracted from patient records, including information on the diagnostic accuracy of ultrasound guided cutting needle biopsies (UCNB) and potential complications.

We found that NB expressed the different SSTRs and that receptor 2 was the most frequently expressed before chemotherapy. Furthermore, NB tumors showed immunoreactivity for SV2, VMAT 1 and VMAT2 alongside CgA and syn. The immunoreactivity of SV2 was comparable to CgA and superior to syn. Patients with NB had higher blood concentrations of CgA and NSE compared with controls. Patients with advanced stage disease, MYCN amplification and 1 p deletion had higher concentrations of both CgA and NSE while only NSE was correlated to outcome with higher concentrations in the deceased patients.

A high urinary excretion of homovanillic acid and dopamine were correlated to inferior outcome. UCNB were found to be safe and may provide all necessary diagnostic requirements for adequate therapy stratification according to current treatment protocols.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 50
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1514
Keywords
Neuroendocrine, Immunohistochemistry, Urinary Catecholamine Metabolites, Markers, Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-364682 (URN)978-91-513-0499-1 (ISBN)
Public defence
2018-12-20, Rosénsalen, Akademiska barnsjukhuset, ingång 95/96, nbv, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2018-11-29 Created: 2018-10-31 Last updated: 2018-12-27

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Georgantzi, KleopatraTsolakis, Apostolos VStridsberg, MatsChristofferson, RolfJanson, Eva Tiensuu

Search in DiVA

By author/editor
Georgantzi, KleopatraTsolakis, Apostolos VStridsberg, MatsChristofferson, RolfJanson, Eva Tiensuu
By organisation
PediatricsEndocrine OncologyBiochemical endocrinologyPaediatric Surgery
In the same journal
Pediatric Blood & Cancer
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 790 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf