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PubMed2003

[Metastatic prostate cancer].

Metastatic prostate cancer is an uncurable disease. Treatment is only palliative. Median survival of patients is 3 years. Prostate cancer is an hormonodependent cancer, androgen blockade is the most active treatment. However hormone resistance occurs after a median interval of 2 years. The major symptom is pain, others are urinary obstruction, neurological complications of bone metastases and hematological disorders. Androgen deprivation is the first-line treatment, impotency and osteoporosis being the main side effects. Other treatments are radiotherapy, radiopharmaceutics and chemotherapy. The most important treatment issue is quality of life.

Androgen Antagonists↗

PubMed2000

Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort.

BACKGROUND: Prostate cancer tends to affect older men and to progress relatively slowly. Since the prevalence of comorbidity increases with advancing age, competing causes of death are important contributors to death rates among prostate cancer patients. Accurate determination of the underlying causes of death in older men dying with prostate cancer may thus also be more difficult. METHODS: We compared the distribution of underlying causes of death in decedents from a population-based cohort of elderly prostate cancer patients to that from a population-based comparison cohort of elderly men without prostate cancer. Among decedents from the prostate cancer patient cohort, we examined associations of patient demographics, disease stage, and initial treatment, with assignment of a prostate cancer underlying cause of death (versus any other cause) by use of multivariable logistic regression. In the subgroup of prostate cancer patient decedents having underlying causes of death other than prostate cancer, the underlying cause distribution was compared with that in nonprostate cancer cohort decedents. RESULTS: Prostate cancer was the underlying cause for 39% (95% confidence interval [CI] = 36.3-41.9) of the decedents in the prostate cancer cohort. Causes of death among prostate cancer patients not dying of prostate cancer were similar to those among the nonprostate cancer cohort decedents. However, in those who were aggressively treated, the adjusted odds of other cancer causes of death were 51% higher (odds ratio [OR] = 1.51; 95% CI = 1.08-2.10) than that in nonprostate cancer patient decedents, while in those treated with watchful waiting the adjusted odds were 34% lower (OR = 0.66; 95% CI = 0.47-0.93). CONCLUSIONS: Initial treatment may influence the underlying cause of death reported in vital statistics for prostate cancer patients.

Aged↗

PubMedDate not supplied

Update on prostate cancer screening.

Prostate cancer is the second most common cause of death in men; it is diagnosed in about 1 in 10 men. Significant risk factors include, but are not limited to, race and age; the peak age at diagnosis is the seventh decade. A through screening program, sensitive to the risk factors and targeted to patients with curable prostate cancer, can decrease the rates of mortality and morbidity associated with this disease, without overtreating patients who have latent cancer. Screening methods include annual digital rectal examinations and prostate-specific antigen tests. Staging is important when treatment options are considered and treatment morbidity rate is weighed against disease mortality rate. Research concerning genetics changes and chemoprevention trials of vitamins and hormonal agents are targeted toward primary prevention. Implications for practice should include primary prevention, screening and detection, public education, and monitoring of the disease.

Aged↗

PubMed2005

Predictors of subsequent prostate cancer in men with a prostate specific antigen of 2.6 to 4.0 ng/ml and an initially negative biopsy.

PURPOSE: Almost 75% of men with a prostate specific antigen (PSA) of 2.6 to 4.0 ng/ml have no evidence of prostate cancer on biopsy. Deciding whether and when to repeat the biopsy is challenging. We determined if patient specific variables might identify men at increased risk for the subsequent detection of prostate cancer. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study. Our study group consisted of 1,202 men with PSA 2.6 to 4.0 ng/ml and a previously negative prostate biopsy. Patient specific variables were analyzed for their value in predicting a future diagnosis of prostate cancer. RESULTS: Of 1,011 men with adequate followup 136 (13.5%) were subsequently diagnosed with prostate cancer. Mean followup +/- SD in men without prostate cancer was 72 +/- 36 months. Prostate cancer was subsequently diagnosed in 35% of men with high grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy (p <0.0001), in 18% with abnormal or suspicious digital rectal examination (DRE) (p = 0.02) and 16% with an annual PSA velocity of 0 ng/ml (p = 0.002). Multivariate analysis identified HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, family history of prostate cancer and annual PSA velocity 0 ng/ml as predictors of prostate cancer. CONCLUSIONS: Men with a PSA of 2.6 to 4.0 ng/ml and negative biopsy should be advised to undergo repeat biopsy if they have HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, a family history of prostate cancer or a PSA velocity of 0 ng/ml or greater.

Aged↗

PubMed1998

Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells.

OBJECTIVES: Recently, it was confirmed that angiogenesis is important in the development and spread of a variety of human cancers, including prostate cancer (PCa). Tumor neovascularization is thought to be controlled by chemical signals, known as angiogenic factors (AF). To date, little is known regarding the existence and role of AF in PCa. We previously reported on vascular endothelial growth factor (VEGF) in PCa. Currently, we compare VEGF expression with that of interleukin-8 (IL-8), another putative regulator of angiogenesis. We evaluated the expression of these two important AF in PCa and explored the role of inflammatory cytokines IL-1 and tumor necrosis factor (TNF) in their regulation. METHODS: Ex vivo studies involved previously reported immunohistochemical analysis for VEGF and recent evaluation of IL-8 expression and distribution in archival tissue samples of PCa, benign prostatic hyperplasia (BPH), and normal prostate tissue. In vitro studies used PCa cells (DU-145) grown in culture and stimulated with cytokines thought to induce VEGF and IL-8 (ie, IL-1 alpha, IL-1 beta, TNF-alpha, and TNF-beta). After 24 hours, with or without cytokines, cell culture supernatants were analyzed by enzyme-linked immunosorbent assay or radioimmunoassay for VEGF or IL-8 levels. RESULTS: Immunohistochemical studies of prostate tissue showed that PCa cells stained positively for VEGF and IL-8. Benign prostatic hyperplasia and normal prostate cells displayed little staining for either AF. Low levels of VEGF and IL-8 were produced by unstimulated DU-145 cells. Induction of DU-145 cells with cytokines resulted in differential stimulation whereby TNF was the predominant inducer of VEGF, whereas IL-1 was the predominant inducer of IL-8. CONCLUSIONS: Our results indicate that significant levels of VEGF and IL-8 are present in PCa, but not BPH or normal prostate cells in vivo. In vitro studies suggest that differential regulation of AF expression occurs in PCa. Because IL-1 and TNF are present in the PCa tumor microenvironment, it is likely that differential regulation of AF also occurs in human PCa and contributes to differential tumor growth and metastasis.

Endothelial Growth Factors↗

PubMed2003

Significance of capsular attachment and invasion of cancer tissues in prostate cancer.

BACKGROUND: There is a discrepancy in tumor node metastasis (TNM) staging of capsular attachment and invasion; the condition was classified as pT3 in 1987, then as pT2 in 1992. Because capsular finding associated with radical prostatectomy is an important prognostic factor, the present study was conducted to characterize clinicopathological states of cancer tissues attached to and invading the capsule. METHODS: Specimens removed by radical prostatectomy exhibiting pT2 or pT3 from 90 patients who did not receive any treatment before surgery were classified as Loc (24%, cancer tissues localized and apart from capsule), Inv (59%, attached to and invading but not penetrating capsule) and Pen (17%, penetrating capsule). Their clinicopathological profiles were examined. RESULTS: Gleason score, volume of cancer tissues, seminal vesicle invasion, positive surgical margin and regional lymph node metastasis of Inv were distributed between those of Loc and Pen. Postoperative management was decided as routine check-up or endocrine therapy according to pathological findings. Median follow-up was 59 months. Prostate-specific antigen (PSA) relapse occurred in 13 patients, one of whom died of prostate cancer. The remaining of these patients lived. Rate of PSA relapse was not different between Loc and Inv, mainly due to endocrine therapy to Inv with high risk factors. CONCLUSION: Pathological profile of Inv lies between those of Loc and Pen. Therefore, pT2a (1997) would be subclassified as Loc and Inv. Patients with Inv may be required to receive the respective management according to clinicopathological profile, which would be different to that of Loc.

Aged↗

PubMedDate not supplied

Longitudinal screening for prostate cancer with prostate-specific antigen.

OBJECTIVE: To determine for the first 4 years of serial prostate-specific antigen (PSA)-based screening trends in compliance, prevalence of abnormal screening test results, cancer detection rates, and stage and grade of cancers detected. DESIGN: A community-based study of serial screening for prostate cancer with serum PSA measurements. SETTING: University medical center. SUBJECTS: A total of 10 248 male volunteers at least 50 years old who were screened at 6-month intervals for a minimum of 48 months. MAIN OUTCOME MEASURES: The proportion of men who returned for serial screening, the proportion with elevated PSA levels, the proportion with newly elevated PSA levels, prostate cancer detection rates, and the distribution of tumor stages and grades at diagnosis. RESULTS: At 48 months, 79% of volunteers returned for screening. During this interval there was a decrease in the proportion of volunteers with serum PSA levels higher than 4.0 ng/mL (from 10% to 6%-7%), in cancer detection rates (from 3% to <1%), and in the proportion with clinically advanced cancer (from 6% to 2%). In men who underwent surgery, the proportion with high-grade cancer decreased (from 11% to 6%), and the proportion with pathologically advanced cancer was proportionately reduced but not significantly reduced (from 33% to 27%). CONCLUSIONS: With serial PSA-based screening, the proportion of men with abnormal test results decreased, and the prostate cancer detection rate decreased to near the reported population-based incidence rate. There was also a shift to detection of cancers at an earlier clinical stage and detection of lower-grade cancers. If PSA screening is ultimately shown to be beneficial, then appropriate cost-benefit analyses will be required to determine how the shifts in cancer detection rate and cancer stage will affect the economics of serial PSA-based screening.

Aged↗

PubMed2005

Prostate stem cells and prostate cancer.

Understanding prostate stem cells (PSCs) may provide insight for the design of therapeutics for prostate cancer. We have developed a quantitative in vivo colony-forming assay and have demonstrated that the Sca-1 antigen is present on the surface of a prostate cell subpopulation that possesses multiple stem cell properties. Immunofluorescent analysis demonstrates that Sca-1 is expressed by both basal and luminal cells in the proximal region of the adult prostate, but is not expressed by either lineage in more distal regions. The proximal region has been suggested as the PSC niche based on BrdU label-retention studies and the presence of distinct smooth-muscle cells that produce high levels of TGF-beta. Sca-1 is also expressed by nearly all cells within fetal prostate epithelial chords, suggesting Sca-1 may be conserved on PSCs throughout development. Malignant epithelial cells from TRAMP mice, as well as normal prostate cells with lentiviral-mediated alteration of the PTEN/AKT signaling pathway, give rise to PIN lesions and prostate cancer in vivo. Alteration of PTEN/AKT signaling in Sca-1-enriched PSCs also results in PIN lesions, suggesting that PSCs can serve as one target for prostate carcinogenesis.

Animals↗

PubMed2003

Magnetic resonance imaging in the radiation treatment planning of localized prostate cancer using intra-prostatic fiducial markers for computed tomography co-registration.

PURPOSE: To assess the feasibility, and potential implications, of using intra-prostatic fiducial markers, rather than bony landmarks, for the co-registration of computed tomography (CT) and magnetic resonance (MR) images in the radiation treatment planning of localized prostate cancer. METHODS: All men treated with conformal therapy for localized prostate cancer underwent routine pre-treatment insertion of prostatic fiducial markers to assist with gross target volume (GTV) delineation and to identify prostate positioning during therapy. Six of these men were selected for investigation. Phantom MRI measurements were obtained to quantify image distortion, to determine the most suitable gold alloy marker composition, and to identify the spin-echo sequences that optimized both marker identification and the contrast between the prostate and the surrounding tissues. The GTV for each patient was contoured independently by three radiation oncologists on axial planning CT slices, and on axial MRI slices fused to the CT slices by matching the implanted fiducial markers. From each set of contours the scan common volume (SCV), and the scan encompassing volume (SEV), were obtained. The ratio SEV/SCV for a given scan is a measure of inter-observer variation in contouring. For each of the 18 patient-observer combinations the observer common volume (OCV) and the observer encompassing volume (OEV) was obtained. The ratio OEV/OCV for a given patient-observer combination is a measure of the inter-modality variation in contouring. The distance from the treatment planning isocenter to the prostate contours was measured and the discrepancy between the CT- and the MR-defined contour recorded. The discrepancies between the CT- and MR-defined contours of the posterior prostate were recorded in the sagittal plane at 1-cm intervals above and below the isocenter. RESULTS: Phantom measurements demonstrated trivial image distortion within the required field of view, and an 18K Au/Cu alloy to be the marker composition most suitable for CT-MRI image fusion purposes. Inter-observer variation in prostate contouring was significantly less for MR compared to CT. The mean SEV/SCV ratio was 1.58 (confidence interval (CI): 1.47-1.69) for CT scans and 1.37 (CI: 1.33-1.41) for MR scans (paired t-test; P=0.036). The overall magnitude of contoured GTV was similar for MR and CT; however, there were spatial discrepancies in contouring between the two modalities. The greatest systematic discrepancy was at the posterior apical prostate border, which was defined 3.6 mm (SD 3.5 mm) more posterior on MR- than CT-defined contouring. CONCLUSIONS: Prostate contouring on MR is associated with less inter-observer variation than on CT. In addition, we have demonstrated the feasibility of using intra-prostatic fiducial markers, rather than bony landmarks, for the co-registration of CT and MR images in the radiation treatment planning of localized prostate cancer. This technique, together with on-line correction of treatment set-up according to the fiducial marker position on electronic portal imaging, may enable a reduction in the planning target volume (PTV) margin needed to account for inter-observer error in target delineation, and for prostate motion.

Biomarkers↗

PubMed2005

Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia.

Studies suggest that astrocytes and microglia in the spinal cord are involved in the development of persistent pain induced by tissue inflammation and nerve injury. However, the role of glial cells in bone cancer pain is not well understood. The present study evaluated the spinal glial activation in a novel rat model of bone cancer pain produced by injecting AT-3.1 prostate cancer cells into the unilateral tibia of male Copenhagen rats. The structural damage to the tibia was monitored by radiological analysis. The thermal hyperalgesia, mechanical hyperalgesia and allodynia, and spontaneous flinch were measured. The results showed that: (1) inoculation of prostate cancer cells, but not the vehicle Hank's solution, induced progressive bone destruction at the proximal epiphysis of the tibia from day 7-20 post inoculation; (2) the inoculation also induced progressive thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia, and spontaneous flinches; (3) astrocytes and microglia were significantly activated in the spinal cord ipsilateral to the cancer leg, characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglial marker); (4) IL-1beta was up-regulated in the ipsilateral spinal cord, evidenced by an increase of IL-1beta immunostained astrocytes. These results demonstrate that injection of AT-3.1 prostate cancer cells into the tibia produces progressive hyperalgesia and allodynia associated with the progression of tibia destruction, indicating the successful establishment of a novel male rat model of bone cancer pain. Further, bone cancer activates spinal glial cells, which may release IL-1beta and other cytokines and contribute to hyperalgesia.

Animals↗

PubMed2002

Establishment and characterization of osseous prostate cancer models: intra-tibial injection of human prostate cancer cells.

BACKGROUND: To improve the therapy of advanced prostate cancer (CaP), it is critical to develop animal models that mimic CaP bone metastases. Unlike the human disease, CaP xenograft models rarely metastasize spontaneously to bone from the orthotopic site of primary tumor growth. METHODS: Single-cell suspensions of LNCaP, PC-3, LuCaP 35, and LuCaP 23.1 CaP cells were injected directly into tibia of SCID mice. Immunohistochemistry and bone histomorphometrical analyses were performed to characterize these osseous-CaP models. RESULTS: LuCaP 23.1 yields an osteoblastic response, LNCaP yields mixed lesions, and LuCaP 35 and PC-3 result in osteolytic responses. We have detected osteoprotegerin, RANK ligand, parathyroid hormone-related protein, and endothelin-1, proteins associated with bone growth and remodeling, in the CaP cells grown in the bone. CONCLUSIONS: These animal models can be used to study biological interactions, pathways, and potential therapeutic targets, and also to evaluate new agents for treatment and prevention of CaP bone metastasis.

Animals↗

PubMed2004

Screening a combinatorial peptide library to develop a human glandular kallikrein 2-activated prodrug as targeted therapy for prostate cancer.

OBJECTIVE: Prostate cancer cells secrete the unique protease human glandular kallikrein 2 (hK2) that represents a target for proteolytic activation of cytotoxic prodrugs. The objective of this study was to identify hK2-selective peptide substrates that could be coupled to a cytotoxic analogue of thapsigargin, a potent inhibitor of the sarcoplasmic/endoplasmic reticulum calcium ATPase pump that induces cell proliferation-independent apoptosis through dysregulation of intracellular calcium levels. METHODS: To identify peptide sequence requirements for hK2, a combination of membrane-bound peptides (SPOT analysis) and combinatorial chemistry using fluorescence-quenched peptide substrates was used. Peptide substrates were then coupled to 8-O-(12[L-leucinoylamino]dodecanoyl)-8-O-debutanoylthapsigargin (L12ADT), a potent analogue of thapsigargin, to produce a prodrug that was then characterized for hK2 hydrolysis, plasma stability, and in vitro cytotoxicity. RESULTS: Both techniques indicated that a peptide with two arginines NH2-terminal of the scissile bond produced the highest rates of hydrolysis. A lead peptide substrate with the sequence Gly-Lys-Ala-Phe-Arg-Arg (GKAFRR) was hydrolyzed by hK2 with a Km of 26.5 micromol/L, kcat of 1.09 s(-1), and a kcat/Km ratio of 41,132 s(-1) mol/L(-1). The GKAFRR-L12ADT prodrug was rapidly hydrolyzed by hK2 and was stable in plasma, whereas the GKAFRR-L peptide substrate was unstable in human plasma. The hK2-activated thapsigargin prodrug was not activated by cathepsin B, cathepsin D, and urokinase but was an excellent substrate for plasmin. The GKAFRR-L12ADT was selectively cytotoxic in vitro to cancer cells in the presence of enzymatically active hK2. CONCLUSION: The hK2-activated thapsigargin prodrug represents potential novel targeted therapy for prostate cancer.

Amino Acid Sequence↗

PubMed2003

Prostate cancer update.

Prostate cancer continues to be the most commonly diagnosed malignancy in men of the western world. Its diagnosis, evaluation, and treatment therapies are constantly evolving. This paper summarizes and clarifies the most up-to-date information on prostate cancer prevention and treatment.

Humans↗

PubMed2002

Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men.

The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better biomarkers for early detection of PCA using protein profiling technologies that can simultaneously resolve and analyze multiple proteins. Evaluating multiple proteins will be essential to establishing signature proteomic patterns that distinguish cancer from noncancer as well as identify all genetic subtypes of the cancer and their biological activity. In this study, we used a protein biochip surface enhanced laser desorption/ionization mass spectrometry approach coupled with an artificial intelligence learning algorithm to differentiate PCA from noncancer cohorts. Surface enhanced laser desorption/ionization mass spectrometry protein profiles of serum from 167 PCA patients, 77 patients with benign prostate hyperplasia, and 82 age-matched unaffected healthy men were used to train and develop a decision tree classification algorithm that used a nine-protein mass pattern that correctly classified 96% of the samples. A blinded test set, separated from the training set by a stratified random sampling before the analysis, was used to determine the sensitivity and specificity of the classification system. A sensitivity of 83%, a specificity of 97%, and a positive predictive value of 96% for the study population and 91% for the general population were obtained when comparing the PCA versus noncancer (benign prostate hyperplasia/healthy men) groups. This high-throughput proteomic classification system will provide a highly accurate and innovative approach for the early detection/diagnosis of PCA.

Aged↗

PubMed2006

Rectosigmoid cancer after radiotherapy for prostate cancer can be detected early and successfully treated.

The clinical features and outcomes of rectosigmoid cancers (RSCs) occurring after radiotherapy (RT) for prostate cancer were reviewed to determine whether they are significantly different to RSC occurring without those precedents, whether the subsequent RSC could be either predicted or detected early, and whether they can be effectively treated. Eight patients who had been treated by RT for prostate cancer subsequently developed lower gastrointestinal tract symptoms consistent with proctopathy, however, investigation by endoscopy indicated RSC. These cases were reviewed in detail. The most common presenting symptom was mild bleeding. All eight RSCs were detected before the development of metastatic disease and successfully treated. Only one required an anteroposterior resection. Otherwise, there were no unusual features about any of the cases that would have predicted the occurrence of RSC or enabled earlier detection. No complications occurred that could be attributed to prior RT. Six recommendations for clinicians are offered on the basis of these cases and the relevant published work. In particular, when symptoms of proctopathy occur after RT for prostate cancer the conclusion that radiation proctopathy is the cause should not be drawn until confirmed by endoscopy. Prior RT did not increase the risks involved in colorectal surgery in this setting.

Aged↗

PubMed2004

Serum insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in localized, metastasized prostate cancer and benign prostatic hyperplasia.

OBJECTIVE: Insulin-like growth factors (IGF-I and IGF-II) are important mitogenic peptides and are thought to be significant factors involved in normal and malignant cellular proliferation including benign prostatic hyperplasia (BPH) and prostate cancer (PC). In particular, the association between IGF-I and PC has received much attention. Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier protein in serum for the IGF-I, thus is an important functional modulator of it. On the other hand, one of the functions of prostate-specific antigen (PSA) is to cleave IGFBP-3. Epidemiological studies have shown that decreased levels of serum IGFBP-3 are associated with increased PC risk. Controversial results have also been reported on the value of serum IGF-I and/or IGFBP-3 in the detection of PC, especially of metastatic PC; as increased, decreased or unchanged when compared to BPH. The aim of the present study was to investigate whether serum IGF-I and IGFBP-3 levels change in localized and metastasized PC cases compared with BPH as the control cases. METHOD: The study included 45 BPH, 24 localized PC and 19 metastasized PC cases. Serum IGF-I and IGFBP-3 levels were measured by two-site immunoradiometric assay kits, and serum total and free PSA levels were assayed by chemiluminescence method. RESULTS: Serum IGF-I levels in both localized and metastasized PC cases were similar to BPH cases (138.3 +/- 58.2, 137.7 +/- 39.0 and 147.7 +/- 44.2 ng/ml, respectively), whereas serum IGFBP-3 levels were lower in metastasized PC group than in BPH group (1,795.6 +/- 305.6 and 2,196.0 +/- 505.7 ng/ml; p = 0.005). In localized PC, serum IGFBP-3 levels (1,911.00 +/- 349.58 ng/ml) were similar to metastasized PC. There were significant correlations between serum IGFBP-3 and serum free PSA in three groups (r = -0.46, p = 0.02 for localized PC; r = -0.56, p = 0.01 for metastasized PC, and r = -0.31, p = 0.03 for BPH). CONCLUSION: These data reveal that serum IGF-I levels may not change either in localized or metastasized PC, and that decreased serum IGFBP-3 levels may be attributed to its proteolysis by PSA which is increased in PC.

Aged↗

PubMed1996

Steroid-growth factor interaction in human prostate cancer. 2. Effects of transforming growth factors on androgen metabolism of prostate cancer cells.

The ability of human prostate cancer cells to metabolize androgens was assessed through administration of physiological concentration (0.5-10 nM) of tritiated testosterone (T) as precursor and one-step analysis of both T degradation and products' formation by reverse-phase HPLC and on-line radioactive detection after either 24 h or 72 h incubation. Overall, different prostate cancer cells degraded T quite differently, favoring alternatively reductive or oxidative metabolic pathways. In particular, both LNCaP and DU145 cells retained high levels of unconverted T, with a limited production of androstenedione and its 17-keto derivatives and relatively high amounts of dihydrotestosterone (DHT) and 3 alpha-androstanediol (3 alpha-diol). In contrast, PC3 cells quickly degraded T and exhibited high formation rates of androstenedione and 17-keto metabolites, while neither dihydrotestosterone nor 3 alpha-diol were detected after short or longer incubation times. The effects of both TGF alpha (50 ng/mL) and TGF beta 1 (5 ng/mL) on rates and direction of T metabolism were also explored. In LNCaP cells TGF alpha induced a significant (P < 0.04) decrease of the reductive metabolism of T with a corresponding enhancement of the oxidative pathway (P < 0.002), while TGF beta 1 did not significantly affect T metabolism. On the other hand, both reductive and oxidative pathways were only partially influenced by either growth factor in DU145 and PC3 cells, although TGF alpha significantly raised 5 alpha-androstanedione formation and reduced androsterone production in DU145 cells. All the above evidence was confirmed at both 24 h and 72 h or using increasing doses of TGF alpha and TGF beta 1, a peak activity of 50 ng/mL and 5 ng/mL, respectively, being generally encountered. Overall, our data suggest that TGFs may have a role in the growth regulation of hormone-responsive prostate tumor cells through changes of the intracellular contents of biologically active androgen metabolites.

Androgens↗

PubMed2006

Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of < or =10 ng/mL and biopsy Gleason score of < or =6, and their influence on PSA progression-free survival after radical prostatectomy.

OBJECTIVE: To investigate how many men with low-risk prostate cancer had positive lymph nodes detected by radio-guided surgery and whether they had a higher biochemical relapse rate after radical prostatectomy, because in such patients most urologists dispense with operative lymph node staging, as nomograms indicate only a low percentage of lymph node metastases. PATIENTS AND METHODS: The study included 474 men with a prostate-specific antigen (PSA) level of < or = 10 ng/mL, biopsy Gleason score of < or = 6 and positive biopsies in one (group 1, 315 men) or both lobes (group 2, 159 men); follow-up data were available in 357 men. Men with adjuvant radiation or hormone therapy before the occurrence of biochemical relapse were excluded. RESULTS: Positive lymph nodes were detected in 17 men in group 1, and in 18 in group 2. In more than half of the patients (19/35) these nodes were found outside the region of standard lymphadenectomy. Men with node-positive disease had a higher biochemical relapse rate (P < 0.001). When the tumour was organ-confined and well differentiated in node-positive disease (Gleason score < or = 6) the biochemical relapse rate was lower than in men with higher tumour stage and grade. CONCLUSIONS: When dissecting pelvic lymph nodes, extended or sentinel lymphadenectomy should be preferred. Removing the diseased nodes could improve the PSA progression-free survival, especially in well differentiated organ-confined disease.

Adult↗