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A Bergh

Publications and source records attributed to A Bergh.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Gene for hereditary prostatic cancer has been located. New possibilities for early identification of men at risk].

Prostate cancer is currently the most common malignancy among men in Sweden, and an estimated 5-10 per cent of cases are hereditary. Several epidemiological studies have shown men whose close relatives are affected to be at 2-4-fold increased risk of developing prostate cancer. In a recent genetic linkage study of 91 Swedish and North American families with hereditary prostate cancer, the first susceptibility locus, HPC 1 (hereditary prostate cancer 1), was localised at positions 1q24-25 on the long arm of chromosome 1. In Sweden, we recommend men with a strong family history of prostate cancer to undergo annual prostate-specific antigen testing and digital rectal examination from the age of 50.

Chromosome Mapping↗
PubMed1998

Predictive value of bcl-2 immunoreactivity in prostate cancer patients treated with radiotherapy.

BACKGROUND AND PURPOSE: Recent experimental evidence suggests that overexpression of bcl-2, a protein functioning by blocking apoptosis, may influence the treatment outcome in human tumours, including prostate cancer. To test the clinical implications of this hypothesis, tumours from patients with prostate cancer treated with external beam radiotherapy were investigated for bcl-2 immunoreactivity (IR) and correlated with prognosis and treatment outcome. MATERIALS AND METHODS: Bcl-2 IR was evaluated in archival tumour specimens obtained through transurethral resection from 42 patients with localized prostate cancer (T0-T4, N0 and M0). Bcl-2 IR expression was related to stage, grade and cancer-specific survival. Specimens were obtained prior to administrating routine radiotherapy for all patients. RESULTS: Bcl-2 IR was present in 19/42 (45%) tumours. The bcl-2-positive patients had a significantly longer cancer-specific survival than the bcl-2-negative patients (10.3 versus 3.4 years, P<0.04). At follow-up (7-19 years), nine patients were still alive, 26 patients had died of prostate cancer and seven patients had died of other causes. CONCLUSIONS: This study indicates that pre-treatment bcl-2 overexpression is related to a favourable outcome in prostate cancer treated with radiotherapy. Low bcl-2 along with a high stage may be a predictor of poor prognosis and these patients might benefit from additional treatment.

Aged↗
PubMed1998

Evidence for a prostate cancer susceptibility locus on the X chromosome.

Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.

Adult↗
PubMed1998

Short-term cellular effects induced by castration therapy in relation to clinical outcome in prostate cancer.

To explore the relationship between short-term effects of castration therapy and clinical response, biopsies obtained before and a week after castration therapy from 15 responding and 13 non-responding patients with prostate cancer were investigated. The biopsies were assessed for regressive morphology, apoptotic index by morphological criteria, nuclear area, and immunoreactivity (IR) for Ki-67, p53, bcl-2, bax and Fas. The index was defined as the percentage of immunoreactive cells in a tumour. Regressive morphology was observed in 14 out of 15 responding tumours after therapy, compared with 4 out of 13 non-responders (P < 0.001). Median tumour epithelial cell nuclear area and Ki-67 index decreased equally in both groups. The median apoptotic index increased from 2.6 to 3.5 after castration among responders (P < 0.05), whereas it remained at 2.8 among non-responders. p53 IR was present in three tumours before castration; after therapy p53 reactivity was seen in three additional tumours belonging to the responding group. Median bcl-2 index increased in responders from 1.5 to 10.0 (P < 0.05), and in non-responders from 0.08 to 2.7 (P < 0.05). Bax IR and Fas IR were present in all tumours before therapy and unchanged after therapy. Thus, regressive morphology and an increase in apoptotic index were related to a favourable clinical response. These data suggest that it might be possible to predict the effect of castration therapy by examining tumour biopsies shortly after treatment.

Aged↗
PubMed1998

Testosterone stimulates angiogenesis and vascular regrowth in the ventral prostate in castrated adult rats.

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.

Animals↗
PubMed1998

Apoptosis and other mechanisms in androgen ablation treatment and androgen independent progression of prostate cancer: a review.

Patients with advanced prostate cancer commonly present with disseminated disease. For these patients, androgen ablation is a first-line treatment. This mode of therapy usually has an initially palliative effect on tumor-related symptoms and slows growth, although virtually all tumors eventually relapse to an androgen-independent, more aggressively growing phenotype. However, surprisingly little is known about the actions mediating the initial palliative effect as well as the initiation of androgen-independent tumor growth. In this review, some current concepts on mechanisms of androgen ablation treatment and androgen-independent progression of prostate cancer is highlighted. Special attention is given to the involvement of apoptosis in these processes.

Androgen Antagonists↗
PubMed1997

Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4): an experimental study in nude mice.

BACKGROUND: Prostate cancer is one of the leading causes of death among men, despite achievements in diagnosis and therapy. Radioimmunolocalization and radioimmunotherapy of malignant tumors have demonstrated increasing potential and may become useful tools in the management of prostate cancer. METHODS: Nude mice were inoculated subcutaneously with cells from the poorly differentiated human prostate cancer cell line DU-145. The intact monoclonal antibody (MoAb) E4 and an intact anticytokeratin-8 MoAb, TS1, used for comparison were labeled with 125I and injected intraperitoneally (i.p.) in the mice. Repetitive quantitative scintigraphic recordings were performed during 1 month. The mice were killed at Day 29 after injection of the radiolabeled MoAb. The tumors and the organs were dissected and weighed. The remaining activity was measured in a gamma well counter. One part of the tumor was immediately fixed in Bouin's solution for autoradiography and the other in formaldehyde for microscopy. RESULTS: The study demonstrated significant radioimmunolocalization of the MoAb E4 into the DU-145 prostate tumor tissue in the animal model, with an average radiation dose of 0.08 Gy/MBq in the tumor. TS1 localized preferentially in necrotic parts of the tumor, yielding a tumor dose of 0.02 Gy/MBq. CONCLUSIONS: The MoAb E4 is a promising radiotracer for prostate cancer and may be used in radioimmunotherapy. As in earlier studies, TS1 shows significant radioimmunolocalization into necrotic tumor tissue, which also exists in prostate cancer.

Animals↗
PubMed1997

Combined castration and fractionated radiotherapy in an experimental prostatic adenocarcinoma.

PURPOSE: The present study using the Dunning R3327-PAP rat prostatic adenocarcinoma model was designed to study the effect on tumor growth of castration prior to or after irradiation with 20-25 Gy as compared with either irradiation or castration alone. METHODS AND MATERIALS: Rats were bilaterally orchidectomized. During the irradiation procedure the nonanesthetized animals were held in a metallic frame with a strong cotton net and they were observed by means of a video camera. The suboptimal irradiation dose was given once daily with a 4-MeV linear accelerator, 4-5 Gy/fraction, during 5 consecutive days. Tumor volumes and rat weights were followed. At the end point of the study the animals were sacrificed and the tumors were morphometrically analyzed. RESULTS: The combination of irradiation and castration delayed tumor regrowth better than irradiation alone with the same suboptimal dose. Castration before irradiation delayed tumor regrowth more efficiently than castration after irradiation. However, castration alone delayed tumor regrowth even more effectively than suboptimal irradiation doses combined with castration. CONCLUSIONS: In combination with suboptimal irradiation neoadjuvant androgen deprivation was more inhibitory to rat prostatic adenocarcinoma regrowth than adjuvant androgen deprivation. Irradiation with suboptimal doses combined with castration may cause an earlier relapse to androgen-independent tumor growth than castration alone.

Adenocarcinoma↗
PubMed1997

Early age at diagnosis in families providing evidence of linkage to the hereditary prostate cancer locus (HPC1) on chromosome 1.

In a recent study of 91 families having at least three first degree relatives with prostate cancer, we reported the localization of a major susceptibility locus for prostate cancer (HPC1) to chromosome 1 [band q24; J. R. Smith et al., Science (Washington DC), 274: 1371-1373, 1996]. There was significant evidence for locus heterogeneity, with an estimate of 34% of the families being linked to this locus. In this report, we investigate the importance of age at diagnosis of prostate cancer and number of affected individuals within a family as variables in the linkage analysis of an expanded set of markers on 1q24. Under two different models for the prostate cancer locus, we find that the evidence for linkage to HPC1 is provided primarily by large (five or more members affected) families with an early average age at diagnosis. Specifically, for 40 North American families with an average age at diagnosis <65 years, the multipoint lod score is 3.96, whereas for 39 families with an older average age at diagnosis, this value is -0.84. Assuming heterogeneity, the proportion of families linked is 66% for the 14 families with the earliest average ages at diagnoses, but it decreases to 7% for the families with the latest ages at diagnoses. A similar age effect is observed in 12 Swedish pedigrees analyzed. To test the hypotheses generated by these analyses, we examined an additional group of 13 newly identified prostate cancer families. Overall, these families provided additional evidence for linkage to this region (nonparametric linkage Z = 1.91; P = 0.04 at marker D1S1660), contributed primarily by the families in this group with early age at diagnosis [nonparametric linkage Z = 2.50 (P = 0.01) at D1S422]. These results are consistent with the existence of a locus in this region that predisposes men to develop early-onset prostate cancer.

Age Factors↗
PubMed1997

Vascular density is a predictor of cancer-specific survival in prostatic carcinoma.

BACKGROUND: Microvessel density has been shown to give prognostic information in a variety of solid tumors, but its role in prostatic carcinoma needs further elucidation. METHODS: Intratumoral density of von Willebrand factor-positive microvessels was assessed in 98 cases of prostatic carcinoma, diagnosed at transurethral resection of the prostate (TURP) between 1975-1983, using two methods: 1) volume density of microvessels and 2) vascular count in the 2-3 most vascularized fields. RESULTS: Volume density and vascular counts were highly correlated. In Kaplan-Meyer analysis, mean cancer-specific survival time for patients with a vascular count < 135 was significantly longer than for patients with a vascular count > 135 (P = 0.0064). The same results applied to patients with WHO grade II tumors (P = 0.01). Excluding metastasis in a multivariate analysis, both tumor stage and vascular count had an independent predictive value for cancer-specific survival in patients with WHO grade II tumors. CONCLUSIONS: Microvessel density may predict cancer-specific survival in prostatic carcinoma.

Aged↗
PubMed1997

Expression of transforming growth factor-beta receptor type I and type II in rat ventral prostate and Dunning R3327 PAP adenocarcinoma in response to castration and oestrogen treatment.

In the normal prostate, transforming growth factor-beta 1 (TGF-beta 1) inhibits epithelial cell growth and is associated with apoptosis. The role of TGF-beta 1 in prostate cancer remains, however, unclear. In this work, the expression of TGF-beta receptor type I and II (TGF beta-RI and TGF beta-RII) in the Dunning R3327 PAP adenocarcinoma was studied, after castration and oestrogen treatment. Since castration induces apoptosis in the rat ventral prostate (VP) [21], but not in the Dunning R3327 PAP tumour [46], the TGF-beta receptor levels in the tumour were compared to the receptor levels in the VP. Methods used were competitive reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. In the VP, TGF beta-RI and TGF beta-RII expressions were increased after castration, indicating a negative regulation of TGF beta receptors by androgens. In the Dunning tumour, TGF beta-RI and TGF beta-RII levels were elevated and only TGF beta-RI showed a clear-cut increase after castration. The receptors were located in epithelial and smooth muscle cells in the VP and mainly in epithelial cells in the Dunning tumour. In conclusion, the elevated TGF beta receptor levels and the diminished androgen regulation of TGF beta-RII in the tumour distinguish the Dunning R3327 PAP tumour from the normal prostate and need to be further elucidated.

Activin Receptors, Type I↗
PubMed1997

Decrement of blood flow precedes the involution of the ventral prostate in the rat after castration.

Blood flow to the rat ventral prostate (VP), dorsolateral prostate (DP), and Dunning R3327 prostatic tumors was measured at different times up to 7 days after castration, using the microsphere method. In the VP organ weight was decreased from day 3 onwards. Blood flow was, however, already significantly decreased from day 1. The reduced blood flow in VP in 1-3 and 7-day castrated animals could be reversed by testosterone treatment. Organ weight was slightly decreased but blood flow was unaffected by castration in DP. Castration left Dunning tumor volume and blood flow unaffected. Using immunohistochemistry, androgen receptors were observed in epithelial and stromal cells in VP, DP and Dunning tumors, but not in blood vessels. Castration is known to induce apoptosis in the VP, but not in the DP or in Dunning tumors. This suggests that a reduction in blood flow might be an important component for the castration-induced involution and apoptosis in prostatic tissue. The reason why castration reduces blood flow only in the VP, and not in the DP or Dunning tumor is unknown.

Animals↗
PubMed1997

Atrial natriuretic peptide, brain natriuretic peptide and c-type natriuretic peptide: effects on testicular microcirculation and immunohistochemical localization.

The effect of local injection of atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides and an ANP antagonist (HS-142-1) on testicular microcirculation and vasomotion was studied using laser Doppler flowmetry. The natriuretic peptides were also localized immunohistochemically within the testis. ANP, BNP-32, CNP-22 and CNP-53 all caused a dose-related increase in testicular blood flow. The effect of ANP was blocked by concomitant injection of the ANP antagonist. Immunoreactive (ir) CNP and ir BNP were found in Leydig cells whereas in ANP was observed in the seminiferous tubules. It is suggested that the natriuretic peptides could play a role in local regulation of the testicular microcirculation.

Animals↗
PubMed1997

Effects of vasoactive intestinal peptide (VIP) on the testicular vasculature of the rat.

Using laser Doppler flowmetry, the effects of unilateral intratesticular injection of vasoactive intestinal peptide (VIP) on testicular blood flow and mean arterial blood pressure were studied in anaesthetized adult rats. At doses of 50 and 500 ng, VIP increased blood flow by 29 +/- 8 and by 77 +/- 25% (p < 0.05), respectively (means +/- SEM) at 5 mm, but not at 15 mm, from the injection site. Blood pressure was not significantly affected by 50 ng, but was slightly reduced (by -8 +/- 2%) after treatment with 500 ng VIP. The highest dose of VIP (5 micrograms) reduced blood pressure (by -30 +/- 9%), and decreased blood flow at 15 mm, but not at 5 mm, from the injection site. It is concluded that VIP can act as a vasodilator in the rat testis.

Animals↗
PubMed1997

Is nitric oxide involved in the regulation of the rat testicular vasculature?

Using immunohistochemistry, endothelial nitric oxide synthase (NOS), and neuronal NOS were localized in the endothelium of rat testicular arteries and in Leydig cells, respectively. NADPH-diaphorase activity, indicating NOS activity, however, was present only in endothelial cells. In order to examine the role of nitric oxide (NO) in the regulation of rat testicular vasculature, intact and hCG-pretreated (50-100 IU hCG given s.c. 6 h earlier) animals were given injections of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg i.v.). In all rats this resulted in a major increase in blood pressure. In intact, unstimulated animals, testicular vascular resistance was unaffected, and testicular blood flow consequently increased. In hCG-treated animals, in contrast, vascular resistance increased in an hCG dose-related way. L-NAME treatment also increased the hCG-induced accumulation of polymorphonuclear leukocytes in testicular venules. Treatment with N(G)-nitro-D-arginine methyl ester (D-NAME, 10 mg/kg i.v.), an inactive isomer of L-NAME, had no effect on the testicular vasculature. The study suggests that NO plays only a limited role in the regulation of testicular blood flow under basal conditions. After hCG treatment, however, NOS activity appears to be increased (increased endothelial NADPH-diaphorase staining), suggesting that NO in this situation is of importance to increase blood flow and to inhibit leukocyte accumulation.

Animals↗
PubMed1997

Cell proliferation assessed by Ki-67 immunoreactivity on formalin fixed tissues is a predictive factor for survival in prostate cancer.

PURPOSE: Proliferation rate may be an important determinant of tumor progression. To evaluate the predictive value of proliferation, immunoreactivity for the proliferation associated antigen Ki-67 was related to survival in a series of patients with prostate cancer. MATERIALS AND METHODS: Formalin fixed tissue, obtained by transurethral resection from 125 previously untreated prostate tumors, was examined with an immunohistochemical method for Ki-67. Ki-67 index was defined as the percentage of immunoreactive cells in a tumor. Patients were followed with surveillance after transurethral resection. The cause of death was determined by examination of patient records 11 to 19 years postoperatively (mean followup 71 months). At evaluation 17 patients (14%) were still at risk and 55 (44%) had died of prostate cancer. RESULTS: Mean Ki-67 index was 2.1. Ki-67 index correlated with grade (p < 0.0005) and weakly with stage (p = 0.019). Mean survival of patients with a Ki-67 index of more than 3 was less than half that of patients with a Ki-67 index of less than 3 (53 versus 132 months, p < 0.00005). The difference in survival remained in an analysis of the intermediately differentiated tumors (61 versus 126 months, p = 0.0032). In a Cox multiple regression analysis for cancer specific survival, including Ki-67 index, grade, stage, metastasis and age, Ki-67 index remained an independent predictive factor. CONCLUSIONS: Our study indicates that proliferation rate, assessed by Ki-67 immunoreactivity in formalin fixed tissues, is a predictive marker for outcome in prostate cancer.

Aged↗
PubMed1997

Growth, feeding practices and infections in black infants.

OBJECTIVE: To investigate the growth, early feeding practices and prevalence of infections in black infants. DESIGN: Longitudinal study with prospective documentation of data. SETTING: Kalafong Hospital, Pretoria. PATIENTS: Term, appropriately grown infants with a positive rapid plasma reagin test on cord blood were enrolled. Infants who on follow-up did not have congenital syphilis were studied. RESULTS: At birth the mean weight-for-age Z-scores corresponded with those of the National Center of Health Statistics (NCHS) reference population and increased during the first 3 months. A fall-off in growth performance in respect of weight gain occurred from 3 months and continued until 15 months when the study was terminated. At 6 and 12 months, 86% and 81% of infants respectively were receiving breast-milk. By 3 months, 78% of infants were receiving a supplementary food. At 9 months, 40% of infants had experienced an infection during the preceding 3 months. During the study, upper airway infections comprised 74% of all episodes of infection. CONCLUSIONS: Compared with the NCHS reference population, black infants grow adequately during the first 3 months of life. This is followed by a persistent fall-off in growth performance associated with the introduction of supplementary food.

Anthropometry↗