[Risk prediction and function evaluation by T-cell epitope model and expression model of HLA-DPB1 mismatching in unrelated-donor hematopoietic stem cell transplantations].

Objective: To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope (TCE) model and expression model in human leukocyte antigen (HLA)-matched unrelated hematopoietic stem cell transplantation (MUD-HSCT) with HLA-DPB1 mismatching. Methods: A total of 364 (182 pairs) potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively. Of the 182 recipients, there were 121 males and 61 females with an average age of (26.3±14.2) years. Of the 182 donors, there were 148 males and 34 females with an average age of (33.7±7.5) years. Polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) based on LABScan®3D platform were used for high-resolution typing of HLA-A, B, C, DRB1, DQB1, DPB1 gene, and PCR-SBT was used for single nucleotide polymorphism (SNP) typing. TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease (aGVHD) risk. Results: A total of 26 HLA-DPB1 alleles and their 3'-UTR rs9277534 SNP genotypes were detected in this study population, and two new alleles HLA-DPB1*1052∶01 and HLA-DPB1*1119∶01 were found and officially named. The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66% (165/182). In TCE model, the HLA-DPB1 mismatch rates of permissible mismatch (PM) and non-permissible mismatch (non-PM) were 47.80% (87/182) and 42.86% (78/182), respectively. The non-PM in GvH direction was 13.73% (25/182), and which in HvG direction was 29.12% (53/182). A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model. Among of TCE PM group, recipient DP5 mismatches accounted for 34.25% (25/73) were predicted as aGVHD high risk according to expression model. For the TCE non-PM group, both the recipient DP2 mismatches of 6.85% (5/73) and recipient DP5 mismatches of 10.86% (8/73) were predicted to be at high risk for aGVHD. Risk prediction by TCE model and expression model was 27.27% concordant and 16.97% unconcordant. Conclusions: TCE model and expression model are effective tools to predict aGVHD risk of MUD-HSCT. Comprehensive application of the two models is helpful to the hierarchical assessment of HSCT risk.

Associations of IL-1ß and IL-6 gene polymorphisms with Parkinson's disease.

OBJECTIVE: The aim of this study was to explore the associations of interleukin-1ß (IL-1ß) and IL-6 gene polymorphisms with the pathogenesis of Parkinson's disease. PATIENTS AND METHODS: A total of 200 patients with Parkinson's disease in our hospital were collected as the disease group. Meanwhile, 200 healthy subjects were taken as the control group. Peripheral blood samples were drawn from all research subjects. The polymorphic regions of IL-1ß and IL-6 were amplified via polymerase chain reaction (PCR). Moreover, the polymorphisms were detected and analyzed, followed by further analysis based on the changes in gene expressions and Hoehn-Yahr grade of patients. RESULTS: The allele distributions at IL-1ß rs571556428 (p=0.015) and IL-6 rs543214973 (p=0.012) were statistically different between control group and disease group. In disease group, the G allele frequency at IL-1ß rs571556428 and T allele frequency at IL-6 rs543214973 were significantly higher (p<0.05). Genotype distributions at IL-1ß rs572292175 (p=0.017) and rs571556428 (p=0.000), and IL-6 rs543214973 (p=0.002) in disease group were also different from those in control group. In addition, the frequencies of CT genotype at IL-1ß rs572292175, AA genotype at IL-1ß rs571556428 and AA genotype at IL-6 rs543214973 in disease group were significantly lower (p<0.05). After modeling and analysis, it was found that the distribution of recessive model at IL-1ß rs571556428 (p=0.012) and IL-6 rs543214973 (p=0.014) in disease group exhibited significant differences from those in control group. The frequencies of TA haplotype at IL-1ß rs572292175 and rs571556428 (p=0.038) and GA haplotype at IL-6 rs1474348 and rs543214973 (p=0.047) in disease group were lower than those in control group (p<0.05). The polymorphisms at IL-1ß rs571556428 and IL-6 rs1474348 were significantly associated with gene expression (p<0.05). Moreover, the expressions of IL-1ß and IL-6 rose significantly in patients with GG genotype at rs571556428 and CG genotype at rs1474348, respectively (p<0.05). Furthermore, the polymorphism at IL-1ß rs571556428 was significantly correlated with the grade of Parkinson's disease (p=0.000). Parkinson's disease was in a higher grade (grade 4-5) in patients with AA genotype, whereas in a lower grade (grade 1-2) in patients with GG and AG genotypes. CONCLUSIONS: IL-1ß and IL-6 gene polymorphisms are significantly associated with the pathogenesis of Parkinson's disease.

[Intravenous sedation with midazolam and propofol target controlled infusion on patients'perioperative anxiety under the mandibular third molar extraction].

OBJECTIVE: To evaluate whether midazolam with propofol target controlled infusion (TCI) intravenous sedation during the mandibular third molar extraction influences patients'perioperative anxiety. METHODS: The subjects were patients who planned to undergo the mandibular third molar extraction in Peking University School and Hospital of Stomatology, whose state anxiety inventory (SAI) scores were≥38 at the initial visit. They were divided into intravenous sedation group (IVS) and local anesthesia group (LA) on the basis of the planned intravenous sedation. Each group was divided into two subgroups according to the overall SAI scores at the initial visit: IVS-I, LA-I (SAI: 38-50) and IVS-II, LA-II (SAI: 51-80). The anxiety before and after the surgery was evaluated by the SAI scores at the initial visit (T1), before surgery (T2) and 7 days after surgery (T3). The anxiety during the surgery was evaluated by the heart rate, blood pressure and visual analogue scale (VAS) scores. RESULTS: There were no significant differences on SAI at T1, T2, and T3 in the two groups (P>0.05). The heart rate, blood pressure and VAS pain scores of IVS group were significantly lower than those of LA group during the surgery (P<0.001). CONCLUSION: Intravenous sedation with midazolam and propofol TCI was effective on the patients' anxiety during the third molar extraction, which successfully made the patients more comfortable and their heart rate, blood pressure and oxygen saturation more stable during the surgery. But there were no significant differences on the patients'anxiety at the initial visit (T1), before surgery (T2) and 7 days after surgery (T3) according to the SAI scores in the two groups.

Gender difference in radiotherapy-induced carotid stenosis.

Radiotherapy (RT) is often the first choice of treatment for cancer of the larynx. Studies have shown that the incidence of carotid stenosis (CS) after radiotherapy of laryngeal cancer is increasing, and that gender difference in radiotherapy-induced side effects exist. Thus, we examined the gender difference in the incidence of CS and the impact of microinflammatory factors after radiotherapy. We reported this study on patients who received radiotherapy as part of the treatment for laryngeal cancer in the Jilin Province in China. One hundred sixty-four males and 152 females were treated with radiotherapy between 2006 and 2016. The carotid diameter was determined by measuring carotid intima-media thickness in the common, external and internal carotid artery. Microinflammatory conditions were assessed by measuring the level of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Other studied risk factors included age, treatment modalities, radiation dose and energy, the height of the radiation field, and the follow-up time. CS was detected in 161 (50.9%) of the 316 patients. Carotid stenosis was mainly clinically unsuspected, two patients had anamnesis of unconsciousness. Importantly, fewer women (36.1%) had CS than men (64.6%) (p=0.004). Furthermore, male patients showed higher serum levels of hs-CRP, IL-6, and TNF-α. Taken together, our study suggested that women underoing radiotherapy of laryngeal cancer are less likely to have CS than men. Therefore, routine assessment after irradiation of laryngeal cancer seems necessary for clinical detection of asymptomatic CS, particularly in male patients.

A Simple Automated Method for Detecting Recurrence in High-Grade Glioma.

Our aim was to develop an automated multiparametric MR imaging analysis of routinely acquired imaging sequences to identify areas of focally recurrent high-grade glioma. Data from 141 patients treated with radiation therapy with a diagnosis of high-grade glioma were reviewed. Strict inclusion/exclusion criteria identified a homogeneous cohort of 12 patients with a nodular recurrence of high-grade glioma that was amenable to focal re-irradiation (cohort 1). T1WI, FLAIR, and DWI data were used to create subtraction maps across time points. Linear regression was performed to identify the pattern of change in these 3 imaging sequences that best correlated with recurrence. The ability of these parameters to guide treatment decisions in individual patients was assessed in a separate cohort of 4 patients who were treated with radiosurgery for recurrent high-grade glioma (cohort 2). A leave-one-out analysis of cohort 1 revealed that automated subtraction maps consistently predicted the radiologist-identified area of recurrence (median area under the receiver operating characteristic curve = 0.91). The regression model was tested in preradiosurgery MRI in cohort 2 and identified 8 recurrent lesions. Six lesions were treated with radiosurgery and were controlled on follow-up imaging, but the remaining 2 lesions were not treated and progressed, consistent with the predictions of the model. Multiparametric subtraction maps can predict areas of nodular progression in patients with previously treated high-grade gliomas. This automated method based on routine imaging sequences is a valuable tool to be prospectively validated in subsequent studies of treatment planning and posttreatment surveillance.

Primary small cell carcinoma of the vagina with pulmonary metastasis: a case report.

Primary small cell carcinoma of the vagina is extremely rare; no standard treatment has been established despite it being highly aggressive. Here, the authors report on a 43-year-old patient who had a mass on the clitoris and no uterine or bilateral adnexal involvement. Vaginal wall biopsy revealed malignant small cell carcinoma. The carcinoma was composed of epithelial cells with round, hyperchromatic nuclei containing few distinct nucleoli, and scanty cytoplasm. Chest computerized axial tomography and pathological bronchoscopy revealed bilateral pulmonary metastases. She received radiotherapy combined with six cycles of chemotherapy (paclitaxel plus cisplatin), and achieved complete response, with complete suppression of the mass and lung metastases. There was no sign of tumor recurrence or distant metastases after 21 months of follow-up.

SOX4 is a potential prognostic factor in human cancers: a systematic review and meta-analysis.

OBJECTIVE: The aim of the this study was to analyze the status of sex-determining region Y-related high-mobility group box 4 (SOX4) expression in varied human cancers and its correlation with overall survival in patients with human cancers. METHODS: To observe initially the expression status of SOX4 in twenty kinds of human cancers at protein database (The Human Protein Atlas). We systematically and carefully searched the studies from electronic databases and seriously identified according to eligibility criteria. The correlation between SOX4 expression and overall survival in human cancers was evaluated through Review Manager. RESULTS: We found that SOX4 expression was significantly positive in most types of human cancer tissues, and the positive rate of SOX4 expression was about 78 % in overall cancer tissues. Furthermore, a total of 10 studies which included 1348 cancer patients were included in the final analysis. Meta-analysis showed that SOX4 overexpression was correlated with a poor overall survival and the pooled hazard ratio (HR), and corresponding 95 % confidence interval (CI) was 1.67 (95 % CI 1.01-2.78). From subgroup analyses, we present evidence that SOX4 overexpression was an unfavorable prognostic factor for colorectal cancer patients' recurrence-free survival and gastric cancer patients' overall survival, and the pooled HRs (95 % CI) were 1.73 (95 % CI 1.04-2.88) and 3.74 (95 % CI 1.04-13.45), respectively. CONCLUSIONS: In summary, SOX4 is a potential prognostic biomarker in human cancers.

The role of TNF-α, IL-6, IL-10, and GDNF in neuronal apoptosis in neonatal rat with hypoxic-ischemic encephalopathy.

AIM: To examine the dynamic changes of TNF-α, IL-6, IL-10, and GDNF (glial cell-derived neurotrophic factor) in serum or brain tissues of neonatal rat with hypoxic-ischemic encephalopathy and to explore their roles in neuronal apoptosis. MATERIALS AND METHODS: A total of 80 Wistar rats were randomly divided into the sham-operated (control) group and the hypoxia-ischemia (HI) group. To establish the hypoxic-ischemic encephalopathy (HIE) model, the pups from the HI group were subjected to left common carotid artery ligation followed by exposure to 8% O2 and 92% N2. The concentration of TNF-α, IL-6, IL-10, and GDNF in serum or brain tissues was measured by enzyme linked immunosorbent assay (ELISA). Neuronal apoptosis was examined by flow cytometry (FC). Statistical analysis was performed using the SPSS13.0 software. RESULTS: We found that the neuronal apoptosis rate and the levels of TNF-α and IL-6 in rat with hypoxic-ischemic brain damage (HIBD) were significantly increased at 6 h, 24 h, 48 h, and 72 h after hypoxia compared to the control group (p < 0.05). We also found that the neuronal apoptosis rate was positively correlated with the levels of TNF-α and IL-6, and negatively correlated with IL-10 and GDNF. CONCLUSIONS: In neonatal rats with HIE, the brain reaches its peak levels of damage by 24~72 h after the injury. Inflammatory cytokines such as TNF-α and IL-6 promote HIE-induced neuronal apoptosis, whereas IL-10 and GDNF antagonize it.

Statin administration does not improve the mobilization of very small embryonic-like stem cells (VSELs) in contrast to resveratrol treatment in a murine model of acute myocardial infarction.

We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1(+)Lin(-)CD45(-)(CXCR(+)) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1alpha levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1(+)CXCR(+) cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI.

Characterization of HLA-G expression in renal cell carcinoma.

Previous studies showed that human leukocyte antigen (HLA)-G is specifically upregulated in renal cell carcinoma (RCC). However, a larger cohort of RCC patients are necessary to obtain more information. In this study, 109 RCC primary lesions (clear cell, n = 95; chromophobe, n = 4; papillary, n = 4; collecting duct, n = 6) and corresponding adjacent tumor-negative renal tissues (n = 34) were analyzed for the HLA-G expression by immunohistochemistry (IHC). Meanwhile, plasma soluble HLA-G (sHLA-G) from 16 RCC patients and 144 sex- and age-matched normal individuals was detected by enzyme-linked immunosorbent assay. Correlations between lesion HLA-G expression and various clinical parameters were evaluated. Receiver-operating characteristic (ROC) curve analysis was used to determine the feasibility of HLA-G protein staining and sHLA-G as a diagnosis marker for RCC. IHC data showed that HLA-G was observed in 49.5% of clear cell, 50% of either chromophobe or collecting duct RCC lesions but undetectable in papillary RCC and tumor-negative renal tissues. This finding was consistent with the western blot results. sHLA-G was pronouncedly increased in RCC patients when compared with normal controls (median: 39.5 vs 19.2 U/ml, P = 0.002). However, no correlation was observed between HLA-G expression and various clinical parameters. We found that the area under ROC curve for HLA-G expression and sHLA-G was 0.739 [95% confidence interval (95% CI): 0.659-0.816, P = 0.000] and 0.733 (95% CI: 0.619-0.847, P = 0.002), respectively. Our findings indicated that, except the papillary RCC, other types of RCC could express HLA-G. Furthermore, both lesion HLA-G expression and plasma sHLA-G level might be a useful preoperative biomarker for diagnosis.

Valgancyclovir as maintenance therapy for cytomegalovirus retinitis in a lung transplant patient--a case report.

UNLABELLED: The purpose of this article is to report the use of valgancyclovir as maintenance therapy for cytomegalovirus (CMV) retinitis in a lung transplanted patient. RESULT: A 30-year-old woman with underlying pulmonary lymphangioleiomyomatosis received a lung transplant 1 year ago. CMV retinitis developed 4 months later but subsided after intravenous ganciclovir treatment. Unfortunately, the CMV retinitis recurred three times in 1 year while on oral ganciclovir maintenance therapy. To treat the latest relapse, valgancyclovir 900 mg once daily was used as maintenance therapy after intravenous gancyclovir induction. With a 6-month follow-up, the fundoscopic examination revealed old atrophic scar and no active CMV retinits. The patient was able to maintain best-corrected visual acuity of 20/20 in both eyes. In conclusion, Valganciclovir may be used as maintenance therapy in CMV retinitis.

Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblastoma tumorigenicity in situ.

The mutation and/or deletion of tumor suppressor genes have been postulated to play a major role in the genesis and the progression of gliomas. In this study, the functional expression and efficacy in tumor suppression of 3 tumor suppressor genes (p53, p21, and p16) were tested and compared in a rat GBM cell line (RT-2) after retrovirus mediated gene delivery in vitro and in vivo. Significant reductions in tumor cell growth rate were found in p16 and p21 infected cells (60 +/- 12% vs 66 +/- 15%) compared to p53 (35 +/- 9%). In vitro colony formation assay also showed significant reductions after p16 and p21 gene delivery (98 +/- 5% vs 91 +/- 10%) compared to p53 (50 +/- 18%). In addition, the tumor suppression efficacy were investigated and compared in vivo. Retroviral mediated p16 and p21 gene deliveries in glioblastomas resulted in more than 90% reductions in tumor growth (92 +/- 26% vs 90 +/- 22%) compared to p53 (62 +/- 18%). Tumor suppressor gene insertions in situ further prolonged animal survival. Overall p16 and p21 genes showed more powerful tumor suppressor effects than p53. The results were not surprising, as p16 and p21 are more downstream in the cell cycle regulatory pathway compared to p53. Moreover, the mechanism involved in each of their suppressor effects is different. This study demonstrates the feasibility of using tumor suppressor genes in regulating the growth of glioma in vitro and in situ.

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.

Indoor air pollution and pulmonary adenocarcinoma among females: a case-control study in Shenyang, China.

Factors that affect the risk of lung adenocarcinoma among females were investigated in Shenyang, China, using a population-based case-control study design. A total of 72 new cases, ages 35-69, diagnosed with incident, primary pulmonary adenocarnoma, were collected between April 1991 and December 1995, and were 1:1 age-matched with healthy females randomly selected from the general population. A questionnaire covering demographics, diet/nutritional preferences and cooking habits, living conditions, family history of cancer, sources of indoor/outdoor/occupational pollution, exposure to ETS from spousal smoking, workplace exposure, and exposure during childhood, history of menstruation and pregnancy, was given to each subject in a structured in-person interview given by trained field workers. Univariate analysis was performed on the data collected. The results showed that cooking fumes, family history of lung cancer, economic status, and number of live births and intake of vitamin E were risk factors significantly associated with adenocarcinoma of the lung. In particular, exposure to different levels of cooking fumes, an indoor air pollutant, increased the odds ratio of lung adenocarcinoma by 1.33, 7.33 and 1.67, respectively (trend p=0.006). Another important risk factor was family history of lung cancer, which gave an OR of 7.65 (95% CI, 0.90-169.84). Intake of beta-carotene from vegetables and fruit offered protection against lung adenocarcinoma, giving an OR of 0.28 (95% CI, 0.12-0.69). These results were confirmed by multivariable logistic regression analysis.

Benign prostatic hyperplasia-associated prostate-specific antigen (BPSA) shows unique immunoreactivity with anti-PSA monoclonal antibodies.

We previously identified a modified molecular form of prostate-specific antigen that is significantly elevated in the nodular transition zone tissue of prostates with benign prostatic hyperplasia. This prostate-specific antigen form, designated BPSA, is inactive and contains clipped polypeptide bonds at amino-acid residues Lys145-146 and Lys182-183. BPSA is not elevated in prostate cancer tissues and may therefore be a prostate-specific antigen marker to better discriminate benign prostatic hyperplasia from early prostate cancer. In this work we characterize the immunoreactivity of BPSA in competition assays with prostate-specific antigen using anti-prostate-specific antigen mAb recognizing six different epitopes on the prostate-specific antigen molecule. One mAb showed > 50% loss of immunoreactivtiy with BPSA compared with prostate-specific antigen, while the binding of two mAbs was largely unaffected and three mAbs had intermediate reactivity. BPSA purified from prostate tissue and seminal plasma, as well as BPSA generated in vitro by mild trypsin-treatment were found to have a similar pattern of reactivity to the six mAbs. However, other forms of inactive seminal plasma prostate-specific antigen, either intact or clipped at Lys145 only, had immunoreactivity similar to total prostate-specific antigen. These results demonstrate that BPSA has unique immunological properties from other forms of prostate-specific antigen, which should allow the development of BPSA-specific mAbs for the study of benign prostatic hyperplasia. Measurement of BPSA levels in the serum may help discriminate benign prostatic hyperplasia from early prostate cancer.

Pain relief after arthroscopic knee surgery: intravenous morphine, epidural morphine, and intra-articular morphine.

OBJECTIVE: The aim of this study was to compare the analgesic efficacy and side effects of intravenous (IV), epidural, and intra-articular (IA) morphine after arthroscopic knee surgery. DESIGN: Prospective, randomized, double-blind clinical investigation. SETTING: Medical center, university teaching hospital. PATIENTS: Inpatients with an American Society of Anesthesiologists physical status of I or II who were scheduled for elective arthroscopic knee surgery. INTERVENTIONS AND OUTCOME MEASURES: A total of 75 patients scheduled for arthroscopic knee surgery under epidural anesthesia were randomly divided into three groups (n = 25 in each group). At the end of surgery, patients in group 1 received 3 mg of IV morphine, patients in group 2 received 3 mg of epidural morphine, and patients in group 3 received 3 mg of IA morphine. Patients were then observed for 24 hours. During the observation period, the proportion of patients requiring rescue analgesia with intramuscular diclofenac in each group was calculated and the occurrence of morphine-related side effects was recorded. RESULTS: We found that patients who received IV morphine requested more rescue analgesia than those who received either epidural or IA morphine. The proportions of patients requiring rescue analgesia in the IV, epidural, and IA groups were 65%, 13%, and 9%, respectively (p < 0.01 in group 1 vs. group 2 and in group 1 vs. group 3). Epidural morphine was associated with higher incidences of nausea and vomiting, pruritus, and urinary retention than IA morphine (range, p < 0.05-0.01 in group 2 vs. group 3). CONCLUSIONS: Patients who received IA morphine consumed less rescue analgesia than those who received IV morphine. They also reported fewer side effects than those patients who received epidural morphine. Intra-articular morphine may be the method of choice for pain relief after arthroscopic knee surgery.

A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue.

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). PSA in serum is comprised of a variety of both "free" and "complexed" forms that have been used to improve the specificity of PSA for prostate cancer detection. We previously reported that pro PSA (pPSA), the zymogen or precursor form of PSA, is a component of free PSA in the serum of PCa patients. In the current study, we examined prostate tissues to understand the origin and specificity of pPSA. PSA was immuno-affinity purified from matched sets of prostate tissues including peripheral zone cancer (PZ-C); peripheral zone noncancer; and benign tissue from the transition zone (TZ), the primary site of BPH within the prostate. We found that pPSA is differentially elevated in PZ-C, but is largely undetectable in TZ. N-terminal sequencing revealed that the pPSA was comprised primarily of [-2]pPSA and minor levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids, respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable) in TZ (P < 0.0026). No pPSA was detected in 13 of 18 transition zone specimens (72%), but only 2 of the 18 matched cancer specimens (11%) contained no measurable pPSA. These results demonstrate that pPSA is more highly correlated with prostate cancer than with BPH. The pPSA in serum may represent a more cancer-specific form of PSA that could help distinguish prostate cancer from BPH.