Genetic and Transcriptional Analysis of 8q24.21 Cluster in Gastric Cancer.

BACKGROUND/AIM: Previous studies from our research group have shown that trisomy 8 and the amplification of the 8q24.21 region is very frequent in gastric cancer (GC). Little is known about the role of most genes located in this region. Thus, the aim of this study was to understand the possible impact of transcriptional alterations and copy number variation (CNV) of four genes located in the 8q24.21 region - FAM49B, FAM84B, GSDMC and miR-5194 - in GC. MATERIALS AND METHODS: Fifty-one to 85 matched pairs of tumoral and adjacent non-tumoral gastric tissues, from patients with primary GC, were used to analyze gene expression and CNV of the selected genes. We also included 29 H. pylori negative and gastritis negative gastric mucosa tissues from individuals without cancer obtained by endoscopy, as control samples. RESULTS: The expression of FAM49B, GSDMC and miR-5194 was higher in both tumoral and adjacent non-tumoral samples compared to the negative control. The expression of FAM84B showed no significant difference between tumoral samples and negative controls. However, the expression of FAM84B in the adjacent non-tumoral samples was higher compared to negative control and tumoral samples. Moreover, the higher expression of GSDMC was associated with T3 and T4 tumors, with tumors on stage III and IV and with advanced tumors. Higher copy numbers of FAM49B and GSDMC were associated with intestinal tumor type and with moderately or well-differentiated tumors. Higher copy number of FAM84B was associated with moderately or well-differentiated tumors. Furthermore, the expression of all four genes was positively correlated. CONCLUSION: All four genes are upregulated in GC and may play an important role in these neoplasms. GSDMC expression was associated with more aggressive tumors.

Differential regulation of LRRC37A2 in gastric cancer by DNA methylation.

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, LRRC37A2, in clinical samples. LRRC37A2 expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, LRRC37A2 gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing LRRC37A2 expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.Abbreviations: AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; B2M: beta-2-microglobulin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; LRRC37A2: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1.

Cholecystectomy-Associated Complications in Kidney Transplant Recipients Compared With the General Population.

Cholelithiasis is one of the most prevalent diseases in the general population. Among kidney transplant (KT) recipients, atypical clinical presentation may delay the diagnosis and proper treatment. This single-center retrospective cohort study compared cholelithiasis clinical presentation and cholecystectomy-associated complications in 230 KT recipients and in 172 members of the general population. KT recipients had a higher proportion of men, comorbidities, biliary pancreatitis, choledocholithiasis, and acute cholecystitis clinical presentations than the general population. KT recipients presented higher American Society of Anesthesiologists scores and higher rates of emergency surgeries (15.7% vs 9.9%, P = .091), conversion (5.7% vs 1.2%, P = .019), drainage (7.8% vs 2.3%, P = .016), postoperative complications (10% vs 4.7%, P = .047), and longer hospital length of stay (1 vs 1 days, interquartile range, 2 vs 0 days; P < .001). There were 5 deaths, all of which occurred in KT recipients. History of diabetes mellitus, renal function, and surgical conversion were independent risk factors associated with postoperative complications. Male sex and level of renal function were independent risk factors associated with postoperative acute cholecystitis. KT was an independent risk factor associated with postoperative choledocholithiasis (adjusted odds ratio, 5.89; 95% confidence interval, 3.03-15.66) and pancreatitis (adjusted odds ratio, 6.89; 95% confidence interval, 2.99-11.61). In conclusion, KT recipients with cholelithiasis have an increased risk for clinical and surgical complications compared with the general population.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

BACKGROUND: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. AIM: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. METHODS: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. CONCLUSION: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.

Brazilian gastric cancer association guidelines (part 2): update on treatment / Diretrizes da associação brasileira de câncer gástrico (parte 2): atualização sobre o tratamento

ABSTRACT Background : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. Aim : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. Methods: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. Results : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. Conclusion : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.

RESUMO Racional: O II Consenso Brasileiro de Câncer Gástrico da Associação Brasileira de Câncer Gástrico ABCG (Parte 1) foi recentemente publicado. Nesta ocasião inúmeros especialistas que atuam no tratamento desta doença expressaram suas opiniões diante declarações apresentadas. Objetivo: Apresentar as Diretrizes da ABCG (Parte 2) quanto às indicações de tratamento cirúrgico, técnicas operatórias, extensão de ressecção e terapia combinada. Métodos: Para formulação destas diretrizes os autores realizaram extensa e atual revisão referente a cada declaração presente no II Consenso, utilizando as bases Medline/PubMed, Cochrane Library e SciELO, inicialmente com os seguintes descritores: câncer gástrico, gastrectomia, linfadenectomia, terapia combinada. Ainda, cada declaração foi classificada de acordo com o nível de evidência e grau de recomendação. Resultados: Das 43 declarações presentes neste estudo, 11 (25,6%) foram classificadas com nível de evidência A, 20 (46,5%) B e 12 (27,9%) C. Quanto ao grau de recomendação, 18 (41,9%) declarações obtiveram grau de recomendação 1, 14 (32,6%) 2a, 10 (23,3%) 2b e um (2,3%) 3. Conclusão: O complemento das diretrizes aqui presentes possibilita que cirurgiões e oncologistas que atuam no combate ao câncer gástrico possam oferecer o melhor tratamento possível, de acordo com as condições locais disponíveis.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

BACKGROUND: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented. AIM: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients. METHODS: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3. CONCLUSION: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.

II BRAZILIAN CONSENSUS ON GASTRIC CANCER BY THE BRAZILIAN GASTRIC CANCER ASSOCIATION.

BACKGROUND: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. AIM: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. METHODS: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. RESULTS: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. CONCLUSION: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.

The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer.

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Very few therapeutic options are currently available in this neoplasia. The use of 5-Aza-2'-deoxycytidine (5-AZAdC) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses. Epigenetic manipulation of GC cell lines is a useful tool to better understand gene expression regulatory mechanisms for clinical applications. Therefore, we compared the gene expression profile of 5-AZAdC-treated and untreated GC cell lines by a microarray assay. Among the genes identified in this analysis, we selected NRN1 and TNFAIP3 to be evaluated for gene expression by RT-qPCR and DNA methylation by bisulfite DNA next-generation sequencing in 43 and 52 pairs of GC and adjacent non-neoplastic tissue samples, respectively. We identified 83 candidate genes modulated by DNA methylation in GC cell lines. Increased expression of NRN1 and TNFAIP3 was associated with advanced tumours (P < 0.05). We showed that increased NRN1 and TNFAIP3 expression seems to be regulated by DNA demethylation in GC samples: inverse correlations between the mRNA and DNA methylation levels in the promoter of NRN1 (P < 0.05) and the intron of TNFAIP3 (P < 0.05) were detected. Reduced NRN1 promoter methylation was associated with III/IV TNM stage tumours (P = 0.03) and the presence of Helicobacter pylori infection (P = 0.02). The identification of demethylated activated genes in GC may be useful in clinical practice, stratifying patients who are less likely to benefit from 5-AZAdC-based therapies. KEY MESSAGES: Higher expression of NRN1 and TNFAIP3 is associated with advanced gastric cancer (GC). NRN1 promoter hypomethylation contributes to gene upregulation in advanced GC. TNFAIP3 intronic-specific CpG site demethylation contributes to gene upregulation in GC. These findings may be useful to stratify GC patients who are less likely to benefit from DNA demethylating-based therapies.

Ii brazilian consensus on gastric cancer by the brazilian gastric cancer association / Ii consenso brasileiro de câncer gástrico realizado pela associação brasileira de câncer gástrico

ABSTRACT Background: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. Aim: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. Methods: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. Results: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. Conclusion: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.

RESUMO Racional: Desde a publicação do primeiro Consenso Brasileiro sobre Câncer Gástrico em 2012 realizado pela Associação Brasileira de Câncer Gástrico (ABCG), novos conceitos sobre o diagnóstico, estadiamento, tratamento e seguimento foram incorporados. Objetivo: Promover uma atualização aos profissionais que atuam no combate ao câncer gástrico (CG) e fornecer diretrizes quanto ao manejo dos pacientes portadores desta afecção. Métodos: Cinquenta e nove especialistas responderam 67 declarações sobre o diagnóstico, estadiamento, tratamento e prognóstico do CG com cinco alternativas possíveis: 1) concordo plenamente; 2) concordo parcialmente; 3) indeciso; 4) discordo e 5) discordo fortemente. Foi considerado consenso a concordância de pelo menos 80% da soma das respostas "concordo plenamente" e "concordo parcialmente". Este artigo apresenta apenas as respostas dos especialistas participantes. Os comentários sobre cada declaração, assim como uma revisão da literatura serão apresentados em publicações futuras. Resultados: Das 67 declarações, houve consenso em 50 (74%). Em 10 declarações, houve concordância de 100%. Conclusão: O tratamento do câncer gástrico evoluiu consideravelmente nos últimos anos. Este consenso reúne princípios consolidados nas últimas décadas, novos conhecimentos adquiridos recentemente, assim como perspectivas promissoras sobre o manejo desta doença.

Genetic variants in gastric cancer: Risks and clinical implications.

Cancer is a multifactorial disease that involves many molecular alterations. Gastric cancer (GC) is the third leading cause of cancer death worldwide. GC is a highly heterogeneous disease with different molecular and genetics features. Therefore, this review focuses on an overview of the genetic aspects of gastric cancer by highlighting the important impact and role of deletions and/or duplications of chromosomal segments, genomic variants, H. pylori infection and interleukin variants, as found in gene expression and newly proposed molecular classification studies. The challenge is to better understand the mechanisms and different pathways that lead to the development and progression of GC.

Minimally invasive surgery for gastric cancer in Brazil: current status and perspectives-a report from the Brazilian Laparoscopic Oncologic Gastrectomy Group (BLOGG).

The minimally invasive surgery for gastric cancer in Brazil has begun about two years after the first laparoscopic gastrectomy (LG) performed by Kitano in Japan, in 1991. Although the report of first surgeries shows the year of 1993, there was no dissemination of the technique until the years 2010. At that time with the improvement of optical devices, laparoscopic instruments and with the publications coming from Asia, several Brazilian surgeons felt encouraged to go to Korea and Japan to learn the standardization of the LG. After that there was a significant increase in that type of surgery, especially after the IRCAD opened a branch in Brazil. The growing interest for the subject led some services to begin their own experience with the LG and, since the beginning, the results were similar with those found in the open surgery. Nevertheless, there were some differences with the papers published initially in Japan and Korea. In those countries, the surgeries were laparoscopic assisted, meaning that, in the majority of cases, the anastomoses were done through a mini-incision in the end of the procedure. In Brazil since the beginning it was performed completely through laparoscopic approach due to the skills acquired by Brazilian surgeons in bariatric surgeries. Another difference was the stage. While in the east the majority of cases were done in T1 patients, in Brazil, probably due to the lack of early cases, the surgeries were done also in advanced cases. The initial experience of Zilberstein et al. revealed low rates of morbidity without mortality. Comparing laparoscopic and open surgery, the group from Barretos/IRCAD showed shorter surgical time (216×255 minutes), earlier oral or enteral feeding and earlier hospital discharge, with a smaller number of harvested lymph nodes (28 in laparoscopic against 33 in open surgery). There was no significant difference regarding morbidity, mortality and reoperation rate. In the first efforts to publish a multicentric study the Brazilian Gastric Cancer Association (BGCA) collected data from three institutions analyzing 148 patients operated from 2006 to 2016. There were 98 subtotal, 48 total and 2 proximal gastrectomies. The anastomoses were totally laparoscopic in 105, laparoscopic assisted in 21, cervical in 2, and 20 open (after conversion). The reconstruction methods were: 142 Roux-en-Y, two Billroth I, and three other types. The conversion rate was 13.5% (20/148). The D2 dissection was performed in 139 patients. The mean number of harvested lymph nodes was 34.4. If we take only the D2 cases the mean number was 39.5. The morbidity rate was 22.3%. The mortality was 2.7%. The stages were: IA-59, IB-14, IIA-11, IIB-15, IIIA-9, IIIB-19, IIIC-11 and stage IV-three cases. Four patients died from the disease and 10 are alive with disease. The participating services have already begun the robotic gastrectomy with satisfactory results. The intention of this group is to begin now a prospective multicentric study to confirm the data already obtained with the retrospective studies.

BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer.

Different from genetic alterations, the reversible nature of epigenetic modifications provides an interesting opportunity for the development of clinically relevant therapeutics in different tumors. In this study, we aimed to screen and validate candidate genes regulated by the epigenetic marker associated with transcriptional activation, histone acetylation, in gastric cancer (GC). We first compared gene expression profile of trichostatin A-treated and control GC cell lines using microarray assay. Among the 55 differentially expressed genes identified in this analysis, we chose the up-regulated genes BMP8B and BAMBI for further analyses, that included mRNA and histone acetylation quantification in paired GC and nontumor tissue samples. BMP8B expression was reduced in GC compared to nontumor samples (P < 0.01). In addition, reduced BMP8B expression was associated with poorly differentiated GC (P = 0.02). No differences or histopathological associations were identified concerning BAMBI expression. Furthermore, acetylated H3K9 and H4K16 levels at BMP8B were increased in GC compared to nontumors (P < 0.05). However, reduced levels of acetylated H3K9 and H4K16 were associated with poorly differentiated GC (P < 0.05). Reduced levels of acetylated H3K9 was also associated with diffuse-type histological GC (P < 0.05). Notably, reduced BMP8B mRNA and acetylated H4K16 levels were positively correlated in poorly differentiated GC (P < 0.05). Our study demonstrated that BMP8B seems to be a tumor suppressor gene regulated by H4K16 acetylation in poorly differentiated GC. Therefore, BMP8B may be a potential target for TSA-based therapies in this GC sample subset. J. Cell. Biochem. 118: 869-877, 2017. © 2016 Wiley Periodicals, Inc.

CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas.

CDKN1A is a tumor suppressor gene involved in gastric carcinogenesis and is a potential target for histone deacetylase inhibitor-based therapies. Upregulation of CDKN1A is generally observed in several cell lines after histone deacetylase inhibitor treatment; however, little is known about the histone acetylation status associated with this gene in clinical samples, including gastric tumor tissue samples. Therefore, our goal was to quantify the H3K9 and H4K16 acetylation levels associated with three CDKN1A regions in 21 matched pairs of gastric adenocarcinoma and corresponding adjacent non-tumor samples by chromatin immunoprecipitation and to correlate these data with the gene expression. Our results demonstrated that the -402, -20, and +182 CDKN1A regions showed a significantly increased acetylation level in at least one of the histones evaluated (p < 0.05, for all comparisons), and these levels were positively correlated in gastric tumors. However, an inverse correlation was detected between both H3K9 and H4K16 acetylation at the -402 CDKN1A region and mRNA levels in gastric tumors (r = -0.51, p = 0.02; r = -0.60, p < 0.01, respectively). Furthermore, increased H4K16 acetylation at the -20 CDKN1A region was associated with gastric tumors of patients without lymph node metastasis (p = 0.04). These results highlight the complexity of these processes in gastric adenocarcinoma and contribute to a better understanding of CDKN1A regulation in carcinogenesis.

Muscular metastasis from gastric cancer.

The association between gastric cancer and muscle metastasis is extremely rare. Few cases have been reported in the literature. We report a case of a 68-year-old man, with a diagnosis of gastric adenocarcinoma by endoscopy and biopsy. A painful nodule on the right thigh became noticeable during chemotherapy sessions, where positron emission tomography and percutaneous biopsy diagnosed a muscle metastasis of gastric adenocarcinoma. This report demonstrates the importance of further investigation of muscle lesion in patients with gastrointestinal cancer and how we can diagnose and treat these lesions.

Effect of the celexoxib in microscopic changes of the esophageal mucosal of rats induced by esofagojejunostomy.

OBJECTIVE: To evaluate the protective effect of celecoxib in the esophageal mucosa in rats undergoing esofagojejunostomy. METHODS: Sixty male Wistar rats from the vivarium of the University of Health Sciences of Alagoas were used for the experiment. The animals were divided into four groups: Group I, 15 rats undergoing esofagojejunostomy with the use of celecoxib postoperatively; Group II, 15 rats undergoing esofagojejunostomy without the use of celecoxib; Group III, 15 rats undergoing celiotomy with bowel manipulation; and Group IV, 15 rats without surgery and using celecoxib. The observation period was 90 days. After the death of the animals, the distal segment of the esophagus was resected and sent for microscopic analysis. RESULTS: esofagojejunostomy caused macroscopic and microscopic esophagitis. Esophagitis was equal in both groups I and II. In groups III and IV esophageal lesions were not developed. CONCLUSIONS: celecoxib had neither protective nor inducing effect on esophagitis, but had a protective effect on dysplasia of the animals of group I.

Effect of the celexoxib in microscopic changes of the esophageal mucosal of rats induced by esofagojejunostomy / Efeito do celecoxibe nas alterações microscópicas da mucosa esofágica de ratos causadas por esofagojejunostomia

OBJECTIVE: To evaluate the protective effect of celecoxib in the esophageal mucosa in rats undergoing esofagojejunostomy. METHODS: Sixty male Wistar rats from the vivarium of the University of Health Sciences of Alagoas were used for the experiment. The animals were divided into four groups: Group I, 15 rats undergoing esofagojejunostomy with the use of celecoxib postoperatively; Group II, 15 rats undergoing esofagojejunostomy without the use of celecoxib; Group III, 15 rats undergoing celiotomy with bowel manipulation; and Group IV, 15 rats without surgery and using celecoxib. The observation period was 90 days. After the death of the animals, the distal segment of the esophagus was resected and sent for microscopic analysis. RESULTS: esofagojejunostomy caused macroscopic and microscopic esophagitis. Esophagitis was equal in both groups I and II. In groups III and IV esophageal lesions were not developed. CONCLUSIONS: celecoxib had neither protective nor inducing effect on esophagitis, but had a protective effect on dysplasia of the animals of group I. .

OBJETIVO: avaliar o efeito do celecoxibe como função protetora na mucosa esofágica, em ratos machos Wistar, submetidos à esofagojejunostomia. MÉTODOS: sessenta animais oriundos do biotério da Universidade de Ciências da Saúde de Alagoas foram utilizados para o experimento. Os animais foram distribuídos em quatro grupos: Grupo I, 15 ratos que foram submetidos à esofagojejustomia e que utilizaram o celecoxibe no pós-operatório, Grupo II, 15 ratos submetidos à esofagojejunostomia sem uso de celecoxibe, Grupo III, 15 ratos submetidos à celiotomia com manipulação de alças, e Grupo IV, 15 ratos sem cirurgia e que utilizaram celecoxibe. O período de observação foi de 90 dias. Após a morte dos animais, o seguimento distal do esôfago foi ressecado e enviado para análise macro e microscópicas. RESULTADOS: a esofagojejunostomia causou esofagite macro e microscópica. A esofagite foi igual tanto no grupo I quanto no II. Nos animais dos grupos III e IV não foram desenvolvidas lesões esofagianas. CONCLUSÕES: o celecoxibe não teve efeito protetor nem indutor nas esofagites, mas obteve efeito protetor nas displasias dos animais do grupo I. .

Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A.

Gastric cancer is still the second leading cause of cancer-related death worldwide, even though its incidence and mortality have declined over the recent few decades. Epigenetic control using histone deacetylase inhibitors, such as trichostatin A (TSA), is a promising cancer therapy. This study aimed to assess the messenger RNA (mRNA) levels of three histone deacetylases (HDAC1, HDAC2, and HDAC3), two histone acetyltransferases (GCN5 and PCAF), and two possible targets of these histone modifiers (MYC and CDKN1A) in 50 matched pairs of gastric tumors and corresponding adjacent nontumors samples from patients with gastric adenocarcinoma, as well as their correlations and their possible associations with clinicopathological features. Additionally, we evaluated whether these genes are sensitive to TSA in gastric cancer cell lines. Our results demonstrated downregulation of HDAC1, PCAF, and CDKN1A in gastric tumors compared with adjacent nontumors (P < 0.05). On the other hand, upregulation of HDAC2, GCN5, and MYC was observed in gastric tumors compared with adjacent nontumors (P < 0.05). The mRNA level of MYC was correlated to HDAC3 and GCN5 (P < 0.05), whereas CDKN1A was correlated to HDAC1 and GCN5 (P < 0.05 and P < 0.01, respectively). In addition, the reduced expression of PCAF was associated with intestinal-type gastric cancer (P = 0.03) and TNM stages I/II (P = 0.01). The increased expression of GCN5 was associated with advanced stage gastric cancer (P = 0.02) and tumor invasion (P = 0.03). The gastric cell lines treated with TSA showed different patterns of histone deacetylase and acetyltransferase mRNA expression, downregulation of MYC, and upregulation of CDKN1A. Our findings suggest that alteration of histone modifier genes play an important role in gastric carcinogenesis, contributing to MYC and CDKN1A deregulation. In addition, all genes studied here are modulated by TSA, although this modulation appears to be dependent of the genetic background of the cell line.

Optimal management of gastric cancer: results from an international RAND/UCLA expert panel.

OBJECTIVE: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. METHODS: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. RESULTS: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. CONCLUSIONS: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.

Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia.