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PubMed1988

[Clinical studies against chronic prostatitis and prostatitis-like syndrome (1). Clinico-statistical observation].

We clinically evaluated 605 cases of chronic prostatis and other resembling disorders. The incidence was 4.34% of all out-patients (7.54% of male patients). The average age was 38.1 years, and many were adolescents. A greater number of out-patients were seen in October, November, and December (p less than 0.01) and June (p less than 0.05). The type of disease was chronic prostatitis in 48.1% (bacterial in 5.3%, non-bacterial in 42.8%) and prostatitis-like syndrome in 51.9%. The incidence among male patients was 3.63% for chronic prostatitis (bacterial in 0.40%, non-bacterial in 3.23%), and 3.91% for prostatitis-like syndrome. In the case of chronic prostatis, the abnormal finding rate (p less than 0.01), tenderness (p less than 0.01), induration (p less than 0.05) on prostatic palpation, non-pretreated rate (p less than 0.01), urological past history (p less than 0.05) except prostatitis and urological complications (p less than 0.01) were significantly higher. On the other hand, the negative rate on urine culture (p less than 0.01), no abnormal findings on palpation (p less than 0.01), discomfort (p less than 0.01), discomfort with tenderness (p less than 0.01) and past prostatitis episodes (p less than 0.01) were seen significantly more in the case of prostatitis-like syndrome. In conclusion, chronic prostatitis with inflammatory change on prostate and prostatitis-like syndrome without inflammation have similar clinical features, but should be diagnosed as totally different types of disease.

Adolescent↗
PubMed1996

[Prostate-specific antigen in the diagnosis of organ-confined treatable prostate carcinoma].

Prostate cancer is now the most common cancer and the second most common cause of death from cancer among men. Several studies have shown a frequency of autopsy-detected cancer of 40% in men over 50 years of age. In contrast, the lifetime probability of prostate cancer being diagnosed clinically is only 8%. Thus histologically documented prostate cancer only becomes clinically relevant if the tumors are > 0.5 cm3 and the life expectancy exceeds 10 years. Therapy with curative intention is only possible for organ confined disease. Because disease specific survival is about 80-90% after 10 years for conservative treatment of organ confined disease, early detection of prostate cancer is useful for patients with a life expectancy > 10 years. Organ confined prostate cancer is usually asymptomatic. The use of prostate specific antigen (PSA) combined with digital rectal examination (DRE) results in a 2-3 fold increase in prostatic carcinoma detection rate, especially of organ confined disease, by PSA. In men with a minimally elevated PSA-value of 4-10 ng/ml (Hybritech Assays), 25% will have a prostatic carcinoma regardless of the finding of the DRE, which would have reached clinical significance in the follow-up. The indication for biopsy should be established at an early date. There is no support for the common opinion that early detection programs detect clinically unimportant cancers. 95% of tumor volumes are > 0.5 cm3. Furthermore only 3-5% of subjects show prostate cancer in detection programs though 8% will develop clinical symptoms of prostate cancer during their lifetime. This difference is a reason for longitudinal programs with PSA and DRE control once a year, as proposed by the American Cancer Society and the American and Canadian Urological Association, in contrast to other health care organizations, which would wait with general screening until data from prospective randomized trials with beneficial effects of screening are available. To introduce prostate cancer therapy with curative intention for symptomatic patients as well, the cancer should be detected below a PSA level of 10 ng/ml. Insufficient specificity of PSA (2-4 patients have to undergo biopsies to detect one cancer patient) is still an unsolved problem.

Aged↗
PubMed1996

The role of prostate-specific antigen in the chemoprevention of prostate cancer.

An understanding of the natural history of changes in prostate-specific antigen (PSA) may be valuable as a surrogate view of prostate dynamics, as a method to differentiate between benign and malignant growth, and as a means to assess the use of PSA as a tool for monitoring activity of chemoprevention agents. Although PSA appears to be useful as a noninvasive marker of prostatic growth, PSA changes should not be confused with a direct measure of tumor growth. Serum PSA levels are a function of tumor volume but are also influenced by the volume of benign epithelium, grade of carcinoma (if any), inflammation, androgen levels, growth factors, and the extracellular matrix. The biological functions of PSA in the prostate and in its secretions need to be more completely elucidated in order that PSA measurements may more accurately describe prostate dynamics. The expression of PSA is androgen-regulated. It is one of the most abundant prostate-derived proteins in the seminal fluid. Seminogelin, a major protein in seminal fluid, is cleaved by PSA, and this cleavage is important in the liquefaction of semen. Less is known about other PSA substrates. Current PSA studies indicate that cancer cases exhibit an early slow linear PSA phase followed by a rapid exponential phase, and that PSA levels begin to increase exponentially approximately 7-9 years before diagnosis. The establishment of age-specific PSA reference ranges (ASRR) and of PSA velocity (PSAV) rates provide elements of a baseline from which prediction models could measure malignant potential of a prostatic carcinoma. Moreover, recent discoveries of different molecular forms of PSA in serum may allow a much more accurate differentiation of benign and malignant growth as well as a more potent measure of the impact of chemoprevention agents. If PSA doubling time is approximately 2.4-3.0 years and accurately reflects tumor doubling time, and if the average man has less than 0.5 ml of latent prostatic tumor tissue and the average stage T2 cancer is approximately 4 ml when detected, then the available PSA data suggest that the 3 doublings necessary to change from 0.5-4.0 ml, would take 7-12 years for a typical small volume tumor to reach the size of most stage T2 tumors. The findings that histologic cancers appear at much younger ages than previously known is disturbing. It indicates that disease initiation may begin sooner than ever thought likely. "Normal" PSA levels for younger men (< 40 years of age) may need to be studied, and an emphasis upon premalignant lesions in this age group may be necessary. Younger men may represent the most appropriate population and premalignant lesions the most relevant clinical factor for prostate cancer chemoprevention studies and trials. The molecular composition and molecular changes of PSA derived from premalignant lesions have yet to be elucidated, but such investigations may lead to a more complete understanding of the possible progression or transformation of normal prostate cells to premalignancy and subsequently to carcinoma. High grade prostatic intraepithelial neoplasia (PIN) in and of itself does not account for elevated serum PSA levels, but subtle changes in the molecular dynamics of PSA may reveal the influence of androgens and the impact of chemopreventive agents.

Adult↗
PubMed1997

Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements.

OBJECTIVE: To determine the detection rate of prostate cancer in a screening population of men with prostate-specific antigen (PSA) concentrations of 2.6 to 4.0 ng/mL and a benign prostate examination, to assess the clinicopathological features of the cancers detected, and to assess the usefulness of measuring the ratio of free to total PSA to reduce the number of prostatic biopsies. DESIGN: A community-based study of serial screening for prostate cancer with serum PSA measurements and prostate examinations. SETTING: University medical center. SUBJECTS: A total of 914 consecutive screening volunteers aged 50 years or older with serum PSA levels of 2.6 to 4.0 ng/mL who had a benign prostate examination and no prior screening tests suspicious for prostate cancer, 332 (36%) of whom underwent biopsy of the prostate. MAIN OUTCOME MEASURES: Cancer detection rate, clinical and pathological features of cancers detected, and specificity for cancer detection using measurements of percentage of free PSA. RESULTS: Cancer was detected in 22% (73/332) of men who underwent biopsy. All cancers detected were clinically localized, and 81% (42/52) that were surgically staged were pathologically organ confined. Ten percent of the cancers were clinically low-volume and low-grade tumors, and 17% of those surgically staged were low-volume and low-grade or moderately low-grade tumors (possibly harmless). Using a percentage of free PSA cutoff of 27% or less as a criterion for performing prostatic biopsy would have detected 90% of cancers, avoided 18% of benign biopsies, and yielded a positive predictive value of 24% in men who underwent biopsy. CONCLUSIONS: There is an appreciable rate of detectable prostate cancer in men with serum PSA levels of 2.6 to 4.0 ng/mL. The great majority of cancers detected have the features of medically important tumors. Free serum PSA measurements may reduce the number of additional biopsies required by the lower PSA cutoff.

Aged↗
PubMedDate not supplied

Conformal high dose rate iridium-192 boost brachytherapy in locally advanced prostate cancer: superior prostate-specific antigen response compared with external beam treatment.

PURPOSE: Prostate-specific antigen levels are used to judge disease control of prostate cancer. No published data attest to the greater ability of conformal brachytherapy to control disease compared with conventional radiation at a single institution. This report compares the biochemical response rates in patients with stages T2b to T3c prostate cancer treated with conformal brachytherapy boost and external beam radiation with the rates in patients treated with conventional external radiation alone. MATERIALS AND METHODS: From November 1991 through November 1995, 58 patients received 45.6 Gy pelvic external irradiation and three high dose rate iridium-192 conformal boost implants of 5.5 to 6.5 Gy each. They were compared with 278 similarly staged patients treated from January 1987 through December 1991 with external beam radiation to prostate-only fields (median dose 66.6 Gy). No patient received androgen deprivation. Patient outcome was analyzed for biochemical control. Biochemical failure was defined as a prostate-specific antigen level > 1.5 ng/mL and rising on two consecutive values. If serial posttreatment prostate-specific antigen levels were showing a continuous downward trend, failure was not scored. RESULTS: Median follow-up was 43 months for the conventionally treated group and 26 months for the brachytherapy boost group. The median pretreatment prostate-specific antigen level was 14.3 ng/mL for the external-beam-radiation-alone group and 14.0 ng/mL for the brachytherapy boost group. The median Gleason scores were 6 and 7, respectively, for the two groups. The biochemical control rate was significantly higher in the brachytherapy boost treatment group. Three-year actuarial biochemical control rates were 85% versus 52% for the conformally and conventionally treated patients, respectively. In a multivariate analysis, the use of conformal brachytherapy boost and pretreatment prostate-specific antigen level were significant prognostic determinants of biochemical control. The 3-year actuarial rates of biochemical control for conformally versus conventionally treated patients, respectively, were 83% versus 72% for a pretreatment prostate-specific antigen level of 4.1 to 10.0 ng/mL, 85% versus 47% for a prostate-specific antigen level of 10.1 to 20.0 ng/mL, and 89% versus 29% for prostate-specific antigen > 20 ng/mL. When the analysis was limited to patients in both groups with a minimum 12-month follow-up, the brachytherapy boost group continued to show a higher biochemical control rate compared with the conventional radiation group (3-year actuarial rates of 86% vs 53%). DISCUSSION: These preliminary results show a significant improvement in the biochemical response rate with conformal boost brachytherapy and pelvic external radiation compared with conventional radiation alone. These results, coupled with our previously reported acceptable toxicity rates, support the use of this technique.

Aged↗
PubMed2002

Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer.

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and 1 BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and 11 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for delta-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer.

Adult↗
PubMed1979

A radioimmune assay for human prostatic acid phosphatase-levels in prostatic disease.

Prostatic acid phosphatase from human seminal fluid was purified to homogeneity. The enzyme was characterized as to its purity, molecular weight and amino acid composition. Analytical isoelectric focusing of purified enzyme on polyacrylamide gels resolved the enzyme activity into eleven discrete bands, apparently due to various amounts of sialic acid associated with the glycoprotein. Antisera raised against the purified enzyme produced only one precipitan arc on immunoelectrophoresis. A double antibody radioimmune assay was developed and used to evaluate serum prostatic acid phosphatase in 226 patients without prostatic disease, in 186 patients with benign prostatic hyperplasia and in 93 patients with prostatic carcinoma. No statistical difference was noted in serum prostatic acid phosphatase between patients with benign prostatic hyperplasia and in those without prostatic disease Serum prostatic acid phosphatase was elevated in 94% of the patients with metastatic prostatic carcinoma. Significant elevations were also found in carcinoma patients without metastases.

Acid Phosphatase↗
PubMed1982

Serum prostatic acid phosphatase determination in prostatic diseases: a critical comparison of an enzymatic and a radioimmunologic assay.

A prospective study comparing a new radioimmunologic and a classical enzymatic assay for prostatic acid phosphatase was done to evaluate their respective roles in patients with prostatic diseases. We studied 50 patients with cancer of the prostate, 101 with benign prostatic hypertrophy and 17 with prostatitis as well as patients with nonprostatic malignancy, and various hematological and bone diseases. The results showed a low incidence of elevated values in patients with early cancer of the prostate and a high incidence of false positive values with the radioimmunoassay in patients with benign prostatic diseases, especially prostatitis. These data suggest that tests for serum prostatic acid phosphatase levels remain disappointing in the assessment of prostatic disease regardless of the technique used.

Acid Phosphatase↗
PubMed1996

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Adenocarcinoma↗
PubMed2001

Three-dimensional grayscale ultrasound: evaluation of prostate cancer compared with benign prostatic hyperplasia.

OBJECTIVES: To compare the accuracy of the detection, localization, and staging of prostate cancer using transrectal three-dimensional (3D) grayscale ultrasonography (3D-US) with conventional transrectal two-dimensional grayscale ultrasonography (2D-US). METHODS: Fifty patients with clinical localized prostate cancer scheduled to undergo radical retropubic prostatectomy and 50 patients with clinical benign prostatic hyperplasia underwent transrectal ultrasound investigations (2D and 3D). The prostate images were retrospectively analyzed by two ultrasound experts unaware of the clinical findings. The images of the prostate cancer group were correlated with the whole-mount histologic specimens of the prostate. RESULTS: All percentages are given for experts 1 and 2. The sensitivity, specificity, and accuracy for the detection of prostate cancer without considering the definitive localization of the tumor for 2D-US was 72% and 76%, 50% and 54%, and 63% and 64%, respectively; for 3D-US, the rates were 82% and 88%, 40% and 42%, and 61% and 65%. The sensitivity, specificity, and accuracy of the combination of 2D-US with 3D-US was 88% and 90%, 36% and 38%, and 62% and 64%, respectively. The sensitivity, specificity, and accuracy for the exact localization of the prostate tumor for 2D-US was 44% and 46%, 50% and 54%, and 47% and 50%, respectively; for 3D-US, they were 52% and 62%, 40% and 42%, and 46% and 52%. The staging of prostate cancer using 3D-US was correct in 49% (expert 1) and in 57% (expert 2) of patients. No difference was observed between 2D-US and 3D-US for accurate staging. Both experts judged the interpretation of 3D-US images as superior to that of 2D-US images. CONCLUSIONS: Although 3D-US had statistically significant increased sensitivity in the detection of lesions and decreased specificity compared with 2D-US, 3D-US did not result in significant clinical improvement in the detection and staging of prostate cancer.

Adenocarcinoma↗
PubMed1998

A prostate gland volume of more than 75 cm3 predicts for a favorable outcome after radical prostatectomy for localized prostate cancer.

OBJECTIVES: Both the benign and malignant prostatic epithelial components of the prostate gland contribute to the serum prostate-specific antigen (PSA) level. Therefore, for a given PSA, the presence of benign hyperplastic prostate tissue (BHPT) may indicate a lower cancer burden. This study was performed to assess the impact of varying amounts of BHPT on PSA failure free (bNED) survival after radical prostatectomy for localized prostate cancer. METHODS: Cox regression multivariable analyses were performed to assess the ability of the clinical stage, PSA, biopsy Gleason score, and prostate gland volume to predict time to postoperative PSA failure in 885 patients. RESULTS: In addition to the PSA (P < 0.0001), biopsy Gleason score of 8 to 10 (P < 0.0001) and of 7 (P = 0.05), and clinical Stage T2c,3a (P < 0.0001) and T2b (P = 0.0016), the prostatectomy prostate gland volume (P < 0.0001) was a significant predictor of time to postoperative PSA failure. Patients with a prostatectomy prostate gland volume greater than 75 cm3 had a 100% 4-year bNED survival and favorable pathologic characteristics (pathologic Stage T2, 85%; prostatectomy Gleason score 6 or less, 78% and 7, 22%; and negative margins, 95%) despite a preoperative PSA of 10 to 20 ng/mL and more than 20 ng/mL in 28% and 13% of these men, respectively. In 75% of these cases, lead time bias because of PSA driven repeat biopsies provided an explanation. CONCLUSIONS: Lead time bias because of PSA driven repeat biopsy accounted for the high 4-year bNED survival and favorable pathologic findings for most patients who had prostate cancer coexisting in a prostate gland comprised of BHPT and a total gland volume in excess of 75 cm3. An additional explanation is needed, however, for the remaining patients.

Follow-Up Studies↗
PubMed2000

Telomerase activity in needle biopsies from prostate cancer and benign prostates.

BACKGROUND: Telomerase activation is thought to be essential for the immortality of cancer cells. It may be a prognostic factor in small volume well differentiated prostate cancers and hence a guide for the aggressiveness of the approach. The length of the chromosome tips (telomeres) are maintained by a specific enzyme (telomerase) independently of the normal cell division cycle. Although telomerase is not expressed in most normal human tissues, it is expressed in most human tumours. For the detection of telomerase in small prostate needle biopsy samples a recently developed telomeric repeat amplification protocol (TRAP) assay was used. The aim of the present study was: to measure telomerase activity in human prostate samples, and to evaluate the applicability of this assay on specimens from a prostate biopsy. MATERIALS AND METHODS: From 36 patients referred for lower urinary tract symptoms (LUTS) or suspicion of having prostate cancer a total of 288 prostate biopsy samples were obtained (8 in each patient). When the digital rectal examination was abnormal and/or when the PSA level was elevated in L.U.T.S., or asymptomatic patients' tissue samples were obtained by transrectal ultrasound (TRUS) guided biopsies. Samples were tested for telomerase activity by a modified TRAP and forwarded for histology. RESULTS: In 19 out of 36 patients prostate cancer was diagnosed on histology. In 11 of these 19 tumours substantial telomerase activity was detected, whereas only very low telomerase activity existed in 2 of 17 samples from benign prostatic hypertrophy (BPH) patients. In this small series the relative telomerase activity in prostate cancer correlated with histopathological grade. CONCLUSIONS: Our results show the applicability of a TRAP assay to measure telomerase activity in small needle biopsied prostate samples. In poorly differentiated and metastatic cancer we observed that levels of telomerase activity were high. To establish accuracy and to distinguish the 'relative good from the ugly' further study is needed.

Biomarkers, Tumor↗
PubMed2004

Role of free to total prostate specific antigen ratio in serum in the diagnosis of prostatic enlargement.

This study was aimed to demonstrate the significance of free/total Prostate Specific Antigen (PSA) ratio in the diagnosis of prostatic enlargement. The study was carried out in a total number of 100 subjects, of which 58 had benign prostatic hyperplasia (BPH), 42 had carcinoma prostate and 50 were age matched control. The subjects were collected from Dhaka Medical College Hospital (DMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU). Venous blood (5ml) was drawn from each subject before digital rectal examination or pre-urethral manipulation for estimation of PSA. Final diagnosis was made by histopathological examination, specimen being obtained by transurethral resection of prostate (TURP), open prostatectomy and per rectal tru-cut biopsy with biopsy gun. The study showed a highly significant difference of serum PSA and free/total PSA ratio in differentiating BPH from carcinoma prostate. Free/total PSA ratio was highly significant in differentiating between BPH and carcinoma prostate (p<0.001) and carcinoma prostate and control (p<0.001). In the marginally elevated PSA, free/total PSA ratio reduced biopsy by 81-85% in BPH and carcinoma prostate respectively. The overall specificity, positive predictive value and efficiency of free/total PSA was much higher than that of total PSA in differentiating BPH from carcinoma prostate.

Aged↗
PubMed2004

Inverse association between prostatic polyunsaturated fatty acid and risk of locally advanced prostate carcinoma.

BACKGROUND: An effect of fatty acids has been implicated in men with advanced-stage prostate carcinoma and in men who have died of the disease. To evaluate the influence of fatty acids in men with prostate carcinoma at earlier stages, the authors examined the relation between prostatic concentrations of fatty acids and locally advanced prostate carcinoma in men with clinically organ-confined disease. METHODS: Fatty acids were measured by capillary gas chromatography in fresh, nonmalignant prostate tissue specimens collected during surgery from 196 men undergoing radical prostatectomy for localized prostate carcinoma. Two-sided, two-sample Student t tests compared mean concentrations in men with extraprostatic disease (pT3-4N0-1M0) with control men with organ-confined disease. Logistic regression accounted for clinical stage, prostate-specific antigen level, Gleason sum, and other factors. RESULTS: Percent total prostatic polyunsaturated fatty acid (PUFA) was found to be inversely associated with risk of locally advanced prostate carcinoma (n=52) (odds ratio [OR]=0.93, 95% confidence interval [95% CI], 0.87-0.99; P=0.035). Risk of seminal vesicle involvement accounted for this association (OR=0.86, 95% CI, 0.78-0.95; P=0.003). Percent omega-3 fatty acid (eicosapentanoic + docosahexanoic acids) and percent arachidonic acid also were found to be inversely related to the risk of seminal vesicle involvement (OR=0.52, 95% CI, 0.30-0.90; P=0.02; and OR=0.84, 95% CI,; 0.75-0.95; P=0.005, respectively). CONCLUSIONS: Prostatic PUFA levels appear to influence the risk of locally advanced prostate carcinoma in men with clinically organ-confined disease. This association may be mediated through the immune system.

Aged↗
PubMed2004

Therapeutic potential of curcumin in prostate cancer--V: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells.

BACKGROUND: There is increasing evidence that the stringent selective pressure imposed by androgen ablation therapy on the residual prostate cancer cells may actually accelerate the development of the hormone refractory and bone metastatic phenotype. The propensity of prostate cancer to establish osseous metastases is very likely mediated by the osteomimetic properties of the prostate cancer cells. Prostate cancer cells acquire these "bone-like" properties in order to survive in the bony microenvironment. This process is facilitated by common growth factor trophisms between the bone stromal cells, osteoblasts, and the prostate cancer cells wherein a number of growth factors and their receptors are involved. Thus, a general inhibition of the tyrosine kinase signaling pathways may have a therapeutic advantage in interfering with the metastatic potential of these prostate cancer cells. This study focuses on the potential of curcumin, a plant based non-toxic tyrosine kinase inhibitor in interfering with the development of bone like properties of C4-2B, a highly metastatic derivative of LNCaP prostate cancer cell line. METHODS: C4-2B prostate cancer cells were analyzed for their constitutive expression and ligand inducible activation of growth factor receptors such as EGF-R and CSF1-R. Expression of bone-specific transcription factors such as Cbfa-1 and the production of PTHRP were followed. The ability of the C4-2B cells to mineralize under specific conditions was analyzed. The activation status of the transcription factor NF-kappa B was also followed. RESULTS: Curcumin inhibited the ligand-stimulated autophosphorylation of EGF-R and CSF1-R that were crucially involved in the development of osteomimetic properties of C4-2B cells. When C4-2B cells were grown under promineralization conditions, curcumin prevented the formation of the mineralized nodules. It also inhibited the expression of the core-binding factor a-1 in C4-2B cells which was responsible for the expression of several bone-specific proteins. The IKK activity was severely impaired, showing marked NF-kappa B inhibition. The experiments indicate that curcumin can also interfere with the development of the osteoblast and the osteoclast-like properties by these prostate cancer cells. CONCLUSIONS: The highly metastatic C4-2B prostate cancer cell line is already "programmed" to exhibit the bone-like properties that would at least in part explain its affinity to set up osseous metastases. Curcumin is able to interfere with the osteoblastic component as well as the osteoclastic component of this phenotype, by interfering with the growth factor receptor pathways and by inhibiting the NF-kappa B activation process. It is concluded that curcumin may inhibit the growth factor collaboration between the prostate cancer cells and the osteoblast/stromal cells, thus exhibiting a potential to prevent the establishment of bony metastases.

Antineoplastic Agents↗
PubMed2005

History of diabetes, clinical features of prostate cancer, and prostate cancer recurrence-data from CaPSURE (United States).

OBJECTIVES: There is a growing epidemiologic literature suggesting an inverse association between history of diabetes and risk of incident prostate cancer. To our knowledge, the relationship between diabetes and tumor features and risk of recurrence among men with prostate cancer has not been examined previously. We hypothesized that men with diabetes would present with more favorable prostate cancer and experience lower risk of recurrence. METHODS: We identified 691 men with diabetes at the time of prostate cancer diagnosis, among 6722 men diagnosed with prostate cancer in 1989 to 2002 within CaPSURE(TM), a community-based prostate cancer registry study. We compared clinical and socio-demographic variables by diabetes status, using chi2 tests, t-tests, and multinomial logistic regression. We examined recurrence rates for prostate cancer among patients with and without diabetes using Kaplan-Meier log-rank tests and Cox proportional hazard models. RESULTS: In multivariate analyses, history of diabetes was not associated with any diagnostic clinical parameter, and treatment-specific recurrence rates for prostate cancer generally did not differ by diabetes history. Among men with low-prognostic risk or who were younger at prostate cancer diagnosis, being diabetic (versus not) was associated with an elevated risk of recurrence after radiation therapy, in multivariate analyses. CONCLUSIONS: Contrary to data suggesting that diabetes may be modestly protective against risk of incident prostate cancer, we did not observe any evidence of an inverse association between history of diabetes and aggressiveness at diagnosis or risk of recurrence, in this population of men with prostate cancer.

Age Factors↗
PubMed2006

Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized controlled trial.

OBJECTIVES: Randomized controlled trials are currently conducted to assess whether the mortality from prostate cancer is reduced by early detection with the use of prostate-specific antigen (PSA) measurements in serum. To be effective, such a program should be able to reduce the absolute number of men diagnosed with metastatic prostate cancer (for which no cure is available). The aim of the present report is to evaluate whether PSA-based screening reduces the risk of being diagnosed with metastatic prostate cancer. METHODS: A population-based, prospective, randomized, controlled screening trial for prostate cancer started in 1995 (the Göteborg branch of the European Randomized Study of Screening for Prostate Cancer [ERSPC]). Ten thousand, randomly selected men aged 50-66 yr were invited for biennial PSA testing, with 10,000 men serving as passive controls for whom diagnosis of metastatic prostate cancer was monitored by using the Swedish Cancer Registry. RESULTS: After a follow-up of 10 yr, the risk of being diagnosed with metastatic prostate cancer was reduced by 48.9%-that is, decreasing from 47 cases in the control group to 24 cases in the group randomized to PSA-based screening (p=0.0084). However, the risk of being diagnosed with prostate cancer increased 1.8-fold with PSA-based screening. CONCLUSIONS: Biennial PSA screening reduces the risk of being diagnosed with metastatic prostate cancer, the first prerequisite for achieving decreased cancer mortality in younger men. This putative benefit is balanced by a 1.8-fold increased risk for diagnosis of prostate cancer.

Aged↗
PubMed2006

Association between family history of prostate and breast cancer among African-American men with prostate cancer.

OBJECTIVES: To explore the familial aggregation of prostate and breast cancer using data from a population-based case-control study of African-American men participating in the Flint Men's Health Study. METHODS: A detailed family history questionnaire was administered to 121 African-American men with prostate cancer and 179 African-American male controls. The family history data of prostate and breast cancer in first-degree relatives were compared between men with and without prostate cancer using standard statistical methods. RESULTS: In the Flint Men's Health Study, men with prostate cancer were more likely than controls to report having a brother with prostate cancer (age-adjusted odds ratio 4.80, 95% confidence interval 2.01 to 11.44) or a sister with breast cancer (age-adjusted odds ratio 3.80, 95% confidence interval 1.57 to 9.22). CONCLUSIONS: Although a family history of prostate cancer is a recognized prostate cancer risk factor consistent across different races, few studies have examined the co-clustering of breast and prostate cancer within African-American families. Future studies should focus on racially heterogeneous populations to further explore the observation from the Flint Men's Health Study that having a brother with prostate cancer or a sister with breast cancer may be associated with prostate cancer occurrence. This research may have implications for both gene identification and early detection strategies.

Adult↗