| 1. |
- Mogren, Ingrid, et al.
(författare)
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Reproductive factors have low impact on the risk of different primary brain tumours in offspring
- 2003
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Ingår i: Neuroepidemiology. - : S. Karger. - 0251-5350 .- 1423-0208. ; 22:4, s. 249-254
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of our study was to investigate whether reproductive factors influence the risk of primary brain tumours (PBT) in offspring. Methods: Data on all deliveries in two Swedish counties from 1955 to 1990 were extracted from two birth registries. The follow-up period closed at the end of 1994, with subjects followed up to early middle age. Incidence rates of malignancy for 1958-1994 were obtained from the Swedish Cancer Registry. Standardised incidence ratios (SIR) and relative risks were calculated for astrocytomas, primitive neuroectodermal tumour, ependymoma and meningiomas in offspring. Results: Few associations were detected. High birth weight indicated an increased risk for astrocytomas grade I and II for all primary brain tumours, and the risk was close to significance for astrocytomas grade I-II (SIR = 3.64; CI = 0.98-9.31). For children under 15 years of age the risk for astrocytomas grade I and II was further increased (SIR = 4.44; Cl = 1.19-11.38). Conclusions:A consistent pattern of non-association indicated a low impact of intrauterine environment on the future development of primary brain tumours in offspring up to early middle age.
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| 2. |
- Virtanen, Ismo, et al.
(författare)
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Laminin isoforms in fetal and adult human adrenal cortex
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 88:10, s. 4960-4966
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Tidskriftsartikel (refereegranskat)abstract
- Laminin has been proposed to influence the function of human adrenal cortex. We have studied the distribution of laminin (Ln) chains using immunofluorescence in human fetal and adult adrenal cortex. In the fetal gland Ln alpha2- and alpha5-chains were weakly expressed in the definitive zone, whereas Ln alpha4-, beta1-, and gamma1-chains occurred around vessels. In the adult gland, Ln alpha2-, alpha5-, and gamma1-chains were found in epithelial basement membranes (BM) in all cortical zones, Ln alpha4-chain in vessels, Ln beta1-chain in outer zone, and Ln beta2-chain in the two inner zones of the cortex, respectively. Among the integrins in adult gland, integrin alpha(3)-subunit was confined to basal surfaces of cortical cells, alpha(6) to vessels, alpha(1) to the stroma, and alpha(2) diffusely to epithelial cells. Lutheran glycoprotein and dystroglycan occurred in the fetal gland diffusely in the definitive zone and throughout the epithelium in the adult. The isoform composition of BM of the adult adrenal gland is distinct, with Ln-2 and -10 in BM of the outer zone and Ln-4 and -11 in BM of the two inner zones. The results suggest that integrin alpha(3)beta(1) and Lutheran are candidate receptors for Ln-10 and -11, whereas dystroglycan probably binds Ln-2 and -4.
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| 3. |
- Daşu, Alexandru, et al.
(författare)
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Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
- 2003
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 48:17, s. 2829-2842
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Tidskriftsartikel (refereegranskat)abstract
- The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.
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| 4. |
- Dong, Ying, et al.
(författare)
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Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers
- 2003
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 9:5, s. 1710-20
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The wild-type or variant mRNAs of several kallikrein (KLK) genes, such as KLK4, are highly expressed in ovarian carcinomas and may have potential as tumor markers. Two of these KLK genes (KLK5 and KLK7) and their proteins (hK5 and hK7) were first identified in the skin epidermis, where hK5 may be the physiological activator of hK7. The purpose of this study was to reexamine the expression of KLK5/hK5 and KLK7/hK7 and their association and to determine whether cancer-related variant transcripts were expressed.EXPERIMENTAL DESIGN: The expression of KLK5/hK5 and KLK7/hK7 was analyzed in the same cohort (n = 37) of benign (n = 4) and malignant ovarian tissue (n = 23) samples and primary cultured cells (n = 21) and in 8 ovarian cancer cell lines using semiquantitative RT-PCR; Southern, Northern, and Western blot analyses; and immunohistochemistry techniques.RESULTS: We showed the concordant higher expression of both KLK5/hK5 and KLK7/hK7 in ovarian carcinomas, especially late-stage serous carcinomas, compared with normal ovaries and benign adenomas. We also found that one novel KLK5 transcript with a short 5'-untranslated region and a novel KLK7 transcript with a long 3'-untranslated region were highly expressed in the ovarian cancer cell lines OVCAR-3 and PEO1, respectively, but were expressed at very low levels in normal ovarian epithelial cells. Both Western blot and immunohistochemistry analyses showed that these two enzymes are secreted from ovarian carcinoma cells.CONCLUSIONS: Our study demonstrated that hK5 and hK7, or more specifically, the short KLK5 and long KLK7 transcripts, may be useful as tumor markers for epithelial-derived serous carcinomas. However, additional clinical studies assessing serum levels of these putative biomarkers are required to confirm their usefulness in the diagnosis and/or monitoring of these tumors.
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| 5. |
- El-Salhy, Magdy, et al.
(författare)
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Triple therapy with octreotide, galanin, and serotonin reduces the size and blood vessel density and increases apoptosis of a rat colon carcinoma
- 2003
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Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 111:1-3, s. 145-152
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Tidskriftsartikel (refereegranskat)abstract
- A rat colonic adenocarcinoma was implanted subcutaneously in female nude (C57BL/6JBom-nu) mice. After 7 days, the animals were divided into different groups. One group received triple therapy with octreotide, galanin, and serotonin, 10 μg/kg body weight of each, twice daily. The second group served as controls and received only saline solution. Three groups received 10 μg/kg body weight twice daily of octreotide, galanin, or serotonin. The last group consisted of controls that received only saline solution. The treatment lasted for 5 days. The tumour volume, wet weight, and relative volume density of blood vessels were significantly decreased after the triple treatment, as compared to controls. Apoptotic index was significantly increased, but the proliferation index was not affected in the group of mice that received triple therapy. There was no significant difference between controls and mice treated with octreotide, galanin, or serotonin regarding tumour volume or weight. The relative volume density of blood vessels was decreased in tumours treated with galanin, but not with octreotide or serotonin. There was no statistical difference in the proliferation index between controls and animals treated with octreotide, galanin, or serotonin, as compared with controls. Tumour necrosis and increased apoptosis may be responsible for the reduction in the volume and weight of the tumour after triple therapy. Tumour necrosis may be caused by the induction of tumour ischemia due to a reduction in tumour blood flow, which is caused by decreased incidence of tumour-feeding blood vessels, and by constriction of tumour-feeding arterioles. These results are promising and may offer treatment for colon cancer.
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| 6. |
- Hultdin, Magnus, et al.
(författare)
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Association between telomere length and V-H gene mutation status in chronic lymphocytic leukaemia : clinical and biological implications
- 2003
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 88:4, s. 593-598
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Tidskriftsartikel (refereegranskat)abstract
- The immunoglobulin V-H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V-H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated VH genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and VH gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between VH gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 63 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months), Furthermore, the I-g gene sequence data revealed that samples with high mutations frequency (> 6%) had long telomeres (similar to 8 kbp). Thus, both the telomere and VH gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. (C) 2003 Cancer Research UK.
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| 7. |
- Häggström Rudolfsson, Stina, et al.
(författare)
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Localized expression of angiopoietin 1 and 2 may explain unique characteristics of the rat testicular microvasculature.
- 2003
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Ingår i: Biology of Reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 69:4, s. 1231-7
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Tidskriftsartikel (refereegranskat)abstract
- The testicular vasculature is unique in several ways. The unfenestrated endothelial cells constitute one part of the blood-testis barrier, and testicular microvessels are normally resistant to inflammation mediators. At the same time that angiogenic factors and inflammation mediators are constitutively produced, the proportion of proliferating endothelial cells is considerably higher than in other organs, but new blood vessels are not formed. Hormonal stimulation of the testis with hCG increase endothelial cell proliferation, vascular permeability, and sensitivity to locally injected inflammation mediators. In the present study, we examined whether local expression of angiopoietin (ang) 1, an inhibitor of vascular leakage and sprouting angiogenesis, and its antagonist, ang 2, could be involved in establishing this vascular phenotype. Using reverse transcription-polymerase chain reaction and immunohistochemistry, we demonstrate that testicular vascular endothelial growth factor-A (VEGF-A), ang 1, ang 2, and the ang-receptor tie 2 are expressed in the testis and that hormonal stimulation with hCG is accompanied by increased expression of VEGF-A and ang 2. The ang 1 protein is expressed in testicular microvessels under basal conditions, and it is largely unaffected after hCG stimulation. Expression of ang 2 in microvessels, in contrast, is low under basal conditions and is up-regulated by hCG. Intratesticular injection of human recombinant ang 1 protein inhibits hCG-induced increase in vascular permeability. Injection of ang 2 in the testis increases endothelial cell proliferation and the volume of the interstitial space. We therefore suggest that ang 1 stabilizes testicular microvessels under basal conditions and that a shift in this balance caused by increased ang 2, together with increased VEGF-A, allows vascular leakage, high endothelial cell proliferation, and presumably, vascular growth after hormonal stimulation.
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| 8. |
- Jonsson, Håkan, 1956-, et al.
(författare)
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Detection of Breast Cancer with Mammography in the First Screening Round in Relation to Expected Incidence in Different Age Groups
- 2003
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 42:1, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- The ratio (R) of prevalence of screening-detected breast cancer in the first screening round (P) was compared with the expected incidence rate (I) for different age groups in several screening programs. Published data on the first screening round from three Swedish randomized trials and six counties with service screening were used. The women invited to take part in the screening were aged 40/74 years. Not only P and I but also R increased with increasing age. With the youngest age group as reference, the increase was statistically significant for both invasive cancer and invasive cancer and carcinoma in situ together. The studied ratio (R) can be thought of as a measure of efficiency in detecting breast cancer cases in mammography screening. The reasons for the increase are probably that the breast tissue of younger women is denser, which makes the cancer more difficult to detect by mammography, and that slow-growing cancers tend to appear more frequently in older women.
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| 9. |
- Jonsson, Håkan, 1956-, et al.
(författare)
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Service screening with mammography of women aged 70-74 years in Sweden : effects on breast cancer mortality
- 2003
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Ingår i: Cancer Detection and Prevention. - 0361-090X .- 1873-443X. ; 27:3, s. 360-369
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Tidskriftsartikel (refereegranskat)abstract
- Since the benefit of mammography screening for women 70 years and older is unclear, the aim of the present study was to evaluate the effect on breast cancer mortality of the population-based service-screening program in Sweden inviting women 70-74 years. Among the counties with service-screening programs in Sweden which started 1986-1990 those with upper age limit 74 years were compared to counties with 69 years as upper age limit with respect to refined breast cancer mortality. Allowance was made for potential biases namely inclusion of cases diagnosed before invitation and lead time. Two methods for estimation of breast cancer mortality were used; underlying cause of death (UCD) and excess mortality. With a mean follow-up of 10.1 years a reduction of the breast cancer excess mortality was estimated at 24%. Using the underlying cause of death the corresponding result was 6%. A non-significant reduction in breast cancer mortality was found in the counties with service-screening program including the age group 70-74 years in Sweden. The estimated reduction was larger when using excess mortality compared to the use of individual underlying cause of death.
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| 10. |
- Kronblad, Åsa, et al.
(författare)
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Regional cyclin D1 overexpression or hypoxia correlate inversely with heterogeneous oestrogen receptor-alpha expression in human breast cancer.
- 2003
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Ingår i: In Vivo. - 0258-851X. ; 17:4, s. 311-8
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Tidskriftsartikel (refereegranskat)abstract
- Substance P (SP) has been implicated in the pathophysiology of ulcerative colitis (UC) and it has been suggested that blocking of its effect would be advantageous in this disease. Eosinophils have also been implicated in the pathophysiology of UC. In the present study, specimens from the sigmoid colon of UC patients were investigated by the use of antisera against SP and the neurokinin-1 receptor (NK-1R) and staining for demonstration of eosinophils. The degrees of SP innervation and NK-1R immunoreaction, as well as the levels of eosinophil infiltration, varied between different patients. Interestingly, NK-1R immunoreaction in the epithelium was often seen to be the most marked where there were numerous eosinophils in the underlying mucosa and where the mucosa showed a marked morphologic derangement. The observations suggest that there are marked fluctuations in effects of SP and eosinophils during the disease. The infiltrating eosinophils may be involved in the destruction of the mucosal tissue. Furthermore, for the majority of cases where there is marked derangement of the mucosa, it is apparent that there is an upregulation of the NK-1 receptor in the epithelium in parallel with the infiltration of the eosinophils.
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