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PubMed1996

Screening and early detection of prostate cancer will decrease morbidity and mortality from prostate cancer: the argument against.

The ability of prostate specific antigen, digital rectal examination and transurethral ultrasound, either individually or in combination, to detect unsuspected prostate cancer is beyond doubt. Early detection programmes have revealed prostate cancer in 6% of men over 50 years of age. Most are stage T1c, or confined to the prostate but, protagonists claim that, on the basis of size, they are 'clinically significant'. Mortality from this disease should be reduced by their treatment. Available statistics suggest that the lifetime incidence of 'screen-detected' cancers will far exceed the likelihood of dying from prostate cancer. Given the current operative mortality of total prostatectomy and the physical and psychological morbidity of screening, biopsy and treatment, it is far from certain that mortality or morbidity from prostate cancer will be decreased. Long-term outcome data for T1c prostate cancer do not exist. Is the likelihood of prostate cancer death the same for prostate-specific antigen thresholds of 2, 3 or 4 ng/ml, or from tumours found in 1 of 6, or 1 of 12 needle biopsies? None of this is known. European men deserve the benefit of scientifically based information before being exposed to another North American fashion. Prospective randomised trials investigating mortality, quality of life and cost benefit are the only solution.

Aged↗

PubMed1997

Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer: DAPROCA study 9002. Danish Prostatic Cancer Group.

PURPOSE: We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer. MATERIALS AND METHODS: In a double-blind multicenter study 131 patients with progressing metastatic hormone refractory prostate cancer were randomized to receive 280 mg. estramustine phosphate 2 times daily versus placebo. End points were clinical progression and death. Adverse events, decrease in prostate specific antigen (PSA) and subjective response were also assessed. RESULTS: Adverse events were common in both groups but breast tenderness/gynecomastia and diarrhea were more frequent among patients in the estramustine phosphate group. Subjective responses were few (9 of 50 estramustine phosphate and 4 of 57 placebo cases, p = 0.15). Median observation time for survival was 43 months and 124 patients died. Median time to subjective progression and median overall survival did not differ significantly between the 2 groups at 4.6 and 9.4 months in the estramustine phosphate group versus 5.0 and 6.1 months in the placebo group. Of 61 patients in the estramustine phosphate group 29 achieved a reduction in PSA of more than 25% at 1 month of followup compared to only 3 of 68 receiving placebo. A decrease in PSA after 1 month correlated significantly with survival. CONCLUSIONS: Although this study did not prove estramustine phosphate to be superior to placebo in terms of protocol end points, it generates the hypothesis that prolonged survival may be achieved with estramustine phosphate treatment in a subgroup of patients and that this may be predicted by a decrease in PSA after 1 month of therapy.

Aged↗

PubMed1999

Expression of the prostate cancer metastasis suppressor gene KAI1 in primary prostate cancers: a biphasic relationship with tumour grade.

The KAI1 gene, isolated from human chromosome 11p11.2, has been implicated as a prostate cancer metastasis suppressor gene. Recent studies have demonstrated that the expression of KAI1 protein is reduced in metastases of human prostate cancers and is inversely correlated with tumour grade. The objectives of the present work were to determine whether alterations of KAI1 at a genetic level in localized prostate cancers correlate with degrees of differentiation. This paper reports the application of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis to two different regions of the KAI1 gene on 35 microdissected primary prostate cancer specimens and demonstrates a biphasic pattern of KAI1 expression according to histological grade. KAI1 mRNA, relative to the housekeeping gene beta -actin, was elevated in low-grade primary prostate cancer (2.7+/-0.4) compared with non-malignant (hyperplastic) prostatic tisues (0.92+/-0.02, p< 0.05), yet reduced in high-grade primary cancers (0.61+/-0.11, p< 0. 05). These data demonstrate, for the first time, that KAI1 is biphasically expressed in primary prostate cancers and suggest that hyperexpression of KAI1 in low-grade prostate cancer may be associated with restraint of tumour progression, whereas a relative decrease in KAI1 gene expression may accompany more aggressive cancers through loss of such restraint. This differential expression of the metastasis suppressor gene KAI1 in primary prostate cancers may have important prognostic implications for the development of subsequent metastases. Should the level of KAI1 in primary prostate cancer be correlated with patient outcome such information may, in the future, enable more intensive adjuvant therapy to be directed to those patients identified to be at greatest risk of metastasis.

Antigens, CD↗

PubMed2004

Alcohol and the risk of prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: To examine the association between alcohol and the risk of prostate cancer/benign prostatic hyperplasia (BPH) in a population with a wide range of alcohol consumption, using a hospital-based, case-control study. Data from several epidemiologic studies have allowed us to exclude a strong association between alcohol drinking and prostate cancer risk. However, limited information is available for BPH. Also, it is unclear whether various types of alcoholic beverages may have a different impact on risk. METHODS: We conducted this hospital-based case-control study in Italy between 1991 and 2002. A total of 2663 men younger than 75 years had incident, histologically confirmed prostate carcinoma (1294 cases) or symptomatic obstructive BPH (1369 cases) (maximal flow rate less than 15 mL/s) refractory to medical treatment. A total of 1451 patients younger than 75 years were used as controls. Odds ratios and corresponding 95% confidence intervals were estimated using unconditional multiple logistic regression models including terms for age, center, education, body mass index, physical activity, and family history of prostate cancer. RESULTS: Alcohol consumption showed no consistent association with prostate cancer risk, but a statistically significant inverse trend in risk for BPH. Compared with abstainers, the odds ratio was 0.88 for fewer than three drinks, 0.71 for three to four drinks, 0.79 for five to six drinks, and 0.65 for seven or more drinks per day. The patterns of risk were similar with reference to different alcoholic beverages. The inverse relation between elevated alcohol consumption and BPH was apparently stronger in subjects with a lower body mass index. CONCLUSIONS: Alcohol drinking is unrelated to prostate cancer risk. The inverse relationship with BPH may be related to the hormonal correlates (ie, lower androgen levels) of heavy alcohol drinkers.

Adenocarcinoma↗

PubMed2005

Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI.

PURPOSE: To differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. MATERIAL AND METHODS: Tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. RESULTS: Axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm(3). In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420 % (p < 0.001) and 424 % (p < 0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. CONCLUSION: The results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model.

Animals↗

PubMed2001

Pathological features of prostate cancer detected on initial and repeat prostate biopsy: results of the prospective European Prostate Cancer Detection study.

PURPOSE: We evaluated pathological features of prostate cancer detected on repeat prostate biopsy in men with a serum total prostate-specific antigen (PSA) level between 4 and 10 ng/ml who were diagnosed with benign prostatic tissue after an initial biopsy and compared them to those cancers detected on initial prostate biopsy. MATERIALS AND METHODS: In this prospective European prostate cancer detection study, 1,051 men with a total PSA level between 4 and 10 ng/ml underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Initial biopsy was positive (CaP) in 231 of 1,051 enrolled subjects and negative (benign histology) in 820 subjects. Of these 820 subjects, CaP was detected in 10% (83/820) upon repeat biopsy. Of cancers detected on initial and repeat biopsy, 148/231 (64%) and 56/83 (67.5%) had clinically localized disease, respectively, and were offered radical prostatectomy. 10/148 (6.7%) and 3/56 (5.3%), respectively, opted for radiation therapy and thus, 138/148 (93.3%) and 53/56 (94.7%), respectively, underwent radical retropubic prostatectomy. There were statistically significant differences with respect to multifocality (P = 0.009) and cancer location (P < 0.001) with cancers on repeat biopsy showing a lower rate of multifocality and a more apico-dorsal location. In contrast, there were no differences with respect to stage (P = 0.2), Gleason score (P = 0.36), percentage Gleason grade 4/5 (P = 0.1), serum PSA (P = 0.62), and patient age (P = 0.517). CONCLUSIONS: At least 10% of patients with negative prostatic biopsy results will be diagnosed with CaP on repeat biopsy. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy are similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Cancers missed on initial biopsy and subsequently detected on repeat biopsy are located in a more apico-dorsal location. Repeat biopsies should thus be directed to this rather spared area in order to improve cancer detection rates.

Age Factors↗

PubMed2000

[Treatment of localized prostatic cancer--different alternatives. Patients with localized prostatic cancer must actively participate in the choice of therapy].

The treatment options currently available for patients with clinically localized prostate cancer are radical prostatectomy, irradiation and deferred symptom-guided treatment. Today we do not have any controlled data indicating that any of these treatments is better than the other. Management policies that have evolved are, at best, based on structured comparisons of data from uncontrolled treatment series. In such comparisons the differences between the various treatment options with respect to disease-specific survival up to 10 to 15 years after diagnosis are modest. These comparisons are based on patient series diagnosed 15 to 20 years ago, i.e. before prostate specific antigen (PSA) was available as a marker for prostate cancer. The utilization of PSA has dramatically changed the conditions for diagnosing prostate cancer, in that with PSA we find more men with prostate cancer with smaller tumors at diagnosis. Today we find many tumors because of an elevated PSA followed by systematic biopsies in men without palpable prostatic lesions. Thus it is difficult to translate long-term outcome data from older patient series to the current situation in which tumors are found under changed clinical conditions. Consequently, a patient can only be informed about the different treatment options and their side effects. In the treatment decision process he has to balance a possible benefit in survival against side effects, according to his own preferences. We need randomized studies comparing the different treatment options. Such research is under way in Scandinavia, but due to the long course of the disease we will probably have to wait many years before we can answer the questions which sparked these studies.

Antineoplastic Agents↗

PubMed2004

Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy.

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

Carbohydrates↗

PubMed1995

[Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using endorectal 1H magnetic resonance spectroscopy].

BACKGROUND: We evaluate the usefulness of 1H endorectal resonance spectroscopy to characterize prostate pathology. METHODS: With an endorectal surface coil we have studied 20 individuals with normal (1), benign hyperplastic (9) and malignant (10) prostates. RESULTS: The major findings of our studies were that the patients with cancer have a significantly lower citrate-to-choline ratio (cit/cho) and creatin-to-choline ratio (cre/cho) than the patients with BPH (p < 0.05). There is well correlation between cit/cho and gland-to-stroma ratio of the BPH tissue as well as histological grade of the cancer tissue. 1H spectroscopy offers the advantages of differential diagnosis between benign and malignant prostates. We, however, failed to demonstrate cancer in 2 cases; the lesion was too small in one case, and out of the region of interest in the other. It is necessary that the foci in the prostate is at least 1.5 X 1.5 X 1.5 cm3 of the volume in order to obtain genuine spectrogram of carcinoma. CONCLUSION: Endorectal 1H magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Adult↗

PubMed2003

Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients.

Prostate specific membrane antigen (PSMA) is a folate gamma glutamyl carboxypeptidase that is oriented on the plasma membrane of normal and prostate cancer cells. A cytosolic version of PSMA, PSM', results from alternative splicing of the PSMA gene. Two additional alternatively spliced variants of PSMA, PSM-C and PSM-D, have been described recently. The ratio of PSMA to PSM' mRNA was higher in a small number of prostate cancer specimens compared to normal prostate cancer and benign prostatic hypertrophy (Su et al. Cancer Res 1995;55:1441). The intent of our study was to measure the gene expression of PSMA and the 3 PSMA splice variants in a large number of patient's tissues. A real-time, quantitative PCR assay was developed to quantify PSMA, PSM', PSM-C and PSM-D. Discrimination among the variants was achieved by designing unique primers and TaqMan probes for each gene. Amplification and detection was specific for the desired splice variant and was sensitive to one gene copy per reaction. The assay was used to quantify the gene expression in specimens of normal, benign, primary and metastatic prostate cancer from 72 patients. The mean PSMA expression (relative to 18S rRNA) was 2- to 3-fold lower in normal prostate (n = 4) compared to primary (n = 55, p = 0.31) and metastatic (n = 20, p = 0.33) prostate cancer. There was no difference in the PSMA expression between benign and cancerous prostate tissue from the same patients (n = 35). The ratio of PSMA to PSM' was lowest in the normal prostate and increased with increasing Gleason score (p < 0.001). The increased ratio in these tissues was a reflection of both increasing PSMA levels and decreasing PSM' mRNA. The expression of PSM-C did not differ in any of the tissue categories studied. The expression of PSM-D was similar in normal and primary prostate cancer but was 2-fold higher in lymph node (p < 0.005) and bone metastases (p < 0.05) compared to the primary tumors. Our results of the first detailed quantitative analysis of PSMA mRNA expression in patient's tissues demonstrate that PSMA and the 3 PSMA splice variants are expressed in normal, benign, cancerous and metastatic prostate cancer. We note increased PSMA expression in some malignant tissues, however, these increases are modest in magnitude. We also report that the expression of a novel splice variant, PSM-D, is elevated in prostate cancer metastases.

Alternative Splicing↗

PubMed2005

Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells.

Prostate cancer is the second leading cause of cancer deaths among men in the United States. Studies show that people with diets rich in tomato-based foods have reduced risks of cancer, viz., prostate cancer. This is attributed, in part, to lycopene, the most abundant carotenoid in tomatoes. Thus, we studied the effect of lycopene at physiologically attainable concentrations on apoptosis, cellular proliferation, and necrosis in LNCaP human prostate cancer cells. Cells at 37 degrees C and >80% confluency were treated with media alone (0.32% tetrahydrofuran vehicle) or with increasing concentrations (0.3-3.0 microM) of lycopene overnight. After washing monolayers, analyses by high-performance liquid chromatography (HPLC) showed that cellular accumulation of lycopene was 5.5 +/- 0.8, 14.0 +/- 3.2, and 36.7 +/- 12.3 pmole/10(6) cells for 0.3, 1.0, and 3.0 muM, respectively, and not detected in control cells. Lycopene did not alter cellular proliferation because bromodeoxyuridine (BrdU) incorporation and cell numbers were identical among groups. However, results of a 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay showed that mitochondrial function decreased 61%-83% with increasing concentrations of lycopene (P < 0.001). Cytotoxicity and necrosis did not contribute to this effect because lactate dehydrogenase (LDH) release (1.5%-1.8%) and trypan blue exclusion (89%-93%) were similar. Subsequently, we demonstrated that increasing concentrations of lycopene significantly (P < 0.05) reduced mitochondrial transmembrane potential, induced the release of mitochondrial cytochrome c, and increased annexin V binding, confirming induction of apoptosis. Thus, lycopene at physiologically relevant concentrations did not affect cellular proliferation or promote necrosis but clearly altered mitochondrial function and induced apoptosis in LNCaP human prostate cancer cells.

Anticarcinogenic Agents↗

PubMed2001

Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells.

Prostate cancer is one of the most common cancers in men and it is the second leading cause of cancer related death in men in the United States. Recent dietary and epidemiological studies have suggested the benefit of dietary intake of fruits and vegetables in lowering the incidence of prostate cancer. A diet rich in fruits and vegetables provides phytochemicals, particularly indole-3-carbinol (I3C), which may be responsible for the prevention of many types of cancer, including hormone-related cancers such as prostate. Studies to elucidate the role and the molecular mechanism(s) of action of I3C in prostate cancer, however, have not been conducted. In the current study, we investigated whether I3C had any effect against prostate cancer cells and, if so, attempts were made to identify the potential molecular mechanism(s) by which I3C elicits its biological effects on prostate cancer cells. Here we report for the first time that I3C inhibits the growth of PC-3 prostate cancer cells. Induction of G1 cell cycle arrest was also observed in PC-3 cells treated with I3C, which may be due to the observed effects of I3C in the up-regulation of p21(WAF1) and p27(Kip1) CDK inhibitors, followed by their association with cyclin D1 and E and down-regulation of CDK6 protein kinase levels and activity. The induction of p21(WAF1) appears to be transcriptionally upregulated and independent of the p53 responsive element. In addition, I3C inhibited the hyperpohosphorylation of the Retinoblastoma (Rb) protein in PC-3 cells. Induction of apoptosis was also observed in this cell line when treated with I3C, as measured by DNA laddering and poly (ADP-ribose) polymersae (PARP) cleavage. We also found an up-regulation of Bax, and down-regulation of Bcl-2 in I3C-treated cells. These effects may also be mediated by the down-regulation of NF-kappaB observed in I3C treated PC-3 cells. From these results, we conclude that I3C inhibits the growth of PC-3 prostate cancer cells by inducing G1 cell cycle arrest leading to apoptosis, and regulates the expression of apoptosis-related genes. These findings suggest that I3C may be an effective chemopreventive or therapeutic agent against prostate cancer.

Anticarcinogenic Agents↗

PubMed2002

Early versus deferred androgen suppression in the treatment of advanced prostatic cancer.

BACKGROUND: Prostate cancer is a leading cause of cancer death in men. Treatment goals for men with advanced prostate cancer include prolonging survival, preventing or delaying symptoms due to disease progression, improving and maintaining quality of life, reducing treatment related morbidity. Androgen suppression therapy is considered a mainstay of treatment for men with advanced prostate cancer. However it is not clear whether early androgen suppression for men with locally advanced disease or asymptomatic metastases improves length and quality of life compared to androgen suppression deferred until signs and symptoms of clinical progression. OBJECTIVES: This systematic review assessed the efficacy and adverse effects of primary therapy with early versus deferred androgen suppression therapy in men with advanced prostate cancer. SEARCH STRATEGY: Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, CancerLIT, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies including those of the Blue Cross and Blue Shield Association Technology Evaluation Center/Evidence-based Practice Center of the Agency for Healthcare Research and Quality (BCBS/TEC-AHRQ) report No.4. SELECTION CRITERIA: All published randomized trials were eligible for inclusion provided they: randomized men with advanced prostate cancer to early versus deferred androgen suppression; reported overall, progression-free, and cancer-specific survival, and/or adverse events; did not utilize androgen suppression as adjuvant therapy to radiation treatment. DATA COLLECTION AND ANALYSIS: An independent reviewer using a standardized form extracted information on trial characteristics, interventions, and outcomes. Results were reviewed for accuracy and discrepancies resolved by discussion. The main outcome measure for comparing effectiveness was the overall survival at 1, 2, 5 and 10 years. Progression-free survival, cancer-specific survival, complications due to disease progression and the incidence of adverse effects of treatment were also measured. MAIN RESULTS: Four trials involving 2,167 patients were included in this review. All of the trials were conducted prior to use of prostate specific antigen (PSA) testing. There was variability between studies regarding the treatments used and the requirements for initiation of treatments. The percent overall survival at 1, 2, 5, and 10 years for the early treatment group was 88%, 73%, 44%, and 18%. For the deferred therapy group the percent overall survival was 86%, 71%, 37%, and 12%. The pooled estimate for the difference in overall survival favored early therapy but was significant only at 10 years when few patients had survived [OR = 1.16 (95% CI: 0.90 to 1.49) at 1 year, 1.08 (95% CI: 0.89 to 1.33) at 2 years, 1.19 (95% CI: 0.95 to 1.50) at 5 years, and 1.50 (95% CI: 1.04 to 2.16) at 10 years]. The pooled estimate of prostate cancer specific survival at 2, 5, and 10 years favored early therapy though the confidence intervals were wide and the results not statistically different. The risk differences at 2, 5, and 10 years were 2.7%, 5.8%, and 4.6%. Although each study used unique definitions of progression free survival, all studies found progression free survival was consistently better in the early intervention group at all time points. Complications due to disease progression were only reported in one study but were more frequent in the deferred treatment group. Adverse events due to treatment were also only reported in one study but occurred more frequently in the early treatment group. REVIEWER'S CONCLUSIONS: The evidence from randomized controlled trials is limited by the variability in study design, stage of cancer and subjects enrolled, interventions utilized, definitions and reporting of outcomes and the lack of PSA testing for diagnostic and monitoring purposes. However, the available information suggests that early androgen suppression for treatment of advanced prostate cancer reduces disease progression and complications due to progression. Early androgen suppression may provide a small but statistically significant improvement in overall survival at 10 years. There was no statistically significant difference in prostate cancer specific survival but a clinically important difference could not be excluded. These outcomes need to be evaluated with the evidence suggesting higher costs and more frequent treatment related adverse effects with early therapy. Additional studies are required to evaluate more definitively the efficacy and adverse effects of early versus delayed androgen suppression in men with prostate cancer. In particular trials should evaluate patients with advanced prostate cancer diagnosed by PSA testing and men with persistent or rising PSA levels following treatment options (e.g. radical prostatectomy, radiation therapy or observation) for clinically localized disease.

Androgen Antagonists↗

PubMed2003

Increased expression of bone morphogenetic protein-7 in bone metastatic prostate cancer.

BACKGROUND: Prostate cancer frequently metastasizes to bone. The skeletal metastases of prostate cancer origin are osteoblastic rather than osteolytic. Recently, the expression of bone morphogenetic proteins (BMPs) in prostate cancer cell lines was detected. The present study indicated the existence of BMP-7 in normal prostate tissue, but its function has not been clarified. The mechanism by which prostate cancer causes osteoblastic metastasis is not clear. We investigated the expression of BMP-7 and -6 in normal and metastatic bone tissues to clarify the biological relationship between the expression of BMPs and bone metastasis in prostatic cancer. METHODS: Six samples of normal bone tissue and nine samples of bone metastasis tissue were collected during the autopsies of six patients with prostate cancer. Total RNA was extracted from these samples. After reverse transcription (RT) of the RNA samples, the expression of BMP-6 and -7 in each sample was measured by the real-time quantitative polymerase chain reaction (PCR). Glyceraldehyde phosphate dehydrogenase (GAPDH) was used as an internal standard. RESULTS: Although the expression of BMP-7 was detected in five out of seven (71%) metastatic bone lesions of prostate cancer, it was not detected in normal bone tissues. The expression level of BMP-7 was significantly higher in metastatic bone lesions than in normal bone (P < 0.05). There was no significant difference between the level of expression of BMP-6 in metastatic bone lesions from prostate cancer and the level in normal bone tissue (P = 0.81). CONCLUSIONS: These results suggest that high expression of BMP-7 in metastatic bone lesions of prostate cancer is related to osteoblastic metastasis. BMP-7 in the bone metastasis tissue indicates that the cells expressing BMP-7 probably originated from the prostate, because we have detected high expression of BMP-7 in the prostate. Prostate 54: 268-274, 2003.

Bone Morphogenetic Protein 6↗

PubMed1997

A multicenter study on the detection of prostate cancer by digital rectal examination and prostate-specific antigen in men with or without urinary symptoms. Cooperative Group for Diagnosis of Prostate Cancer.

OBJECTIVE: The use of prostate-specific antigen (PSA) for prostatic cancer screening and the practical utility of the concept of PSA density are controversial. The aim this multicenter study was to assess the usefulness of PSA as a diagnostic procedure for prostate cancer in patients with urinary symptoms, and compare it with digital rectal examination (DRE). METHODS: We performed a multicenter study in 18 hospitals to assess the value of PSA in the diagnosis of prostate cancer. 2,054 outpatients, aged above 50 years, were included in the study. Patients with suspected prostatitis or severe systemic disease were excluded. PSA levels were measured in all patients (IMx) and a DRE was also performed. Patients with PSA levels > 3 ng/ml and/or a suspicious DRE underwent transrectal ultrasound and a prostate biopsy. RESULTS: PSA levels > 3 ng/ml and/or a suspect DRE were found in 680 (33%) patients, in 587 (29%) of whom a biopsy was performed. A cancer of the prostate was diagnosed in 131 patients. The cancer detection rate was 5.89% for PSA > 4 ng/ml, 4.38% for DRE and 6.37% for the combination of both methods. The combination of PSA and DRE allows for increasing the diagnostic sensitivity which would be achieved with either test alone. CONCLUSION: We recommended the use of PSA and DRE in combination as a diagnostic procedure for prostate cancer, since these are complementary methods which allow for detecting a population at a high risk of suffering prostate cancer.

Aged↗

PubMed2006

Histopathological characteristics of a novel knock-in mouse prostate cancer model.

Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP) model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system) similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50%) and showed a significant correlation with age (P = 0.001). Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid, analogous to the human situation. The similarities of the KIMAP mouse model with tumors of the human prostate suggest the use of this experimental model to complement studies of human prostate cancer.

Adenocarcinoma↗

PubMed2000

[Hereditary prostate cancer].

Familial prostate cancer patients are sometimes encountered. Hereditary prostate cancer is a more specific form of familial prostate cancer that is inherited by a susceptibility gene consistent with Mendelian inheritance. Early age at onset is the most important characteristic. No clear differences in either stage, grade or prognosis have been found between hereditary and sporadic prostate cancer. No susceptibility genes have been isolated yet, but several genes may exist. In Japan, doctors are not generally aware of hereditary and familial prostate cancer. Family history is one of the most important risk factors of prostate cancer. We should make an effort to find prostate cancer patients at an early stage in the high risk families.

Adult↗

PubMed2006

Combination therapy of androgen-independent prostate cancer using a prostate restricted replicative adenovirus and a replication-defective adenovirus encoding human endostatin-angiostatin fusion gene.

Although prostate-restricted replicative adenovirus has exhibited significant antitumor efficacy in preclinical studies, it is necessary to develop more potent adenoviruses for prostate cancer gene therapy. We evaluated the synergistic killing effect of prostate-restricted replicative adenovirus and AdEndoAngio, a replication-defective adenovirus expressing the endostatin-angiostatin fusion protein (EndoAngio). When coadministered with AdEndoAngio, prostate-restricted replicative adenovirus significantly elevated EndoAngio expression, suggesting that AdEndoAngio coreplicates with prostate-restricted replicative adenovirus. Conditioned medium from prostate cancer cells infected by prostate-restricted replicative adenovirus plus AdEndoAngio inhibited the growth, tubular network formation, and migration of human umbilical vein endothelial cells better than conditioned medium from prostate cancer cells infected by AdEndoAngio alone. Furthermore, in vivo animal studies showed that the coadministration of prostate-restricted replicative adenovirus plus AdEndoAngio resulted in the complete regression of seven out of eight treated androgen-independent CWR22rv tumors, with a tumor nodule maintaining a small size for 14 weeks. The residual single tumor exhibited extreme pathologic features together with more endostatin-reactive antibody-labeled tumor cells and fewer CD31-reactive antibody-labeled capillaries than the AdEndoAngio-treated tumors. These results show that combination therapy using prostate-restricted replicative adenovirus together with antiangiogenic therapy has more potent antitumor effects and advantages than single prostate-restricted replicative adenovirus and deserves more extensive investigation.

Adenoviridae↗