Pathobiological Implications of the Expression of EGFR, pAkt, NF-κB and MIC-1 in Prostate Cancer Stem Cells and Their Progenies

The progression of prostate cancers (PCs) to locally invasive, androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse. The present study was undertaken to establish the possibility of using a combination of specific oncogenic products, including epidermal growth factor receptor (EGFR), pAkt, nuclear factor-kappaB (NF-κB) and macrophage inhibitory cytokine-1 (MIC-1) as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages. The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR, Ser473-pAkt, NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of 76 cases of prostatic adenocarcinoma specimens during the disease progression and these biomarkers were expressed in a small subpopulation of CD133+ PC cells and the bulk tumor mass of CD133− PC cells. Importantly, all of these biomarkers were also overexpressed in 80–100% of 30 PC metastasis bone tissue specimens. Moreover, the results have indicated that the EGF-EGFR signaling pathway can provide critical functions for the self-renewal of side population (SP) cells endowed with stem cell-like features from highly invasive WPE1-NB26 cells. Of therapeutic interest, the targeting of EGFR, pAkt, NF-κB or MIC-1 was also effective at suppressing the basal and EGF-promoted prostasphere formation by SP WPE1-NB26 cells, inducing disintegration of SP cell-derived prostaspheres and decreasing the viability of SP and non-SP WPE1-NB26 cell fractions. Also, the targeting of these oncogenic products induced the caspase-dependent apoptosis in chemoresistant SP WPE1-NB26 cells and enhanced their sensibility to the cytotoxic effects induced by docetaxel. These findings suggest that the combined use of EGFR, pAkt, NF-κB and/or MIC-1 may represent promising strategies for improving the accuracy of current diagnostic and prognostic methods and efficacy of treatments of PC patients in considering the disease heterogeneity, thereby preventing PC progression to metastatic and lethal disease states

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

HIV AIDS Related Knowledge, Attitude and Practice among High School Students in Eastern Nepal

Abstrac

Comparative attitude and plans of the medical students and young

Introduction: Many doctors are leaving Nepal to work abroad. To understand this problem better, we decided to study the attitude and plans of young doctors and medical students. Materials and methods: This cross-sectional study was conducted at Kathmandu Medical College involving 65 �rstyear medical students, 100 interns and 100 house of�cers. The data collected was entered in Microsoft excel and analysed by SPSS (Statistical Package for Social Sciences) programme. Chi-square test was used to compare two proportions

Laboratory approach To a Case Of Leukemia

Abstrac

Original Research Article Correlation of serum free prostate-specific antigen level with histological findings in

patients with prostatic diseas

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Middle pancreatectomy for selected pancreatic neck tumour

Original Article Incidence of tuberculosis in enlarged neck nodes, our experience

Objectives: To determine the incidence of tuberculous lymphadenitis in enlarged neck nodes. Materials and methods: Continuous prospective study is carried out in the department of otorhinolaryngology head & neck surgery, Kathmandu Medical College, Kathmandu, during two years, from January 2006 to January 2008. The study included a group of 155 patients with cervical lymphadenopathy. Each patient underwent a detail clinical Ear, Nose and Throat (ENT) examination and a battery of investigations which included Fine Needle Aspiration Cytology (FNAC) of the nodes, Montoux’s test, blood Erythrocyte Sedimentation Rate (ESR) and chest X-ray. Those patients with tubercular lymphadenitis were referred to Directly Observed Therapy System (DOTS) clinic for anti-tubercular therapy. Others with reactive lymphadenitis were treated with antibiotic and those with metastatic neck nodes were treated accordingly. Results: Of the 155 cases with enlarged neck nodes, 83 (54%) had tubercular lymphadenitis. Fifty two (33%) cases had reactive lymphadenitis and 17 (11%) cases were diagnosed with metastatic neck nodes. Fine needle aspiration cytology was found to be highly effective in the diagnosis of tubercular lymphadenitis with 94 % accuracy. Majority of patients were otherwise healthy adults, aged between 8 – 71 years. No difference was observed between male and female in this study. Posterior triangle (PT) nodes were most commonly affected group of nodes accounting for 35 (42%) case