Evaluation of immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 in oral and oropharyngeal squamous cell carcinoma

J Oral Pathol Med (2012) 41 : 40–46 Background: The purpose of this study was to evaluate whether the immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 can predict therapy response and survival in patients with oral and oropharyngeal squamous cell carcinoma treated with preoperative chemoradiation. Methods: Biomarker expression was evaluated by immunohistochemistry in formalin‐fixed, paraffin‐embedded pretreatment biopsies of 111 homogenously treated patients. We assessed the association between clinicopathological variables including response to neoadjuvant chemoradiotherapy as well as the survival of the patients and the expression of the biomarkers as both dichotomized (positive vs. negative) and continuous variables. Results: Biomarker overexpression on the basis of pre‐selected cutoff points was seen in 66 of 111 (59%) cases for p53, in 77 (69%) for p21, in 48 (43%) for p27, in 81 (73%) for cyclin D1, and in 54 (49%) cases for Ki67, respectively. None of the examined biomarkers was able to predict response to neoadjuvant chemoradiotherapy or was associated with survival outcome. Post‐treatment pathologic TNM stage (P < 0.001), pathologic response (P < 0.001), and perineural invasion (P < 0.001) were the only factors having a significant effect on recurrence‐free survival. Post‐treatment pathologic N stage (P = 0.005), post‐treatment pathologic TNM stage (P < 0.001), pathologic response (P < 0.001), and perineural invasion (P = 0.001) had a significant impact on overall survival. Conclusions: Our results suggest that the biomarkers p53, p21, p27, cyclin D1, and Ki67 have no impact on treatment response and survival in patients with oral and oropharyngeal cancer treated with preoperative chemoradiation.     

A longitudinal three-center study of craniofacial morphology at 6 and 12 years of age in patients with complete bilateral cleft lip and palate

In this longitudinal study, the craniofacial morphology and evaluated soft tissue profile changes, at 6 and 12 years of age in patients with complete bilateral cleft lip and palate (CBCLP) were compared. Lateral cephalograms from 148 patients with CBCLP, treated consecutively at three European cleft centers, Gothenburg (n (A) = 37), Nijmegen (n (B) = 26), and Oslo (n (C) = 85), were evaluated. Eighteen hard tissue and ten soft tissue landmarks were digitized. Paired t test, Pearson's correlation coefficients, and multiple regression models were applied for statistical analysis. ANOVA and Tukey-B, as a post hoc test, were used to evaluate the increments and compare centers. Hard and soft tissue data were superimposed using the generalized Procrustes analysis. For Nijmegen, the increments of the variables SNA, ANB, SN-NL, SN-ML, NL-ML, Snss, and Snpg were significantly different than the two other centers (p = 0.041 to <0.001). SNPg increments were significantly different between Nijmegen and Oslo (p = 0.002). The three cleft centers followed different treatment protocols, but the main differences in craniofacial morphology until 12 years of age were the growth pattern and the maxillary and upper incisor variables. Follow-up of these patients until facial growth has ceased, which may elucidate components for improving treatment outcome.     

The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in rheumatologic disorders: a comprehensive review

The hydroxy-methyl-glutaryl-CoA reductase inhibitors (statins) are used extensively in the treatment for hyperlipidemia. They have also demonstrated a benefit in a variety of other disease processes, including a wide range of rheumatologic disorders. These secondary actions are known as pleiotropic effects. Our paper serves as a focused and updated discussion on the pleiotropic effects of statins in rheumatologic disorders and emphasizes the importance of randomized, placebo-controlled trials to further elucidate this interesting phenomenon.     

Deregulated Chromatin Remodeling in the Pathobiology of Brain Tumors

Brain tumors encompass a heterogeneous group of malignant tumors with variable histopathology, aggressiveness, clinical outcome and prognosis. Current gene expression profiling studies indicate interplay of genetic and epigenetic alterations in their pathobiology. A central molecular event underlying epigenetics is the alteration of chromatin structure by post-translational modifications of DNA and histones as well as nucleosome repositioning. Dynamic remodeling of the fundamental nucleosomal structure of chromatin or covalent histone marks located in core histones regulate main cellular processes including DNA methylation, replication, DNA-damage repair as well as gene expression. Deregulation of these processes has been linked to tumor suppressor gene silencing, cancer initiation and progression. The reversible nature of deregulated chromatin structure by DNA methylation and histone deacetylation inhibitors, leading to re-expression of tumor suppressor genes, makes chromatin-remodeling pathways as promising therapeutic targets. In fact, a considerable number of these inhibitors are being tested today either alone or in combination with other agents or conventional treatments in the management of brain tumors with considerable success. In this review, we focus on the mechanisms underpinning deregulated chromatin remodeling in brain tumors, discuss their potential clinical implications and highlight the advances toward new therapeutic strategies.     

Quality evaluation of the available Internet information regarding pain during orthodontic treatment

Objective:To investigate the quality of the data disseminated via the Internet regarding pain experienced by orthodontic patients.Materials and Methods:A systematic online search was performed for ‘orthodontic pain’ and ‘braces pain’ separately using five search engines. The first 25 results from each search term–engine combination were pooled for analysis. After excluding advertising sites, discussion groups, video feeds, and links to scientific articles, 25 Web pages were evaluated in terms of accuracy, readability, accessibility, usability, and reliability using recommended research methodology; reference textbook material, the Flesch Reading Ease Score; and the LIDA instrument. Author and information details were also recorded.Results:Overall, the results indicated a variable quality of the available informational material. Although the readability of the Web sites was generally acceptable, the individual LIDA categories were rated of medium or low quality, with average scores ranging from 16.9% to 86.2%. The orthodontic relevance of the Web sites was not accompanied by the highest assessment results, and vice versa.Conclusions:The quality of the orthodontic pain information cited by Web sources appears to be highly variable. Further structural development of health information technology along with public referral to reliable sources by specialists are recommended.