| 1. |
- Häggström, S, et al.
(författare)
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Effects of finasteride on vascular endothelial growth factor.
- 2002
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 36:3, s. 182-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Finasteride has been shown to reduce prostate bleeding in patients with benign prostatic hyperplasia (BPH). The mechanisms behind this are not known, but it has been suggested that finasteride reduces bleeding by inhibiting angiogenesis in the prostate. Studies in animals have shown that castration rapidly induces involution of the prostate vasculature, and androgen-stimulated prostate growth may be angiogenesis dependent. The objective of this study was to explore the response to finasteride on the vasculature and the expression of vascular endothelial growth factor (VEGF), a potent regulatory factor of angiogenesis in human prostate tissue.MATERIAL AND METHODS: Patients with BPH were randomly assigned to 3 months of treatment either with finasteride (5 mg/day) or placebo before undergoing transurethral resection of the prostate (TURP). Prostate tissue VEGF expression was quantified by Western blot and the vascular density determined in Factor VIII immunostained tissue sections. Serum concentrations of VEGF were measured with ELISA technique.RESULTS: Patients treated with finasteride (n = 15) showed a decrease in prostate tissue VEGF(165) expression compared with placebo (n = 13) treated patients (p < 0.05), but the vascular density and the serum VEGF levels were unaffected.CONCLUSIONS: This study shows that finasteride treatment decreases VEGF expression in the human prostate.
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| 2. |
- Franck-Lissbrant, I, et al.
(författare)
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Testosterone stimulates angiogenesis and vascular regrowth in the ventral prostate in castrated adult rats.
- 1998
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 139:2, s. 451-6
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Tidskriftsartikel (refereegranskat)abstract
- The castration-induced regression and testosterone stimulated regrowth of the vasculature in the rat ventral prostate lobe were studied using stereological techniques. Seven days after castration, the endothelial cell proliferation rate (bromodeoxyuridine labeling index); the total weights of blood vessel walls, blood vessel lumina, endothelial cells, glandular epithelial cells; and total organ weight were all decreased. Within 2 days after sc treatment with testosterone, the total weights of blood vessel walls, endothelial cells, and vascular lumina, as well as the endothelial cell proliferation rate, were all normalized. In contrast to the rapid response of the vasculature, the total weight of glandular epithelium and total organ weight were not normalized during the 4 days of testosterone treatment. Growth of the vasculature apparently precedes growth of the glandular epithelium. The testosterone- dependent factors stimulating the vasculature are unknown, but factors derived from epithelial cells, mast cells (which accumulate in the prostate during the first day of testosterone treatment), and tissue macrophages could all be involved. Castration-induced regression and testosterone-stimulated regrowth of the prostatic vasculature can be used as an experimental model to study factors regulating angiogenesis and organ growth in the prostate.
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| 3. |
- Hedlund, P. O., et al.
(författare)
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Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer : Part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 42:3, s. 220-229
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP, Estradurin®) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. Material and methods. In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240mg i.m. twice a month for 2months and thereafter monthly, or flutamide (Eulexin®) 250mg t.i.d. per os in combination with either triptorelin (Decapeptyl®) 3.75mg i.m. per month or on an optional basis bilateral orchidectomy. Results. At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). Conclusions. PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis. © 2008 Taylor & Francis.
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| 4. |
- Häggström, S, et al.
(författare)
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Castration-induced reduction of vascular endothelial growth factor expression in benign human prostate tissue is lost in advanced prostate cancer.
- 2001
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 88:1, s. 110-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the role of vascular response in the castration-induced regression of benign and malignant human prostate tissue, as recent studies show that castration rapidly decreases blood flow and induces endothelial cell death, which may be important for subsequent epithelial cell death and involution of the glandular tissue of the prostate.MATERIALS AND METHODS: The expression of vascular endothelial growth factor (VEGF) and its receptors was analysed using the quantitative reverse transcriptase-polymerase chain reaction, in benign and tumour areas of core biopsies taken before, and approximately 1 week after castration therapy. The castration-induced VEGF response was related to therapy-induced changes in tumour cell apoptotic index and subsequent response in serum prostate-specific antigen (PSA). In another set of patients, serum VEGF was quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after castration therapy.RESULTS: VEGF mRNA was down-regulated after castration in benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels were reduced in some of the patients but unchanged or increased in others. In most patients whose tumour tissue responded with VEGF reduction, there was a corresponding increase in tumour cell apoptosis. Serum VEGF levels were not significantly changed after castration. Almost all patients responded with a substantial reduction in serum PSA after castration.CONCLUSION: Castration reduces VEGF mRNA expression in benign prostate tissue and generally in those prostate tumours where castration also induces tumour cell apoptosis. This suggests that a therapy-induced down-regulation of VEGF could be important for tumour cell death.
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| 5. |
- Häggström, S, et al.
(författare)
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Expression of vascular endothelial growth factor and its receptors in the rat ventral prostate and Dunning R3327 PAP adenocarcinoma before and after castration.
- 1998
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Ingår i: The Prostate. - 0270-4137 .- 1097-0045. ; 36:2, s. 71-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiogenesis is important for prostate organogenesis and prostate cancer progression. It is not yet known whether androgens promote part of their control of prostate structure and function by influencing angiogenesis. The aim of this study was to explore the possible androgenic regulation of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk-1/KDR in the rat ventral prostate (VP) and Dunning R3327 PAP adenocarcinoma.METHODS: RNA was prepared from VP and tumors of intact and castrated rats. VEGF, flt-1, and flk-1/KDR mRNA levels were determined using competitive RT-PCR.RESULTS: VEGF121, VEGF165, and VEGF189 together with flt-1 and flk-1/KDR mRNA were detected. The VEGF, but not flt-1 mRNA levels were significantly decreased in the VP after castration. The Dunning tumor expressed high levels of mRNA for VEGF and its receptors compared to the VP. The flt-1 mRNA level in the tumor increased after castration, while the VEGF mRNA levels were unchanged.CONCLUSIONS: Decreased mRNA expression of VEGF, but not flt-1, was found in the rat VP after castration. However, in the Dunning tumor, castration did not alter the expression of VEGF mRNA. Moreover, elevated levels of both mRNA for VEGF and its receptors relative to the VP were observed, indicating that the VEGF system may be important for Dunning tumor development.
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| 6. |
- Häggström, S, et al.
(författare)
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Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats.
- 1999
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Ingår i: Journal of Urology. - 0022-5347 .- 1527-3792. ; 161:5, s. 1620-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Recent studies suggest that the vasculature is important for the control of prostate growth. Castration induces an involution of the prostate gland and its vasculature. Replacement of testosterone stimulates endothelial cell proliferation and normalizes vascular volumes and blood flow several days before organ regrowth. Antiangiogenesis treatment inhibits the growth of prostate tumors. Understanding the regulation of the prostate vasculature may therefore provide important knowledge of the mechanisms responsible for the growth of non-malignant and malignant prostate tissue. Castration induced regression and testosterone stimulated regrowth of the prostatic vasculature have here been used to study the involvement of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk-1/KDR in the regulation of the prostatic vasculature.MATERIALS AND METHODS: VEGF, flt-1, and flk-1/KDR levels were quantified in the rat ventral prostate following castration and testosterone replacement. Methods used were competitive RT-PCR, Western blot and immunohistochemistry.RESULTS: VEGF mRNA and protein levels were significantly decreased by castration and testosterone treatment induced VEGF synthesis in the rat ventral prostate epithelium. Flt-1 and flk-1/KDR receptor levels were unaffected by castration and testosterone treatment.CONCLUSIONS: Castration down regulates VEGF and testosterone induces VEGF synthesis in epithelial cells in the rat ventral prostate.
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| 7. |
- Häggström, S, et al.
(författare)
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Vascular endothelial growth factor content in metastasizing and nonmetastasizing Dunning prostatic adenocarcinoma.
- 2000
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Ingår i: The Prostate. - 0270-4137 .- 1097-0045. ; 45:1, s. 42-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor angiogenesis is important in progressive tumor growth and metastasis. In the normal rat prostate and in androgen-sensitive prostate tumors androgen ablation causes an involution of the vasculature and a decrease in the vascular endothelial growth factor (VEGF) levels before regression of the prostate gland. To examine whether angiogenesis and metastasis are regulated by VEGF in androgen-insensitive and metastasizing prostate tumors, five Dunning rat prostate cancer sublines were tested; the androgen-sensitive, nonmetastasizing R3327 PAP, and the androgen-insensitive, low metastasizing AT-1, and the three androgen-insensitive, metastasizing AT-2, AT-3, and MatLyLu Dunning prostatic adenocarcinomas.METHODS: VEGF levels were quantified in the rat dorsolateral prostate and in the five Dunning sublines using competitive RT-PCR, Western blot, and Elisa. Vascular density was determined by factor VIII staining.RESULTS: VEGF mRNA was increased in all tumors compared with normal prostates. The two metastatic sublines AT-3 and MatLyLu and the nonmetastatic subline AT-1 showed the highest VEGF mRNA expression. VEGF protein levels in the prostate gland showed increased expression in the metastatic sublines, AT-2, AT-3, and MatLyLu, compared with the nonmetastatic AT-1 subline and the ventral prostate. VEGF proteins in serum were highest in the metastatic AT-3 subline. The vessel density was highest in the two highly metastatic sublines AT-3 and MatLyLu.CONCLUSIONS: Our results suggest that VEGF levels are associated with microvessel density and the previously established metastatic pattern of these rat prostate tumor systems.
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| 8. |
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| 9. |
- Rydh, Anders, et al.
(författare)
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Quantitative bone scintigraphy. A methodological evaluation in prostate cancer.
- 2000
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 41:2, s. 183-8
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). MATERIAL AND METHODS: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). RESULTS: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. CONCLUSION: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.
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| 10. |
- Rydh, Anders, et al.
(författare)
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Radioimmunoscintigraphy using an anti-prostate monoclonal antibody (E4) : a dosimetric evaluation.
- 2001
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Ingår i: Urological research. - : Springer Science and Business Media LLC. - 0300-5623 .- 1434-0879. ; 29:3, s. 216-20
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate different strategies to increase the tumour radiation dose for experimental radioimmunotherapy using 125I-labelled monoclonal antibody (MAb) E4 in a nude mice model xenografted with DU-145 tumours. The effects from a single injection of the 125I-labelled MAb E4, the same total amount of radiolabelled MAb E4 divided into three repeated injections, and the effect of pre-targeting with non-labelled MAb E4 for reducing the amount of shed antigen were investigated. Based on repetitive quantitative radioimmunoscintigraphies, calculation of the tumour radiation dose delivered from the 125I-nuclide was performed for each strategy. The single injection strategy without pretargeting rendered the highest mean tumour radiation dose, i.e. 0.23 Gy/MBq. Pretargeting with non-labelled MAb E4 before a single injection of [125I]E4 resulted in a slightly lower mean tumour radiation dose, i.e. 0.19 Gy/MBq, compared to the single injection alone. An even lower mean tumour radiation dose, i.e. 0.14 Gy/MBq, was obtained when the same total administered amount of activity was divided into three separate injections given in 10-day intervals. We concluded that the single injection strategy is the most efficient when using MAb E4 in this tumour model. The tumour radiation doses were not increased by dividing the same amount of activity into three injections or by pretargeting with non-labelled MAb E4.
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