Linking Pre-Diabetes with Benign Prostate Hyperplasia. IGFBP-3: A Conductor of Benign Prostate Hyperplasia Development Orchestra?

Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity.     

SOSORT consensus paper: school screening for scoliosis. Where are we today?

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4^th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure.     

The direct cost of "Thriasio" school screening program

Background

Adolescent girls treated with a brace for scoliosis are submitted to prolonged stress related to both the disease and the therapy. Currently proposed quality of life questionnaires are focused on the outcome of therapy. Bad Sobernheim Stress Questionnaire (BSSQ) enables monitoring of patients being under treatment with a brace or exercises. The aim of the study was to assess the stress level in conservatively managed scoliotic girls using BSSQ.

Materials and methods

111 girls, aged 14,2 ± 2,2 years, mean Cobb angle of the primary curve 42,8° ± 17,0° and mean Bunnell angle of 11,4° ± 4,5° were examined with two versions of BSSQ (Deformity and Brace). The analysis considered the type of treatment, curve location, correlation of the total score with age, Cobb angle and Bunnell rotation angle.

Results

The BSSQ Deformity revealed the median of 17 points in patients managed with exercises (from 4 to 24 points), 18 in patients managed with a brace (from 8 to 24 points) and 12 in patients before surgery (from 3 to 21 points). Braced patients who completed both questionnaires (n = 50) revealed significantly higher score with BSSQ Deformity (median = 18) comparing to BSSQ Brace (median = 9). There was a correlation between the total score of BSSQ Deformity and the Cobb angle (r = -0,34), Bunnell primary curve rotation (r = -0,34) and Bunnell sum of rotation (r = -0,33) but not with the age of patients.

Conclusion

Scoliotic adolescents managed with exercises and brace suffered little stress from the deformity. The brace increased the level of stress over the stress induced by the deformity. The stress level correlated with clinical deformity (Bunnell angle), radiological deformity (Cobb angle) and the type of treatment (exercises, bracing, surgery). Bad Sobernheim Stress Questionnaires are simple and helpful in the management of girls treated conservatively for idiopathic scoliosis.     

The Aminoacyl-tRNA Synthetase and tRNA Expression Levels Are Deregulated in Cancer and Correlate Independently with Patient Survival

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes that load amino acids to their cognate tRNA molecules. The expression of certain ARSs and tRNAs has been shown to be deregulated in cancer, presumably to accommodate elevated protein synthesis requirements. In this work, the expression of cytoplasmic ARSs and tRNAs in ten TCGA cancers has been systematically examined. ARSs were found to be mostly upregulated in tumours and their upregulation often correlated with worse patient survival. tRNAs were found to be either upregulated or downregulated in tumours and their expression sometimes correlated to worse survival outcomes. However, although the expression of most ARSs and tRNAs was deregulated in tumours when compared to healthy adjacent tissues, only in a few cases, and independently, did it correlate to patient survival. These data point to the general uncoupling of concomitant ARS and tRNA expression deregulation and patient survival, highlighting the different ARS and tRNA requirements in cancers.     

Bone mineral density and genetic markers involved in three connected pathways (focal adhesion, actin cytoskeleton regulation and cell cycle): the CUMAGAS-BMD information system

The focal adhesion, the actin cytoskeleton and cell-cycle are connected pathways and their genes are implicated in the pathogenesis of low BMD. Data from 211 studies that investigated the association between BMD and gene variants involved in these pathways were catalogued in a web-based information system and analyzed. In individual studies, significant association was found for 16 variants in lumbar spine, 11 in femoral neck and 5 in hip. In meta-analysis, significant results were shown for the variants COL1A1 rs1800012 (in lumbar spine and femoral neck), COL1A1 rs1107946 (in lumbar spine), TGFB1 rs1982073 (in femoral neck and hip) and TGFB1 rs1800469 (in lumbar spine).     

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and cervical cancer risk: a meta-analysis

This meta-analysis aims to examine whether the genotype status of MspI and Ile462Val polymorphisms in Cytochrome-P450 1A1 (CYP1A1) is associated with cervical cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random effects models. Concerning MspI polymorphism, six studies were eligible (722 cases and 770 controls); four studies were eligible (350 cases and 519 controls) for Ile462Val. MspI polymorphism was associated with elevated cervical cancer risk (for heterozygous TC vs. TT carriers OR = 1.50, 95% CI: 0.93–2.42, random effects; for homozygous CC vs. TT carriers OR = 2.66, 95% CI: 1.14–6.19, random effects). Similarly, Ile462Val polymorphism was associated with elevated cervical cancer risk (for heterozygous Ile/Val vs. Ile/Ile carriers OR = 2.36, 95% CI: 1.10–5.08, random effects; for homozygous Val/Val vs. Ile/Ile carriers OR = 2.73, 95% CI: 1.21–6.15, fixed effects). The results were replicated upon Caucasian subjects, who represented the majority of existing data. The two examined CYP1A1 genotype polymorphisms seem to confer additional risk for cervical cancer. Accumulation of further data seems mandatory for future race-specific analyses and for the demonstration of CYP1A1-smoking interactions.     

Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping,in Comparison to Cytology

Objectives

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening.

Methods

The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein.

Results

Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology).

Conclusion

HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.     

Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma

Proteoglycans (PGs) are implicated in the growth and progression of malignant tumors. In this study, we examined the concentration and localization of PGs in advanced (stage IV) laryngeal squamous cell carcinoma (LSCC) and compared with human normal larynx (HNL). LSCC and HNL sections were examined immunohistochemically with a panel of antibodies, and tissues extracts were analyzed by biochemical methods including immunoblotting and high performance liquid chromatography (HPLC). The results demonstrated significant destruction of cartilage in LSCC, which was followed by marked decrease of aggrecan and link protein. In contrast to the loss of aggrecan in LSCC, accumulation of versican and decorin was observed in the tumor-associated stroma. Biochemical analyses indicated that aggrecan, versican, decorin and biglycan comprise the vast majority of total PGs in both healthy and cancerous tissue. In LSCC the absolute amounts of KS/CS/DS-containing PGs were dramatically decreased about 18-fold in comparison to HNL. This decrease is due to the loss of aggrecan. Disaccharide analysis of CS/DSPGs from LSCC showed a significant reduction of 6-sulfated Delta-disaccharides (Deltadi-6S) with a parallel increase of 4-sulfated Delta-disaccharides (Deltadi-4S) as compared to HNL. The obtained data clearly demonstrate that tumor progression is closely related to specific alteration of matrix PGs in LSCC. The altered composition of PGs in cartilage, as well as in tumor-associated stroma, is crucial for the biological behaviour of cancer cells in the diseased tissue.