OBJECTIVE: To explore the expression of perforin and granzyme-B in peripheral blood lymphocyte (PBL) in patients with prostate cancer (PCa) and the clinical significance. METHODS: The expressions of perforin and granzyme-B in PBL were detected by fluorescence quantitative reverse transcription polymerase chain reaction. The results of perforin and granzyme-B expression were compared among patients with PCa (n=60), patients with BPH (benign prostatic hyperplasia, n=40) and healthy controls (n=20). RESULTS: Th e expressions of perforin and granzyme-B in patients with PCa were significantly lower than that in patients with BPH or that in the healthy controls (P<0.05), respectively. Furthermore, in PCa patients with low pathological grade, the expressions of perforin and granzyme-B in PBL was statistically higher than that in patients with high pathological grade (P<0.05). The expressions of perforin and granzyme-B in PCa patients at high clinical stage was statistically lower than that in PCa patients at low clinical stage (P<0.05). CONCLUSION The results of this study suggest that development and progression of PCa might be associated with poor immune status of patients.
Case-Control Studies ; Granzymes ; metabolism ; Humans ; Lymphocytes ; enzymology ; Male ; Perforin ; metabolism ; Prostatic Hyperplasia ; Prostatic Neoplasms ; immunology

OBJECTIVETo study the morphologic features and clinical significance of atypical small acinar proliferation (ASAP) suspicious but not diagnostic of cancer in prostatic biopsies.

METHODSThe slides of 11 cases of prostatic needle biopsies collected during a two-year period with the diagnosis of ASAP were reviewed. Immunohistochemical study for 34betaE12, p63 and P504S was performed on the archival paraffin sections.

RESULTSAll the 11 ASAP cases were characterized by the presence of a few compacted small acini in the prostatic stroma. Six cases had acini of less than three in number. The acini were round or slightly irregular in shape. The nuclei were enlarged, round or irregular, arranged in single layer and focally separated by broad interval. The nucleoli were usually prominent. Cytoplasm was amphophilic or pale and the lumen border was often well-defined. Basophilic mucus was also seen in some of the lumen. Immunohistochemical study for 34betaE12 and p63 was negative, while that for P504S was positive. In 4 of the 11 cases, the acini were more than three in number, round or slightly irregular, but without cytologic atypia. The nuclei were slightly enlarged with small or inconspicuous nucleoli. Immunohistochemical study for 34betaE12 and p63 was negative or at most focally positive. P504S staining was either negative or weakly positive. Second repeat biopsy was carried out in all cases, and 4 of them (36%) showed definite adenocarcinomatous changes. The positive cases were those with fewer acini but definite cytologic atypia in the initial biopsy.

CONCLUSIONSASAP is a morphologic interpretation closely associated with prostatic adenocarcinoma. The histologic features are suspicious of but not diagnostic of cancer, due to insufficient criteria in terms of acinar number, cytologic or architectural abnormalities. The positive rate in subsequent repeat biopsy is higher than that for cases with usual nodular hyperplasia.

Adenocarcinoma ; enzymology ; pathology ; Aged ; Biopsy ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Prostate ; enzymology ; pathology ; Prostatic Hyperplasia ; enzymology ; pathology ; Prostatic Intraepithelial Neoplasia ; enzymology ; pathology ; Prostatic Neoplasms ; enzymology ; pathology ; Racemases and Epimerases ; metabolism

ObjectiveTo explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer .

METHODSData about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed.

RESULTSTotally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05).

CONCLUSIONSSRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; metabolism ; Data Mining ; Humans ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Prostatic Neoplasms ; enzymology ; mortality ; pathology ; surgery ; Prostatic Neoplasms, Castration-Resistant ; enzymology

Prostaglandin synthase (PGS) can catalyze the production of various types of prostaglandins and regulate the expression levels of related substances. The regulation mechanisms of the PGS gene are closely related with the occurrence and development of prostate diseases. However, few studies are reported on the regulation mechanisms of PGS in prostatic diseases, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), or on the relationship between PGS gene regulation and prostate diseases. This review aims to analyze their correlation and provide some ideas for the prevention and control of BPH and PCa by intervention of the prostaglandin synthase regulatory pathway.
Gene Expression Regulation ; Humans ; Male ; Prostaglandin-Endoperoxide Synthases ; genetics ; physiology ; Prostatic Hyperplasia ; enzymology ; genetics ; prevention & control ; Prostatic Neoplasms ; enzymology ; genetics ; prevention & control

The over expression of fatty acid synthase (FAS), a key enzyme in biosynthesis of fatty acid, can enhance enzyme activity and result in the malignant behavior, special material metabolism and energy metabolism of tumors. The expression of FAS is significantly higher in prostate cancer than in normal prostate tissues, which shows that FAS can be used as a marker in the early diagnosis of prostate cancer. The abnormally increased expression of FAS in prostate cancer may offer a new target for the drug treatment of the disease.
Biomarkers, Tumor ; metabolism ; Early Diagnosis ; Fatty Acid Synthases ; metabolism ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; enzymology

Objective: To investigate the expressions of JNK and p-JNK in advanced prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their implications. METHODS: Using immunohistochemistry, we detected the expressions of JNK and p-JNK proteins in 40 cases of paraffin wax-embedded PCa and 21 cases of BPH tissues and analyzed their relationships with advanced PCa and BPH as well as with the pathologic features of advanced PCa. RESULTS: Statistically significant differences were not found in the positive expression rate of the JNK protein between BPH and PCa (42.86% vs 52.50%, P>0.05), non-metastatic and metastatic PCa (53.85% vs 51.85%, P >0.05), Gleason ≤7 and Gleason >7 (58.82% vs 47.82%, P >0.05), PSA ≤20 μg/L and PSA >20 μg/L (57.14% vs 51.52%, P >0.05), or survival >5 yr and survival ≤5 yr (60.00% vs 45.00%, P >0.05), nor in the expression level of p-JNK between BPH and PCa (33.33% vs 35.00%, P >0.05), non-metastatic and metastatic PCa (30.77% vs 37.03%, P >0.05), Gleason ≤7 and Gleason >7 (35.29% vs 34.78%, P >0.05), or PSA ≤20 μg/L and PSA >20 μg/L (43.75% vs 10.93%, P >0.05). However, the expression of p-JNK was significantly higher in the survival >5 yr than in the survival ≤5 yr group of the PCa patients (50.00% vs 20.00%, P <0.05). CONCLUSIONS PCa patients with highly expressed p-JNK have a longer survival time and the high positive rate of p-JNK is associated with the prognosis of PCa.
Humans ; Immunohistochemistry ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Male ; Neoplasm Grading ; Neoplasm Proteins ; metabolism ; Prognosis ; Prostate-Specific Antigen ; metabolism ; Prostatic Hyperplasia ; enzymology ; mortality ; pathology ; Prostatic Neoplasms ; enzymology ; mortality ; pathology

ObjectiveTo explore the expression of pituitary tumor transforming gene 1 (PTTG1) during the transformation of prostate cancer from androgen-dependent (ADPC) to androgen-independent (AIPC).

METHODSWe established an AIPC cell model LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone-deprived medium for over 3 months. The cell model was verified and the PTTG1 expression in the LNCaP cells was detected by Western blot and RT-PCR during hormone deprivation.

RESULTSThe AIPC cell model LNCaP-AI was successfully established. The PTTG1 expression was gradually increased in the LNCaP cells with the prolonged time of hormone deprivation and the expressions of matrix metalloproteinases MMP-2 and -9 were elevated at the same time.

CONCLUSIONSThe expression of PTTG1 is increased gradually in AIPC, which may be a target of gene therapy for advanced prostate cancer.

Blotting, Western ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasms, Hormone-Dependent ; Prostatic Neoplasms ; enzymology ; genetics ; Securin ; genetics

OBJECTIVETo evaluate the therapeutic effects of strontium-89 on osseous metastases of prostate cancer by bone scanning and bone alkaline phosphatase (B-AKP) measurement.

METHODSOne week before and within 6 months after strontium-89 therapy, bone scanning and B-AKP measurement were performed in 73 patients with bone metastases of prostate cancer. 1. According to the number of osseous lesions on bone imaging, the patients were divided into Grade 0, 1, 2 and 3, and the numbers of bone lesions before and after therapy were compared by t-test. 2. Tumor to non-tumor ratios(T/NT) before and after treatment were calculated and compared. 3. Changes in B-AKP before and after therapy were compared.

RESULTS1. Among the 73 patients, bone scanning revealed 618 bone lesions, averaging 8.6 +/- 7.4 before treatment. The number decreased to 349, averaging 3.8 +/- 6.7 after treatment, which showed a significant reduction (t = 4.079, P < 0.01). 2. After therapy, T/NT of bone lesions decreased significantly (t = 7.907, P < 0.01) from 5.36 +/- 4.67 to 3.17 +/- 2.95. 3. B-AKP decreased significantly (t = 3.349, P < 0.002) from (28.4 +/- 14.8) microgram/L to (20.9 +/- 11.7) microgram/L. 4. By bone scanning combined with B-AKP measurement, 5 false positive cases and 6 false negative cases were corrected.

CONCLUSIONThere is certain complementarity between bone scanning and B-AKP measurement, and they should be used in a combined way to achieve accurate evaluation of the therapeutic effects of strontium-89.

Aged ; Alkaline Phosphatase ; analysis ; Bone Neoplasms ; enzymology ; radiotherapy ; secondary ; Bone and Bones ; diagnostic imaging ; enzymology ; Humans ; Male ; Middle Aged ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; radiotherapy ; Radionuclide Imaging ; Strontium ; therapeutic use

Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases. Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells. Here, we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion. Finally, we offer pre-clinical evidence that this receptor is a viable target for therapy.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Bone Marrow ; enzymology ; pathology ; Bone Neoplasms ; prevention & control ; secondary ; Enzyme Activation ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptor, Platelet-Derived Growth Factor alpha ; antagonists & inhibitors ; genetics ; immunology ; metabolism ; Signal Transduction ; Transcriptional Activation

Glycogen synthase kinase3 (GSK3α and GSK3β) are serine/threonine protein kinases acting on numerous substrates and involved in the regulation of various cellular functions such as their proliferation, survival, glycogen metabolism, and autophagy. Accumulating evidence indicates that the expression of GSK3α is increased mainly in androgendependent while that of GSK3β in androgenindependent prostate cancer, and that GSK3β is also involved in the regulation of the transactivation of the androgen receptor (AR) and growth of prostate cancer. Animal experiments have proved that some GSK3 inhibitors, such as lithium, can significantly suppress tumor growth in different animal models of prostate cancer. The GSK3 inhibitor is promising to be an important agent for the clinical management of prostate cancer.
Androgens ; Animals ; Cell Line, Tumor ; Glycogen Synthase Kinase 3 ; antagonists & inhibitors ; metabolism ; Glycogen Synthase Kinase 3 beta ; antagonists & inhibitors ; metabolism ; Humans ; Male ; Neoplasm Proteins ; metabolism ; Neoplasms, Hormone-Dependent ; enzymology ; metabolism ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptors, Androgen ; metabolism