HLA-DR, -DP, -DQ expression status of parathyroid tissue as a potential parathyroid donor selection criteria and review of literature.

BACKGROUND: Basic and clinical studies about parathyroid allotransplantation have to be utilized with more definitive criteria for longer graft survival. Several reports demonstrated different isolation and cultivation methods for parathyroid cells to minimize their immunogenicity. In this study, we aim to compare and evaluate the clinical characteristics and the status of HLA class II expression changes in parathyroid tissue. METHODS: A total of 22 parathyroid hyperplasia tissue donors was included in this study. Clinical characteristics were evaluated and compared with the HLA-DR, -DP, -DQ mRNA, and protein expression levels which were determined by qRT-PCR and Western blot. RESULTS: We have compared the clinical characteristics (age, dialysis duration, frequency, recurrency of hyperparathyroidism and, calcimimetic usage) and HLA class II expression. HLA class II mRNA and protein levels showed varied expression patterns between tissues. Only, the HLA-DP has high mRNA expression levels without affecting the protein level when compared with the ages of the tissue donors. In addition, the HLA-DR, HLA-DP, and HLA-DQα1 protein expression levels showed a permanent and varied expression rate between tissues. CONCLUSION: Expression of HLA class II molecules in parathyroid cells appears to constitute a decisive factor. Despite the lack of clinical outcomes, present data proposes new insight with a detailed understanding of parathyroid immunogenicity. In the future, randomized controlled clinical trials are needed for the accurate assessment of the effect of the varied HLA class II expression profiles in parathyroid tissue.

Investigating differential miRNA expression profiling using serum and urine specimens for detecting potential biomarkers for early prostate cancer diagnosis

Background/aim: MicroRNAs (miRNAs) are known up-to-date candidate biomarkers for several diseases. In addition, obtaining miRNA from different body fluids such as serum, plasma, saliva, and urine is relatively easy to handle. Herein we aimed to detect miRNAs as biomarkers for early stage prostate cancer (PC). For this purpose, we used urine and serum samples to detect any significant differences in miRNA profiles between patients and healthy controls. Materials and methods: Total ribonucleic acid (RNA) in urine and serum samples were isolated from eight untreated PC patients, thirty healthy individuals were screened for miRNA profile, and candidate miRNAs were validated. Whole urinary and serum miRNA profile was analyzed using Affymetrix GeneChip miRNA 4.0 Arrays. Candidate miRNAs were investigated by stem-loop reverse transcription- polymerase chain reaction. Results: When we analyzed the urinary samples of PC patients, 49 miRNAs were detected to be upregulated and 14 miRNAs were found to be downregulated when compared with healthy controls. According to the serum samples, 19 miRNAs were found to be upregulated, and 21 miRNAs were found to be downregulated when compared with healthy individuals as well. Interestingly, we detected only four overlapping miRNAs (MIR320A, MIR4535, MIR4706, MIR6750) that commonly increase or decrease in both serum and urine samples. Among them, MIR320A was found to be downregulated, and MIR4535, MIR4706, and MIR6750 were found to be upregulated for urine samples. However, only MIR6750 was upregulated and the other three miRNAs were downregulated for serum samples. Conclusion: Notably, the expression profile of MIR320A was significantly altered in urine specimens of prostate cancer patients. We considered that MIR320A has been evaluated as a valuable biomarker that can be used in the early diagnosis of PC.

Achieving the balance: Biphasic effects of genistein on PC-3 cells.

This study examined the response of PC-3 cells to physiological (0.5, 2.5, 5, 10 µM) and pharmacological (50 µM) concentrations of genistein which is a main bioactive compound in soy. Following 48 hr genistein treatment, cell-based assays and genome-wide microarray were performed. It was evidenced that maximal physiologically achievable concentrations of genistein (0.5-10 µM) lead to significant increase in cell viability (p < 0.05) and decrease in migration at 0.5 µM (p = 0.000) and 10 µM (p = 0.001). The highest percentage of apoptotic cells was obtained at 50 µM. Microarray analysis gave the most critical pathways such as cell cycle regulation and proliferation, tumorigenesis, DNA damage and repair, stress response, and apoptosis. Physiological concentrations (≤10 µM) induced activation of CDKs, MAPKs, and RPSKs, while high concentrations of genistein (>10 µM) appeared to have a novel mechanism of action, specifically down-regulating TGF-ß by decreasing specifically SMAD 2/3,4 which are in the downstream TGF-ß signaling cascade. PRACTICAL APPLICATIONS: This study highlights for the first time that maximal physiologically achievable concentrations of genistein (0.5-10 µM) have proliferative effects evidenced by alterations in global gene expression patterns of PC-3 cells. Our results particularly represent a closer examination of dietary genistein consumption for the prevention and/or treatment of cancer that maximal physiologically achievable concentrations of genistein could have detrimental effects on individuals with prostate cancer. Further studies as in vivo would be necessary to remove shadows on the effect of genistein on prostate cancer progression.

Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1-year follow-up.

BACKGROUND: Permanent hypoparathyroidism is a serious problem and requires medications indefinitely. Parathyroid allotransplantation (PA) with short-term immunosuppression is definitive choice but long-term results are not clear. METHOD: We performed PA from two donors to two recipients. Both recipients were 39-year-old females. Donors were a 32-year-old female and a 36-year-old male, who both have chronic kidney disease. Routine tests, viral markers, and cross-matches were analyzed individually. The parathyroid glands were resected from the living donors, fragmented quickly in the operation room and injected into the left deltoid muscles of the two recipients. RESULTS: Methylprednisolone was administered on post-PA day one and two. Recipients were discharged from the hospital without complications. Calcium and PTH levels were observed throughout 1 year. We did not observe any complications during the follow-up period. Medications ceased in post-transplantation week 1 for Case 1 and after 1 month for Case 2. CONCLUSION: Fresh tissue PA with short-term immunosuppression appears to be a promising technique that is easy to perform, is cost-effective, has low risk of side effects and minimal complications with compatibility for HLA conditions. A longer follow-up period and more case studies are needed to determine the risks and benefits of this procedure for future cases.

Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence.

Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1) Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2) chemoprevention drugs including agents interfering with androgen action, and (3) antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.