Immunohistochemical expression of DNA methyltransferases 1, 3a, and 3b in actinic cheilitis and lip squamous cell carcinomas.

BACKGROUND: Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer. METHODS: Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b. RESULTS: Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05). CONCLUSIONS: The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer.

Characterization of multiscroll attractors using Lyapunov exponents and Lagrangian coherent structures.

The present work aims to apply a recently proposed method for estimating Lyapunov exponents to characterize-with the aid of the metric entropy and the fractal dimension-the degree of information and the topological structure associated with multiscroll attractors. In particular, the employed methodology offers the possibility of obtaining the whole Lyapunov spectrum directly from the state equations without employing any linearization procedure or time series-based analysis. As a main result, the predictability and the complexity associated with the phase trajectory were quantified as the number of scrolls are progressively increased for a particular piecewise linear model. In general, it is shown here that the trajectory tends to increase its complexity and unpredictability following an exponential behaviour with the addition of scrolls towards to an upper bound limit, except for some degenerated situations where a non-uniform grid of scrolls is attained. Moreover, the approach employed here also provides an easy way for estimating the finite time Lyapunov exponents of the dynamics and, consequently, the Lagrangian coherent structures for the vector field. These structures are particularly important to understand the stretching/folding behaviour underlying the chaotic multiscroll structure and can provide a better insight of phase space partition and exploration as new scrolls are progressively added to the attractor.

Osteonecrosis of the jaws: a review and update in etiology and treatment.

INTRODUCTION: Osteonecrosis of the jaws can result either from radiation, used in radiotherapy for treatment of malignant tumors, or medications used for bone remodeling and anti-angiogenesis such as bisphosphonates. These conditions can be associated with triggering factors such as infection, trauma and decreased vascularity. The management of patients with osteonecrosis of the jaws requires caution since there is no specific treatment that acts isolated and decidedly. However, different treatment modalities can be employed in an associated manner to control and stabilize lesions. OBJECTIVE: To review the current knowledge on etiology and management of osteonecrosis of the jaws, both radio-induced and medication-related, aiming to improve knowledge of professionals seeking to improve the quality of life of their patients. METHODS: Literature review in PubMed as well as manual search for relevant publications in reference list of selected articles. Articles in English ranging from 1983 to 2017, which assessed osteonecrosis of the jaws as main objective, were selected and analyzed. RESULTS: Infections, traumas and decreased vascularity have a triggering role for osteonecrosis of the jaws. Prophylactic and/or stabilizing measures can be employed in association with therapeutic modalities to properly manage osteonecrosis of the jaws patients. CONCLUSION: Selecting an appropriate therapy for osteonecrosis of the jaws management based on current literature is a rational decision that can help lead to a proper treatment plan.

Integrins and their extracellular-matrix ligands in gastric-cancer.

Extracellular matrix (ECM) proteins and their specific cellular receptors, play an important role in the regulation of epithelial morphogenesis and differentiation. Alterations in their expression and function have been found in a number of malignant tumours and these changes may help to explain their dedifferentiation and altered behaviour. In this study we have investigated expression and distribution of the epithelial beta 1 integrins (alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 1) and their ECM ligands (fibronectin, tenascin and laminin) in normal and neoplastic tissue. An up-regulation of two isoforms of fibronectin, and tenascin was seen in tumour associated matrix compared to normal stroma. Loss or down regulation of alpha integrin chains was seen more frequently in poorly differentiated carcinomas (alpha 2 p=0.002; alpha 3 p=0.013; alpha 6 p=0.0012) irrespective of tumour type (diffuse or intestinal) than in well/moderately differentiated tumours. Cell adhesion assays revealed that the ability of gastric carcinoma cell lines to bind matrix glycoproteins correlated to their degree of differentiation. Furthermore, poorly differentiated cell lines showed a down-regulation of alpha 2 and alpha 6 integrin expression. These data indicate that architectural and cytological differentiation in gastric carcinoma relates to altered patterns of expression of matrix glycoproteins and their receptors. The traditional Lauren classification seems to reflect these differences in cell-matrix interactions. Differing patterns of expression of those molecules involved in cell-matrix interactions may prove to be a more objective and biologically more relevant means of classifying gastric cancer.

Mefenamic acid enteropathy.

The clinical, radiological, and histological features of two patients with severe intestinal damage induced by mefenamic acid and mimicking coeliac disease are described. Symptoms rapidly reverted on withdrawal of the drug, and in one case, did not relapse during treatment with other non-steroidal anti-inflammatory drugs.

Immunohistochemical detection of the p53 gene-product in gastric-cancer patients - aberrant expression but no prognostic-significance.

The aim of the present study was to examine whether immunohistochemical p53 expression could be identified as an independent predictor for disease recurrence and survival and to assess any relation to tumour type, metastatic potential and response to different therapeutic regimens. We examined gastric carcinomas from 125 patients using a mouse monoclonal antibody (DO7). Seventy two of the tumours showed positive nuclear staining. No special relation was observed either according to tumour type, grade or stage classification of the tumours nor to the lymph node status. Survival analysis showed no significant advantage of the p53 negative patients. Expression of p53 in our series did not prove to be a valuable prognostic marker for survival nor did it correlate with other standard prognostic markers.

Gastric carcinomas of intestinal type concur with distant changes in the gastric mucosa. A multicenter study in the Atlantic basin.

Population studies in the Pacific Basin showed that gastric carcinomas of intestinal type often concur with distant mucosal changes (DMCs). In the present work, the presence of DMCs was investigated in populations dwelling in the Atlantic Basin. A total of 1737 gastrectomy specimens were reviewed: 627 in New York, 435 in Reykjavik, 198 in Buenos Aires, 186 in Florence, 174 in London and the remaining 117 in Stockholm. A total of 17,282 sections were carefully scrutinized. The following DMCs were investigated: intramucosal glandular cysts, gastric cells with ciliated metaplasia, with large or small mucus negative vacuoles, and extensive intestinal metaplasia (IM). The highest frequencies of DMCs were found in Florence for specimens with intestinal type carcinoma: 41.3% had intramucosal cysts, 22.4% had cells with ciliated metaplasia, 12.9% cells with large vacuoles, and 50.9% had high IM. The highest frequency of gastric cells with small vacuoles was recorded in New York (9.1%), also in specimens with intestinal type carcinoma. Significantly lower DMCs percentages were found in specimens with carcinomas of diffuse type, and miscellaneous gastric diseases. The occurrence of DMCs was not influenced to a significant degree by the number of sections available per gastrectomy. Since environmental factors trigger the evolution of intestinal type carcinomas and as DMCs also occurred in specimens without carcinoma-although at a significantly lower rate--it is conceivable that DMCs are also evoked by environmental factors (before a gastric carcinoma ensues). DMCs were found in specimens having intestinal carcinomas either in the cardia, the corpus or the antrum. Thus, DMCs seem to provide the adequate "soil" for the development of gastric carcinomas of intestinal type, independently of the future localization of that tumor in the stomach.

Osteonecrosis of the jaws: a review and update in etiology and treatment / Osteonecrose da mandíbula: revisão e atualização em etiologia e tratamento

Abstract Introduction Osteonecrosis of the jaws can result either from radiation, used in radiotherapy for treatment of malignant tumors, or medications used for bone remodeling and anti-angiogenesis such as bisphosphonates. These conditions can be associated with triggering factors such as infection, trauma and decreased vascularity. The management of patients with osteonecrosis of the jaws requires caution since there is no specific treatment that acts isolated and decidedly. However, different treatment modalities can be employed in an associated manner to control and stabilize lesions. Objective To review the current knowledge on etiology and management of osteonecrosis of the jaws, both radio-induced and medication-related, aiming to improve knowledge of professionals seeking to improve the quality of life of their patients. Methods Literature review in PubMed as well as manual search for relevant publications in reference list of selected articles. Articles in English ranging from 1983 to 2017, which assessed osteonecrosis of the jaws as main objective, were selected and analyzed. Results Infections, traumas and decreased vascularity have a triggering role for osteonecrosis of the jaws. Prophylactic and/or stabilizing measures can be employed in association with therapeutic modalities to properly manage osteonecrosis of the jaws patients. Conclusion Selecting an appropriate therapy for osteonecrosis of the jaws management based on current literature is a rational decision that can help lead to a proper treatment plan.

Resumo Introdução A osteonecrose da mandíbula pode resultar da radiação usada na radioterapia para tratamento de tumores malignos ou de medicamentos usados para remodelação óssea e antiangiogênese, como os bifosfonatos. Essas condições podem ser associadas a fatores desencadeantes, como infecção, trauma e diminuição da vascularização. O tratamento de pacientes com osteonecrose da mandíbula requer cautela, pois não existe um tratamento específico que atue de maneira isolada e decisiva. No entanto, diferentes modalidades de tratamento podem ser empregadas de forma associada para controlar e estabilizar lesões. Objetivo Revisar os conhecimentos atuais sobre a etiologia e o tratamento da osteonecrose da mandíbula, tanto induzidos por radiação quanto relacionados à medicação, para melhorar o conhecimento dos profissionais que busquem a qualidade de vida de seus pacientes. Método Revisão de literatura na base de dados PubMed, bem como pesquisa manual de publicações relevantes na lista de referência de artigos selecionados. Foram selecionados e analisados artigos em inglês publicados de 1983 a 2017, que avaliaram osteonecrose da mandíbula como seu principal objetivo. Resultados Infecções, traumas e diminuição da vascularização são fatores desencadeantes da osteonecrose da mandíbula. Medidas profiláticas e/ou estabilizadoras podem ser usadas em associação com modalidades terapêuticas para o tratamento adequado de pacientes com osteonecrose da mandíbula. Conclusão Selecionar uma terapia apropriada para o tratamento de osteonecrose da mandíbula com base na literatura atual é uma decisão racional que pode ajudar a estabelecer a um plano de tratamento adequado.

The aetiology of gastric stump carcinoma in the rat.

This study investigated the aetiology of gastric stump carcinoma in the rat. These carcinomas were induced by duodenogastric reflux without the need to administer carcinogens. Carcinoma was only detected when pancreatic exocrine secretions were present in the reflux. Malignant change was associated with dysplasia but not intestinal metaplasia or adenocystic proliferation of glands. The extent of resection increased tumour yield, but a truncal vagotomy did not. No difference was detected in intragastric pH, bacterial flora, or bile acid concentration between animals with and without carcinoma.

Expression of sialyl-Tn in gastric cancer: correlation with known prognostic factors.

Sialyl-Tn (STn) is a core region carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins. Expression of STn has been associated with poor prognosis in colon and ovarian cancer, independent of other prognostic factors such as tumour grade, stage or histological type. Recent studies have suggested that STn expression may be an independent prognostic variable in gastric cancer. We have examined 158 patients with gastric cancer using the antibody B72.3 (Biomira, Edmonton, Alberta, Canada). Of these, 110 patients (70%) expressed STn. Expression of STn did not correlate with tumour differentiation or the Ming classification, but expression was noted more frequently in the relatively good prognosis intestinal type of tumours (chi 2 = 6.9, P = 0.03). Conversely, early-stage cancers showed a significantly lower frequency of expression than more advanced cases (chi 2 = 13.75, P = 0.003). In this patient group, STn expression did not influence survival, and in multivariate regression analysis only tumour stage and Lauren classification were found to be independent prognostic variables.

Clinical and histological sequelae of Roux-en-Y diversion.

Nine post-Polya gastrectomy patients with symptoms of reflux gastritis were studied immediately before and 6 months after Roux-en-Y diversion with a 60 cm jejunal loop. Endoscopy, histology, HIDA radionuclide studies and acid secretory studies were performed to determine the effect of Roux-en-Y diversion. Symptomatic results were pleasing in that all patients were graded as Visick I or II. There was a statistically significant improvement in endoscopic evidence of mucosal damage (median score of 6 reduced to median of 1) and visible bile reflux (median score of 10.5 reduced to 0). Foveolar hyperplasia, superficial chronic gastritis and histological precursors of malignancy all improved. There was a significant decrease in the reflux of 99mTc-labelled HIDA into the gastric remnant while acid secretion remained unchanged. Roux-en-Y diversion with a 60 cm jejunal loop provides not only symptomatic relief but scintigraphic, endoscopic and histological evidence of pancreatobiliary diversion.

Duodenal content reflux esophagitis in the rat: an animal model for the ulcer-associated cell lineage (UACL)?

We have studied the histological changes observed in the mucosa of 10 rats in the region of a esophagojejunostomy to evaluate it as a model for the ulcer-associated cell lineage (UACL). In man, the UACL has a distinctive morphology, proliferative organization, and pattern of trefoil peptide localization. We have therefore examined these aspects aided by immunohistochemistry and in situ hybridization to the trefoil peptides TFF1, TFF2, and TFF3. Only TFF2 was studied by immunohistochemistry, whereas the mRNAs for all three peptides were examined by in situ hybridization using 35S-labeled riboprobes. The marker MIB-1 to the Ki67 proliferation-related antigen was used to examine the proliferative organization of UACL-like changes. In all cases, columnar epithelialization of the distal esophagus was seen, and in all, glands with morphological and gene expression attributes of the UACL were identified. TFF3 mRNA localized patchily throughout the UACL, whereas TFF1 mRNA was found in the upper portions of the lineage and TFF2 mRNA and its product in the acini. These lineages showed virtually no intrinsic proliferative activity. These appearances are similar to those seen in early human UACL, and we therefore propose this that this represents the first published animal model of this lineage.

Observer variation and discriminatory value of biopsy features in inflammatory bowel disease.

If skilled histopathologists disagree over the same biopsy specimen, at least one must have an incorrect interpretation. Thus, disagreement is associated with, although not the cause of, diagnostic error. The present study aimed to determine the magnitude of variation among 10 observers with a special interest in gastrointestinal histopathology. They independently interpreted the same biopsy specimens for morphological features which may discriminate between patients with Crohn's disease and ulcerative colitis and normal subjects. Thirty of 41 features had agreement measures significantly better than expected by chance (p < 0.05). The range of agreement in the 45 observer pairs over the final diagnosis was 65-76%. There was good agreement in discriminating between normal slides and those showing confirmed inflammatory bowel disease. For normal slides, however, the term nonspecific inflammation was often applied and without any consistency. In addition, true Crohn's disease slides were often and consistently thought to be ulcerative colitis. Having identified 11 important discriminatory morphological features, two multiple regression analyses were then carried out to produce a scoring system for inflammatory bowel disease. These results suggest there is considerable room for improvement in the reliability of colonic biopsy specimen interpretation and that this could probably be achieved using more exact definitions of morphological features and diseases.