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.     

PEAZ-1: a new human prostate neoplastic epithelial cell line.

BACKGROUND: The generation of prostatic cell lines provides in vitro models for experimental studies of the pathogenesis of prostate carcinoma. Therefore, we established and characterized a new human prostate epithelial cell line, PEAZ-1 (prostate epithelial Arizona-1). METHODS: The PEAZ-1 cells were grown from a primary human prostate carcinoma specimen obtained from radical prostatectomy. The isolated cells were characterized by immunobiochemistry, immunohistochemistry, and tumorigenicity studies. RESULTS: PEAZ-1 cells are near diploid, tumorigenic, and androgen independent for cell growth. PEAZ-1 cells express N-cadherin, alpha- and beta-catenins, and p120 at cell-cell contacts, cytoplasmic laminin 5, vinculin, paxillin, and phosphotyrosine at focal adhesions, vimentin, and cytokeratins 8 and 18. They do not express plakoglobin, E-cadherin, and PSA, and do not form desmosomes and hemidesomomes. PEAZ-1 respond to ocadaic acid, a pro-apoptotic agent, by expression of p53. CONCLUSIONS: PEAZ-1 cells is a human prostate cancer cell line that has a number of mesenchymal characteristics.     

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.     

Prostate-specific antigen (PSA) protein does not affect growth of prostate cancer cells in vitro or prostate cancer xenografts in vivo

BACKGROUND: Prostate-specific antigen (PSA) is produced in high amounts by normal and malignant prostate cancer cells. PSA is a serine protease with substrates that include semenogelin I and II, insulin-like growth factor binding protein 3, fibronectin, and laminin. PSA, via its enzymatic activity, may play a role in growth, invasion, and metastasis of prostate cancer cells. Recent data also suggest that the PSA protein itself, independent of enzymatic activity, may also function as an endothelial cell-specific inhibitor of angiogenesis. METHODS: Human (PC3, DU145) and rat (AT2, AT6) prostate cancer cell lines were transfected with the full PSA gene encoding preproPSA protein. PSA-producing clones of each cell line were selected and the amount of enzymatically active PSA produced by each cell line determined using a PSA-specific fluorescent peptide substrate. In vitro and in vivo growth characteristics of PSA-producing transfectants were compared to neomycin controls and wild type cells. RESULTS: All selected clones produced and secreted PSA (5-120 ng/ml/10(5) cells). None of the PSA-transfected cell lines produced detectable amounts of enzymatically active PSA. Production of enzymatically inactive PSA by prostate cancer cell lines did not alter growth kinetics in vitro. PSA-producing xenograft doubling times in vivo were similar to neomycin controls and wild type. CONCLUSION: Although recent reports suggest the PSA protein itself may be antiangiogenic, our results demonstrate that production of PSA protein by prostate cancer cells does not significantly alter growth in vitro or in vivo.     

Detection of prostate cancer in males with prostatism

The present study was designed to compare the prostate cancer detection rate, sensitivity, specificity, and positive predictive value of digital rectal examination (DRE) and serum prostatic specific antigen (PSA) in a consecutive cohort of males presenting to a single institution with clinically significant prostatism. The study population was comprised of 224 consecutive males with clinically significant prostatism referred to the Prostate Center at the Medical College of Wisconsin between June 1990 and December 1991. Subjects were considered to have clinically significant prostatism if they elected to pursue medical or surgical therapy following exclusion of carcinoma of the prostate. The initial examination consisted of a Boyarsky symptom score assessment, DRE, uroflowmetry, postvoid residual determination, serum PSA level, and transrectal prostatic ultrasonography. Subjects with an abnormality on DRE or serum PSA > 4 ng/dl were advised to undergo transrectal prostatic biopsy. Of the 224 subjects, 40 (17.9%) had an abnormal DRE and 57 (25.4%) had an elevated serum PSA > 4 ng/dl. The overall detection rate of prostate cancer in the study population was 6.7%. The prostate cancer detection rates for PSA alone and DRE alone were 5.8% and 5.3%, respectively. The sensitivity, specificity, and positive predictive values of PSA alone were 86.7%, 80.9%, and 25.0% and of DRE alone 80.0%, 86.3%, and 30.0%, respectively. Receiver operator characteristic (ROC) curves were constructed for the entire study population in order to compare the screening measures serum PSA and PSA density. The area under the curves was 0.88 for both tests, indicating that these screening tests for prostate cancer were not significantly different. The present study demonstrated that males with clinically significant prostatism represent a high risk cohort for detecting prostate cancer. DRE and PSA are equally effective measures for detecting prostate cancer. PSA density does not offer any advantage over serum PSA in screening for prostate cancer, except in the subset of patients with a normal DRE and serum PSA levels between 4.0 and 9.9 ng/dl. © 1994 Wiley-Liss, Inc.     

A potential autocrine pathway for growth hormone releasing hormone (GHRH) and its receptor in human prostate cancer cell lines

BACKGROUND: Recent studies have shown that GHRH antagonists inhibit prostate tumour growth and IGF-II production both in vivo and in vitro. The mechanism underlying these observations is unknown, but may involve an interaction with a prostatic GHRH receptor (GHRH-R), raising the possibility of an autocrine pathway for the GHRH axis in the prostate. METHODS: GHRH and GHRH-R mRNA expression was examined by RT-PCR in human prostate cancer cell lines, and the authenticity of PCR products was confirmed by Southern analysis and cDNA sequencing. Immunohistochemical techniques were used to examine the expression of GHRH protein in prostate cancer cell lines. RESULTS: GHRH-R (mRNA) and GHRH (mRNA and protein) are co-expressed in the ALVA-41, DU145, LNCaP and PC3 human prostate cancer cell lines. CONCLUSIONS: These observations suggest the presence of an intact prostatic GHRH autocrine pathway which may stimulate prostate cell proliferation. This pathway may be disrupted by GHRH antagonists.     

Overexpression of the EphA2 tyrosine kinase in prostate cancer.

BACKGROUND: Molecules that are highly expressed by human prostate cancers may serve as therapeutically relevant targets or tumor markers. Tyrosine kinases are frequently overexpressed in metastatic tumor cells and this prompted us to screen for tyrosine kinases that are overexpressed in prostate cancer cells. METHODS: Expression levels of the EphA2 receptor tyrosine kinase were determined by Western blot analysis in canine and human prostate cancer cell lines and in immortalized and transformed variants of 267B1 prostatic epithelial cells. EphA2 levels in benign human prostate and prostate cancers were also determined in formalin-fixed, paraffin-embedded tissues using immunohistochemical staining. RESULTS: Metastatic prostate cancer cells overexpressed EphA2 by 10-100 fold as compared with non-invasive prostatic epithelial cells. EphA2 immunoreactivity in vivo was also significantly greater in human prostate cancers as compared with benign prostate epithelium. CONCLUSIONS: The EphA2 receptor tyrosine kinase is differentially expressed in human and canine prostate cancer cell lines and overexpressed in human prostate cancers as compared with benign prostate tissues. Metastasis-derived canine prostate carcinoma cell lines overexpress EphA2 and may provide pre-clinical models to further evaluate the role of EphA2 in prostate carcinogenesis. Further investigations are needed to determine the utility of EphA2 as a tumor marker and a novel target in human prostate cancer.     

The effect of hyperthermia on human prostatic carcinoma cell lines: evaluation in vitro

The effect of hyperthermia on established human prostate carcinoma cell lines (PC-3, DU-145) and related sublines (1-LN, 125-1L) was investigated in vitro. Cells were exposed to heat treatment at 43C or 37C for varying time intervals, (one hr or two hrs) and cell survival was evaluated by the colony formation assay and by measurement of cellular growth rate. While one hr exposure at 43C did show a mean inhibition of colony formation, ranging from 29 to 41%, a statistically significant increase in inhibition rate (p less than 0.001) was observed at two hr exposure, ranging from 57 to 92%. This study is a report of the cytotoxic effect of hyperthermia on established human prostatic tumor cell lines. These in vitro results indicate that hyperthermia may become a potentially useful form of adjunctive therapy for local control of prostatic cancer. However, the temperature and exposure time may have an important impact on cell kill when this new modality for cancer treatment is proposed for a clinical trial.     

Monomethylated selenium inhibits growth of LNCaP human prostate cancer xenograft accompanied by a decrease in the expression of androgen receptor and prostate-specific antigen (PSA)

OBJECTIVES: Epidemiological studies and prevention trials suggest selenium is a promising preventive agent for prostate cancer. Selenium-containing compounds inhibited the growth of prostate cancer cell lines including androgen sensitive LNCaP and androgen insensitive DU145 and PC3 cells in vitro. Previous study revealed a novel mechanism of selenium action in which selenium (methylseleninic acid (MSA)) markedly reduced androgen receptor (AR) signaling in prostate cancer cells, suggesting that selenium might act as an antiandrogen, which could serve as a therapeutic agent for prostate cancer. In this study, we tested whether selenium (methylselenocysteine (MSC)) affects tumor growth of human prostate cancer cells by targeting AR signaling in vivo. METHODS: Prostate tumor xenografts were established in nude mice by co-inoculating LNCaP cells with Matrigel. The mice-bearing tumors were treated with or without MSC (100 microg/mouse/day) via intraperitoneal injection for 2 weeks. The effect of MSC on tumor growth, AR, and prostate-specific antigen (PSA) expression was examined. RESULTS: Methylselenocysteine (MSC) significantly inhibited LNCaP tumor growth (P < 0.05). AR expression in tumor tissues and serum PSA levels were considerably decreased in MSC-treated mice compared to the vehicle controls. CONCLUSIONS: Pharmacological dose of MSC inhibits the growth of LNCaP human prostate cancer in vivo accompanied by a decrease in the expression of AR and PSA. These findings suggest that selenium (MSC) can serve as a therapeutic agent aimed at disruption of AR signaling for prostate cancer.     

Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer

PURPOSE: We investigate the potential use of the phytotherapeutic PC-SPES to treat human prostate cancer, and evaluate its in vivo and in vitro activity, and clinical efficacy. MATERIALS AND METHODS: PC-SPES was evaluated for its ability to induce apoptosis on prostate cancer cell lines LNCaP, PC3 and DU145. The effect of oral PC-SPES on growth of PC3 tumors present in male immunodeficient mice was studied. A total of 30 male nude mice were divided in 5 groups. In groups 1 control and 2 full dose therapy was started the same day of the tumor injection. In groups 3 control, 4 half dose and 5 full dose PC-SPES therapy was initiated 1 week after tumor injection. A total of 69 patients with prostate cancer were treated with 3 capsules of 320 mg. PC-SPES daily. Serum prostate specific antigen (PSA) responses and side effects were evaluated. RESULTS: All of the cultured prostate cancer cell lines had a significant dose dependent induction of apoptosis following exposure to an alcoholic PC-SPES extract. Immunodeficient mice xenografted with the PC3 cell line had reduced tumor volume compared with sham treated controls when they were treated with a PC-SPES extract from the time of tumor cell implantation (931 +/- 89 versus 1,424 +/- 685 mm.3, p not significant) but not when the treatment was begun 1 week after tumor cell implantation. The testis, prostate, bladder and seminal vesicles of the treated mice were significantly reduced in weight compared with the sham treated animals. Of the patients with prostate cancer 82% had decreased serum PSA 2 months, 78% 6 months and 88% 12 months after treatment with PC-SPES. Side effects in the treated patient population included nipple tenderness in 42% and phlebitis requiring heparinization in 2%. CONCLUSIONS: An extract of the phytotherapeutic agent PC-SPES proved to be active in inducing apoptosis of hormone sensitive and insensitive prostate cancer cells in vitro, and in suppressing the growth rate of a hormone insensitive prostate cancer cell line in vivo. The overwhelming majority of patients with prostate cancer treated with the agent experienced a decrease in serum PSA but also demonstrated a side effect profile comparable to estrogen treatment.     

Prostate small cell carcinoma: report of two cases that differed in treatment responsiveness

Case 1 : A 76-year-old man with a chief complaint of dysuria had an elevated prostate specific antigen (PSA) level of 24.9. He underwent a transperineal needle biopsy of the prostate, and the histopathological diagnosis was prostatic small cell carcinoma. The cancer was clinically diagnosed as T3bN1M1 with multiple lung metastases. He started receiving hormonal therapy. After three months of hormonal therapy, the multiple lung metastases disappeared. Thereafter, the serum PSA level and the tumor volume increased and he died 12 months from the start of therapy. Case 2: A 79-year-old man was referred to our hospital with a chief complaint of dysuria. The serum level of PSA was elevated to 10.4. Transperineal prostate biopsy revealed prostatic small cell carcinoma. The cancer was clinically diagnosed as T3bN1M1, and hormonal therapy was started. Subsequently, although his serum PSA level declined, his condition worsened rapidly and he died five months after the start of therapy.     

Secretion of prostatic specific antigen, proliferative activity and androgen response in epithelial-stromal co-cultures from human prostate carcinoma

We investigate the proliferative activity, prostatic specific antigen (PSA) secretion, morphology and androgen response of human prostate tumour epithelial cells co-cultured with stromal cells in a bicameral system. Stromal and epithelial cells were isolated from prostate adenocarcinoma by enzyme digestion and cultured in defined media. Immunocytochemistry for prostate carcinoma tumour antigen (PCTA-1) was performed for culture purity evaluation. Also, the morphology of the epithelial cells in co-culture was evaluated by electron microscopy. PSA was determined by microparticle enzyme immunoassay (MEIA) automatized protocol and the proliferation was evaluated by a commercial spectrophotometric kit, based on formazan salt formation. Both cell cultures showed more than 90% of purity. The epithelial cell co-cultures showed marked membrane processes and cell interdigitations. The proliferative activity of the epithelial cells was increased in presence of stromal cells. Also, PSA secretion was significantly increased and maintained for at least 14 days, whereas the androgen response for PSA secretion was evidenced only in co-culture condition. Primary co-cultures of epithelial and stromal cells from human prostate carcinoma are able to maintain, for a prolonged time, proliferative and secretory properties as well hormone response, and represent a valuable tool for cellular and molecular studies on prostate cancer.     

Human cell lines as an in vitro/in vivo model for prostate carcinogenesis and progression

BACKGROUND: The study of prostate carcinogenesis and tumor progression is made difficult by the lack of appropriate in vitro and in vivo models. High prevalence of prostatic intra-epithelial neoplasia and latent prostatic carcinoma, representing multiple steps in carcinogenesis to invasive carcinoma, are relevant targets for cancer prevention. From the RWPE-1, immortalized, non-tumorigenic, human prostate epithelial cell line, we have derived four tumorigenic cell lines with progressive malignant characteristics. METHODS: Cell lines were derived by exposure of RWPE-1 to N-methyl-N-nitrosourea (MNU), selected and cloned in vivo and in vitro, and characterized by prostatic epithelial and differentiation markers, karyotype analysis, anchorage-independent growth, invasiveness, tumorigenicity, and pathology of the derived tumors. RESULTS: Cytokeratins 8 and 18, androgen receptor, and prostate-specific antigen expression in response to androgen, confirm prostatic epithelial origin. RWPE-1 cells do not grow in agar and are not tumorigenic in mice, but the growth, tumorigenicity, and tumor pathology of the MNU cell lines correlate with their invasive ability. The WPE1-NA22 (least malignant) form small, well-differentiated, and WPE1-NB26 cells (most malignant) form large, poorly differentiated, invasive tumors. Overall, loss of heterozygosity for chromosomes 7q, 13q, 18q, and 22, and gain of 5, 9q, 11q, and 20, was observed. The MNU cell lines, in order of increasing malignancy are; WPE1-NA22, WPE1-NB14, WPE1-NB11, and WPE1-NB26. CONCLUSIONS: This family of cell lines with a common lineage represents a unique and relevant model which mimics stages in prostatic intra-epithelial neoplasia (PIN) and progression to invasive cancer, and can be used to study carcinogenesis, progression, intervention, and chemoprevention.     

Characterization of a transplantable hormone-responsive human prostatic cancer xenograft TEN12 and its androgen-resistant sublines

BACKGROUND: Models for human prostate cancer can facilitate the study of resistance to endocrine therapy, aid drug discovery, and pre-clinical assessment. METHODS: Characteristics thought relevant to the growth in athymic nude mice of TEN12, an androgen-dependent transplantable prostatic cell line derived from a primary prostate carcinoma, and its two androgen-independent sublines, TEN12F and TEN12C, have been assessed immunocytochemically. RESULTS: The xenografts of the parental TEN12 line are moderately differentiated with both papillary and glandular regions, pleomorphic nuclei and abundant mitotic figures and are extremely vascular. The cells express androgen receptor (AR), PSA, VEGF, EGFR, c-erbB2, and TGFalpha. Both TEN12F and TEN12C xenografts possessed a more anaplastic morphology and displayed significantly lower growth rates, reduced blood vessel density (BVD), decreased MIB-1 antigen and E-cadherin expression and increased cytoplasmic AR and HSP90 staining. Elevated EGFR (membrane) but not c-erbB2 expression was demonstrated in the TEN12F line only. Castration of mice bearing TEN12 xenografts rapidly induced the appearance of cytoplasmic AR in the cells, PSA levels decreased initially but recovered to below pre-castration levels whilst reduced TGFalpha and loss of VEGF expression was seen in the long-term castrates. CONCLUSIONS: TEN12 and its sublines offer additional in vivo models to study the factors involved in the progression of prostatic cancer to androgen-independence.     

Changes of phenotypic expression of prostatic antigen in secondary transitional cell carcinoma of the prostate: evidence for induction phenomenon as a mechanism for acquisition of prostatic antigens in prostatic transitional cell carcinoma

BACKGROUND: In vitro and experimental studies of mesenchymal-epithelial interaction for the prostatic stroma have demonstrated that the prostatic stroma is capable of inducing the nonprostatic epithelium to acquire many features of prostatic epithelium. We investigated whether this phenomenon could be observed in vivo in human prostatic stroma. MATERIALS AND METHODS Sixty transitional cell carcinoma (TCC) of the urinary bladder: (a) 20 with glandular lumen; (b) 20 without glandular lumen: (c) 10 mixed TCC-adenocarcinoma (ACA); and (d) 10 with synchronous or metachronous TCC of the prostate; and three primary TCC of the prostate were examined and submitted for immunostaining for prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). RESULTS: There was a spectrum of immunostaining for PSA ranging from negative reactivity in TCC without glandular lumen of the urinary bladder, to focal and weak reactivity in single cells with varying degrees of nonmucinous glandular differentiation and to strong reactivity in groups of cells in primary and synchronous or metachronous TCC in the prostate. The areas of carcinoma geographically closest to the prostate and with the most extensive nonmucinous glandular differentiation displayed the most frequent and strongest immunoreactivity for PSA. The immunoreactivity for PAP was usually stronger than for PSA. Four cases of TCC and mixed TCC-ACA were immunoreactive only for PAP. Furthermore, there was a change in the phenotype of TCC in the urinary bladder as it spread into the prostate. For 10 TCC in the urinary bladder with synchronous or metachronous tumor in the prostate, all TCC in the urinary bladder were negative for PAP and PSA, whereas six TCC in the prostate were focally positive. CONCLUSIONS: The spectrum of immunoreactivity for PAP and PSA and the change in immunoreactivity of TCC of the urinary bladder as it spreads into the prostate are likely induced by the prostatic stroma through the mechanism of mesenchymal-epithelial interaction. Prostate 47:172-182, 2001.     

Expression, purification, and characterization of active recombinant prostate-specific antigen in Pichia pastoris (yeast)

BACKGROUND: Prostate-specific antigen (PSA), a member of the kallikrein family of serine proteases, is a chymotrypsin-like glycoprotein produced by the prostate epithelium. Elevated serum PSA (> 4 ng/ml) is a tumor marker for prostatic cancer and benign prostatic hypertrophy; increasing serum PSA over time is indicative of metastatic disease. It has been suggested that PSA may contribute to tumor metastasis through degradation of extracellular matrix glycoproteins, as well as cleavage of IGF binding protein-3, a modulator of IGF-1. To elucidate the role of PSA in the development and progression of prostatic cancer, it is necessary to have a reliable, cost-effective source of enzymatically active protein. Previous efforts to express recombinant PSA (rPSA) produced inactive proPSA, or mixtures of active and inactive PSA requiring activation by removal of the propeptide. We describe the expression of active recombinant mature PSA in yeast. METHODS: Stable chromosomal integration of a construct consisting of the yeast alpha-factor signal sequence preceding the mature PSA sequence resulted in secretion of rPSA. The rPSA was purified from the yeast cell culture supernatant to homogeneity by strong cation-exchange chromatography, and characterized by SDS-PAGE, Western analysis, electrospray mass spectrometry, N-glycanase digestion, N-terminal amino acid sequencing, and inactivation by a PSA-specific inhibitor. RESULTS: We report the production of active, mature rPSA in Pichia pastoris. Two forms of rPSA varying slightly in glycosylation were identified. The specific activity of the rPSA was equal to that of human seminal plasma PSA (0.56 micromol/min mg) as determined using a chromogenic substrate. CONCLUSIONS: Large-scale production of active rPSA will be useful in the exploration of PSA effects on tumor cell proliferation, migration and metastasis. In addition, a large supply of enzyme should facilitate the discovery of novel inhibitors for in vitro and in vivo evaluation, and may provide a reproducible source of rPSA for use as a standard in diagnostic testing.     

PSA、PSAD和PSAT在前列腺穿刺活检中的价值

目的 研究血清前列腺特异性抗原(PSA)及其密度(PSAD)和移行带密度(PSAT)在前列腺穿刺活检中的价值.方法 选取本院2014年5月至2015年5月收治的150例患者进行前列腺穿刺活检,分析并比较PSA、PSAD、PSAT在前列腺穿刺活检中的差异及其在确诊疾病方面的价值.结果 在前列腺穿刺活检的150例中发现PSA＜4 ng/mL有8例,4 ng/mL≤PSA≤20 ng/mL有66例,PSA ＞20 ng/mL有76例.其中在PSA＜4 ng/mL的8例中,活检结果良性前列腺增生6例,前列腺小细胞癌1例,前列腺横纹肌肉瘤1例.在4 ng/mL≤PSA≤20 ng/mL的66例中,活检结果诊断为前列腺癌增生患者54例,活检阳性率为81.8％,PSA平均值为(13.98±1.51) ng/mL,PSAD平均值为(0.32±0.18);PSAT平均值为(0.35±0.18);活检前列腺癌12例,活检阳性率为19.2％,PSA平均值为(14.29±1.48) ng/mL,PSAD平均值为(0.42±0.15),PSAT平均值为(0.82±0.15);将其分为良性前列腺增生组和前列腺癌组,两组差异具有统计学意义(P＜0.05).当PSAD ＞0.13或PSAT＞ 0.15时,前列腺癌的敏感性分别为92.86％和96.94％.在PSA＞ 20 ng/mL的76例中,前列腺癌有68例,活检阳性率89.47％.结论 在4 ng/mL≤PSA≤20 ng/mL时,PSAD和PSAT对前列腺增生和前列腺癌的鉴别诊断具有重要意义,其中又以PSAT更为准确;PSA＞ 20ng/mL时,应高度怀疑前列腺癌,及时确诊治疗.     

Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia

BACKGROUND: YKL-40, also called human cartilage glycoprotein-39 (HC gp-39) and chitotriosidase are homologs of family 18 glycosyl hydrolases secreted by human macrophages. Although high levels of YKL-40 and chitotriosidase are associated with several diseases, the physiological functions of these enzymes are still unclear. YKL-40, a growth factor for connective tissue cells, a migration factor for endothelial and vascular smooth muscle cells, is expressed by several types of solid human carcinoma, including prostate carcinoma. PURPOSE: The purpose of this study was to compare serum YKL-40 levels and chitotriosidase activity both in benign prostatic hyperplasia and primary prostate cancer. METHODS: YKL-40 and chitotriosidase were determined in serum samples from 93 patients with primary prostate cancer and 61 patients with benign prostatic hyperplasia. Serum YKL-40 levels were measured by ELISA and chitotriosidase activity was determined by fluorometer. PSA levels were also measured by using an automated system. RESULTS: Serum YKL-40 levels were significantly higher (P < 0.001) in patients with prostate cancer compared with control group whereas there was no significant difference between BPH and control group. Serum chitotriosidase activities were significantly higher in carcinoma patients with high Gleason score than the control group (P < 0.001). No significant difference was observed in BPH patients (P > 0.05). Both YKL-40 and chitotriosidase were found statistically significant higher in primary prostate cancer and BPH. CONCLUSION: High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the progression of malignant diseases, whereas no significant elevation was observed in benign prostatic hyperplasia. Meanwhile, high serum chitotriosidase activity was observed only in patients with Gleason high grade, indicating possible macrophage involvement in cancer progression. Further studies are needed to elucidate the biologic role of YKL-40 in cancer aggressiveness and in progression of malignant diseases.