Prostatic Acid Phosphatase Levels Research Articles

RET Signaling Is Required for Survival and Normal Function of Nonpeptidergic Nociceptors

Small unmyelinated sensory neurons classified as nociceptors are divided into two subpopulations based on phenotypic differences, including expression of neurotrophic factor receptors. Approximately half of unmyelinated nociceptors express the NGF receptor TrkA, and half express the GDNF family ligand (GFL) receptor Ret. The function of NGF/TrkA signaling in the TrkA population of nociceptors has been extensively studied, and NGF/TrkA signaling is a well established mediator of pain. The GFLs are analgesic in models of neuropathic pain emphasizing the importance of understanding the physiological function of GFL/Ret signaling in nociceptors. However, perinatal lethality of Ret-null mice has precluded the study of the physiological role of GFL/Ret signaling in the survival, maintenance, and function of nociceptors in viable mice. We deleted Ret exclusively in nociceptors by crossing nociceptor-specific Na(v)1.8 Cre and Ret conditional mice to produce Ret-Na(v)1.8 conditional knock-out (CKO) mice. Loss of Ret exclusively in nociceptors results in a reduction in nociceptor number and size, indicating that Ret signaling is important for the survival and trophic support of these cells. Ret-Na(v)1.8 CKO mice exhibit reduced epidermal innervation but normal central projections. In addition, Ret-Na(v)1.8 CKO mice have increased sensitivity to cold and increased formalin-induced pain, demonstrating that Ret signaling modulates the function of nociceptors in vivo. Enhanced inflammation-induced pain may be mediated by decreased prostatic acid phosphatase (PAP), as PAP levels are markedly reduced in Ret-Na(v)1.8 CKO mice. The results of this study identify the physiological role of endogenous Ret signaling in the survival and function of nociceptors.

EVALUATION OF CHANGES IN THE LEVELS OF PROSTATE SPECIFIC ANTIGEN (PSA) AND PROSTATIC ACID PHOSPHATASE IN PATIENTS PRESENTING WITH URINARY RETENTION AND PROSTATE DISEASE

Prostate specific antigen (PSA) has established itself as the most useful marker for adenocarcinoma of the prostate (ADCA) adenocarcinoma of the prostate and in the recent years has almost replaced the total acid phosphatase and prostatic acid phosphatase prostatic acid phosphatase (PAP) for screening, diagnosis and monitoring the prostate carcinoma patients. The prostate specific antigen levels also rise in benign prostatic hypertrophy benign prostatic hypertrophy but to a lesser extent and high values are usually diagnostic of malignant disease. A cross-sectional comparative study was planned to see the effect of urinary retention and catheterization on plasma concentration of adenocarcinoma of the prostate and prostatic acid phosphatase and the value of this effect in the diagnosis of patients as having benign prostatic hypertrophy or adenocarcinoma of prostate. Sixty patients with prostatic disease were included in the study. Adenocarcinoma of the prostate and prostatic acid phosphatase levels were assessed in all patients. The patients were divided into two groups; group I are those presented with urinary retention and catheterization and group II those presented without urinary retention (without catheter). Following histological examination of prostatic tissues, the patients were diagnosed as cases of benign prostatic hyperplasia or adenocarcinoma of prostate. The data were analyzed using t-test. Benign prostatic hypertrophy was detected in 48 patients whereas 12 patients were diagnosed with adenocarcinoma of the prostate. In the study, 66.2% of benign prostatic hypertrophy and 50% of adenocarcinoma of the prostate patients presented with urinary retention and catheterization. It was observed that prostate specific antigen levels were significantly raised in benign prostatic patients with urinary retention and catheterization as compared to those with no retention. There was, however, no significant rise in prostatic acid phosphatase levels in those patients. In conclusion, prostatic acid phosphatase is still a very good tumor marker of prostatic disease in differentiating the malignant from the benign disease. It appears to be particularly important in patients with benign prostatic hyperplasia and urinary retention as catheterization appears to raise significantly the levels of prostate specific antigen but not those of prostatic acid phosphates. This finding means that patients presenting with urinary retention and catheterization and high prostatic acid phosphates levels are more likely having carcinoma of the prostate because retention and catheterization don’t significantly raise the prostatic acid phosphates levels in benign prostatic hypertrophy as they raise prostate specific antigen levels in such patients.

A phase II trial of an adenovirus/PSA vaccine for prostate cancer

3065 Background: Our phase I adenovirus/PSA vaccine trial has proven the vaccine is safe. We are conducting a phase II clinical trial with two separate protocols for patients with recurrent or hormone-refractory prostate cancer assessing toxicity, immune responses, and change in PSA levels. Methods: In Protocol 1 men with recurrent prostate cancer after definitive initial treatment were randomized to arm A (vaccine injection alone at days 0, 30, and 60) or arm B (vaccine injection 14 days after initiation of androgen deprivation therapy). In Protocol 2 men with hormone-refractory disease receive the vaccine alone at days 0, 30, and 60. Each injection consists of 108 pfu of Ad/PSA vaccine suspended in a collagen matrix. All patients return at regular intervals for physical, chemical, radiologic, and immunologic evaluations. Twenty-five patients will be enrolled in arms A and B in Protocol 1 and 32 in Protocol 2. Results: To date 10 patients have completed 3 monthly injections and have been followed a median of 5 months. Median patient age is 70 years (range 61–84), and median enrollment PSA levels are 0.79 ng/ml (range 0.24–3.93) in Protocol 1 and 5.47 ng/ml (range 0.29–11.17) in Protocol 2. Preliminary results show 86% in both protocols demonstrating anti-PSA T cell responses above preinjection levels. 25% have stable serum PSA levels, 50% have decreased levels, and 25% have increased levels. 11% have stable serum prostatic acid phosphatase (PAP) levels, 56% have decreased levels, and 33% have increased levels. Conclusions: These early results from the first few months of this phase II trial demonstrate the induction of anti-PSA T-cell responses in a high percentage of the vaccinated patients and stabilization or declines in serum PSA and PAP levels. No serious vaccine-related toxicities have been identified. No significant financial relationships to disclose.

A 1-Year, Open Label, Randomized Phase II Dose Finding Study of Degarelix for the Treatment of Prostate Cancer in North America

Degarelix is a gonadotropin-releasing hormone receptor antagonist (blocker) with rapid onset of action suppressing gonadotropins, testosterone and prostate specific antigen in prostate cancer. In the present open label, randomized study in North America we evaluated the efficacy and safety of a starting dose of 200 mg degarelix followed by monthly injections of 60 or 80 mg during 1 year of prostate cancer treatment. A total of 127 patients (median age 76 years, range 47 to 93) with histologically confirmed prostate cancer were enrolled in the study. Efficacy was assessed by measuring serum testosterone and prostate specific antigen. Median baseline testosterone and prostate specific antigen levels were 4.13 ng/ml (P25-P75 3.03-5.11) and 13.4 ng/ml (P25-P75 6.80-25.7), respectively. The starting dose induced a rapid suppression of testosterone in that 88% of the patients had testosterone levels of 0.5 ng/ml or less 1 month after the injection. For patients who had testosterone levels of 0.5 ng/ml or less after 1 month, 93% and 98% of those receiving maintenance doses of 60 and 80 mg, respectively, had testosterone levels that were consistently 0.5 ng/ml or less at all monthly measurements from 1 month to 1 year. No evidence of testosterone surge was detected. In both groups prostate specific antigen decreased by 96% after 1 year and median time to 90% reduction in prostate specific antigen was 56 days. Six patients (5%) withdrew from the study due to adverse events. Degarelix treatment for 1 year resulted in a fast, profound and sustained suppression of testosterone and prostate specific antigen with no evidence of testosterone surge. Degarelix was well tolerated.

Prostatic Acid Phosphatase Adversely Affects Cause-Specific Survival in Patients with Intermediate to High-Risk Prostate Cancer Treated with Brachytherapy

To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT). From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS. The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393). The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.

Highly sensitive and rapid tandem bioluminescent immunoassay using aequorin labeled Fab fragment and biotinylated firefly luciferase

We established a simultaneous bioluminescent assay utilizing aequorin (Aq) and biotinylated firefly luciferase (b-Luc); furthermore, we developed a highly sensitive and rapid tandem bioluminescent immunoassay (BLIA) involving the Aq-labeled Fab fragment and b-Luc–streptavidin complex. Minimum detection limits of Aq and b-Luc were 9.4 × 10 −21 mol assay −1 (blank + 3S.D.) and 3.6 × 10 −19 mol assay −1 (blank + 3S.D.), respectively. Measurements of two luminescent proteins were completed in 4 s with a single assay medium. In this study, prostatic acid phosphatase (PAP) and prostate specific antigen (PSA), which served as analytes, were measured in the tandem BLIA. PAP and PSA were detected by the Aq-labeled anti-Dig Fab fragment and b-Luc–streptavidin complex, respectively. The measurable ranges of PAP and PSA were 0.04–100 and 0.2–200 ng mL −1, respectively. This technique was also applied to the simultaneous measurement of PSA and α-fetoprotein (AFP). Measurable ranges of PSA and AFP were 0.2–200 and 1.95–1000 ng mL −1, respectively. Levels of PAP and PSA or PSA and AFP in human serum could be accurately determined with the proposed BLIA. Satisfactory correlations were observed between results obtained from the proposed BLIA and those derived from commercial kits.

Long-Term Prostate Cancer Control Using Palladium-103 Brachytherapy and External Beam Radiotherapy in Patients with a High Likelihood of Extracapsular Cancer Extension

To report the long-term biochemical control rates with brachytherapy-based treatment for patients with prostate cancer at high risk of extracapsular cancer extension. A total of 243 consecutive patients with at least one higher risk factor (Gleason score of 7 or worse, prostate-specific antigen [PSA] level greater than 10 ng/mL, or elevated prostatic acid phosphatase level greater than 2.5 U) who were treated with palladium-103 plus supplemental external beam radiotherapy from 1992 through 1996 were included in this study. Patients received 41 Gy external beam radiotherapy to a limited pelvic field, followed 4 weeks later by a palladium-103 boost. The prescribed minimal palladium-103 dose to the prostate was 80 to 90 Gy. Freedom from biochemical failure was defined as a serum PSA level of 0.2 ng/mL or less at the last follow-up visit. Of the 243 patients, 41 developed biochemical failure. The overall actuarial freedom from biochemical progression rate at 13 years was 81%, with 198 patients followed up for longer than 5 years. The overall actuarial freedom from failure rate for the 93 patients with a PSA level of 10 ng/mL or greater and Gleason score of 7 or greater was 74% at 5 years and 72% at 10 years. The overall actuarial freedom from failure rate for the 66 patients with elevated prostatic acid phosphatase was 65% at 10 years. The absolute risk of failure decreased progressively with time, falling to 1% by 6 years after treatment. On Cox proportional hazard multivariate analysis, considering each factor as a continuous variable, the strongest predictor of failure was the acid phosphatase level (P <0.0001), followed by Gleason score (P = 0.42) and PSA level (P = 0.15). The evidence from this patient group at high risk of extracapsular cancer extension suggests that the relatively high tumor control rates with brachytherapy-based therapy are durable.

Mensuração de hormônios andrógenos, estrógeno, fosfatase ácida prostática (PAP) e antígeno prostático específico (PSA) em cães adultos com próstata normal e hiperplásica

As doenças prostáticas constituem um problema comum em cães adultos e idosos. Uma das afecções mais freqüentes é a hiperplasia prostática benigna (HPB) que, tanto no cão como no homem, está associada ao avanço da idade e ao desequilíbrio hormonal. No presente trabalho foram mensurados hormônios andrógenos, estrógeno, fosfatase ácida prostática (PAP) e antígeno prostático específico (PSA) de 37 cães com idade superior a três anos, em função do aspecto microscópico da próstata. Encontraram-se baixos níveis de estrógeno e altas concentrações de PSA nos animais com algum tipo de hiperplasia. Os valores de PAP sérico e urinário também foram maiores nos cães com hiperplasia.

Cellular prostatic acid phosphatase: a protein tyrosine phosphatase involved in androgen-independent proliferation of prostate cancer

Human prostatic acid phosphatase (PAcP) was used as a valuable surrogate marker for monitoring prostate cancer prior to the availability of prostate-specific antigen (PSA). Even though the level of PAcP is increased in the circulation of prostate cancer patients, its intracellular level and activity are greatly diminished in prostate cancer cells. Recent advances in understanding the function of the cellular form of PAcP (cPAcP) have shed some light on its role in prostate carcinogenesis, which may have potential applications for prostate cancer therapy. It is now evident that cPAcP functions as a neutral protein tyrosine phosphatase (PTP) in prostate cancer cells and dephosphorylates HER-2/ErbB-2/Neu (HER-2: human epidermal growth factor receptor-2) at the phosphotyrosine (p-Tyr) residues. Dephosphorylation of HER-2 at its p-Tyr residues results in the down-regulation of its specific activity, which leads to decreases in growth and tumorigenicity of those cancer cells. Conversely, decreased cPAcP expression correlates with hyperphosphorylation of HER-2 at tyrosine residues and activation of downstream extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling, which results in prostate cancer progression as well as androgen-independent growth of prostate cancer cells. These in vitro results on the effect of cPAcP on androgen-independent growth of prostate cancer cells corroborate the clinical findings that cPAcP level is greatly decreased in advanced prostate cancer and provide insights into one of the molecular mechanisms involved in prostate cancer progression. Results from experiments using xenograft animal models further indicate a novel role of cPAcP as a tumor suppressor. Future studies are warranted to clarify the use of cPAcP as a therapeutic agent in human prostate cancer patients.

Proteomic Analysis of Formalin-fixed Prostate Cancer Tissue

Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.

Vitamin D receptor agonists induce prostatic acid phosphatase to reduce cell growth and HER-2 signaling in LNCaP-derived human prostate cancer cells

We have previously shown that concentrations of 1α,25-dihydroxyvitamin D 3 (1,25D) that induce G 0/G 1 cell cycle arrest in androgen-dependent LNCaP prostate cancer cells also decrease expression of c-Myc, a proto-oncogene that stimulates progression from G 1 to S phase of the cell cycle. Since both c-Myc expression and cell cycle progression are regulated by tyrosine kinase activation, we examined the ability of 1,25D to alter tyrosine kinase signaling in LNCaP cells and the androgen-independent LNCaP C81 (C81 LN) cell line. 1,25D selectively reduced protein tyrosine phosphorylation within both the LNCaP and C81 LN cells. This reduction in tyrosine kinase signaling appears to result from elevated levels of cellular prostatic acid phosphatase (PAcP). Western blots and biochemical assays revealed 1,25D increases the level of active PAcP in both cell lines. In addition, 1,25D decreased tyrosine phosphorylation of HER-2, an EGFR family member inactivated by PAcP, and the HER-2 downstream adaptor protein p52 Shc in C81 LN cells. Inhibition of HER-2 signaling by AG825 reduces growth of C81 LN cells and the parental LNCaP cells. These data therefore suggest that 1,25D-mediated decreases in LNCaP and C81 LN cell growth are in part due to decreases in tyrosine kinase signaling that result from up-regulation of PAcP.

Prostatic acid phosphatase is a possible tumor marker for intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (LBCL) is a rare and aggressive subtype of diffuse LBCL characterized by disseminated intravascular proliferation of neoplastic lymphocytes. Obstruction of blood flow by tumor cells in a variety of organs can cause an array of clinical changes, including alteration of the neural and spinal system and the respiratory system, as well as skin lesions. It is usually very difficult to diagnose intravascular LBCL in a patient simply from clinical symptoms or laboratory examinations. We here document our findings that serum prostatic acid phosphatase levels in both males and a female (2.2-24.0 microg/L) reflect the presence of intravascular LBCL, changing synchronously in response to chemotherapy. To determine whether prostatic acid phosphatase (PAP) might be a useful tumor marker for early diagnosis, we reviewed five intravascular LBCLs. Immunohistochemically, tumor cells in all cases were positive for anti-PAP antibody. The results were further confirmed in one case by Western-blot analysis and in another by the detection of amplified messenger RNA for PAP in microdissected tumor cells, respectively. PAP has not been detected in 17 lymphomas (diffuse LBCL, 8 cases; follicular lymphoma, 3 cases; T-cell lymphoma, 3 cases; Hodgkin lymphoma, 3 cases) by Western blot analyses. We conclude that serum PAP is a useful tumor marker for intravascular LBCL and that it deserves further investigation in this context.

Long-term outcomes after treatment with external beam radiation therapy and palladium 103 for patients with higher risk prostate carcinoma: influence of prostatic acid phosphatase.

The objective of this study was to define the long-term prognostic significance of prostatic acid phosphatase (PAP) levels in patients with higher risk, early-stage prostate carcinoma. One hundred sixty-one consecutive patients with Stage T1-T3 prostate carcinoma (according to the 1992 criteria of the American Joint Committee on Cancer) were treated from 1992 through 1996. Each patient had a Gleason score > or = 7 and/or a prostate specific antigen (PSA) level > 10 ng/mL. The original biopsy slides for 130 of 161 patients were retrieved and rereviewed by a single pathologist (L.T.). Enzymatic PAP measurements were determined using a standard method. Values up to 2.5 Units were considered normal. Patients received 41 grays (Gy) of external beam radiation therapy to a limited pelvic field followed 4 weeks later by a palladium 103 (Pd-103) boost using transrectal ultrasound and fluoroscopic guidance as described previously. The prescribed minimum Pd-103 dose to the prostate was 80 Gy (pre-National Institute of Standards and Technology [NIST]-99). Freedom from biochemical failure was defined as a serum PSA level < or =0.2 ng/mL at last follow-up. There was little correlation between pretreatment PSA levels, Gleason scores, and PAP measurements. Thirty-eight patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 10 years is 79%, with 118 patients followed for > 5 years. In a multivariate Cox proportional hazards analysis that considered each factor as a continuous variable, the strongest predictor of failure was PAP (P = 0.0001), followed by Gleason score (P = 0.13), and PSA (P = 0.04). PAP was especially helpful in stratifying patients with pretreatment PSA levels between 4 ng/mL and 20 ng/mL, for whom the prognosis does not different when they are subdivided into PSA categories. When the PAP subgroup analysis was limited to this relatively favorable group, there was a wide range of prognoses. The biochemical cure rate was remarkably high among the 161 patients evaluated. The fact that the PAP was the strongest predictor of long-term biochemical failure in patients with otherwise higher risk features reported here suggests that it may be a more accurate indicator of micrometastatic disease compared with the Gleason score and the PSA level. This report adds to the rationale for reintroducing PAP measurement into general practice.

Suppressing tumor progression of in vitro prostate cancer cells by emitted psychosomatic power through Zen meditation.

Human prostate cancer PC3 cells were treated in vitro with psychosomatic power emitted by a Buddhist-Zen Master. A significant decrease of growth rate was observed as determined by MTT assay after 48 hours. These cells also had two- to three-fold higher levels of prostatic acid phosphatase (PAcP) activity, a prostate tissue-specific differentiation antigen. In addition, the treated cells formed fewer and smaller colonies in soft agar as compared with control cells, which displayed anchorage-independent growth. These observations provide insight into the suppressive effects of healing power through the practice of Buddhist-Zen meditation on tumor progression. The emitted bioenergy may be suggested as an alternative and feasible approach for cancer research and patient treatment.

Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease

Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease

Comparative analysis of prostatic acid phosphatase and prostate-specific antigen mRNA levels in hyperplastic prostate stimulated with steroid hormones and growth factors.

Prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) are the markers of human prostatic gland. However, it is still not completely understood if and how, steroid hormones and growth factors affect their expression and metabolism in the respect to the major pathologies of the gland. Appropriate studies were carried out on histopathologically diagnosed benign prostatic hyperplasia--BPH (n = 42) using tissue slices and cells derived from them. They were incubated with steroid hormones: 5-alpha-dihydrotestosterone (DHT), estradiol (E) and growth factors: epidermal growth factor (EGF), basic fibroblastic growth factor (bFGF) under culture conditions for up to 24 hours. P-labelled specific oligonucleotide probes were used to analyze total RNA isolated from each sample for the presence of PAP and PSA mRNAs. DHT, E, bFGF, EGF or both DHT + bFGF and DHT + EGF increased PAP and PSA mRNA levels in a time- and dose-dependent manner. The highest and statistically significant increase (P < 0.001) for PAP mRNA was observed when DHT + bFGF were present in the medium while for PSA mRNA if DHT + EGF were added to the medium. Slow but constant decrease of PAP and PSA mRNA levels was observed in the absence of each of these factors in the incubation medium. The results suggest that early expression of PSA and PAP genes and/or their mRNA stability strongly depend on DHT while differ in their response to EGF and bFGF.

Protection of prostatic acid phosphatase activity in human serum samples by plasmin inhibitors

Background: The level of prostatic acid phosphatase in serum is an established marker for prostate carcinoma. Methods: Inactivation of homogeneous prostatic acid phosphatase from human seminal fluid by purified plasmin and human serum was studied in the presence and absence of bovine pancreatic trypsin inhibitor, a plasmin inhibitor, or phenylmethylsulfonylfluoride, a serine protease inhibitor. Results: Plasmin or serine protease inhibitors protect against prostatic acid phosphatase inactivation in serum samples. Conclusion: The immediate addition of serine protease inhibitors to serum samples taken for prostatic acid phosphatase determinations should provide more accurate results and permit extended storage of samples. The stabilization of the enzyme activity and immunological properties of prostatic acid phosphatase in blood samples by these protease inhibitors resurrects the clinical significance of prostatic acid phosphatase measurements in prostate cancer screenings.

INDUCTION OF TUMOR SPECIFIC CYTOTOXIC T LYMPHOCYTES IN PROSTATE CANCER USING PROSTATIC ACID PHOSPHATASE DERIVED HLA-A2402 BINDING PEPTIDE

Human prostatic acid phosphatase is a prostate specific differentiation antigen. Prostatic acid phosphatase levels increase in the serum of patients with prostate cancer and its peptide from positions 299 to 307 (PAP 299-307) is recognized by HLA-A2 restricted cytotoxic T lymphocytes. We investigated whether HLA-A2402 binding prostatic acid phosphatase derived peptides induce HLA-A2402 restricted, tumor specific cytotoxic T lymphocytes from the peripheral blood mononuclear cells of patients with prostate cancer. Peptide binding activity was measured with RMA-S-A*A2402 cell lines and flow cytometry. Cytotoxic T-lymphocyte activity of the peripheral blood mononuclear cells of patients with prostate cancer and healthy donors was measured by interferon-gamma and (51)creatinine release assays. Prostatic acid phosphatase expression in the tumor cell lines at the messenger RNA and protein levels was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively. An HLA-A2402 binding, prostatic acid phosphatase derived peptide consisting of the prostatic acid phosphatase amino acid sequence from positions 213 to 221 (PAP 213-221, LYCESVHNF) showed the ability to induce HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes, which are cytoxic to prostatic acid phosphatase positive tumor cells from the peripheral blood mononuclear cells of patients with prostate cancer. PAP 213-221 may be appropriate as a cancer vaccine for specific immunotherapy in patients with HLA-A2402 positive prostate cancer.

DIFFERENTIAL RESPONSIVENESS OF PROSTATIC ACID PHOSPHATASE AND PROSTATE-SPECIFIC ANTIGEN mRNA TO ANDROGEN IN PROSTATE CANCER CELLS

Androgens regulate the expression of both human prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), two major prostate epithelium-specific differentiation antigens. Due to the important role of these two enzymes as prostate epithelium differentiation markers, we investigated their regulation of expression at the mRNA level in LNCaP human prostate carcinoma cells. Interestingly, phenol red, a pH indicator in the culture medium, promoted cell growth. To eliminate this non-specific effect, a phenol red-free, steroid-reduced medium was utilized. When high-density cells were grown in that medium, 5α-dihydrotestosterone (DHT) suppressed PAcP but stimulated PSA. However, tumor promoter phorbol ester 12- o -tetradecanoyl phorbol-13-acetate (TPA) functioned as a potent inhibitor of both PAcP and PSA expression. Prolonged treatment with DHT as well as TPA resulted in a similar down-regulation of protein kinase C and cellular PAcP activities. Thus, the levels of PAcP and PSA mRNA are differentially regulated by androgens in LNCaP cells.

Elevation of prostate-specific markers after cardiopulmonary resuscitation.

BACKGROUND-Prostate-specific antigen (PSA), acid phosphatase (AP), and prostatic acid phosphatase (PAP) are serum markers for adenocarcinoma of the prostate gland. Previous studies indicated that prostatic ischemia may also produce elevations of PSA. Cardiopulmonary resuscitation (CPR) is frequently associated with profound tissue hypoperfusion. The present study investigated whether PSA, AP, and PAP are influenced by prolonged CPR. METHODS AND RESULTS-PSA, AP, and PAP were assessed immediately, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after prolonged CPR (>5 minutes) in 14 male and 5 female patients. No changes were noted in women. In men, serum levels increased significantly after CPR and gradually decreased to near baseline values after 7 days. PSA, AP, and PAP values above the normal range were observed in 63%, 71%, and 64% of all patients, respectively. Compared with survivors, nonsurvivors exhibited higher peak serum levels of PSA (98.6+/-14.3 versus 1.1+/-2.2 mcg/L; P<0.03), AP (57.0+/-71 versus 8.6+/-8.8 U/L; P<0.05), and PAP (47.0+/-62 versus 5.7+/-8.0 U/L; P=NS). Patients with poor neurological outcome exhibited higher peak serum levels of PSA (86.4+/-135.5 versus 12.0+/-23.8 mcg/L; P<0.05), AP (50.9+/-68.1 versus 8.7+/-9.6 U/L; P=NS), and PAP (41.6+/-59.5 versus 5.8+/-8.8 U/L; P=NS) than patients with good neurological outcome. CONCLUSIONS-Prolonged CPR is frequently associated with increases of PSA, AP, and PAP serum levels. Therefore, PSA cannot be used for diagnosis of adenocarcinoma of the prostate during the first weeks after CPR. Further evaluation of these parameters as additional prognostic markers after CPR is warranted.