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J E Damber

Publications and source records attributed to J E Damber.

At least 37 records · Page 2Linked to original sources
PubMed2000

Quantitative bone scintigraphy. A methodological evaluation in prostate cancer.

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.

Aged↗
PubMed2000

Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival.

Tumor associated macrophages (TAM) influence diverse processes such as angiogenesis, tumor cell proliferation, and metastasis during tumor progression. In a variety of tumor types, the amount of TAM has been associated with prognosis, but their role in prostate cancer has not been elucidated. The purpose of this study was to investigate the role of TAM in a series of 85 cases of prostatic carcinoma, diagnosed at transurethral resection of the prostate between 1975-1983, using immunohistochemistry and morphometrical techniques. Macrophage density was assessed as the maximum number of TAM per field in the three most macrophage dense areas (TAMmax) and as the average volume density of TAM in an estimate of the whole resected tumor. Furthermore, the individual cell profile area of TAM was assessed with an image analyzer. Macrophage variables were thereafter related to histological grade, tumor stage, metastasis as well as to vascular density, tumor cell proliferation and survival. Patients with a volume density of TAM in the fourth quartile had a shorter median cancer specific survival time than patients in the first to third quartile (3.3 vs. 5.9 years, p=0.005). Furthermore, an increased macrophage cell profile area was related to poor clinical outcome (4.6 vs. 5.9 years, p=0.039) whereas TAMmax gave no prognostic information. In a multivariate analysis, metastasis and the volume density of macrophages gave independent prognostic information (p=0.0008, p=0.010). However, when excluding metastasis from the analysis, only Gleason score was an independent predictor of cancer specific survival (p= 0.005). The volume density of TAM, the macrophage cell profile area and TAMmax increased with increasing Gleason score (p=0.001, p=0.0001, p=0.0001 respectively). A correlation was found between the volume density of TAM and tumor cell proliferation (rs=0.44, p=0.001) and an increased macrophage cell profile area was associated to microvessel density (rs=0.42, p=0.0001). Together these results suggest that both the functional state (as reflected by cell size), number and location of the macrophages are of importance for their influence on prostate tumors, but macrophage quantification is not a strong independent prognostic factor.

Adenocarcinoma↗
PubMed1999

Age specific risks of familial prostate carcinoma: a basis for screening recommendations in high risk populations.

BACKGROUND: A positive family history is one of the strongest known risk factors for prostate carcinoma in addition to age and race. In this article, the authors present age specific risks for developing prostate carcinoma in families with an aggregation of prostate carcinoma. METHODS: Data from a population-based cohort study including 5706 sons of Swedish men who had been diagnosed with prostate carcinoma between 1959 and 1963 were used. The age specific incidence rates were calculated for different cohorts of prostate carcinoma families with respect to patient age at the time of prostate carcinoma diagnosis and the number of men affected. RESULTS: Both patient age at the time of prostate carcinoma diagnosis and the number of men affected in the families influenced the risk of developing prostate carcinoma significantly. Unaffected men in families with two or more cases of prostate carcinoma have a very high risk of developing prostate carcinoma at a young age. The cumulative risks in these families are 5%, 15%, and 30% by ages 60 years, 70 years, and 80 years, respectively, compared with only 0.45%, 3%, and 10%, respectively, at the same ages in the general population. CONCLUSIONS: The findings of the current study together with data from the literature support the case for the screening of high risk families. The authors also conclude that men with at least two close relatives with prostate carcinoma have a very high risk of developing prostate carcinoma before age 70 years. The authors recommend these men undergo testing for prostate specific antigen and a digital rectal examination annually between the ages 50 years 70 years, ages at which patients usually are offered curative treatment for localized tumors. Screening of individuals before age 50 years may be recommended in selected families with a history of prostate carcinoma of very early onset.

Age Distribution↗
PubMed1999

Early castration-induced upregulation of transforming growth factor beta1 and its receptors is associated with tumor cell apoptosis and a major decline in serum prostate-specific antigen in prostate cancer patients.

BACKGROUND: The mechanism behind castration-induced apoptosis in prostate cells is unknown, but data from other species suggest that transforming growth factor beta1 (TGF-beta1) may be involved. METHODS: By using quantitative RT-PCR and immunohistochemistry, expression of TGF-beta1 and its receptors type I and II (RI and RII) was studied in normal and tumor areas of core biopsies taken before and 2-11 days after castration therapy. The TGF-beta responses were related to changes in apoptotic index and to changes in serum prostate-specific antigen (PSA). RESULTS: In normal prostate tissue, apoptosis was generally increased by castration, and apoptosis was accompanied by an increase in TGF-beta1 and RII mRNA levels (P < 0.05). In tumors, apoptosis was seen only in 44% of the cases and in these, but not in the others, TGF-beta1, RI, and RII mRNA levels were increased (P < 0.05). In the patients showing a prognostically favorable PSA response (nadir PSA <5 ng/ml), but not in the others, RI and RII mRNA levels were significantly upregulated (P < 0.05). CONCLUSIONS: Short-term upregulation of TGF-beta1 and its receptors is associated with apoptosis in human prostate and prostate cancer, and possibly with a favorable clinical outcome after castration therapy.

Apoptosis↗
PubMed1999

Expression of gonadotropin-releasing hormone receptor mRNA in the rat ventral prostate and dunning R3327 PAP adenocarcinoma before and after castration.

BACKGROUND: Continuous administration of gonadotropin-releasing hormone (GnRH) agonists in prostate cancer patients results in involution of the tumors due to suppression of androgen production. In addition to the effect of GnRH at the hypothalamic-pituitary level, experiments in vitro on breast, ovary, and prostatic cells have shown an inhibition of cell proliferation, indicating the presence of local GnRH receptors (GnRH-R). The aim of the present study was to investigate the expression of GnRH-R mRNA in the normal rat ventral prostate (VP) and Dunning R3327 PAP adenocarcinoma and to evaluate the effects of castration on receptor mRNA expression. METHODS: RNA was prepared from ovaries, pituitaries, VP, and Dunning tumors from both intact and castrated animals. GnRH-R mRNA levels were quantified by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: GnRH-R mRNA was detected in normal VP and Dunning tumors. Normal VP showed lower amounts of GnRH-R mRNA compared to Dunning tumors. An elevation of mRNA expression was observed 7 days after castration in Dunning tumors. CONCLUSIONS: GnRH-R mRNA was found in both VP and Dunning tumors, indicating the presence of a local GnRH system. Normal VP showed lower amounts of GnRH-R mRNA when compared to malignant tissues. GnRH-R mRNA levels were elevated in Dunning tumors following castration.

Adenocarcinoma↗
PubMed1999

Transient ischemia induces apoptosis in the ventral prostate of the rat.

The mechanisms involved in the castration-induced involution of the ventral prostate (VP) are not fully understood. It was recently reported that castration decreases blood flow in the VP in rats and that this occurs before the apoptotic involution of the organ. However, it is unknown whether a decrease in blood flow may trigger apoptosis in the VP, and this was therefore examined in this study. The right iliac artery was clamped for 1 h in adult male rats. After 24 h of reperfusion, the VPs were frozen or fixed. In situ end-labeling (ISEL) was used to identify apoptotic cells, and testosterone repressed prostatic message-2 (TRPM-2) was measured. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was used to identify proliferating cells. Clamping the right iliac artery reduced blood flow in the right VP to 0.17 of that in the contralateral lobe. This relative ischemia resulted in a threefold increase in the volume density of apoptotic epithelial cells on the treated side, but left cell proliferation unaffected. Testosterone substitution did not change this pattern. This study suggests that a transient period of relative ischemia may induce apoptosis in the rat ventral prostate. This may be of importance for the understanding of castration-induced prostatic involution.

Animals↗
PubMed1999

Alterations of transforming growth factor beta1 (TGF-beta1) and TGFbeta receptor expressions with progression in Dunning rat prostatic adenocarcinoma sublines.

Transforming growth factor-beta1 (TGF-beta1) inhibits epithelial cell proliferation in the normal prostate. Prostate tumours express high levels of TGF-beta1, and seem to acquire resistance to its anti-proliferative effects with tumour progression. In this study, TGFbeta variations with tumour progression were examined in the Dunning prostatic adenocarcinoma model. Expression of TGF-beta1 and TGFbeta receptor type I and type II (TGFbeta-RI and TGFbeta-RII) in rat dorsolateral prostate (DLP) and Dunning tumour sublines (PAP, AT-1, AT-2, AT-3 and MatLyLu) was examined in vitro and in vivo, using competitive reverse transcription-polymerase chain reaction (RT-PCR), Northern and Western blot, and immunohistochemistry. All tumours expressed elevated levels of TGF-beta1 and TGFbeta-RI mRNA, when compared with the DLP (P < or = 0.05). All tumours except MatLyLu also expressed elevated levels of TGFbeta-RII mRNA (P < or = 0.05). Interestingly, TGFbeta-RII protein levels were very low in the highly metastatic AT-3 and MatLyLu tumours in vivo, when compared with levels in the PAP, AT-1, and AT-2 tumours. This difference was not detected for the AT-1, AT-2, and AT-3 cells in vitro. Immunostaining of TGF-beta1, TGFbeta-RI, and TGFbeta-RII was localised principally in normal and tumour epithelial cells, and occasionally in smooth muscle cells. In conclusion, high expression of TGF-beta1 and TGFbeta-RI and low expression of TGFbeta-RII may contribute to tumour progression and metastasis in the Dunning prostatic adenocarcinoma model.

Activin Receptors, Type I↗
PubMed1999

Hereditary prostate cancer.

Recent research makes it probable that there is a hereditary form of prostate cancer. By identifying prostate cancer cases in the Swedish twin registry it was possible to show a pronounced difference in proband concordance rates and correlation of liability between monozygotic and dizygotic twin pairs, which indicates strongly that genetic factors are important for prostate cancer. In a nation-wide register cohort study it was found that the risk for prostate cancer was approximately two times higher among sons to prostate cancer patients when compared to Swedish men in general. By linkage analyses at least two loci for putative prostate cancer genes have been identified, one on chromosome 1 (1q24-25) and one on the X-chromosome (Xq27-28). Before genetic testing becomes available it was suggested that men with the familiar aggregation of prostate cancer should be evaluated with a PSA test on a regular basis.

Aged↗
PubMed1999

Predictive value of prostate-specific antigen, tumour stage and tumour grade for the outcome of bone scintigraphy in patients with newly diagnosed prostate cancer.

OBJECTIVE: In order to evaluate the negative predictive value of a low prostate-specific antigen (PSA) for a positive bone scan, we performed a retrospective study in a patient material from the Umea region in Northern Sweden. We also evaluated whether different tumour grades could influence this predictive value. MATERIAL AND METHODS: Four-hundred-and-forty-six patients of newly diagnosed prostate cancer were reviewed. We analysed different levels of PSA, tumour grade, tumour stage and combinations of these parameters for their use in making a positive bone scintigraphy (BS) prediction. RESULTS: Among 214 patients with PSA <20 ng/ml, 9 showed a positive BS. When tumours of grades 2 and 3 were excluded, the number of positive BS predictions decreased to 6. For 350 of these 446 patients, a classification according to TNM was available; 162 of these 350 had a PSA value <20 ng/ml, and when this group comprised only small and well-differentiated tumours (T1-2, G1), only one of the remaining 81 patients had a positive BS result. CONCLUSIONS: We conclude that in most patients with small and well-differentiated tumours (T1-2, G1) and PSA <20, BS staging need not be carried out.

Aged↗
PubMed1999

Prostate cancer registration in four Swedish regions 1996-- differences in incidence, age structure and management.

INTRODUCTION: In 1996 registration of prostate cancer in four of the six Swedish regions was started to facilitate evaluation of geographical variations in incidence and treatment. MATERIAL AND METHODS: For all cases of prostate cancer, personal identification number, tumour stage, tumour grade and primary treatment were registered. RESULTS: In the four regions covered by the register, 3541 cases of prostate cancer were registered. Altogether there were 5795 cases of prostate cancer diagnosed in Sweden the same year. The age-standardized incidence varied from 89/100000 to 169/100000 among counties. The proportion of localized tumours correlated positively to the incidence (p < 0.05) and negatively to mean age at diagnosis (p < 0.01). There was also a significant positive correlation between the proportion of localized tumours and the percentage of patients given curative treatment. All registered variables showed large geographical variations, especially concerning percentage of T1c tumours, treatment of localized tumours and choice of palliative treatment. CONCLUSION: Diagnostic activity varied considerably among counties, resulting in large variation in age-standardized incidence. High incidence is associated with a larger proportion of localized tumours, which, in turn, is associated with early age at diagnosis. In counties where a policy of detecting tumours early is practised, curative treatment is also given more often. Treatment of localized tumours and preference for palliative treatment seem to depend on local traditions. The lack of cytological and histopathological standards makes geographical comparisons based on tumour grade impossible.

Age Distribution↗
PubMed1999

Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.

The anti-tumour effect of the 131I-labelled antiprostate monoclonal antibody (MAb) E4 was studied in an experimental model with 41 nude mice, subcutaneously xenografted with a human prostate cancer cell line (DU-145). The mice were divided into four study groups, i.e. one receiving single and another repeated injections of the radiolabelled MAb. A third group was injected with non-labelled MAb, and the fourth served as an untreated control group. The tumour volumes increased similarly in all groups during the 27-day observation period. The tumour tissue was morphologically disintegrated in the group that received repeated radioimmunotherapy (RIT). The tumours from this group contained large fluid-filled cystic parts and demonstrated pronounced cellular and subcellular polymorphism in the remaining viable tumour tissue. The untreated control tumours and single therapy tumours remained solid. The proportion of the total tumour volume that consisted of viable tumour cells, as determined by morphometric techniques, was significantly lower in the 131I-E4-treated groups. The use of 131I-labelled E4 MAb has thus demonstrated a promising therapeutic potential.

Animals↗
PubMed1999

In Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer.

Prostate cancer clusters in some families, and an estimated 5%-10% of all cases are estimated to result from inheritance of prostate cancer-susceptibility genes. We previously reported evidence of linkage to the 1q24-25 region (HPC1) in 91 North American and Swedish families each with multiple cases of prostate cancer (Smith et al. 1996). In the present report we analyze 40 (12 original and 28 newly identified) Swedish families with hereditary prostate cancer (HPC) that, on the basis of 40 markers spanning a 25-cM interval within 1q24-25, have evidence of linkage. In the complete set of families, a maximum two-point LOD score of 1.10 was observed at D1S413 (at a recombination fraction [theta] of.1), with a maximum NPL (nonparametric linkage) Z score of 1.64 at D1S202 (P=.05). The evidence of linkage to this region originated almost exclusively from the subset of 12 early-onset (age <65 years) families, which yielded a maximum LOD score of 2.38 at D1S413 (straight theta=0) and an NPL Z score of 1.95 at D1S422 (P=.03). Estimates from heterogeneity tests suggest that, within Sweden, as many as 50% of early-onset families had evidence of linkage to the HPC1 region. These results are consistent with the hypothesis of linkage to HPC1 in a subset of families with prostate cancer, particularly those with an early age at diagnosis.

Age of Onset↗
PubMed1999

Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats.

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.

Animals↗
PubMed1998

Familial prostate cancer and possible associated malignancies: nation-wide register cohort study in Sweden.

There is a familial aggregation of prostate cancer, and 5 to 10% of all prostate cancers are estimated to be inherited in an autosomal-dominant mode. A population-based cohort study was performed in order to study familial prostate cancer and associated malignancies. A nation-wide register cohort study was conducted using an unselected study population. The cohort of 5,595 sons and 5,089 daughters of Swedish men found to have prostate cancer between 1959 and 1963 was identified. All types of cancer reported between 1958 and 1992 in this cohort were identified through linkage to the Swedish Cancer Registry. The expected number of different cancers was calculated using incidence rates obtained from the Registry. A highly significant increased overall standardized incidence ratio (SIR) of 1.65 (95% CI, 1.49-1.83) was obtained for prostate cancer, with 370 observed cases compared with 224 expected prostate cancers. The SIR was 3.18 among cases 45 to 49 years old at diagnosis, with the risk gradually decreasing to a SIR of 1.45 among cases over 80 years of age. Among sons and daughters with a father whose prostate cancer was diagnosed at an early age (<70 years), an increased risk for colorectal cancer SIR 1.48 (1.10-1.95) was observed. No significant difference in cancer risk for other sites was observed among the daughters and sons of men with prostate cancer. This cohort study confirms earlier studies that a positive family history of prostate cancer is an important risk factor for developing this disease. Though increased risk was found for all ages, it was more pronounced in younger men. Since no other malignancy was significantly associated with prostate cancer, it is most likely that familial prostate cancer is "site-specific".

Age Factors↗
PubMed1998

Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer.

BACKGROUND: Prostate tumors express high levels of transforming growth factor-beta1 (TGF-beta1) and seem to acquire resistance to its antiproliferative effects with tumor progression. Moreover, TGF-beta1 could be involved in tumor-promoting processes such as angiogenesis, cell migration, and immunosuppression. METHODS: Immunoreactivity for TGF-beta1 and its receptors type I and type II (TGFbeta-RI and TGFbeta-RII), tumor vascular count, and cell proliferation were studied in 73 cases of prostate cancer, diagnosed between 1975-1983 and followed with surveillance. RESULTS: Patients with tumor overproduction of TGF-beta1 had shorter median cancer-specific survival than patients with normal TGF-beta1 immunoreactivity (5.0 vs. 10 years, P = 0.006). Furthermore, increased TGF-beta1 staining was associated with tumor grade, high vascular counts, and metastasis (P = 0.02, 0.02, and 0.01, respectively). Patients with loss of tumor TGFbeta-RII expression in combination with TGF-beta1 overproduction showed particularly short survival (2.6 vs. 10 years, P = 0.0000), when compared to patients with normal immunoreactivity. CONCLUSIONS: Overproduction of TGF-beta1 and loss of TGFbeta-RII expression are associated with poor clinical outcome in prostate cancer, and TGF-beta1 may promote tumor progression by stimulating angiogenesis and metastasis.

Aged↗
PubMed1998

Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats.

METHODS: Dunning R3327 PAP prostate tumors were transplanted in 125 rats, the rats were divided into five groups, and tumor development was examined for 24 weeks during treatment with diets containing 33% of soy flour (SD), rye bran (RB), heat-treated rye bran (HRB), or rye endosperm (RE). RESULTS: In the SD, RB, and HRB groups, significantly fewer palpable tumors and lower tumor volume were detected 14 and 16 weeks after transplantation when compared with the control, fiber-free dietary (FF) group. The body weight was lower 16 weeks after tumor transplantation in the RB and HRB groups when compared with the control group (P < 0.05). Rats in the RB and the HRB groups had a significant lower energy intake than the FF group during the first metabolic observation period, 3-6 weeks after tumor transplantation (P < 0.05), whereas the energy intake was the same in all groups during the second metabolic observation period, 13-16 weeks after tumor transplantation. However, when the tumor volume was adjusted for the body weight of the animals, there were still significant lower tumor volumes in the SD, RB, and HRB groups compared with the FF group (P < 0.05). A significant increase in daily urinary excretion of the isoflavonoids, daidzein, O-desmethylangolensin, equol, and Genistein, was observed in the rats fed SD, and of the ligands enterolactone and enterodiol in the rats fed RB and HRB during both metabolic periods. There were no differences in testosterone levels between the groups. CONCLUSIONS: The present study shows that SD inhibits implanted prostate cancer growth. Although RB and HRB had a protective effect, further studies are needed to exclude the possibility that a low energy intake played a role in this respect. The results suggest that phytoestrogens (isoflavonoids and ligands), may be responsible for the delayed prostate tumor growth.

Adenocarcinoma↗
PubMed1998

Expression of vascular endothelial growth factor and its receptors in the rat ventral prostate and Dunning R3327 PAP adenocarcinoma before and after castration.

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.

Adenocarcinoma↗