Linear and volumetric gain after vertical bone augmentation in the posterior mandible using an autologous cortical tenting method.

This study was performed to evaluate the linear and volumetric effects of a technique for reconstruction of the posterior atrophic mandible, including the final bone gain of the graft, by three-dimensional assessment. Thirteen individuals were recruited into the study and submitted to a total of 15 mandibular autogenous bone block surgeries. Cone beam computed tomography images were obtained at three different times. Bone graft length and thickness, and the volume, height, and width of the graft were measured. Data were compared statistically among the time points using the Friedman test, and cluster analysis was performed to identify the association between the study variables and the resorption rate (α = 0.05). Linear analysis of the width and height of the recipient area at the different time points revealed a statistically significant difference. The final average increase in height was 1.6 mm; all subjects showed an average volume gain of 3.412mm3, and 77% of the subjects showed an average graft resorption of 0.688mm3 construction of three-dimensional vertical defects of the posterior mandible resulted in good healing with minimal complications and minimal bone graft resorption, favouring vertical bone gain.

Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3.

Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Despite its high degree of heritability, current genetic studies have failed to reveal individual loci of large effect size. In lieu of focusing on individual genes, we investigated regulatory units (regulons) in BD to identify candidate transcription factors (TFs) that regulate large groups of differentially expressed genes. Network-based approaches should elucidate the molecular pathways governing the pathophysiology of BD and reveal targets for potential therapeutic intervention. The data from a large-scale microarray study was used to reconstruct the transcriptional associations in the human prefrontal cortex, and results from two independent microarray data sets to obtain BD gene signatures. The regulatory network was derived by mapping the significant interactions between known TFs and all potential targets. Five regulons were identified in both transcriptional network models: early growth response 3 (EGR3), TSC22 domain family, member 4 (TSC22D4), interleukin enhancer-binding factor 2 (ILF2), Y-box binding protein 1 (YBX1) and MAP-kinase-activating death domain (MADD). With a high stringency threshold, the consensus across tests was achieved only for the EGR3 regulon. We identified EGR3 in the prefrontal cortex as a potential key target, robustly repressed in both BD signatures. Considering that EGR3 translates environmental stimuli into long-term changes in the brain, disruption in biological pathways involving EGR3 may induce an impaired response to stress and influence on risk for psychiatric disorders, particularly BD.

On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors.

In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.

On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors

In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.

Gompertzian growth pattern correlated with phenotypic organization of colon carcinoma, malignant glioma and non-small cell lung carcinoma cell lines.

In the current study we present a Gompertzian model for cell growth as a function of cell phenotype using six human tumour cell lines (A-549, NCI-H596, NCI-H520, HT-29, SW-620 and U-251). Monolayer cells in exponential growth at various densities were quantified over a week by sulforhodamine B staining assay to produce cell-growth curves. A Gompertz equation was fitted to experimental data to obtain, for each cell line, three empirical growth parameters (initial cell density, cell-growth rate and carrying capacity - the maximal cell density). A cell-shape parameter named deformation coefficient D (a morphological relationship among spreading and confluent cells) was established and compared by regression analysis with the relative growth rate parameter K described by the Gompertz equation. We have found that coefficient D is directly proportional to the growth parameter K. The fit curve significantly matches the empirical data (P < 0.05), with a correlation coefficient of 0.9152. Therefore, a transformed Gompertzian growth function was obtained accordingly to D. The degree of correlation between the Gompertzian growth parameter and the coefficient D allows a new interpretation of the growth parameter K on the basis of morphological measurements of a set of tumour cell types, supporting the idea that cell-growth kinetics can be modulated by phenotypic organization of attached cells.

Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non-small cell lung carcinoma cell lines

In the present study, we examined the relationship between cell phenotype and cell survival of three human non-small cell lung carcinoma cell lines (A549, NCI-H596 and NCI-H520). Cells in exponential growth at various densities were incubated for 24 h at 37ºC in a 5 percent CO2 humidified atmosphere and then exposed to UV radiation for 1 min (256 nm, 40 W, source-to-target distance 100 cm). After two days the surviving cells were quantified by sulforhodamine á staining and DNA fragmentation assay. The differences in UV sensitivity at 60 x 10(3) cells/cm(2) among the cell lines were not related to the proliferative state of the cells but to the extent of intercellular contact. In contrast to A549 and NCI-H596, irradiated NCI-H520 cells presented lower DNA fragmentation and an aggregated cell culture phenotype even prior to confluence, suggesting that a contact-effect mechanism provides further protection against UV radiation

Neoplasias associadas ao carcinoma epidermóide do esôfago / Neoplasms associated to esophageal epidermoid carcinoma

INTRODUÇÄO. O carcinoma epidermóide de esôfago (CEE) tem uma importante associaçäo com neoplasias do trato aerodigestivo e, provavelmente, compartilham dos mesmos fatores de risco. Além destes, outras neoplasias podem estar associadas com o carcinoma de esôfago. OBJETIVO. Analisar, retrospectivamente, pacientes com carcinoma epidermóide de esôfago tratados pelo Grupo de Cirurgia do Esôfago, Estômago e Intestino Delgado (GCEEID) do Hospital de Clínicas de Porto Alegre (HCPA), no período de janeiro/88 a junho/95, os quais tinham neoplasias associadas ao CEE. PACIENTES E MÉTODOS. Dentre os 261 pacientes estudados, 19 (7,28 por cento) tinham neoplasia associada ao CEE. Dez pacientes apresentaram tumores sincrônicos e 9, metacrônicos. O sexo predominante foi o masculino, com 17 casos. A média de idade ficou em 62,52 anos no momento do diagnóstico da neoplasia esofágica. RESULTADOS. Os tumores aerodigestivos, na sua totalidade carcinomas escamosos, representaram o tipo histológico predominante da neoplasia associada em 68,42 por cento dos casos. O sítio mais freqüente da neoplasia aerodigestiva associada foi a árvore respiratória (53,8 por cento), seguido da cavidade oral e orofaringe (23 por cento) e laringe (23 por cento). Dos 19 pacientes, 12 eram tabagistas e nove ingeriam bebidas alcoólicas regularmente. Para o tratamento do CEE, optou-se por cirurgia em seis pacientes. A neoplasia associada foi tratada com cirurgia radical em 11 pacientes e radioterapia em cinco. Surpreendentemente, foram diagnosticados quatro casos (21 por cento) de adenocarcinomas gßstricos associados ao CEE, tratados com cirurgia radical em três pacientes. CONCLUSÄO. Os autores ressaltam a importância do estadiamento criterioso dos pacientes com CEE devido a associaçäo significativa com outras neoplasias, principalmente com tumores aerodigestivos. Alertam para o seguimento desses pacientes e discutem a possibilidade de fatores de risco comuns: fumo e álcool. Nesta casuística, encontrou-se associaçäo importante com neoplasias gástricas.