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| 2. |
- Stattin, P, et al.
(författare)
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Leptin is associated with increased prostate cancer risk : a nested case-referent study.
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 86:3, s. 1341-1345
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Tidskriftsartikel (refereegranskat)abstract
- A Western lifestyle has been implicated in the pathogenesis of prostate cancer. However, no clear association between obesity and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin are present in the prostate. Leptin may, thus, be associated with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in Northern Sweden. Blood pressure, body mass index, and use of tobacco were recorded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and sex hormone-binding globulin were analyzed in stored samples. Their influences on prostate cancer were estimated by conditional logistic regression analysis. Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables, testosterone, and IGF-I and its binding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium. Moderately elevated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic intraepithelial neoplasia lesions, or to indirect actions through other mechanisms. A critical fat mass related to an interior milieu favorable for prostate cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.
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| 5. |
- Finne, P, et al.
(författare)
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Algorithms based on prostate-specific antigen (PSA), free PSA, digital rectal examination and prostate volume reduce false-positive PSA results in prostate cancer screening.
- 2004
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Ingår i: Int J Cancer. - : Wiley. ; 111:2, s. 310-315
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to determine whether multivariate algorithms based on serum total PSA, the free proportion of PSA, age, digital rectal examination and prostate volume can reduce the rate of false-positive PSA results in prostate cancer screening more effectively than the proportion of free PSA alone at 95% sensitivity. A total of 1,775 consecutive 55- to 67-year-old men with a serum PSA of 4-10 g/l in the European Randomized Study of Screening for Prostate Cancer were included. To predict the presence of cancer, multivariate algorithms were constructed using logistic regression (LR) and a multilayer perceptron neural network with Bayesian regularization (BR-MLP). A prospective setting was simulated by dividing the data set chronologically into one set for training and validation (67%, n = 1,183) and one test set (33%, n = 592). The diagnostic models were calibrated using the training set to obtain 95% sensitivity. When applied to the test set, the LR model, the BR-MLP model and the proportion of free PSA reached 92%, 87% and 94% sensitivity and reduced 29%, 36% and 22% of the false-positive PSA results, respectively. At a fixed sensitivity of 95% in the test set, the LR model eliminated more false-positive PSA results (22%) than the proportion of free PSA alone (17%) (p < 0.001), whereas the BR-MLP model did not (19%) (p = 0.178). The area under the ROC curve was larger for the LR model (0.764, p = 0.030) and the BR-MLP model (0.760, p = 0.049) than for the proportion of free PSA (0.718). A multivariate algorithm can be used to reduce unnecessary prostate biopsies in screening more effectively than the proportion of free PSA alone, but the algorithms will require updating when clinical practice develops with time. © 2004 Wiley-Liss, Inc.
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| 6. |
- Kaaks, R, et al.
(författare)
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Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls.
- 2003
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Ingår i: European Journal of Cancer Prevention. - 0959-8278 .- 1473-5709. ; 12:4, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Despite strong indirect evidence that androgens stimulate prostate cancer development, data from most analytical studies on this association have been negative. To further investigate this issue, we studied the interrelationships between androgenicity and insulin-like growth factor I (IGF-I), insulin and leptin. Within a prospective cohort study, we measured testosterone, sex hormone-binding globulin (SHBG) and IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, insulin and leptin, in plasma from 149 cases and 298 controls. Testosterone correlated positively with SHBG, whereas testosterone and SHBG correlated inversely with IGF-I, IGFBP-3, insulin, leptin and body mass index (BMI). Indices of free testosterone showed an inverse linear correlation with leptin (P<0.01), and a strong drop in the 5th quintile of BMI. However, levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I, with a significant increase in the second quintile of IGF-I compared with other levels. The absence of an association between plasma levels of androgens and prostate cancer risk in analytical studies, despite the strong indirect evidence of their tumour-stimulating effects, may reflect the complex and mostly inverse associations of androgenicity to IGF-I, insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer.
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| 7. |
- Kölby, Lars, 1963, et al.
(författare)
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A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
- 2001
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Ingår i: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
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Tidskriftsartikel (refereegranskat)abstract
- A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
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| 8. |
- Paju, A, et al.
(författare)
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Expression and characterization of trypsinogen produced in the human male genital tract
- 2000
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Ingår i: American Journal of Pathology. - 1525-2191. ; 157:6, s. 2011-2021
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Tidskriftsartikel (refereegranskat)abstract
- Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.
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| 10. |
- Stenman, Anders, et al.
(författare)
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Model-on-Demand Identification for Control : An Experimental Study and Feasibility Analysis for MOD-Based Predictive Control
- 2000
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Ingår i: Proceedings of the 12th IFAC Symposium on System Identification. - Linköping : Linköping University Electronic Press. - 9780080435459 ; , s. 439-444
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Konferensbidrag (refereegranskat)abstract
- An experimental study of "Model-on-Demand" (MoD) identification is made on a pilot-scale brine-water mixing tank. MoD estimation is compared against semi-physical modeling techniques using identification data generated from a systematically designed m-level Pseudo Random Sequence (PRS) input. The estimated models are the basis for evaluating the usefulness of MoD-based Model Predictive Control (MPC). For this application, MoD-MPC is shown to provide better performance at high bandwidths compared to a linear MPC controller.
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