Gene fusions prevalent in prostate cancer (CaP) lead to the elevated expression of the ERG proto-oncogene. ERG activation present in 50–70% of prostate tumors underscores one of the most common oncogenic alterations in CaP. Despite numerous reports of gene fusions and mRNA expression, ERG oncoprotein status in CaP still remains to be defined. Furthermore, development of ERG protein-based assays may provide a new dimension to evaluation of gene fusions involving diverse androgen-regulated promoters and the ERG protein-coding sequence. Through exhaustive evaluations of 132 whole-mount prostates (261 tumor foci and over 200 000 benign glands) for the ERG oncoprotein nuclear expression, we demonstrated 99.9% specificity for detecting prostate tumor cells using a highly specific anti-ERG monoclonal antibody. The ERG oncoprotein expression correlated well with fusion transcript or gene fusion in randomly selected specimens. Strong concordance of ERG-positive foci of prostatic intraepithelial neoplasia (PIN) with ERG-positive carcinoma (82 out of 85 sections with PIN, 96.5%) affirms the biological role of ERG in clonal selection of prostate tumors in 65% (86 out of 132) of patients. Conversely, ERG negative PINs were associated with ERG-negative carcinoma. Taken together, the homogeneous and strong ERG expression detected in individual tumors establishes the potential for ERG oncoprotein-based stratification of CaP.
Preschool children constitute 11.5% of total population in Egypt. They are exposed to injuries and accidents due to curiosity, lack of experience and increased mobility. Day care institutions for preschoolers increased nowadays to help working mothers for caring for their children. The nursery school teacher has crucial role in caring for children, supervision and prevention of health hazards. They should be well trained on first aid and emergency control to save children lives. Aim of study: to develop, implement and evaluate an educational training program for newly graduate nursery school teachers about first aid of some emergency situations occurring to preschooler. Subjects & methods: An intervention study, the participants were 60 newly graduate nursery teachers from Faculty of Specific Education, Zagazig University at 2008. Data were collected using questionnaire to test teacher's knowledge concerning first aid. This forms the 1 st part of the study. The 2 nd part included a health education program which was designed to meet participant's needs. It was performed by researchers on 20 sessions, 30-45 minutes per session, the participants were divided into small groups in practical sessions. The 3 rd part was an evaluation of the program. It was done by statistical analysis for pre and post results of participant knowledge questionnaires. An observation check list was used to assess their practice towards 1 st aid for wounds, fractures, epilepsy, fainting, epistaxis, suffocation and burns. Results: the participated group of teachers were females,20 ± 2 years old, mostly from rural area, they already taught knowledge concerning growth and development of children, first aid measures in the 3 rd academic year in the faculty but non of them practice these topics. There was high significant improvement of knowledge and practice of the studied group in the post test in comparison to pre test. Knowledge and practice increased, on the average, from 0-10% to 80-95% in first aid of wound, fractures, epileptic convulsions, fainting, epistaxis, suffocation and burn. Conclusion: the designed health education and training program led to significant improvement of knowledge and practice of nursery school teachers in first aid and dealing with emergency situations occurring to preschoolers. Recommendation: Adding practical course for first aid and emergency for the undergraduate curriculum in Faculty of Specific Education. Refreshing educational training courses for all nursery school teachers.
The fusion between ERG coding sequences and the TMPRSS2 promoter is the most prevalent in prostate cancer (CaP). The presence of two main types of TMPRSS2-ERG fusion transcripts in CaP specimens, Type I and Type II, prompted us to hypothesize that the cumulative actions of different ERG variants may impact CaP development/progression. Using TMPRSS2-ERG3 (Type I) and TMPRSS2-ERG8 (Type II) expression vectors, we determined that the TMPRSS2- ERG8 encoded protein is deficient in transcriptional regulation compared to TMPRSS2-ERG3. Co-transfection of vectors resulted in decreased transcriptional regulation compared to TMPRSS2-ERG3 alone, suggesting transdominance of ERG8. Expression of exogenous ERG8 protein resulted in a decrease in endogenous ERG3 protein levels in TMPRSS2-ERG positive VCaP cells, with a concomitant decrease in C-MYC. Further, we showed a physical association between ERG3 and ERG8 in live cells by the bimolecular fluorescence complementation assay, providing a basis for the observed effects. Inhibitory effects of TMPRSS2-ERG8 on TMPRSS2- ERG3 were also corroborated by gene expression data from human prostate cancers, which showed a positive correlation between C-MYC expression and TMPRSS2-ERG3/TMPRSS2- ERG8 ratio. We propose that an elevated TMPRSS2-ERG3/TMPRSS2-ERG8 ratio results in elevated C-MYC in CaP, providing a strong rationale for the biomarker and therapeutic utility of ERG splice variants, along with C-MYC.
Overdiagnosis and overtreatment of prostate cancer (CaP) is attributable to widespread reliance on PSA screening in the US. This has prompted us and others to search for improved biomarkers for CaP, to facilitate early detection and disease stratification. In this regard, autoantibodies (AAbs) against tumor antigens could serve as potential candidates for diagnosis and prognosis of CaP. Towards this, our goals were: i) To investigate whether AAbs against ERG oncoprotein (overexpressed in 25-50% of Caucasian American and African American CaP) are present in the sera of CaP patients; ii) To evaluate an AAb panel to enhance CaP detection. The results using an enzyme-linked immunosorbent assay (ELISA) showed that anti-ERG AAbs are present in a significantly higher proportion in the sera of CaP patients compared to healthy controls (p = 0.0001). Furthermore, a panel of AAbs against ERG, AMACR and human endogenous retrovirus-K Gag successfully differentiated CaP patient sera from healthy controls (AUC = 0.791). These results demonstrate for the first time that anti-ERG AAbs are present in the sera of CaP patients. In addition, the data also suggest that AAbs against ERG together with AMACR and HERV-K Gag may be a useful panel of biomarkers for diagnosis and prognosis of CaP.
Background: Superior hypogastric plexus neurolytic (SHP-N) block is the mainstay management for pelvic cancer pain of visceral origin when oral opioids fail due to inefficacy or intolerance to side effects. Unfortunately, SHP-N has the potential to control pelvic pain in 62%-72% of patients at best, because chronic pelvic pain may assume additional characteristics other than visceral. Objective: Combining SHP-N with pulsed radiofrequency (PRF) of the sacral roots might block most of the pain characteristics emanating from the pelvic structures and improve the success rate of SHP-N in controlling pelvic and perineal cancer pain. Study Design: This study was a prospective randomized controlled clinical trial. Settings: The research took place in the interventional pain unit of a tertiary center in the university hospital. Methods: Fifty-eight patients complaining of cancer-related chronic pelvic and perineal pain were randomized to either the PRF + SHP group (n = 29), which received SHP-N combined with PRF of the sacral roots S2-4, or the SHP group (n = 29), which received SHP-N alone. The outcome variables were the percentage of patients who showed a > 50% reduction in their Visual Analog Scale (VAS) pain score, the VAS pain score, and global perceived effect evaluated during a 3-month follow-up period. Results: The percentage of patients who showed a > 50% reduction in their VAS pain score was significantly higher in the SHP + PRF group compared to the SHP group when assessed at one month (92.9% [n = 26] vs 57.7% [n = 15]; P = .003) and 3 months (85.7% [n = 24) vs 53.8% [n = 14]; P = .01) post procedure, respectively. However, no significant difference was observed between the 2 groups at the 6-month evaluation (SHP + PRF [57.1% (n = 16)] vs SHP [50% (n = 13)]; P = .59). There was a statistically significant reduction of VAS in the SHP + PRF group in comparison to the SHP group at one month (2.8 ± 0.9 vs 3.5 ± 1.2 [mean difference, -0.7 (95% confidence interval [CI], -1.29 to -0.1), P = .01]), 2 months (2.8 ± 0.9 vs 3.5 ± 1.2 [mean difference, -0.64 (95% CI, -1.23 to -0.05), P = .03]), and 3 months (2.7 ± 1 vs 3.4 ± 1.2 [mean difference, -0.67 (95% CI, -1.29 to -0.05)], P = .03]) post procedure, respectively; however, the 2 groups did not significantly differ at 2 weeks, 4, 5, and 6 months post procedure. Regarding postprocedural analgesic consumption, there were trends towards reduced opioid consumption at all postprocedural measured time points in the SHP+PRF group compared to the SHP group; these differences reached statistical significance at 2 months (median, 30 [interquartile range (IQR), 0.00-30] vs median, 45 [IQR, 30-90]; P = .046) and 3 months (median, 0.00 [IQR, 0.00-30] vs median, 30 [IQR, 0.00-67.5]; P = .016) post procedure, respectively. Limitations: The study follow-up period is limited to 6 months only. Conclusions: SHP-N combined with PRF of the sacral roots (S2, 3, 4) provided a better analgesic effect than SHP-N alone for patients with chronic pelvic and perineal pain related to pelvic cancer. Trial Registry: ClinicalTrials.gov. NCT03228316. Key words: Pelvic pain, pulsed radiofrequency, sacral roots, superior hypogastric plexus
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