Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Cornell University, January, 2008. / Vita. Includes bibliographical references (leaves 96-108).

Globally, breast cancer is the most abundant cancer form in women, in Sweden about 20 women are diagnosed with breast cancer every day .Interactions between genetic and external factors are the contributing factors while metastasis formation is the leading cause of death. Cancer is in need of vessels,to get the nutrients and oxygen it needs in order to survive. Therefore,the aim of the study is to analyze and compare the groups of high and low differential cancer vessels of the respective form, and to see if any type contained more vessels than the other. The study is based on 20 invasive ductal breast cancer samples, ten of them were high differentiated and the other ten were low differentiated. To assess the number of vessels, immunhistochemical staining with CD31 antibody was performedCD31 is an adhesion molecule present on endothelial cells. The group of low differentiated gradebreast cancer tissue had significantly more vessels compared with the high differentiated breast cancer tissues. To prove these test results, more cancers must be analyzed.

Angiogenesis has a crucial influence on tumour development and identification of microvessels in malignant breast cancer tissue is an indicator for worse prognosis. Angiogenesis is partially governed by the family of vascular endothelial growth factors (VEGF) and their receptors, by which the VEGF-A-protein seems to be the most important factor.     The aims of this work were to first establish a method for immunohistological (IH)-staining of the VEGF-A-protein for clinical use and then to label and evaluate the expression of this protein in 31 Nottingham Histology Graded (NHG I-III) breast carcinoma.      Formaldehyde-fixated tissues from invasive breast neoplasms and control tissues were labelled with monoclonal antibodies against VEGF-A and CD31-proteins using a semi-automated IH-system from Ventana BenchMark. Positively stained vessels were counted from digital copies of microscopic pictures related to mm2 tissue.     A method of IH-labelling with VEGF-A protein was successfully established before staining of the breast tissue and in 19 of the 31 breast cancers. Vessels were counted for both antibodies. The VEGF-A-antibody stained 2.7 ± 2.3 (mean ± SD) vessels/mm2 and the CD31-antibody stained 27.3 ± 19.3 in the breast carcinoma tissue. The percent of VEGF-A-stained vessels in relation to CD31-stained were 7.6% in the NHG-I- (n=3), 7.8% in the NHG-II- (n=10) and 15.0% in the NHG-III-group (n=6).     The results demonstrate that increased NHG-grade and lower differentiation can be associated with higher percent of vessels expressing VEGF-A-protein. The result was not statistically certified because of the small number of stained breast cancers and additional investigations are recommended before clinical use.

No description available.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Background: Angiogenesis is recognised as a critical step in tumour progression. The angiogenic switch is activated by various trigger signals, such as hypoxia, low pH, and genetic mutations. Renal cell carcinoma (RCC) is often an aggressive tumour, and advanced disease has limited treatment options and bad prognosis. This study was focused on markers of angiogenesis in RCC: endoglin (CD105) and CD31 assessing microvessel density (MVD), and carbonic anhydrase (CA) IX and hypoxia-inducible factor (HIF)-2α expressed at hypoxia. Upregulation of HIF is also associated with inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene, which is common in conventional/clear cell (c)RCC. Method: A tumour bank containing 308 tumours from patients operated 1982-2003 was used. The tumours were well characterised regarding tumour type, TNM stage, nuclear grade, tumour size, and patient survival. The tumours were prepared in tissue microarrays and fresh frozen in whole sections. To analyse the expression of endoglin, CD31, CA IX, and HIF-2α mRNA, immunohistochemistry and real-time PCR were used. Results: There was a higher endoglin expression in cRCC than in papillary (p)RCC and chromophobe (ch)RCC, and a higher CD31 expression in cRCC than in pRCC. MVD correlated inversely to TNM stage and nuclear grade in cRCC. There was also an inverse correlation between tumour diameter and CD31 expression in cRCCs. Patients with cRCC with high MVD had a more favourable prognosis than patients with lower MVD. Endoglin and CD31 were not independent prognostic factors. The CA IX expression was higher in cRCC than in pRCC and chRCC. Patients with cRCC expressing low CA IX had a significantly less favourable prognosis compared with those with higher expression. CA IX is an independent prognostic factor. There was a higher HIF-2α mRNA expression in cRCC than in pRCC and chRCC. In cRCC, there was a significant inverse correlation between HIF-2α mRNA expression, and TNM stage and nuclear grade. There was also an inverse correlation between HIF-2α mRNA expression and tumour size among patients with cRCC. HIF-2α was not an independent prognostic factor. Conclusion: In these studies, the factors related to hypoxia and vascularity were all inversely correlated to tumour aggressiveness in cRCC. MVD, CA IX, and HIF-2α expression were also higher in cRCC than in pRCC and chRCC. The relationship between angiogenesis, vascularity, and hypoxia is ambiguous. A line of reasoning including mutations increasing angiogenesis in advanced disease may also be applied to RCC. Measurements of individual angiogenic factors seem to provide prognostic information, and can potentially be combined in patient monitoring and treatment.