Gene Expression of GABAA Receptor Subunits and Association with Patient Survival in Glioma.

Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan-Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma.

Low Expression of the NRP1 Gene Is Associated with Shorter Overall Survival in Patients with Sonic Hedgehog and Group 3 Medulloblastoma.

Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor. Neuropilin-1 (NRP1), encoded by the NRP1 gene, is a transmembrane glycoprotein overexpressed in several types of cancer. Previous studies indicate that NRP1 inhibition displays antitumor effects in MB models and higher NRP1 levels are associated with poorer prognosis in MB patients. Here, we used a large MB tumor dataset to examine NRP1 gene expression in different molecular subgroups and subtypes of MB. We found overall widespread NRP1 expression across MB samples. Tumors in the sonic hedgehog (SHH) subgroup showed significantly higher NRP1 transcript levels in comparison with Group 3 and Group 4 tumors, with SHH samples belonging to the α, ß, Δ, and γ subtypes. When all MB subgroups were combined, lower NRP1 expression was associated with significantly shorter patient overall survival (OS). Further analysis showed that low NRP1 was related to poorer OS, specifically in MB subgroups SHH and Group 3 MB. Our findings indicate that patients with SHH and Group 3 tumors that show lower expression of NRP1 in MB have a worse prognosis, which highlights the need for subgroup-specific investigation of the NRP1 role in MB.

Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.

Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression. We have recently provided evidence for upregulation of PDGF expression in UICC stage I-IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. The present study sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC. Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRß, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors. Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. We then analyzed several CRC cell lines for PDGFRα, PDGFRß, VEGFR1, and VEGFR2 protein expression and found these receptors to be variably expressed amongst the investigated cell lines. Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor. Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.

EORTC Risk Model to Predict Progression in Patients With Non-Muscle-Invasive Bladder Cancer: Is It Safe to Use in Clinical Practice?

PURPOSE: To evaluate the validation of European Organization for Research and Treatment of Cancer (EORTC) risk tables to predict progression in Brazilian patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Two hundred five consecutively and prospectively selected patients with NMIBC who underwent transurethral resection were analyzed during 12 years. Six parameters were analyzed: tumor grade, size, and number, pT stage, previous recurrence rate, and carcinoma-in-situ. Time to progression, risk score, and progression probabilities were calculated and compared to probabilities obtained from the EORTC model. The C index was calculated, and accuracy was analyzed for external validation. RESULTS: A total of 152 patients had complete follow-up data, 36 died, and 17 were lost to follow-up. One hundred thirty-seven patients had primary tumors and 68 had recurrent tumors. Progression to muscle-invasive disease occurred in 42 patients (20.5%). Significant characteristics related to progression were male gender, pT1 stage, lesion size ≥ 3 cm, high grade of disease, and no combined intravesical therapy. Mean time to progression was 26.9 months; the 1-year progression rate was 3.4% and the 5-year rate was 19.1%. The C index was 0.86 at 1 year and 0.78 at 5 years. For calibration, 1- and 5-year progression rates were lower than the values predicted by EORTC risk tables, mainly in high-risk groups. Although the EORTC model overestimated the short- and long-term risk of progression, an overlapping of the confidence intervals between both populations was detected. CONCLUSION: The EORTC model successfully stratified progression risks in a Brazilian cohort, although it overestimated progression rates. This scoring system is useful in predicting progression of NMIBC; however, updating new risk markers is essential to improve risk classification and prediction of progression.

Modified femtosecond laser-assisted sutureless anterior lamellar keratoplasty.

A variation of the femtosecond laser-assisted sutureless anterior lamellar keratoplasty technique using a femtosecond laser incision for surgical management of anterior corneal disease is described. Six patients with corneal scars were treated with the laser to create a horizontal lamellar bed interface in the cornea of the donor and recipient eyes, with a manual partial-thickness vertical trephination to complete the excisions. This technique allows matching of donor and host tissue dimensions with precise tissue apposition and greater surface area for healing. No intraoperative adverse events were observed. One patient developed epithelial ingrowth, requiring a successful surgical intervention.

Sonda nasoenteral, aspiração traqueal e pneumonia aspirativa em pacientes hospitalizados com doença cérebro-vascular complicada por disfagia orofaríngea / Nasogastric feeding tube, aspiration and aspiration pneumonia in hospitalized stroke patients with oropharyngeal dysphagia

Racional - Estima-se que dentre os 300.000 a 600.000 indivíduos com doenças neurológicas que são afetados por disfagia orofaríngea nos Estados Unidos todos os anos, 37% deles desenvolverão pneumonia aspirativa, e 3,8% morrerão, se não fizerem parte dos programas de diagnósticos e tratamento da disfagia orofaríngea. Objetivo - Verificar a associação da presença da sonda nasoenteral com aspiração e pneumonia aspirativa, em pacientes com doença cerebrovascular, complicada por diafagia orofaríngea. Casuística e Método - Foram estudados 123 pacientes com disfagia orofaríngea comprovada por exames instrumentais (estudo endoscópico da deglutição FEES e videofluoroscopia da deglutição), que foram realizados em todos os pacientes. Eles foram acompanhados por seis meses, e neste período PA foi diagnosticado em 36 deles. Resultados - Os pacientes com sonda nasoenteral apresentaram maior freqüência de pneumonia aspirativa e de aspiração do que os sem sonda (P=0,0001 e P=0,048, respectivamente). Conclusão - Os pacientes com doença cerebrovascular complicados por disfagia e portadores de sondas nasoenterais promovem acúmulo de secreções na faringe e aumento do ph intragástrico com conseqüente colonização bacteriana. Esta situação aumenta o risco de aspiração e pneumonia. O seu uso deveria ser restrito e bem indicado.

Estudo comparativo da contraçäo cutânea inicial após aplicaçöes sucessivas de laser de CO2, ultrapulsado em pele dorsal de ratos / Comparative study of initial skin tightening after successives passes of the ultrapulse CO2 laser on the dorsal skin of rats

O objetivo deste trabalho foi avaliar a contraçäo em pele de ratos Wistar, após três aplicaçöes sucessivas de laser de CO2 ultrapulsado. Foram utilizados 35 animais, estudados por planimetria digital e histologia. Foram tatuadas 2 figuras de 22mm X 22mm no dorso dos animais, as quais foram denominadas de "controle" e "experimento". As figuras experimento foram submetidas à três aplicaçöes sucessivas de laser de CO2 ultrapulsado com gerador de padröes computadorizado ativado, potência de 300 mJ, energia de 60 W e fluência de 7,5 J/cm2. Com a primeira aplicaçäo, foi observada na figura da pele experimento uma reduçäo imediata de 32,60 por cento. Após a segunda aplicaçäo foi verificada contraçäo de 40,23 por cento e com a terceira, nova alteraçäo se instalou, com diminuiçäo da área da figura em 50,11 por cento em relaçäo ao controle. Concluiu-se que as sucessivas aplicaçöes de laser de CO2 ultrapulsado em ratos induzem contraçöes progressivas sendo que estas foram mais importantes após a primeira aplicaçäo

Análise da intoxicaçäo alcoólica em vítimas fatais de acidentes de trânsito de Curitiba / Alcohol intoxication in traffic related casualties in Curitiba

O presente estudo procura estabelecer um perfil da intoxicaçäo alcoólica em vítimas fatais de acidente de trânsito. Um total de 63 vítimas dentre 103 vítimas fatais de acidentes de trânsito ocorridos em setembro e outubro de 1995, em Curitiba foram analisadas quanto ao sexo, idade, posiçäo do veículo, uso de meios de proteçäo obrigatórios, horários e tipos dos acidentes. Considerou-se como dosagens alcoólicas positivas aquelas maiores ou iguais a 0,5 mg de álcool por decilitro de sangue, pelo método de cromatografia gasosa. A incidência de vítimas alcolizadas foi de 42,85 por cento e a dosagem alcoólica média foi de 2,26 =- 1,05 mg/dl de sangue. Foi observada a predominância de vítimas alcoolizadas em acidentes ocorridos no período noturno (58,07 por cento) de forma estatisticamente significativa. Verificou-se preponderância do sexo masculino em relaçäo ao feminino de 3/1, idade média de 33,4 +- 11,9 anos. Das vítimas alcoolizadas 45,3 por cento eram motoristas, e 81,8 por cento näo usavam cinto de segurança ou capacete. A proporçäo de vítimas alcoolizadas dentre os atropelados (43,5 por cento) era maior que a dos outros acidentes (39,5 por cento) (p=0,7). Este trabalho conclui que é grande a incidência da intoxicaçäo alcoólica relacionada a acidentes de trânsito com vítimas fatais, a maioria no período noturno, atingindo principalmente motoristas adultos jovens do sexo masculino, que näo faziam uso de meios de proteçäo, tanto em vítimas de colisöes como nos atropelamentos em proporçöes semelhantes