A review: drug-drug interactions of epithelial growth factor receptor-tyrosine kinase inhibitors / 中华肿瘤杂志

Mutations in the epithelial growth factor receptor (EGFR) is a driving factor that causes non-small cell lung carcinoma (NSCLC). The epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a crucial discovery in the treatment of lung cancer, particularly the efficacy of EGFR-TKIs is superior to that of the standard chemotherapy for patients with EGFR mutation-positive advanced NSCLC. Patients with NSCLC use EGFR-TKIs and other medications simultaneously is commonly seen, especially among those with comorbidities, which increases the risk of drug-drug interactions (DDIs) of EGFR-TKIs. The most common mechanisms underlying the DDIs of EGFR-TKIs are modulations of cytochrome P450 (CYP) and drug transporters [including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)], as well as gastrointestinal acid-inhibitory drugs [proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RA)]. Inhibitors or inducers of CYP enzymes and drug transporters can inhibit or accelerate the metabolism of EGFR-TKIs, which increase or reduce the exposure of EGFR-TKIs, thereby affect the efficacy and safety of EGFR-TKIs. In addition, PPIs or H(2)RA can decrease the solubility, bioavailability and efficacy of EGFR-TKIs. This review summarizes the mechanisms of DDIs of gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib; the management recommendations for DDIs of those EGFR-TKIs from the Chinese and global guideline, as well as from the recent pre-clinical and clinical studies, which provide the reference and evidence for managing the combination therapies of EGFR-TKIs and other medications in clinics.

Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner

This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential. Importantly, we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser

Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma

BACKGROUND: The purpose of the present study was to investigate the role of the methylation status of the DACT1 gene on the invasion and metastasis of nasopharyngeal carcinoma cells. METHODS: The levels of methylation and expression of the DACT1 gene in nasopharyngeal carcinoma tissues and CNE2 cells were determined by methylation-specific PCR and RT-PCR, respectively. CNE2 cells were treated with 5-aza-2-deoxycytidine, and the variation in the methylation status of the DACT1 gene was detected, as well as the influence of methylation on invasiveness of nasopharyngeal carcinoma cells. RESULTS: The DACT1 gene was hyper-methylated in 44 of 62 cases of nasopharyngeal carcinoma. The DACT1 gene was hyper-methylated in 32 of 38 cases of nasopharyngeal carcinoma with lymph node metastasis, and the DACT1 gene was hyper-methylated in 7 of 24 cases of nasopharyngeal carcinoma without lymph node metastasis. The DACT1 mRNA level was weakly expressed or not expressed in all nasopharyngeal carcinoma tissues with hyper-methylated DACT1 genes; however, the DACT1 mRNA level was highly expressed in nasopharyngeal carcinoma tissues with low expression of the methylated DACT1 gene. The DACT1 gene was hyper-methylated and not expressed in CNE2 cells that did not have 5-aza-2-deoxycytidine treatment. After 5-aza-2-deoxycytidine treatment, the DACT1 gene was demethylated and the expression of DACT1 was restored. Moreover, the invasion ability was inhibited in CNE2 cells treated with 5-aza-2-deoxycytidine. CONCLUSION: The expression of DACT1 was related to the methylation status. High expression of DACT1 may inhibit the invasion and metastasis of nasopharyngeal carcinoma cells.

Protein expression profiles and clinicopathologic characteristics associate with gastric cancer survival

BACKGROUND: Prognosis remains one of most crucial determinants of gastric cancer (GC) treatment, but current methods do not predict prognosis accurately. Identification of additional biomarkers is urgently required to identify patients at risk of poor prognoses. METHODS: Tissue microarrays were used to measure expression of nine GC-associated proteins in GC tissue and normal gastric tissue samples. Hierarchical cluster analysis of microarray data and feature selection for factors associated with survival were performed. Based on these data, prognostic scoring models were established to predict clinical outcomes. Finally, ingenuity pathway analysis (IPA) was used to identify a biological GC network. RESULTS: Eight proteins were upregulated in GC tissues versus normal gastric tissues. Hierarchical cluster analysis and feature selection showed that overall survival was worse in cyclin dependent kinase (CDK)2, Akt1, X-linked inhibitor of apoptosis protein (XIAP), Notch4, and phosphorylated (p)-protein kinase C (PKC) α/ß2 immunopositive patients than in patients that were immunonegative for these proteins. Risk score models based on these five proteins and clinicopathological characteristics were established to determine prognoses of GC patients. These proteins were found to be involved in cancer related-signaling pathways and upstream regulators were identified. CONCLUSION: This study identified proteins that can be used as clinical biomarkers and established a risk score model based on these proteins and clinicopathological characteristics to assess GC prognosis.

Rankl expression predicts poor prognosis in gastric cancer patients: results from a retrospective and single-center analysis

The receptor activator of nuclear factor κB ligand (RANKL)/RANK pathway plays an important role in the prognosis of several solid tumor types, but its role in gastric cancer prognosis has been poorly characterized. A total of 116 gastric cancer patients who underwent surgical resection were enrolled in this study. Expressions of RANKL and RANK in gastric cancer tissues were detected using immunohistochemical staining. Thirty-eight patients (33%) showed a high level of RANKL expression and 61 patients (53%) showed a high level of RANK expression. There was a positive correlation between expressions of RANKL and RANK (P=0.014, r=0.221). A high level of RANKL expression indicated shorter overall survival (OS) (P=0.008), and was associated with a higher pathological tumor/lymph node/metastasis (pTNM) stage (P=0.035), while no significant correlation was detected between RANK expression and clinicopathological parameters. RANKL also predicted poor prognosis in patients with high RANK expression (P=0.008) and Bormann's type III/IV (P=0.002). Furthermore, RANKL expression correlated with pTNM stage according to high RANK expression (P=0.009), while no significance was found in patients with low RANK expression (P=1.000). Together, our results revealed that high expression of RANKL could predict worse outcomes in gastric cancer especially combined with RANK detection, and thereby this pathway could be a useful prognostic indicator of gastric cancer.

Effects of tetrandrine on proliferation and activation of cardiac fibroblasts / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of tetrandrine (Tet) on proliferation and activation of rat cardiac fibroblasts.@*METHODS@#Firstly, the cell counting kit-8 (cck-8) assay was applied to detect the effects of Tet with different concentrations on proliferation of cardiac fibroblasts. Secondly, transforming growth factor (TGF-β)with a concentration of 5 μg/L was used to induce the cardiac fibroblast activation, and Western blot was performed to measure the expression variation of β-catenin, vimentin (Vm), fibronectin (Fn) and smooth muscle α-actin (SMA). At last, the real-time PCR was conducted to measure the expression change of collagen-1(Col-1) and collagen-3(Col-3).@*RESULTS@#The cck-8 assay showed that the Tet with different concentrations respectively, which were 0.5 μmol/L, 1 μmol/L, 2 μmol/L, 4 μmol/L, and 8 μmol/L, significantly inhibited the proliferation of cardiac fibroblasts. The viability was decreased to 94.4%,84.9%,74.9%,63.8%and 50.3% respectively of the control group when the Tet concentration changed, and the difference was statistically significant, P=0.043, P<0.001, P<0.001, P<0.001, P<0.001 respectively. Western blot revealed that the expressions of β-catenin, Fn, SMA and Vm, were up-regulated by TGF-β(5 μg/L), the result showed that the difference was statistically significant, and the P values were 0.001,0.008,0.010,0.001 respectively. Then, the up-regulation of β-catenin, Fn and SMA was attenuated by pre-treatment of Tet, and the result also displayed that the difference was statistically significant, and the P values were 0.009, 0.005, 0.019,respectively. While there was no significant change in the expression of Vm, according to Western blotting, and P>0.05,at the same time, real-time PCR indicated that the up-regulations of Col-1 and Col-3 which were induced by TGF-β were blocked by pre-treatment of Tet, the result showed that the difference was statistically significant, P<0.001.@*CONCLUSION@#According to the experimental results, we can draw the conclusion that: the Tet can significantly inhibit the proliferation of cardiac fibroblasts, meanwhile, it can block the activation of cardiac fibroblasts, which is induced by TGF-β. It is supposed that the Tet may probably have anti myocardial fibrosis, which indicates that it may probably be a medicine which is used to block the cardiac remodeling.

Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-kappaB pathways

Iodine-131 (131I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with 131I. They were then assessed for 131I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and 131I or with a NF-κB inhibitor of BMS-345541 and 131I, non-transfected SW579 cells were assessed in JNK/NFκB pathways. It was observed that 131I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G0/G1 phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and 131I, the non-transfected SW579 cell lines significantly inhibited JNK pathway, NF-κB pathway and the expression of BTG2. However, when treated with BMS-345541 and 131I, only the NF-κB pathway was suppressed. 131I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF-κB pathways.

Ki-67 protein predicts survival in oral squamous carcinoma cells: an immunohistochemical study

Abstract The aim of this study was to identify the expression of Ki-67 and MCM3 in oral squamous cell carcinoma (OSCC) as well as to address the correlation with patient survival and clinical features. Samples were collected from 51 patients with OSCC who presented for follow-up. Immunohistochemical expression of Ki-67 and MCM3 in all groups was performed. The scoring system was previous published by Tsurutani in 2005. We used Kappa index to evaluate observers agreement degree. The associations between protein expression and clinical variables were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). The overall survival time for a patient with positive immunostaining for Ki-67 is shorter than for a patient with negative immunostaining, (log-rank test, p = 0.00882). Patients with tumor size T3 and T4 showed a statistically significant relationship with Ki-67 immunoexpression (log-rank test, p = 0.0174). The relationship between Ki-67 expression and the relation between age, gender, smoking, tumor site, lymph node metastasis and disease stage was not significant. The examiners agreement degree by Kappa presented p value < 0.05. There was not a significant correlation when we evaluated MCM3 expression regarding clinical characteristics and survival rate. From these results, the present study suggests that positive Ki-67 expression found in OSCC patients may contribute to predict the survival in OSCC samples, as well as the relation between the protein and the tumor size.

Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

PURPOSE: Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart. MATERIALS AND METHODS: Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed. RESULTS: Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either. CONCLUSION: We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.

The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma / O complexo destruidor de betacatenina no carcinoma colorretal e no adenoma cólico

ABSTRACT Objective To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Methods Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student’s t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. Results In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p<0.001 and p<0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma. Conclusions These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted.

RESUMO Objetivo Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina. Métodos Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada. Resultados No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma. Conclusões Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma colorretal, o aumento das expressões da betacatenina, GSK3β, 1 axina, e ubiquitina indicaram que o complexo de destruição de betacatenina estava alterado.

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.

Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer

This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.

Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis

We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and −3, and hyaluronan synthases (HAS)-1, −2, and −3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and −3 and HAS-1, −2, and −3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic procedure for suspected lung cancer. Finalizing this conclusion will require a wider study in a randomized and prospective trial.

Cardiac misconceptions among healthy adults: implications for the promotion of health in the community / Crenças erróneas sobre as doenças cardíacas em adultos saudáveis: implicações para a promoção da saúde na comunidade

This study sought to confirm the structure and to investigate the psychometric properties of an experimental Portuguese version of the York Cardiac Beliefs Questionnaire (YCBQ) in a general population sample. It also set out to identify the prevalent misconceptions in the community and to assess the differences according to socio-demographic characteristics. It involved a cross-sectional survey in which both test and validation samples were collected (n = 476), including participants aged between 18 and 40, recruited via e-mail and social networks. The Confirmatory Factor Analysis on both samples suggested a shorter, three factor version of the YCBQ. Also, misconceptions differed significantly according to sociodemographic variables. The validation of the YCBQ for samples in the community constitutes an important starting point to promote research on misconceptions held in the community by specific groups, as well as to provide key points for health promotion.

Este estudo teve como objetivo confirmar a estrutura e investigar as propriedades psicométricas de uma versão experimental portuguesa do York Cardiac Beliefs Questionnaire numa amostra da população geral; identificar as crenças erróneas mais fortes na comunidade; e avaliar as diferenças de acordo com características sociodemográficas. Trata-se de um estudo transversal com uma amostra de teste e outra de validação, incluindo um total de 476 participantes, com idade entre 18 e 40 anos, recrutados via e-mail e nas redes sociais. A Análise Fatorial Confirmatória em ambas as amostras indicou uma versão reduzida do YCBQ de três factores. As crenças erróneas diferiram significativamente de acordo com as variáveis sociodemográficas. A validação do YCBQ para amostras da comunidade constitui um importante ponto de partida para promover a investigação sobre crenças erróneas em grupos específicos da comunidade, assim como fornecer indicadores relevantes para a promoção da saúde.

Early surgical complications after gastric by-pass: a literature review / Complicações cirúrgicas precoces após bypass gástrico: revisão da literatura

INTRODUCTION: Gastric bypass is today the most frequently performed bariatric procedure,but, despite of it, several complications can occur with varied morbimortality. Probably all bariatric surgeons know these complications, but, as bariatric surgery continues to spread, general surgeon must be familiarized to it and its management. Gastric bypass complications can be divided into two groups: early and late complications, taking into account the two weeks period after the surgery. This paper will focus the early ones. METHOD: Literature review was carried out using Medline/PubMed, Cochrane Library, SciELO, and additional information on institutional sites of interest crossing the headings: gastric bypass AND complications; follow-up studies AND complications; postoperative complications AND anastomosis, Roux-en-Y; obesity AND postoperative complications. Search language was English. RESULTS: There were selected 26 studies that matched the headings. Early complications included: anastomotic or staple line leaks, gastrointestinal bleeding, intestinal obstruction and incorrect Roux limb reconstruction. CONCLUSION: Knowledge on strategies on how to reduce the risk and incidence of complications must be acquired, and every surgeon must be familiar with these complications in order to achieve an earlier recognition and perform the best intervention. .

INTRODUÇÃO: O bypass gástrico é hoje o procedimento bariátrico mais realizado, mas, apesar disso, várias complicações podem ocorrer com variada morbimortalidade. Provavelmente todos os cirurgiões bariátricos conhecem essas complicações, mas como a cirurgia bariátrica continua a se espalhar, o cirurgião geral deve estar familiarizado com essas complicações e seu manuseio. As complicações do bypass gástrico podem ser divididas em dois grupos: as precoces e tardias, tendo em conta o período de duas semanas após a operação. Este artigo irá focar as precoces. MÉTODO: Foi realizada revisão da literatura utilizando as bases Medline/PubMed, Cochrane Library, SciELO, e informações adicionais sobre sites institucionais de interesse cruzando os descritores: bypass gástrico AND complicações; seguimento AND complicações; complicações pós-operatórias AND anastomose, Roux-en-Y; obesidade AND complicações pós-operatórias. A língua usada para a busca foi o inglês. RESULTADOS: Foram selecionados 26 artigos que combinavam com os descritores. As complicações imediatas foram: fístula na linha de grampeamento, sangramento gastrointestinal, obstrução intestinal e reconstrução incorreta da alça em Roux. CONCLUSÃO: O conhecimento sobre as estratégias de como reduzir o risco e incidência das complicações deve ser adquirido ao longo do tempo, e cada cirurgião deve estar familiarizado com essas complicações, a fim de reconhecê-las precocemente e realizar a melhor intervenção. .

TGF-ß1 expression is associated with invasion and metastasis of intrahepatic cholangiocarcinoma

BACKGROUND: Transforming growth factor (TGF)-ß is involved in many physiologic processes, it often promotes metastasis, and its high expression is correlated with poor prognosis. In the present study, we analyzed the correlation between transforming growth factor beta 1 (TGF-ß1) expression and prognosis in intrahepatic cholangiocarcinoma RESULTS: We examined the expression of TGF-ß1 in 78 intrahepatic cholangiocarcinomas by immunohistochemistry and correlated the expression with clinicopathological parameters. TGF-ß1 was expressed in 37 of 78 (47.4 %) intrahepatic cholangiocarcinomas. The expression of TGF-ß1 was significantly correlated with lymph node metastasis, distant metastasis, and tumour recurrence. Patients with TGF-ß1-positive tumours had significantly shorter survival time. In a multivariant analysis, the expression of TGF-ß1 and the tumour stage were independent prognostic factors CONCLUSIONS: Our data suggest that expression of TGF-ß1 is a novel prognostic marker for intrahepatic cholangiocarcinoma.

Lentivirus mediated silencing of Ubiquitin Specific Peptidase 39 inhibits cell proliferation of human hepatocellular carcinoma cells in vitro

BACKGROUND: Ubiquitin Specific Peptidase 39 (USP39) is a 65 kDa SR-related protein involved in RNA splicing. Previous studies showed that USP39 is related with tumorigenesis of human breast cancer cells. RESULTS: In the present study, we investigated the functions of USP39 in human hepatocellular carcinoma (HCC) cell line SMMC-7721. We knocked down the expression of USP39 through lentivirus mediated RNA interference. The results of qRT-PCR and western blotting assay showed that both the mRNA and protein levels were suppressed efficiently after USP39 specific shRNA was delivered into SMMC-7721 cells. Cell growth was significantly inhibited as determined by MTT assay. Crystal violet staining indicated that colony numbers and sizes were both reduced after knock-down of USP39. Furthermore, suppression of USP39 arrested cell cycle progression at G2/M phase in SMMC-7721cells. In addition, Annexin V showed that downregulation of USP39 significantly increased the population of apoptotic cells. CONCLUSIONS: All our results suggest that USP39 is important for HCC cell proliferation and is a potential target for molecular therapy of HCC.

Development of a novel method to evaluate sialylation of glycoproteins and analysis of gp96 sialylation in Hela, SW1990 and A549 cell lines

BACKGROUND: Glycoproteins play a critical role in the cellular activities of eukaryotes. Sialic acid is typically the outermost monosaccharide of glycolipids and glycoproteins, and is necessary for normal development. RESULTS: A strategy based on avidin-biotin affinity was established to enrich sialylated glycoproteins from HeLa cervical carcinoma, SW1990 pancreatic adenocarcinoma, and A549 lung adenocarcinoma cells. Using HPLC-MS/MS, western blot, real-time PCR, and enzyme-linked immunosorbent assay, gp96 was identified in all three cell lines. No significant difference in the protein expression of gp96 was detected at the whole cell level, but the amount of bioti-nylated gp96 in SW1990 cells was 30-40 % lower than that in A549 and HeLa cells, and the amount of sialylated gp96 in SW1990 cells was 30 % lower than that in A549 and HeLa cells. Immunoblotting results showed that the expression of sialyltransferase proteins in the total cell lysates from HeLa and A549 cells were higher than that in SW1990 cells. CONCLUSIONS: We established a new method for investigating the expression and sialylation of glycoproteins using metabolic labeling, click chemistry, and avidin-biotin affinity. We successfully used this method to purify sialylated glycoproteins from cancer cell lines. Our results showed that the levels of gp96 sialylation varied across different cancer cell lines, and this may be because of differences in sialyltransferase expression.

Expression levels of heat shock protein 27 and cellular FLICE-like inhibitory protein in prostate cancer correlate with Gleason score sum and pathologic stage

PURPOSE: Heat shock protein (HSP) 27 protects the cell by controlling apoptosis and immune reactions, and c-FLIP (cellular-FLICE inhibitory protein) inhibits apoptosis by inhibiting caspase-8 activity. We investigated the relationship of HSP27 and c-FLIP expression to prostate-specific antigen, Gleason score sum (GSS), and pathologic stage. MATERIALS AND METHODS: Samples from 163 patients between May 2004 and April 2010 were analyzed: 83 from patients that had underwent a radical prostatectomy, and 80 from those that underwent transurethral resection of the prostate to alleviate urinary symptoms from benign prostate hyperplasia. c-FLIP and HSP27 expression were observed by immunohistochemistry staining. Samples with less than 5% expression-positive cells were scored as 1, with 5%-50% were scored as 2, and with more than 50% were scored as 3. Local reactions were identified as 0.5 and evaluated. RESULTS: Both the presence of HSP27 within the tumor and the number of cancer cells positive for HSP27 were significantly correlated to GSS and pathologic stage (p<0.001, p=0.001, p<0.001, p<0.001). The same was true for c-FLIP expression (p<0.001). GSS was more highly correlated to HSP27 expression than to c-FLIP expression (r=0.814 for HSP27, r=0.776 for c-FLIP), as was pathologic stage (r=0.592 for HSP27, r=0.554 for c-FLIP). CONCLUSIONS: In prostate cancer, higher GSS and a more advanced pathologic stage were associated with a higher likelihood of having a HSP27-positive tumor and more HSP27-positive tumor cells. HSP27 expression was correlated with GSS and prostate cancer stage. A more advanced pathologic stage corresponded to a higher likelihood of having a c-FLIP-positive tumor and more c-FLIP-positive tumor cells. HSP27 expression had a higher correlation with prostate cancer stage and GSS than c-FLIP expression did.

Tissue expression, serum and salivary levels of vascular endothelial growth factor in patients with HNSCC / Expressão tecidual, soro e níveis salivares de VEGF em pacientes com carcinoma de células escamosas de cabeça e pescoço

Introduction: Vascular endothelial growth factor is thought to be an important angiogenic factor involved in tumor growth, progression, and metastasis. Objective: The present study evaluated the relation between tissue expression, serum and salivary levels of vascular endothelial growth factor in head and neck squamous cell carcinomas, and their correlation with clinicopathologic features. Methods: Samples were collected from 30 patients with head and neck squamous cell carcinomas and 24 healthy volunteers. Immunohistochemical analysis was used for tissue expression and enzyme-linked immunosorbent assay was employed to measure serum and salivary levels. Results: No vascular endothelial growth factor staining was observed in normal tissues, whereas vascular endothelial growth factor expression was seen in 6 patients (20%). Mean serum level of VEGF was 83.7 ± 104.47 in patients and 50.04 ± 32.94 in controls. Mean salivary level of vascular endothelial growth factor was 174.41 ± 115.07 in patients and 149.58 ± 101.88 in controls. No significant difference was found by Mann-Whitney test between controls and patients (p = 0.411, p = 0.944, respectively). No correlation was found between vascular endothelial growth factor tissue expression and its serum and salivary level. Conclusion: Overexpression of vascular endothelial growth factor was found in head and neck squamous cell carcinoma patients, suggesting its role in the pathogenesis of head and neck squamous cell carcinoma, but no relation was found between tissue expression, serum levels, and salivary levels of this marker. .

Introdução: Acredita-se que o fator de crescimento vascular endotelial (FCEV) seja um importante fator angiogênico envolvido no crescimento, na progressão e na metástase tumoral. Objetivo: O presente estudo avalia a relacão entre a expressão tecidual e os níveis séricos e salivares do FCEV em carcinomas de células escamosas da cabeca e pescoco (CCECPs) e sua correlacão com aspectos clinicopatológicos. Método: Foram coletadas amostras de 30 pacientes com CCECP e de 24 voluntários saudáveis. Utilizamos análise imuno-histoquímica para a expressão tecidual e ELISA para determinação dos níveis séricos e salivares. Resultados: Não foi observada coloração para FCEV nos tecidos normais, enquanto que foi observada expressão de FCEV em seis pacientes (20%). O nível sérico médio de FCEV foi 83,7 ± 104,47 em pacientes e 50,04 ± 32,94 em controles. O nível salivar médio de FCEV foi de 174,41 ± 115,07 em pacientes e 149,58 ± 101,88 em controles. Não foi observada diferenca significativa pelo teste de Mann-Whitney entre controles e pacientes (respectivamente, p = 0,411, p = 0,944). Não foi observada relacão entre a expressão tecidual de FCEV e seus níveis séricos e salivares. Conclusão: A expressão elevada de FCEV foi observada em pacientes com CCECP, e isso sugere seu papel na patogênese de CCECP, mas não foi observada relacão entre a expressão tecidual e os níveis séricos e salivares desse marcador. .