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The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Lunggruppen)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. (Biologisk struktur och funktion)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Lymfomgruppen)
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2007 (English)In: Anticancer Research, ISSN 0250-7005, Vol. 27, no 5A, 3211-3217 p.Article in journal (Refereed) Published
Abstract [en]

Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.

Place, publisher, year, edition, pages
2007. Vol. 27, no 5A, 3211-3217 p.
Keyword [en]
Malignant melanoma, angiogenesis, survival, relapse, vascular endothelial growth factor, hepatocyte growth factor, hepatocyte scatter factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97931ISI: 000250266600022PubMedID: 17970063OAI: oai:DiVA.org:uu-97931DiVA: diva2:173055
Available from: 2008-12-22 Created: 2008-12-22 Last updated: 2011-01-20Bibliographically approved
In thesis
1. Prognostic Factors in Malignant Melanoma
Open this publication in new window or tab >>Prognostic Factors in Malignant Melanoma
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.

This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.

In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.

In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.

We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.

DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.

None of the investigated markers in study III and IV correlated with disease free survival or overall survival.

In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 410Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 410
Keyword
Malignant melanoma, prognostic factors, survival, chemotherapy, radiation
Identifiers
urn:nbn:se:uu:diva-9511 (URN)978-91-554-7378-5 (ISBN)
Public defence
2009-01-16, Skoog Salen, Onkologkliniken, ing 78, Uppsala Universitetssjukhus, 751 85, Uppsala, 09:15
Opponent
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Available from: 2008-12-22 Created: 2008-12-22 Last updated: 2013-06-20Bibliographically approved

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Wagenius, GunnarLarsson, AndersBrattström, DanielUllenhag, GustavHesselius, PatrikBergqvist, Michael

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