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PubMed2001

Initiation of nonselective alpha1-antagonist therapy and occurrence of hypotension-related adverse events among men with benign prostatic hyperplasia: a retrospective cohort study.

BACKGROUND: Treatment of benign prostatic hyperplasia (BPH) with nonselective alpha1 antagonists such as terazosin, doxazosin, and prazosin results in blood pressure reduction due to vasodilation. OBJECTIVE: Using claims data from a large Medigap plan, we examined the effect of initiating nonselective alpha1-antagonist therapy on the incidence of hypotension-related adverse events likely to be associated with vascular alpha-adrenoreceptor antagonism in patients with BPH. METHODS: Medical and prescription claims data were obtained from the MEDSTAT Group for 53,824 men with a diagnosis code for BPH during the study period (January 1995-December 1997). We examined the rate of possible hypotension-related adverse events (diagnosis codes for hypotension, syncope, dizziness, fractures, and other injuries) per 10,000 person-days for men who began therapy with alpha1 antagonists and for a random sample of nonusers, stratified by prior use of other antihypertensive agents. RESULTS: After adjusting for baseline differences in event rates, those who initiated alpha1-antagonist therapy (n = 1564) had a significantly greater increase in hypotension-related adverse-event rates in the 4 months after initiation (vs the 4 months before initiation) than randomly selected nonusers (n = 8641) (increase of 1.82 vs decrease of 0.02 events per 10,000 person-days among those not taking antihypertensive agents; increase of 0.94 vs 0.69 events per 10,000 person-days among those taking other antihypertensive agents; P < 0.01). This increase began earlier and lasted longer among patients taking other antihypertensive agents. Those who discontinued their alpha1 antagonist had a higher rate of hypotensive events at baseline than those who did not (5.09 vs 3.19 events per 10,000 person-days among those using other antihypertensive agents; 3.62 vs 2.27 events per 10,000 person-days among those not using other antihypertensive agents; P < 0.05). CONCLUSIONS: Initiation of nonselective alpha1-antagonist therapy for the treatment of BPH increases the risk of a cluster of clinical events consistent with vascular alpha-adrenoreceptor antagonism. This effect is seen during a 4-month period around the initiation date. Prior initiation of other antihypertensive medication increases this effect. Urologists should consult with a patient's primary care physician about use of other antihypertensive agents before initiating nonselective alpha1-antagonist therapy for BPH.

Accidental Falls↗
PubMed2003

Prostate-specific antigen levels and density in the internal and external glands of the prostate in benign prostatic hyperplasia patients with normal or gray-zone PSA levels.

OBJECTIVE: In patients with benign prostatic hyperplasia (BPH) showing normal prostate-specific antigen (PSA) levels (normal PSA group) and those with BPH showing gray-zone PSA levels (gray-zone PSA group), we assessed PSA levels secreted from the internal and external glands. MATERIALS AND METHODS: We performed transurethral enucleation of the prostate (TUE) in 102 BPH patients with normal PSA and 59 BPH patients with gray-zone PSA at our department from 1999 to 2001. Preoperatively and approximately 6 months postoperatively, we measured serum PSA levels and determined prostatic volumes via transrectal ultrasonography (TRUS) to calculate PSA levels secreted from the internal and external glands as well as various PSA density (PSAD) values. RESULTS: The total PSA level was 1.8 and 6.1 ng/ml in the normal and gray-zone PSA groups, respectively. The PSA level of the external gland was 0.6 and 0.8 ng/ml and the PSAD of the external gland was 0.07 and 0.08 ng/ml/cm(3) in the normal and gray-zone PSA groups, respectively. The internal gland PSA was 1.3 and 5.4 ng/ml and the internal gland PSAD value was 0.11 and 0.30 ng/ml/cm(3) in the normal and gray-zone PSA groups, respectively. CONCLUSIONS: Our results demonstrated that increased PSA levels in BPH cases with gray-zone PSA were attributable to increased PSA secreted from the internal gland rather than from the external gland. In our opinion, the determination of PSA and PSAD of the internal and external gland may be clinically significant in the future.

Aged↗
PubMed1997

[Clinical evaluation of tamsulosin hydrochloride on bladder outlet obstruction associated with benign prostatic hyperplasia: effect on urethral pressure profile and cystometrogram].

The efficacy and safety of tamsulosin hydrochloride were evaluated in 54 patients with bladder outlet obstruction associated with benign prostatic hyperplasia. Oral tamsulosin hydrochloride 0.2 mg was administered once daily for 7 weeks. The international prostate symptom score, residual urine, uroflowmetrogram, urethral pressure profile and cystometrogram were obtained before and after treatment. The international prostate symptom score improved significantly, and the residual urine volume and ratio of residual urine decreased significantly. In uroflometry, voided volume, maximum flow rate and average flow rate increased significantly. In urethral pressure profile, prostatic urethral pressure decreased significantly. In cystometry, bladder capacity at the first sensation increased significantly. No adverse reactions except for slight elevation in laboratory data in 3 patients were observed. In conclusion, tamsulosin hydrochloride is a useful drug in the treatment of bladder outlet obstruction associated with benign prostatic hyperplasia.

Administration, Oral↗
PubMed2002

Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the most common conditions associated with ageing in men. BPH often presents as lower urinary tract symptoms (LUTS) due to difficulties in voiding and irritability of the bladder. We conducted a retrospective cohort study within the Integrated Primary Care Information (IPCI) database, a general practitioners database in The Netherlands, to assess the incidence of LUTS suggestive of BPH (LUTS/BPH) in the general population. MATERIALS: Our study population comprised all males, 45 years or older who were registered for at least 6 months prior to start of follow-up. The study period lasted from 1 January 1995 to 31 December 2000. Cases of LUTS/BPH were defined as persons with a diagnosis of BPH, treatment or surgery for BPH, or urinary symptoms suggestive of BPH that could not be explained by other co-morbidity. RESULTS: The study cohort comprised 80,774 males who contributed 141,035 person-years of follow-up. We identified 2181 incident and 5605 prevalent LUTS/BPH cases. The overall incidence rate of LUTS/BPH was 15 per 1000 man-years (95% CI: 14.8-16.1). The incidence increased linearly (r(2) = 0.99) with age from three cases per 1000 man-years at the age of 45-49 years (95% CI: 2.4-3.6) to a maximum of 38 cases per 1000 man-years at the age of 75-79 years (95% CI: 34.1-42.9). After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop LUTS/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3% (95% CI: 10.2-10.5). The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%). CONCLUSIONS: The incidence rate of LUTS/BPH increases linearly with age and reaches its maximum at the age of 79 years.

Age Distribution↗
PubMed1998

[Plasma TGF-beta1 concentrations in patients with prostate carcinoma or benign prostatic hyperplasia].

Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotrophic growth factor in carcinogenesis and regulars multiple cell functions. We wanted to evaluate the diagnostic meaning of TGF-beta 1 plasma levels in patients with a biopsy proven prostate cancer. The TGF-beta 1 blood level was analysed in 394 patients. In 242 patients (group I) the blood was taken before any prostate manipulation and biopsy. The TGF-beta 1 plasma concentrations were almost similar in the group of patients with a prostate cancer (n = 157) and patients with a benign prostate hyperplasia (n = 85; 14,258 pg/ml versus 14,658 pg/ml, SD 10,516 pg/ml). In 152 patients the blood was taken 6-12 months after radical prostatectomy (group II). There was no significant difference between the patients with a PSA-progress and without PSA-progress after. Our results suggest that TGF-beta 1 plasma levels can not be used to distinguish between patients with prostate cancer and benign prostate hyperplasia.

Biomarkers, Tumor↗
PubMed2005

Dutasteride: a novel dual inhibitor of 5alpha-reductase for benign prostatic hyperplasia.

Dutasteride is a new dual 5alpha-reductase inhibitor for the treatment of benign prostatic hyperplasia. It differs from finasteride as it inhibits both isoenzymes of 5alpha-reductase and results in near-complete suppression of serum dihydro-testosterone. Similar to finasteride, it reduces serum prostatic specific antigen by approximately 50% at 6months and total prostate volume by 25% in 2years. Randomised, placebo-controlled trials conducted over 2years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and the need for surgery. The main side effects are erectile dysfunction, decreased libido, gynaecomastia and ejaculation disorders. However, long-term usage for > 4years did not reveal increased new onset of sexual side effects. In addition, the combination of dutasteride and tamsulosin is well-tolerated and has the added advantage of rapid symptomatic relief. Finally, dutasteride has been shown to possess tumour regression properties invitro and its role in chemoprevention of prostate cancer will be confirmed in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1992

Inhibitory influence of a new steroidal anti-androgen, TZP-4238, on prostatic hyperplasia in the beagle dog.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Old male beagle dogs (5-9 years old) were divided into three experimental groups. Group 1 consisted of BPH controls. Groups 2 and 3 received TZP-4238 0.1 mg/kg/day and chlormadinone acetate (CMA) 0.3 mg/kg/day p.o., respectively, for 5 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In contrast, TZP-4238 (Group 2) or CMA (Group 3) produced marked atrophy of the glandular epithelium. In addition, a histopathological study showed that TZP-4238 or CMA medication for 5 months exerted no effect on the testes and the pituitary luteinizing hormone (LH) cells. Therefore, it is suggested that TZP-4238 (0.1 mg/kg) or CMA (0.3 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes and pituitary LH cells. However, slightly decreased serum testosterone levels were found in TZP-4238-treated animals, due apparently to a direct and/or indirect effect on the testes. Thus, it is suggested that a marginal antigonadotrophic effect cannot be excluded. It is concluded that TZP-4238 is a potent anti-androgen for the treatment of spontaneous canine BPH, without any negative influence on the function of the testes and the pituitary LH cells.

Animals↗
PubMed1998

Immunolocalization of androgen receptor in canine prostatic hyperplasia--effect of antiandrogen.

The effect of a synthetic steroidal anti-androgen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in the dog was investigated. Old male beagle dogs (5 to 8 years old) were divided into the following experimental groups: group 1 consisting of BPH controls, and group 2 which received CMA of 0.3 mg/kg/day orally for 6 months. In group 1, glandular hyperplasia of the prostate was clearly observed. The glandular epithelial cells showed uniformly intense nuclear immunostaining for androgen receptor (AR). In contrast, CMA produced marked atrophy of the glandular epithelium. The interacinar fibromuscular stroma was prominent. Furthermore, nuclear immunostaining for AR in both epithelial and stroma cells was remarkably decreased. These results indicate that the uptake of testosterone and/or its androgenic effect on the prostate may be suppressed by CMA. The decreased AR-immunostaining may be explained by the decrease in the number of AR and/or antibody binding sites for AR.

Androgen Antagonists↗
PubMed2001

Relationship between prostatic atrophy and apoptosis in the canine spontaneous benign prostatic hyperplasia (BPH) following chlormadinone acetate (CMA).

The effect of a synthetic steroidal antiandrogen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into four experimental groups. Group 1 consisted of untreated controls. Groups 2 to 4 received CMA 0.03, 0.1, and 0.3 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In groups 2 to 4, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. To evaluate the frequency of apoptosis, we counted the positive cells stained by the nick end labeling method. In group 1, the apoptotic index was 0.76 +/- 0.03%. In groups 2 to 4, apoptotic index were 15.41 +/- 1.26%, 2.63 +/- 0.98% and 1.45 +/- 0.85%, respectively. Apoptotic cell death was mainly observed in the glandular may be epithelial cells. Based on our data, regression of BPH after treatment with CMA apoptotic cell death.

Androgen Antagonists↗
PubMed1992

A possible role of decreased relaxation mediated by beta-adrenoceptors in bladder outlet obstruction by benign prostatic hyperplasia.

1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues were investigated for beta- and alpha 1-adrenoceptors by radioligand binding and in vitro isometric tension experiments. 2. Hyperplastic and control prostatic tissues had a similar number (per mg protein) of prazosin binding sites with similar affinities. Noradrenaline (NA) induced dose-dependent contraction in both tissues. Contraction induced by either exogenous NA or transmural stimulation was inhibited by prazosin in both tissues, indicating that the same contractile mechanisms mediated by alpha 1-adrenoceptors exist in hyperplastic and control tissues. 3. The number of dihydroalprenolol (DHA) binding sites (per mg protein) was less in hyperplastic tissues than in controls, whereas the affinity to the ligand was identical in both tissues. Isoprenaline caused a marked relaxation of the tonic contraction induced by KCl in control tissues, but not in hyperplastic tissues. Propranolol enhanced exogenous NA- or transmural stimulation-induced contraction more in control tissues than in hyperplastic tissues. Both tissues, however, similarly responded to forskolin by relaxation. 4. These results indicate that decreased beta-adrenoceptor-mediated relaxation in hyperplastic prostatic tissues, which is attributable at least in part to the decreased number of beta-adrenoceptors, may play a role in the urinary obstruction of BPH in addition to mechanical compression of the urethra by the enlarged prostate.

Adult↗
PubMedDate not supplied

Lack of association of VDR polymorphisms with Thai prostate cancer as compared with benign prostate hyperplasia and controls.

While still relatively low as compared to rates in the Western world, prostate cancer is on the increase in Asia, presumably due to change in dietary and other lifestyle factors. One risk factor is reported to be vitamin D (VD) and therefore the function of its receptor (VDR) could be of importance. In the present study polymorphims with functional significance in the Bsm, Apa 1 and Taq 1 genes were therefore compared in 28 prostate cancer (CaP), 44 benign prostate hyperplasia (BPH) and 30 control cases in Thailand. None demonstrated any significant variation in distribution within these three groups and therefore we conclude that vitamin D may not be major risk factor for prostate cancer in this population. However, there is considerable variation in the distribution frequencies from country to country and this, combined with differences in sun exposure, means that the results may not be extrapolated to the general case.

Age Distribution↗
PubMed2002

Decreased suburethral prostatic microvessel density in finasteride treated prostates: a possible mechanism for reduced bleeding in benign prostatic hyperplasia.

PURPOSE: We evaluated the influence of finasteride on prostatic microvessel density to elucidate a mechanism of decreased bleeding in finasteride treated patients with hematuria secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 22 patients with clinical BPH and gross hematuria who underwent prostate reductive surgery between 1998 and 2000 were prospectively evaluated. The prostate from 10 finasteride treated and 12 untreated patients was immunohistochemically stained for CD-34. Microvessel density analysis was performed by quantifying positive stained blood vessels located within the stroma of hyperplastic nodules as well as in the suburethral portion of the prostate. RESULTS: Mean microvessel density plus or minus standard deviation in finasteride treated patients was significantly lower in the suburethral portion of the prostate versus untreated controls (14.0 +/- 2.8 versus 20.2 +/- 5.3 vessels per high power field, p <0.05). In the nodular hyperplasia there was no statistically significant difference in the treatment and control groups (mean 17.5 +/- 2.8 and 16.7 +/- 4.6 vessels per high power field, respectively). CONCLUSIONS: Finasteride significantly decreases suburethral prostatic microvessel density in patients with BPH, which may explain its efficacy for decreasing BPH associated bleeding.

Aged↗
PubMed2002

Clinical predictors in the use of finasteride for control of gross hematuria due to benign prostatic hyperplasia.

PURPOSE: We identify predictors of clinical response as well as response time in patients treated with finasteride for gross hematuria due to benign prostatic hyperplasia. MATERIALS AND METHODS: A retrospective chart review was preformed of 53 patients who had been given 5 mg. finasteride daily for the treatment of active bleeding or a recent history of recurrent bleeding. Urological evaluations were negative for tumor in all patients. A history of prostatectomy, anticoagulant status and prostate size was determined. The degree of hematuria was then graded before and after finasteride treatment according to our previously described system. Of the 53 patients who were actively bleeding at initial evaluation 16 were followed to determine time required for complete resolution of hematuria. RESULTS: Hematuria grade improved after finasteride in 50 (94%) patients. Overall 77% of patients (41 of 53) experienced no further bleeding while taking finasteride. Mean followup was 38 months (range 3 to 86). Of the patients 86% (12 of 14) taking coumadin, 77% (10 of 13) taking aspirin and 73% (19 of 26) on no anticoagulants had no further bleeding once on finasteride. Of the patients who had undergone prior transurethral prostatectomy 84% (26 of 31) experienced no further bleeding versus 68% (15 of 22) of those who had not undergone previous surgery. In the 16 patients who began finasteride while actively bleeding the average time to clear urine was 12 days (range 2 to 45). Prostatic volume correlated with the average time needed for resolution of hematuria, which was 2.7 days or longer for small (less than 40 gm.), 10.3 days or longer for large (40 to 100), 19 days or longer for extra large (100 to 150) and 45 days or longer for extra extra large (greater than 150) glands. Hematuria resolved an average of 5.5 days versus 18.6 days in those who had or had not undergone previous prostatectomy, respectively. CONCLUSIONS: Our long-term followup demonstrates finasteride as a useful treatment for benign prostatic hyperplasia related gross hematuria, which is effective in patients who are on anticoagulants. In patients with larger prostatic volumes a longer time to response and higher incidence of recurrent but lower grade bleeding should be anticipated compared to those who have undergone prior prostatectomy or have a smaller prostate.

5-alpha Reductase Inhibitors↗
PubMed2005

Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia.

PURPOSE: The relationship of lower urinary tract symptoms (LUTS) to objective measures of benign prostatic hyperplasia (BPH), such as prostatic size and urodynamic parameters, has proved difficult to evaluate. Studies in animal models of BPH suggest that autonomic nervous system (ANS) activity is an important determinant of prostatic growth. We investigated the relationship of ANS activity to LUTS as well as to objective measures of BPH in men with BPH. MATERIALS AND METHODS: This study was done in 3,047 men with LUTS secondary to BPH during screening for enrolment at 1 center in a large, multicenter, double-blind, placebo controlled trial designed to assess the long-term effects of medical therapy on BPH progression. A total of 38 men with an American Urological Association (AUA) symptom score of 8 or greater and a maximum urinary flow rate of 4 to less than 15 ml per second had ANS activity assessed based on heart rate, blood pressure, the response to circulatory stress via tilt table, and plasma and urinary catecholamine. These ANS related variables were compared with subjective measures of LUTS (AUA symptom score, quality of life score and BPH impact index), overall health measures (RAND 36-Item Health Survey) and objective clinical measures of BPH (prostate size, post-void residual volume and maximum urinary flow rate). Pearson correlation coefficients were calculated for each ANS variable vs each LUTS and BPH variable. These correlations were further assessed using stepwise multiple regression analysis to determine which BPH and LUTS variables were independently related to the ANS variable. Relationships that were identified as significant then underwent final multiple regression analysis together with control variables to exclude known extraneous and confounding influences on ANS activity. RESULTS: After adjusting for extrinsic influences on ANS activity AUA symptom score (p <0.01), BPH impact index score (p <0.001) and quality of life score (p <0.05) were independently associated with the change in systolic and diastolic blood pressure 1 and 5 minutes after tilt. Additionally, prostate transition zone volume (p <0.001) and the RAND 36-Item Health Survey mental subscale score (p <0.001) were independently associated with the plasma norepinephrine response to tilt. CONCLUSIONS: ANS hyperactivity is significantly associated with the most commonly used measures of LUTS, namely AUA symptom score and BPH impact index score. Also, the magnitude of the serum norepinephrine increase after tilt predicts prostate size. These relationships persist after controlling for extrinsic influences on ANS activity. The current findings may have important implications concerning the pathophysiological mechanisms underlying or influencing LUTS as well as its optimal treatment in men with BPH.

Aged↗
PubMed1998

Temperature controlled high energy transurethral microwave thermotherapy for benign prostatic hyperplasia using a heat shock strategy.

PURPOSE: We evaluate the clinical outcome of temperature controlled high energy transurethral microwave thermotherapy for benign prostatic hyperplasia using heat shock strategy. MATERIALS AND METHODS: A total of 32 patients were evaluated 3, 6 and 12 months after thermotherapy according to symptom scores, uroflowmetry, residual urine volume, sexual functions and side effects. RESULTS: At 12 months symptom score and maximum flow rate had improved 79% from 13.5 to 2.9, and 71% from 10.0 to 17.1 ml. per second, respectively. Furthermore, bother and quality of life scores and residual and voided urine volumes had improved significantly. However, a higher morbidity than previously shown after lower energy protocols was demonstrated. Treatment influenced sexual functions, especially ejaculation quality, and after treatment 29% of the patients had anejaculation. Significantly less energy was required for prostate volumes 40 ml. or greater to reach the same intraprostatic temperature level as those less than 40 ml. as demonstrated by radiometry. CONCLUSIONS: High energy transurethral microwave thermotherapy using a heat shock strategy is an effective treatment for benign prostatic hyperplasia and produces a better outcome than shown with lower energy protocols. However, the morbidity is not negligible and ejaculation quality is affected. Less relative energy is needed for large than small prostate volumes to reach the same intraprostatic temperature level as demonstrated by radiometry.

Ejaculation↗
PubMed1998

The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.

BACKGROUND: Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, is not known. METHODS: In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men. RESULTS: During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001). CONCLUSIONS: Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the risk of surgery and acute urinary retention.

5-alpha Reductase Inhibitors↗
PubMed2005

Cell death mechanisms associated with G2 radiosensitivity in patients with prostate cancer and benign prostatic hyperplasia.

Cells respond to genotoxic insults such as ionizing radiation by halting in the G2 phase of the cell cycle. Delayed cell death (mitotic death) can occur when the cell is released from G2, and specific spindle defects form endopolyploid cells (endoreduplication/tetraploidy). Enhanced G2 chromosomal radiosensitivity has been observed in many cancers and genomic instability syndromes, and it is manifested by radiation-induced chromatid aberrations observed in lymphocytes of patients. Here we compare the G2 chromosomal radiosensitivity in prostate patients with benign prostatic hyperplasia (BPH) or prostate cancer with disease-free controls. We also investigated whether there is a correlation between G2 chromosomal radiosensitivity and aneuploidy (tetraploidy and endoreduplication), which are indicative of mitotic cell death. The G2 assay was carried out on all human blood samples. Metaphase analysis was conducted on the harvested chromosomes by counting the number of aberrations and the mitotic errors (endoreduplication/tetraploidy) separately per 100 metaphases. A total of 1/14 of the controls were radiosensitive in G2 compared to 6/15 of the BPH patients and 15/17 of the prostate cancer patients. Radiation-induced mitotic inhibition was assessed to determine the efficacy of G2 checkpoint control in the prostate patients. There was no significant correlation of G2 radiosensitivity scores and mitotic inhibition in BPH patients (P = 0.057), in contrast to prostate cancer patients, who showed a small but significant positive correlation (P = 0.029). Furthermore, there was no significant correlation between G2 radiosensitivity scores of BPH patients and endoreduplication/ tetraploidy (P = 0.136), which contrasted with an extremely significant correlation observed in prostate cancer patients (P < 0.0001). In conclusion, cells from prostate cancer patients show increased sensitivity to the induction of G2 aberrations from ionizing radiation exposure but paradoxically show reduced mitotic indices and aneuploidy as a function of aberration frequency.

Aged↗
PubMed1998

In vivo differential diagnosis of prostate cancer and benign prostatic hyperplasia: localized proton magnetic resonance spectroscopy using external-body surface coil.

Localized proton-stimulated echo acquisition mode (STEAM) spectroscopy was performed in seven patients with benign prostatic hyperplasia (BPH), six patients with prostate cancer, and seven healthy volunteers to determine whether citrate levels detected using a saddle-type external-body surface coil (two loops of 13 cm x 17 cm) could reliably discriminate BPH from prostatic cancer. Relative area ratios of citrate level to choline plus creatine or citrate to lipid signal were compared with postoperative pathologic histology findings. The metabolic signals were well detectable as much as the line width of water resonance was ranging from 5 to 9 hz. Average SNRs of citrate in BPH and prostate cancer were 11.4 and 1.9, respectively. The major finding was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate central gland. This was significantly (p < 0.01) reflected by lower mean citrate/[creatine+choline] peak area ratio and citrate/lipid peak area ratio observed for region of cancer (0.446 +/- 0.063, 0.097 +/- 0.030) compared with BPH (1.458 +/- 0.107, 0.786 +/- 0.162) and normal central gland (1.418 +/- 0.129, 0.175 +/- 0.011), respectively. These studies demonstrate the potential of citrate spectrum detected by an external-body surface coil as an in vivo marker for discriminating prostate cancer from BPH.

Adult↗