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| 2. |
- Bjartell, Anders, et al.
(författare)
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Immunohistochemical detection of cysteine-rich secretory protein 3 in tissue and in serum from men with cancer or benign enlargement of the prostate gland.
- 2006
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 66:Dec 30, s. 591-603
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Recently, the gene for cysteine-rich secretory protein 3 (CRISP-3) was reported to be highly upregulated in prostate cancer (PCa) compared to benign prostatic tissue. The current aims were to investigate diagnostic use of tissue expression and immunodetection in serum of CRISP-3 for detection or monitoring of PCa. METHODS. Radical prostatectomy specimens and tissue microarrays from transurethral resections and metastases were analyzed for CRISP-3 and PSA by immunohistochemistry. CRISP-3 in tissue homogenates and in serum was measured by an in-house ELISA and PSA by a commercially available immunoassay. RESULTS. Immunostaining for CRISP-3 in benign prostatic epithelium was generally weak or not detectable. Specific and strong immunostaining was found in a major proportion of cells in high-grade prostatic-intraepithelial-neoplasia (HG-PIN,12/17 patients), in most primary tumors (111/115), and in lymph node (11/15) and bone (12/15) metastases. CRISP-3 immunostaining intensity was regularly strong in areas of Gleason grades 4/5, where PSA-immunoreaction was less intense. Serum levels of CRISP-3 were not different in patients with PCa (n = 152) compared to men with BPH (n = 81). There was a very weak co-variation between levels of CRISP-3 versus PSA in serum from PCa patients (P < 0.05). After orchiectomy, levels of CRISP-3 in serum decreased in median with 11% compared to a 97% median decrease of PSA in serum from 15/20 patients with advanced PCa. CONCLUSIONS. Strong immunostaining for CRISP-3 is common in HG-PIN and preserved in most PCa specimens, which warrant further immunohistochemical studies of CRISP-3 in PCa. Serum levels of CRISP-3 do not primarily reflect PCa.
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| 5. |
- Ceder, Jens, et al.
(författare)
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Expression of somatostatin receptor subtypes 2 and 4 in human benign prostatic hyperplasia and prostatic cancer.
- 2002
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 53:1, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The presence of receptor subtypes for the inhibitory peptide somatostatin in prostatic tissue has been a controversial issue with conflicting reports. To elucidate whether prostatic epithelial cells express mRNA for somatostatin receptor (SSTR) subtype 2 and 4, we have investigated the localization of SSTR2 and SSTR4 transcripts in prostatic tissues by in situ hybridization. METHODS: Nonradioactive in situ hybridization was performed with specific fluorescein-labeled SSTR2 and SSTR4 riboprobes on consecutive sections of benign prostatic hyperplasia (BPH) and prostate cancer tissues. RESULTS: We report, for the first time, tissue localization of SSTR2 and SSTR4 mRNA in BPH and malignant cells of human prostate. Hybridization signals for SSTR4 mRNA transcripts were confined to the prostatic epithelium (12 of 16 BPH cases, and in 12 of 13 carcinoma cases), whereas SSTR2 transcripts were predominantly localized in the stromal compartment but also were detectable in epithelial cells in a significant number of specimens (11 of 17 BPH cases, and in 12 of 14 carcinoma cases). Furthermore, the staining intensity for SSTR2 and SSTR4 transcripts is stronger in malignant cells compared with adjacent BPH epithelium. CONCLUSION: The data presented suggest that the expression of SSTR2 and SSTR4 transcripts is up-regulated in malignant cells and that not only SSTR2 agonists, but also compounds targeting the SSTR4 subtype may have a potential role in the treatment of prostate cancer.
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- Giwercman, Yvonne, et al.
(författare)
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The 5alpha-Reductase Type II A49T and V89L High-Activity Allelic Variants are More Common in Men with Prostate Cancer Compared with the General Population.
- 2005
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 48:Jul 20, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare men with prostate disease with those from the general population regarding polymorphisms in the androgen receptor gene and in the 5 alpha-reductase II (SRD5A2) gene. Materials and methods: The SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n = 89), benign prostate hyperplasia (n = 45) and healthy military conscripts (n = 223). Results: The SRD5A2 high-activity allele variants A49T AT and V89L LL were more frequent in CaP-patients compared to general population, p = 0.026 and p = 0.05, respectively. CaP progression was, however, independent of SRD5A2 variants. In contrary, men with GGN < 23 had a higher risk of dying from the disease than their counterparts with longer repeats. Conclusions: Men with CaP were more often genetically predisposed to a higher enzymatic activity in the turn over from T to DHT compared to the general population. In our population, androgen receptor genotype affected CaP outcome.
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- Johnson, Louis Banka, et al.
(författare)
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Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model
- 2004
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Ingår i: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy. METHOD: A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion) were then analysed in ileal venules 2 - 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO) and cell histology were analysed. RESULTS: The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation. CONCLUSION: This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological recruitment of leucocytes and changes in intestinal microflora in the small bowel after radiotherapy.
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| 12. |
- Paju, Annukka, et al.
(författare)
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Increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells
- 2007
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 52:6, s. 1670-1681
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Tumor-associated-trypsin inhibitor (TATI) is frequently coexpressed with trypsinogen in tumors. Recently, we found expression of trypsinogens in prostate cancer. We have now studied whether TATI is also expressed in prostate cancer and if TATI expression is associated with Gleason grade, proliferation, and neuroendocrine differentiation. Methods: Expression of TATI and prostate-specific antigen (PSA) was studied by immunohistochemistryand in situ hybridization, and that of chromogranin A (CgA) and Ki-67 by immunohistochemistry. Immunofluorometric assays were used to quantify TATI and PSA in serum from prostate cancer patients and in medium of 22Rv1 prostate cancer cells. Results: TATI expression was weak in benign prostatic epithelium and moderate to strong in prostate cancer and high-grade prostatic intraepithelial neoplasia. There was no correlation between TATI and Ki-67 immunostaining in a tissue microarray of 115 prostate cancer cores, but strong expression of TATI was associated with higher Gleason grade (p = 0.002) and CgA immunostaining intensity (p = 0.012). Serum TATI was elevated in 44% (29 of 66) of patients with prostate cancer, and the levels correlated with serum PSA (p < 0.0001, r = 0.306). DU145, PC-3, LNCaP, and 22Rv1 cells contained TATI mRNA as determined by RT-PCR, but only 22Rv1 cells produced detectable TATI protein. The synthetic androgen R1881 decreased secretion of TATI from 22Rv1 cells. Conclusions: We demonstrate for the first time that TATI is expressed in the benign and malignant prostate. Increased TATI protein expression is found in high-grade tumors and in 22Rv1 cells in which it is regulated by androgens. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 13. |
- Polistena, Andrea, et al.
(författare)
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Local radiotherapy of exposed murine small bowel : Apoptosis and inflammation
- 2008
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Ingår i: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background. Preoperative radiotherapy of the pelvic abdomen presents with complications mostly affecting the small bowel. The aim of this study was to define the features of early radiation-induced injury on small bowel. Methods. 54 mice were divided into two groups (36 irradiated and 18 sham irradiated). Animals were placed on a special frame and (in the radiated group) the exteriorized segment of ileum was subjected to a single absorbed dose of 19 or 38 Gy radiation using 6 MV high energy photons. Specimens were collected for histology, immunohistochemistry (IHC) and ELISA analysis after 2, 24 and 48 hours. Venous blood was collected for systemic leucocyte count in a Burker chamber. Results. Histology demonstrated progressive infiltration of inflammatory cells with cryptitis and increased apoptosis. MIP-2 (macrophage inflammatory protein) concentration was significantly increased in irradiated animals up to 48 hours. No significant differences were observed in IL-10 (interleukin) and TNF-α (tumour necrosis factor) levels. IHC with CD45 showed a significant increase at 2 hours of infiltrating leucocytes and lymphocytes after irradiation followed by progressive decrease with time. Caspase-3 expression increased significantly in a dose dependent trend in both irradiated groups up to 48 hours. Conclusion. Acute small bowel injury caused by local irradiation is characterised by increased apoptosis of crypt epithelial cells and by lymphocyte infiltration of the underlying tissue. The severity of histological changes tends to be dose dependent and may affect the course of tissue damage.
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| 14. |
- Wegiel, Barbara, et al.
(författare)
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A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer
- 2005
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 24:42, s. 6385-6393
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Tidskriftsartikel (refereegranskat)abstract
- Elevated levels of cyclin A1 expression have been implicated in acute myeloid leukemia and in male germ cell tumors. However, a role of cyclin A1 in tumorigenesis of prostate cancer has not been reported. In the present study, expression of cyclin A1 in patients with prostate cancer and a role of cyclin A1 in mediating expression of vascular endothelial growth factor (VEGF) were investigated. Cyclin A1 was highly expressed in aggressive tumors and was significantly correlated with VEGF expression in 96 patients with prostate cancer. Treatment of LNCaP cells with R1881, a synthetic androgen resulted in increased cyclin A1 expression. Induction of cyclin A1 expression in LNCaP cells led to an increase in VEGF expression and this effect was manifested upon the R1881 treatment. Cyclin A1 failed to mediate VEGF activation in DU-145 cells lacking a functional Rb and an androgen receptor (AR). Although AR expression was induced into DU-145 cells, cyclin A1 was unable to mediate VEGF expression. However, induced coexpression of cyclin A1, Rb and AR in DU-145 cells in the presence of R1881 greatly promoted VEGF promoter activity. This suggests that cyclin A1 mediates VEGF expression in cooperation with Rb- and androgen-dependent pathways in prostate cancer.
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