Characterization and processing of prostate specific antigen (hK3) and human glandular kallikrein (hK2) secreted by LNCaP cells

Prostate specific antigen (PSA, hK3) in serum is predominantly complexed to alpha-1-antichymotrypsin (ACT), but a minor fraction remains in a free form despite the very large excess of serine protease inhibitors and alpha-2-macroglobulin. The fraction of free to total PSA is significantly lower in prostate cancer (CaP) compared to benign prostatic hyperplasia (BPH) which provides improved discrimination of these conditions. The molecular nature of free PSA in the circulation and the reason for its varying concentration in malignant and benign conditions is currently not known. The objective of the present investigation was to study the secretion of PSA and human glandular kallikrein 2 (hK2) by the LNCaP prostate cancer cell line, and to purify and characterize both proteins. LNCaP PSA was thoroughly characterized by immunological characterization, SDS-PAGE, isoelectric focusing, gel filtration, aminoterminal sequencing, reverse-phase chromatography, mass spectrometry and enzymatic activity measurements. LNCAP cells produced approximately equal amounts of zymogen (proPSA) and the one-chain mature form of PSA, whereas there was no evidence for the secretion of any internally cleaved forms. LNCaP cells secreted hK2 into the growth medium at about 3-5% of the amount of PSA. One-chain, mature PSA and hK2 obtained when LNCaP cells were grown in the presence of fetal bovine serum, had no enzymatic activity, but were active when the cells were grown in the absence of serum. Using enzymatically active recombinant hK2, it was possible to activate proPSA secreted by LNCaP cells. ProPSA formed two bands with high isoelectric points (8.2 and 8.4), which disappeared when proPSA was converted to mature PSA with hK2. Cancerous cells produce the zymogen forms of PSA, which by their isoelectric pI points seem to be found in serum of prostate cancer patients, but not BPH patients. Mature, one-chain PSA is inactive in the presence of serum. These findings may be highly relevant for the understanding of the generation of free and complexed PSA in the circulation.     

Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen as a useful marker for monitoring metastatic bone activity in men with prostate cancer

PURPOSE: We investigated the clinical usefulness of measuring the serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen (PICP) as markers for monitoring metastatic bone activity in patients with prostate cancer. MATERIALS AND METHODS: Serum levels of ICTP, PICP, alkaline phosphatase, prostatic acid phosphatase and prostate specific antigen (PSA) were analyzed in 104 untreated patients with prostate cancer, including 62 with and 42 without bone metastasis. Serial measurements of ICTP, PICP and PSA were performed during hormonal therapy in 35 of 62 prostate cancer patients with bone metastasis. RESULTS: Serum levels of all markers except prostatic acid phosphatase were significantly higher with than without bone metastasis. The median values of each marker increased according to the extent of bone metastasis. Serial ICTP, PICP and PSA in 19 patients with a partial response or no change in bone scans demonstrated a downward trend after treatment, while in 16 with progression they showed an upward trend after treatment. The rate of detecting bone metastasis and progression using ICTP were highest compared with other markers based on the percent clinical effectiveness and receiver operating characteristic curves. CONCLUSIONS: Measuring serum ICTP may be useful for detecting bone metastasis and prostate cancer progression, and may augment PSA and bone scan monitoring of metastatic bone activity.     

Seminal plasma contains "BPSA," a molecular form of prostate-specific antigen that is associated with benign prostatic hyperplasia

BACKGROUND: We previously reported that levels of BPSA, a modified form of prostate-specific antigen (PSA), are significantly elevated in prostate transition-zone tissue exhibiting nodular hyperplastic changes associated with the presence of benign prostatic hyperplasia (BPH). BPSA was purified and found to contain a characteristic clip between Lys182 and Ser183. We now describe the identification of BPSA in seminal plasma. METHODS: PSA was purified from seminal plasma by immunoaffinity chromatography. The purified PSA was further resolved by hydrophobic interaction chromatography, and the individual PSA forms were analyzed by gel electrophoresis and N-terminal amino-acid sequencing. RESULTS: BPSA comprised about 8% of the PSA in pooled seminal plasma, and was identical to BPSA purified from prostate tissues. BPSA was cleanly resolved from all active and inactive forms of PSA. Other inactive forms of PSA in seminal plasma consisted largely of PSA clipped at Lys145, though about 30% of the inactive seminal plasma PSA was intact, mature PSA. CONCLUSIONS: BPSA represents a distinct form of inactive PSA in the seminal plasma that may represent a specific marker for the biochemical changes associated with nodular development in the prostate transition zone found in patients with BPH.     

The role of prostate-specific antigen in the diagnosis and treatment of prostatic adenocarcinoma]

Serum prostate-specific antigen (PSA) levels were determined in four groups of patients with prostatic carcinoma: 230 untreated patients with adenocarcinoma of the prostate after careful clinical staging; in 102 patients with localized prostatic carcinoma who were treated by radical prostatectomy; in 183 patients after radiation therapy for adenocarcinoma of the prostate; and in 45 antiandrogen-treated patients with documented metastatic disease. Within each treatment modality PSA proved to be a powerful tool in predicting stage and prognosis of each patient. In the untreated group the PSA level was directly proportional to advancing clinical stage and Gleason score. The rate of increase of PSA in clinical stage A and B cancer patients suggested a doubling time of at least 2 years. In the group of patients who underwent radical prostatectomy, PSA correlated extremely well with the tumor volume and had a high predictive value for pelvic lymph node metastasis. No patient with pelvic lymph node metastasis achieved an undetectable PSA level following radical prostatectomy without adjunctive therapy. Both anti-androgen and radiation treatment were followed initially by dramatic falls in serum PSA concentrations, but the majority of patients soon experienced a reversal of this initial response, signifying early failure and again providing new information unavailable from any other source.     

Clinical relevance of radioimmunologic determination of prostate specific antigen in prostate cancer

To recognize progression of an inoperable prostatic cancer we use clinical parameters and the prostate specific phosphatase. The prostate specific antigen (PSA) is a new, sensitive and specific laboratory tumor marker. With 363 specimens of patients without prostatic cancer we defined for the normal range of this serum parameter. In 98 men with histologically proven prostatic cancers we investigated for the clinical relevancy of the serum level of PSA. We believe, that measurement of serum PSA give important information for clinical management of prostatic cancer.     

Raised prostate-specific antigen in adenocarcinoma of the colon

Serum prostate-specific antigen (PSA) values above 10 ng/ml are considered highly sensitive and specific for prostatic carcinoma in the absence of prostatic inflammation or trauma. However, in rare instances, non-prostatic malignancies have also been associated with raised serum PSA values. We have encountered a patient with increased serum PSA concentration measured by monoclonal antibody assay who had no evidence of prostatic malignant involvement, but suffered from colon cancer. Before operation for colon cancer his PSA was always over 30 ng/ml on several examinations. After total removal of colon cancer serum PSA level fell down to 1.2 ng/ml. Although immunohistochemical staining of colon cancer with monoclonal PSA antibody was not performed, some relationship between raised PSA and colon cancer is strongly suspected. Substances like serine protease which can cross-react with the PSA antibody might be produced by malignant tumour of non-prostatic origin.     

Tissue PSA from fine-needle biopsies of prostatic carcinoma as related to serum PSA, clinical stage, cytological grade, and DNA ploidy

BACKGROUND: The mechanisms behind changes in serum PSA (S-PSA) levels in patients with prostatic carcinoma (CAP) are not completely known. To further elucidate the factors affecting the serum levels of this important tumor marker, we measured PSA concentrations in serum and in aspiration biopsies (tissue PSA; T-PSA) from patients with prostatic disease and correlated the values to tumor stage, cytological grade, and DNA ploidy. METHODS: T-PSA and S-PSA were measured in 91 metastasis-free patients with newly diagnosed, untreated CAP and 13 patients with benign prostatic hyperplasia, and the values were related to tumor stage, cytological grade, and DNA ploidy. RESULTS: Significant negative correlations were found between T-PSA and S-PSA in the total clinical material and various subgroups of patients with CAP. T-PSA showed significant negative associations to T-stage and to cytological grading, and T-PSA concentrations were significantly lower in tetra-/aneuploid tumors than in diploid tumors. On the other hand, S-PSA showed corresponding positive associations and was significantly higher in tetra-/aneuploid tumors than in diploid tumors. CONCLUSIONS: The negative association between S-PSA and T-PSA values indicates that S-PSA values in metastasis-free patients reflect the degree of leakage from the tumor tissue rather than the intracellular concentration of PSA. Factors such as tissue volume, condition of gland structure, and vascularization may thus be more important for S-PSA than the production of PSA in the prostatic tissue.     

Growth of an androgen-sensitive human prostate cancer cell line,LNCaP, in nude mice

This study was undertaken to establish an androgen-sensitive model of human prostatic carcinoma in nude mice. The androgen-sensitive prostatic carcinoma cell line, LNCaP, was suspended in reconstituted basement membrane (Matrigel) and injected subcutaneously into nude mice. The LNCaP cell line was chosen for the study, because the cell line is androgen-sensitive and secretes prostate specific antigen (PSA) into culture media. Following injection of 1 × 10⁶ LNCaP cells with 0.25 ml of Matrigel, 88. of mice exhibited palpable tumor burdens after 12 weeks of observation. In addition, significant levels of PSA were observed in the serum of LNCaP-bearing mice. Bilateral orchiectomy of mice resulted in tumor regression and stabilization of serum PSA levels, compared to testis-intact controls. A significant correlation of PSA to tumor volume and weight was observed. The castrate level of testosterone was confirmed by radioimmunoassay and was similar to testosterone levels in female nude mice. Matrigel allows for a conducive environment to propagate LNCaP cells in nude mice. Furthermore, the growth can be manipulated by castration, leading to involution of tumor and stabilization of serum PSA level. This in vivo model of hormone-sensitive human prostate cancer cell line will serve as a model for the study of prostate tumor biology and treatment. © 1993 Wiley-Liss, Inc.     

Prostate-specific antigen in the follow-up of prostatic adenocarcinoma treated with external beam radiation.

Prostate-specific antigen (PSA) has been shown to be a more sensitive tumor marker than prostatic acid phosphatase (PAP) in prostatic adenocarcinoma: PSA was positive in 54 of our 117 patients (46%) and PAP was positive in 24 (21%). In order to compare the usefulness of these markers during and after radiotherapy serum samples from 24 patients treated with external beam irradiation were analyzed. PAP was only slightly positive in 1 patient (4%) after radiotherapy. His PSA level was highly elevated and he died of progressive disease. In the other 23 patients the cancer was in local control. However, the serum PSA level remained positive in 5 of these patients indicating vital cancer cells may still have been present. An alternative possibility is that metaplastic prostatic cells which secrete PSA were left after radiotherapy, as has been shown to be the case in prostatic hyperplasia. Before radiotherapy increased PSA levels were measured in 3 patients. In 2 of them the level declined to normal within 6 months after radiotherapy. The PAP levels were normal. It is concluded that PSA (positive in 25% of patients after radiotherapy) might be more sensitive than PAP (positive in 4%) in monitoring the effect of radiotherapy in prostatic cancer patients.     

Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma

PURPOSE: Gleason grade and tumor stage are well established prognostic factors in prostate cancer. Histological demonstration of tumor in lymphovascular spaces has been associated with poor prognosis in many tumor types but it is not included in current prostate cancer grading and staging schemes. Whether lymphovascular invasion is an independent prognostic factor for disease progression in prostate cancer is uncertain. We retrospectively investigated lymphovascular invasion as a predictive factor for biochemical failure and cancer specific survival following radical prostatectomy. MATERIALS AND METHODS: The records of 504 patients with prostatic adenocarcinoma undergoing radical prostatectomy were reviewed for lymphovascular invasion. Clinical followup data were available on 459 cases. Mean followup was 44 months (range 1.5 to 144). Multivariate analysis was performed using the Cox model. RESULTS: Lymphovascular invasion was identified in 106 cases (21%). Univariate analysis showed a significant association between lymphovascular invasion and higher preoperative serum prostate specific antigen (PSA), advanced pathological stage, higher Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and perineural invasion (each p <0.001). No association was observed between lymphovascular invasion and patient age at surgery, prostate weight or high grade prostatic intraepithelial neoplasia. Lymphovascular invasion was an independent predictor of PSA recurrence (HR 1.6, 95% CI 1.12 to 2.38, p = 0.01) and cancer specific survival (HR 2.75, 95% CI 1.04 to 2.28, p = 0.041) after controlling for tumor stage, surgical margins and Gleason grade on multivariate analysis. Five-year cancer specific survival was 90% in men with lymphovascular invasion compared to 98% in those without lymphovascular invasion (p <0.001). CONCLUSIONS: Lymphovascular invasion can be identified in approximately 20% of prostate cancer cases. Lymphovascular invasion is an independent risk factor for PSA recurrence and cancer death in patients with prostate cancer.     

Evaluation of prostate-specific antigen and prosttic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

PSA in the screening,staging and follow-up of early-stage prostate cancer

Summary Prostate-specific antigen (PSA) represents a major advance in our tumor marker armamentarium. Although not cancer-specific, it is specific for prostatic epithelium. Sophisticated serum assays have been developed for the detection of the analyte, and serum PSA has been used in the staging, monitoring, and screening of patients. The greastest utility of PSA appears to be in the monitoring of patients with carcinoma of the prostate, most significantly following radical prostatectomy. The role of serum PSA involving patients undergoing radiation therapy and hormonal manipulation is less clear; however, there also appears to be potential in these areas. The usefulness of PSA in screening is hampered by the observation that benign hyperplasia may be associated with elevated serum levels. PSA is a significantly better tumor marker for prostatic disease than prostatic acid phosphatase and should be used by all physicians managing these patients.     

Concentration of enzymatically active prostate-specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models

BACKGROUND: Prostate-specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized. METHODS: The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC-82, LNCaP, LAPC-4) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor-bearing animals, was likewise assayed. RESULTS: Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600-2100 nM). The majority of this PSA is enzymatically active (i.e., 80-90%). Human PC-82 prostate cancer xenografts also have high concentrations of PSA in the ECF (624 +/- 360 nM), and the majority of this PSA is also enzymatically active (i.e., 66 +/- 4%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45 +/- 9 nM) and LAPC-4 (7.3 +/- 0.6 nM). Only a small portion of the total PSA isolated from DHT-containing, serum-free, conditioned media from these cell lines is enzymatically active (i.e., approximately 18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples. CONCLUSIONS: Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC-82 prostate cancer xenografts. In contrast, LNCaP and LAPC-4 human prostate cancer xenograft models secrete approximately 70-300-fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC-82, the most, optimized xenograft model for screening PSA targeted prodrugs.     

Correlation of serum prostate specific antigen and quantitative immunohistochemistry

PURPOSE: Serum prostate specific antigen (PSA) in patients with prostate carcinoma is influenced by prostate size, transition zone volume, and tumor differentiation and volume. Immunohistochemistry studies have demonstrated an inverse correlation between PSA staining intensity and tumor grade, yet to our knowledge tissue expression of PSA has never been correlated with serum PSA. MATERIALS AND METHODS: In 47 radical prostatectomy cases serum PSA was corrected for gland size and tumor volume. Standard immunohistochemistry staining techniques were applied to specimens using monoclonal antibodies to PSA and cytokeratin CAM5.2. Color images of PSA and CAM5.2 immunohistochemistry stained slides were digitally acquired and analyzed using a standard image analysis system. Representative tumor foci in each slide were imaged with a 20x objective and 10x eyepiece. Staining extent and intensity of the tumor epithelium were measured, and stromal elements and luminal areas were excluded from analysis. For each case quantitative PSA staining intensity was expressed relative to keratin staining in adjacent benign epithelium. RESULTS: Gland volume and tumor volume independently correlated with serum PSA. Furthermore, tissue PSA intensity inversely correlated with histological grade of the tumor (p <0.00001). After gland size, tumor volume and grade were considered, corrected quantitative tissue PSA intensity did not significantly correlate with corrected serum PSA. CONCLUSIONS: Immunohistochemistry expression of tissue PSA in prostate carcinoma cannot be used to explain variations in serum PSA. This discrepancy may relate to differences between the amount of PSA produced by prostatic tumors and the amount secreted, and/or the sensitivity of detecting various tissue isoforms of PSA with immunohistochemistry.     

ROLE OF PROSTATE-SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATION IN THE DETECTION OF PROSTATE CANCER

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that is secreted exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Its serum concentration is raised in men with prostatic disease including cancer. We have evaluated its usefulness in the diagnosis of prostate cancer by measuring serum PSA concentrations in 260 men aged 50 years or over. All had abnormalities at digital rectal examination (DRE) involving suspected cancer, signs and symptoms of benign prostatic hyperplasia and equivocal findings on DRE, and miscellaneous other conditions, including hematospermia, chronic prostatitis and microscopic hematuria. Transrectal prostatic needle biopsies were performed in the men with abnormal findings on DRE or elevated serum PSA (above 4ng/ml). Serum PSA ranged from 4.0 to 9.9ng/ml in 14 (5%) of the 260 men. Four of the men in this group (31%) who underwent prostatic biopsy had prostate cancer. Serum PSA levels greater than or equal to 10.0 ng/ml were found in 8 (3%) of the 260 men. 5 of these 8 (63%) who underwent prostatic biopsy had cancer. If DRE alone had been used to screen the men having biopsies, 4 of the 10 cancers (40%) would have been missed. If PSA alone had been used to screen these men, only 1 of the 10 cancers would have been missed. Serum PSA measurement was more reliable than DRE for detecting prostate cancer. Since these two methods do not always detect the same malignant tumor, the combined use of DRE and PSA testing affords a more complete evaluation of the prostate gland for malignant involvement.     

Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate.

PSA is a kallikrein-like, serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. PSA is also present in the serum and can be measured reliably by either a monoclonal immunoradiometric assay or a polyclonal radioimmunoassay. The calculated half-life of serum PSA ranges from 2.2 to 3.2 days and the metabolic clearance rate of this tumor marker follows first-order kinetics. Digital rectal examination, cystoscopic examination and prostate biopsy all can cause spurious elevations of the serum PSA concentration. Conditions such as bacterial prostatitis and acute urinary retention also can falsely elevate the serum PSA level. Because approximately 25% of the patients with BPH only will have an elevated serum PSA concentration and BPH tissue contributes to this PSA value in a variable manner from patient to patient, it is unlikely that PSA by itself will become an effective screening tool for the early diagnosis of prostate cancer. However, if combined with digital rectal examination and/or transrectal ultrasound it may become a vital part of any early detection program. Prostatic intraepithelial neoplasia also may be associated with moderately elevated serum PSA levels. Although there is a direct correlation between the serum PSA concentration and clinical stage, PSA is not sufficiently reliable to determine the clinical stage on an individual basis. This finding also applies to pathological stage. As a result, the preoperative serum PSA concentration cannot be used to decide whether to recommend radical prostatectomy for potential cure. Low preoperative serum PSA concentrations in patients with previously untreated prostate cancers are predictive of a negative bone scan. Thus, in these select patients a staging bone scintigram may not be necessary. With respect to monitoring patients after definitive therapy, PSA is an exquisitely sensitive tumor marker. Irrespective of the treatment modality (radical prostatectomy, radiation therapy or antiandrogen treatment), PSA reflects accurately the tumor status of the patient and is prognostic of eventual outcome; this tumor marker is capable of predicting tumor recurrence months before its detection by any other method. PSA is also a most useful immunocytochemical marker. Its sensitivity and specificity to identify tissue of prostatic origin approach 100%. When compared to PAP, PSA is a more precise and meaningful marker in all clinical situations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inhibition of PAIII rat prostatic adenocarcinoma growth and metastasis by a new diarylsulfonylurea antitumor agent, LY181984.

LY181984 is a compound in a series of orally active diarylsulfonylureas with broad spectrum in vivo activity against syngeneic rodent and human xenograft tumor models. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this antitumor agent on the lymphatic and pulmonary metastasis of the tumor in male Lobund Wistar rats. LY181984 was inactive against the proliferation of PAIII cells in vitro. Following subcutaneous implantation of 10(6) PAIII cells in the tail, oral administration of LY181984 (25.0, 50.0, or 100.0 mg./kg./day) for 30 days had no significant effects on body weight gain. LY181984 treatment produced significant (p less than 0.05) dose-dependent inhibition of primary tumor growth in the tail (max. inhibition = 46% from untreated control levels). In these same animals, LY181984 administration produced significant (p less than 0.05) dose-dependent inhibiton of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 79% and 80% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by oral LY181984 treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (p less than 0.05) reduced by LY181984 administration in a dose-dependent manner (maximal reduction = 78% from control values). While the non-toxic doses (less than 100.0 mg./kg./day for 28 days) of LY181984 produced marked decreases in tumor growth and metastasis, administration of the compound had no effect on the survival of PAIII-bearing rats. These data support the contention that LY181984 represents a new class of orally active antitumor and antimetastatic agents with potential efficacy in the treatment of hormone-insensitive prostatic cancer. Further studies are needed to define maximal efficacy of LY181984 and other sulfonylurea agents in urogenital solid tumor animal models.     

Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were evaluated in 23 patients with benign prostatic hyperplasia (BPH), 115 with prostatic carcinoma, of whom 21 had bone metastasis, and in 16 age-matched control subjects. RESULTS: Patients with newly diagnosed prostate cancer and bone metastasis had a higher urinary excretion of DPD, and a higher serum PSA and ALP than had patients with BPH and those with prostate cancer but no metastasis. Receiver operating curve analysis for PSA, ALP and DPD showed a significant discriminating ability for positive and negative bone scans (P = 0.0684). However, from logistic regression of the combinations, only serum ALP was a significant independent predictor of bone metastasis in patients with prostate cancer. CONCLUSION: Serum ALP or urinary DPD are the best predictors of bone metastasis in patients with prostate cancer; further studies with more patients are required.     

The criteria for avoiding unnecessary computerized tomography and bone scan in staging patients with newly diagnosed prostate cancer: retrospective study of patients at Matsusaka Chuo General Hospital

PURPOSE: Staging for prostate cancer often includes computed tomography (CT) and bone scan in Japan. We examined the criteria of avoiding unnecessary CT and bone scan for the prostate cancer patients at Matsusaka Chuo General Hospital. SUBJECTS AND METHODS: 211 patients were newly diagnosed at our institution between 1998 September and 2004 April. We reviewed data from 208 patients who had a staging CT and bone scan. The data was analysed using Gleason score, clinical T-stage and serum prostatic specific antigen (PSA) level. RESULTS: CT detected lymphadenopathy in 19 patients (9.1%), Bone scan detected bone metastasis in 31 patients (14.9%). However there was no lymphadenopathy detected by CT in the patients with 20 ng/ml or less. In the analysis using PSA and Gleason score, there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and Gleason sum 7 or less. In the analysis using PSA and clinical local stage there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and localized lesion (cT1-2). CONCLUSION: In a new proatate cancer patient CT and bone scan can be avoidable by PSA level of 20 ng/ml or less and cT1-2 or less and Gleason sum 7 or less.     

PSA和SPECT骨显像在前列腺癌诊断治疗中的意义

目的：研究PSA、SPECT骨显像在前列腺癌诊断及治疗中的临床意义。方法：对100例经临床确诊的前列腺癌患者全部行血清PSA测定及全身骨显像。结果：发生骨转移的患者为81％,PSA≥20tμg／I．的患者发生骨转移的为60％。结论：血清PSA与骨显像联检对前列腺癌临床诊断、疗效观察及预后判定具有重要的指导意义。