Navegando por Palavras-chave "Gastric cancer"

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    Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
    (Universidade Federal de São Paulo (UNIFESP), 2016-11-29) Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]; Matos, Delcio [UNIFESP]; http://lattes.cnpq.br/8504991156956921; http://lattes.cnpq.br/8810661976171757; Universidade Federal de São Paulo (UNIFESP)
    Research bases: Breast cancer is the most frequent malignancy in the world, and many of these women develop distant metastases, most often to the bones, lymph nodes, lung, brain and liver. Metastases to the gastrointestinal tract are rare, but when present the stomach is the most common site. The differential diagnosis between gastric metastasis of mammary origin and primary gastric adenocarcinoma is difficult, and the radiological and endoscopic findings are similar and the morphological characteristics often do not allow the diagnosis of the cancer origin, hindering thus the proper treatment. Objective: The motivation and the goal of this research were to search the characterization of the molecular expression profile of markers in the primary site of breast carcinoma in gastric metastasis site and the second synchronous gastric primary or metachronous, in order to identify possible markers that facilitate the diagnosis of gastric metastases of mammary origin. Methods: The proposed research design was retrospective and controlled nature, making up three focus groups with 42 patients each, for a total of 126 patients; The Test group included patients with breast cancer who developed primary gastric adenocarcinoma (n=17) and metastatic mammary carcinoma in the stomach (n=25) diagnosed prior to treatment; the Control group I included patients diagnosed with primary breast carcinoma, without other associated lesions and the Control group II included patients with primary gastric adenocarcinoma, also without other associated lesions. The markers selected for analysis were: estrogen receptor (ER), progesterone receptor (PR), gross cystic disease fluid protein-15 (GCDFP-15) and hepatocyte nuclear factor 4-alpha (HNF4A), which were examined in tumor samples in 126 paraffin blocks, the Test and Controls groups I and II. The sensitivities, specific, accurate, prevalence, predictive values were calculated, estimating the test group the confidence intervals of values. Results: The tumor marker ER showed positive immunoreactivity in 12/25 patients (48.0%) with metastatic breast cancer in the stomach, sensitivity 48.0%, specificity of 100.0% and accuracy of 69.0%, with p<0.001; tumor marker PR showed positive immunoreactivity in 6/25 patients (24.0%) with metastatic breast cancer in the stomach, 24.0% sensitivity, specificity 100.0% and accuracy of 54.8%, with p<0.001; the GCDFP-15 marker showed positive immunoreactivity in 9/25 patients (36.0%) with metastatic breast cancer in the stomach, sensitivity 36.0%, specificity of 100.0% and accuracy of 61.9%, with p<0.001; tumor marker HNF4A showed positive immunoreactivity in 17/17 patients (100.0%) with primary gastric adenocarcinoma and negative in 1 patient with metastatic breast cancer in the stomach, 100.0% sensitivity, high specificity of 96.0% and accuracy of 97.6% with p value <0.001. Conclusion: Based on the results obtained in this research we can conclude that HNF4A, ER, PR and GCDFP-15 markers are effective in the differential diagnosis of primary gastric cancer and gastric metastasis of mammary origin. The marker HNF4A, in particular, can be regarded as highly significant to the exclusion of metastatic mammary carcinoma in the stomach, and thus can confer high power reliability in distinguishing these lesions.
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    Análise da expressão de miR-21-5p e miR-105-5p no soro de pacientes com câncer gástrico
    (Universidade Federal de São Paulo, 2022-09-12) Santos, Yeda Beatriz Louredo dos [UNIFESP]; Santos, Fernanda Wisnieski Caires dos [UNIFESP]; http://lattes.cnpq.br/1101600694934077; https://lattes.cnpq.br/1476540520522096
    O câncer gástrico (CG) é uma das mais frequentes e letais neoplasias do mundo. Contudo, ainda existem poucas ferramentas eficazes para seu diagnóstico, monitoramento e resposta ao tratamento. Estudos sobre biomarcadores são a grande aposta da medicina personalizada nos últimos tempos, principalmente, em materiais biológicos de fácil obtenção como a punção venosa periférica. A maioria dos estudos da literatura em CG busca a identificação de biomarcadores em grupos étnicos restritos. Previamente, nosso grupo de pesquisa identificou miR-21 e miR-105 como alvos modulados epigeneticamente em modelos celulares e tecido gástrico neoplásico provenientes de indivíduos da população brasileira. Objetivo: Avaliar se esses miRNAs podem constituir potenciais biomarcadores minimamente invasivos de diagnóstico, prognóstico e de monitoramento do CG. Métodos: A expressão de miR- 21-5p e miR-105-5p foi avaliada em amostras de soro de 50 participantes com CG e de 14 participantes sem câncer e sem infecção por H. pylori. Os níveis desses miRNAs foram monitorados após o tratamento cirúrgico em 21 participantes com CG de 3 a 48 meses. Os miRNAs foram quantificados por RT-qPCR e normalizados pela combinação dos miRNAs de referência, miR-101-3p + miR-140-3p. Os dados de expressão foram associados às variáveis clínicas e patológicas. Resultados: O miR- 21-5p apresentou expressão aumentada nos pacientes com CG em relação aos participantes sem câncer (P < 0,01). Além disso, a expressão de miR-21-5p foi capaz de discriminar esses indivíduos com acurácia de 84% (AUC = 0,88; P < 0,01). Após a ressecção cirúrgica, não foram observadas alterações significativas na expressão de miR-21-5p. A expressão de miR-105-5p nos participantes com CG não se diferenciou dos controles, porém se alterou pós-cirurgicamente, com redução e aumento máximos de 90% e 64%, respectivamente, de acordo com o tempo de monitoramento do paciente. A expressão de miR-21-5p e miR-105-5p nas amostras pré e pós-cirúrgicas não teve associação às características clínicas e patológicas. Conclusões: O miR- 21-5p e miR-105-5p demonstraram ser potenciais biomarcadores minimamente invasivos para o diagnóstico do CG e de involução e sucesso do tratamento, respectivamente.
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    Análise da expressão e do número de cópias gênicas de microrna da região 8q24.21 no câncer gástrico
    (Universidade Federal de São Paulo (UNIFESP), 2018-05-24) Pereira, Ana Carolina Anauate [UNIFESP]; Smith, Marilia de Arruda Cardoso [UNIFESP]; Marilia de Arruda Cardoso Smith; http://lattes.cnpq.br/0324626849656801; Universidade Federal de São Paulo (UNIFESP)
    Objetivo: Analisar a expressão de miR1204, miR1205, miR1206, miR1207 e miR1208 em tecido gástrico neoplásico e não neoplásico de pacientes com e sem CG, determinar os genes de referência para essa análise, avaliar o número de cópias gênicas desses miRNA, e associar estas variáveis com os parâmetros clínicos e patológicos dos pacientes com CG. Métodos: A expressão dos miRNA alvos miR1204, miR1205, miR1206, miR12075p, miR12073p, e miR1208 foi avaliada por RTqPCR em 65 pares de amostras neoplásicas (T) e margem adjacente não neoplásicas (A) de pacientes com CG, e 20 amostras de tecido gástrico não neoplásica de indivíduos sem câncer submetidos à endoscopia (C), e determinada pelo método ΔCt. O número de cópias dos genes miR1204, miR1205, miR1207, e miR1208 foi determinado por qPCR em 69 amostras T e com o uso do programa Copy Caller. Resultados: O grupo de amostras C não diferiu em relação ao gênero e idade dos pacientes com CG (p>0,05). Apenas o miR1205 apresentou diferença de expressão entre os grupos de amostra A e C, com maior expressão no grupo A (p=0,02). Não foi observada expressão de miR1204 e miR1206 nas amostras de tecido gástrico analisadas. Foi observada uma correlação positiva e forte entre a expressão de miR12075p e miR1208 (p<0,01, ρ=0,71), e uma correlação positiva, mas fraca, entre a expressão de miR1205 e miR12073p (p=0,04, ρ=0,21). Não foi observada associação entre a expressão de miR1205, miR12075p, miR12073p, e miR1208 e o número de cópias dos seus respectivos genes (p>0,05). O aumento do número de cópias do gene miR1207 foi associado aos tumores localizados na região não cárdia do estômago (p=0,01), e a perda do número de cópias do gene miR1208 à presença de infecção por H. pylori (p=0,01). Conclusões: Não foram encontradas diferenças significantes entre a expressão de miR1205, miR12075p, miR12073p, e miR1208 nas amostras T vs A, e entre T vs C. Porém, o miR1205 apresentou expressão aumentada nas amostras A em relação às C. Os resultados sugerem que o miR1205 parece ter um papel importante no início do desenvolvimento do CG. Além disso, a ausência de associação entre a expressão desses miRNA e o número de cópias gênicas indica que a alteração do número de cópias do miR1205 não seja o mecanismo que leva à sua desregulação nas amostras avaliadas.
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    Association between ABCB1 Immunohistochemical Expression and Overall Survival in Gastric Cancer Patients
    (Asian Pacific Organization Cancer Prevention, 2014-01-01) Oliveira, Juliana de [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Artigiani Neto, Ricardo [UNIFESP]; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Silva, Marcelo de Souza [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Gastric cancer (GC) is one of the most common malignancies worldwide. the ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. in contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. the aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.
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    Association of COX2 gene hypomethylation with intestinal type gastric cancer in samples of patients from northern Brazil
    (Springer, 2014-02-01) Vieira de Melo, Cynthia Farias; Gigek, Carolina Oliveira [UNIFESP]; Silva, Juarez Nobrega da; Cardoso Smith, Marilia de Arruda [UNIFESP]; Araujo, Rubistenia Miranda de; Burbano, Rommel Rodriguez; Lima, Eleonidas Moura; Univ Fed Paraiba; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para
    To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate their association with Helicobacter pylori in gastric adenocarcinomas. Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue. the presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analyses were performed using Fisher's exact test. the hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and 36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples, it was found in 13, 7, and 67 %. the presence of H. pylori was detected in 67 % of gastric cancer samples and 67 % in normal gastric samples. the methylation of THBS1 and GPX3 was not significantly different between the types of tumors, normal sample, the presence of H. pylori, or clinicopathological variables studied (P > 0.05). However, the methylation status of the gene COX2 is significantly different between normal tissue and intestinal type gastric cancer (P = 0.02). Therefore, our results suggest that the methylation status of the gene COX2 is associated with the intestinal type of gastric cancer.
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    Association study of SNPs of genes IFNGR1 (rs137854905), GSTT1 (rs71748309), and GSTP1 (rs1695) in gastric cancer development in samples of patient in the northern and northeastern Brazil
    (Springer, 2014-05-01) Soares de Araujo, Rubistenia Miranda; Vieira de Melo, Cynthia Farias; Manes Neto, Fidelis; Silva, Juarez Nobrega da; Soares, Leonardo Ferreira; Cardoso Smith, Marilia de Arruda [UNIFESP]; Sousa, Edilson Carvalho; Rodriguez Burbano, Rommel Mario; Medeiros, Arnaldo Correia de; Lima, Eleonidas Moura; Universidade Federal da Paraíba (UFPB); Hosp Sao Marcos; State Univ Paraiba UEPB; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para
    Cancer is a multifactorial disease with a high mortality rate in Brazil and worldwide. Gastric cancer (GC) is considered the fourth type of malignancy more frequent in the population worldwide and the second leading cause of death. This work aimed to evaluate single nucleotide polymorphisms (SNPs) of IFNGR1, GSTT1, and GSTP1 genes samples in gastric cancer. We analyzed 60 samples of gastric cancer, 26 diffuse and 34 intestinal types, totaling 120 alleles for each SNP. the results were obtained by PCR and allele-specific PCR. Statistical analyzes performed using BioEstat 5.0 software, applying the Fisher's exact test and chi-square. Only the SNP gene GSTP1 (rs1695) were significantly associated with gastric cancer in the samples analyzed (chi (2) = 8.73, P < 0.05). Our results suggest that the GSTP1 gene SNP (rs1695) can be considered a risk factor associated with gastric carcinogenesis.
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    CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas
    (Springer-Verlag Italia Srl, 2017) Wisnieski, Fernanda [UNIFESP]; Calcagno, Danielle Queiroz; Leal, Mariana Ferreira [UNIFESP]; Santos, Leonardo Caires [UNIFESP]; Gigek, Carolina Oliveira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Demachki, Samia; Artigiani, Ricardo [UNIFESP]; Assumpcao, Paulo Pimentel [UNIFESP]; Lourenco, Laercio Gomes [UNIFESP]; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso [UNIFESP]
    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
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    Clinical implication of 14-3-3 epsilon expression in gastric cancer
    (Baishideng Publishing Group Inc, 2012-04-07) Leal, Mariana Ferreira [UNIFESP]; Calcagno, Danielle Queiroz [UNIFESP]; Demachki, Samia; Assumpcao, Paulo Pimentel; Chammas, Roger; Burbano, Rommel Rodriguez; Smith, Marilia de Arruda Cardoso [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para; Universidade de São Paulo (USP)
    AIM: To evaluate for the first time the protein and mRNA expression of 14-3-3 epsilon in gastric carcinogenesis.METHODS: 14-3-3 epsilon protein expression was determined by western blotting, and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples.RESULTS: Authors observed a significant reduction of 14-3-3 epsilon protein expression in gastric cancer (GC) samples compared to their matched non-neoplastic tissue, Reduced levels of 14-3-3 epsilon were also associated with diffuse-type GC and early-onset of this pathology. Our data suggest that reduced 14-3-3 epsilon may have a role in gastric carcinogenesis process.CONCLUSION: Our results reveal that the reduced 14-3-3 epsilon expression in GC and investigation of 14-3-3 epsilon interaction partners may help to elucidate the carcinogenesis process. (C) 2012 Baishideng. All rights reserved.
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    Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line
    (Associação Brasileira de Divulgação Científica, 2010-08-01) Ribeiro, Hercules Ferreira [UNIFESP]; Alcântara, D.f.a.; Matos, L.a.; Sousa, J.m.c.; Leal, Mariana Ferreira [UNIFESP]; Smith, Marilia de Arruda Cardoso [UNIFESP]; Burbano, Rommel Rodríguez [UNIFESP]; Bahia, Marcelo de Oliveira; Universidade Federal do Pará Instituto de Ciências Biológicas Laboratório de Citogenética Humana; Universidade Federal de São Paulo (UNIFESP)
    Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95%) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85%) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.
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    Deregulated expression of Nucleophosmin 1 in gastric cancer and its clinicopathological implications
    (Biomed Central Ltd, 2014-01-10) Leal, Mariana Ferreira [UNIFESP]; Mazzotti, Tatiane Katsue Furuya; Calcagno, Danielle Queiroz [UNIFESP]; Cirilo, Priscila Daniele Ramos; Martinez, Margarita Cortes; Demachki, Samia; Assumpcao, Paulo Pimentel; Chammas, Roger; Burbano, Rommel Rodriguez; Smith, Marilia de Arruda Cardoso [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); São Paulo State Canc Inst; Fed Univ Para
    Background: the process of gastric carcinogenesis still remains to be elucidated. the identification of genes related to this process may help to reduce mortality rates through early diagnosis and the development of new anticancer therapies. Nucleophosmin 1 (NPM1) acts in ribosome biogenesis, centrosome duplication, maintenance of genomic stability, and embryonic development. Recently, NPM1 has been implicated in the tumorigenesis processes. Here, we evaluated NPM1 gene and protein expression in gastric tumors and in corresponding non-neoplastic gastric samples.Methods: NPM1 protein expression was determined by Western blot in 17 pairs of gastric tumors and corresponding non-neoplastic gastric tissue. the protein immunoreactivity was observed in 12 tumor samples. mRNA expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in 22 pairs of gastric tumors and in matched non-neoplastic gastric tissue.Results: NPM1 protein expression was significantly reduced in gastric cancer samples compared to matched non-neoplastic gastric samples (P = 0.019). the protein level of NPM1 was reduced at least 1.5-fold in 35% of tumors compared to paired non-neoplastic gastric tissue. However, NPM1 immunoreactivity was detected in neoplastic and non-neoplastic cells, including in intestinal metaplastic, gastritis and inflammatory cells. NPM1 was mainly expressed in nucleus and nucleolus subcellular compartments. the staining intensity and the percentage of immunoreactive cells varied among the studied cases. the NPM1 mRNA level was reduced at least 1.5-fold in 45.5% of samples and increased in 27.3% of samples. An inverse correlation between protein and mRNA expression was detected (r = -0.509, P = 0.037). Intestinal-type gastric cancer presented higher mRNA levels than diffuse-type (P = 0.026). However, reduced NPM1 protein expression was associated with intestinal-type gastric cancer compared to matched non-neoplastic gastric samples (P = 0.018). in addition, tumors from patients with known distant metastasis presented reduced NPM1 protein levels compared to tumors from patients without distant metastasis (P < 0.001).Conclusion: Although the expression of NPM1 is heterogeneous in gastric tumors, our results suggest that NPM1 down-regulation may have a role in gastric carcinogenesis and may help in the selection of anticancer treatment strategies.
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    Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A
    (Springer, 2014-07-01) Wisnieski, Fernanda [UNIFESP]; Calcagno, Danielle Queiroz [UNIFESP]; Leal, Mariana Ferreira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Gigek, Carolina Oliveira [UNIFESP]; Santos, Leonardo Caires [UNIFESP]; Pontes, Thais Brilhante [UNIFESP]; Rasmussen, Lucas Trevizani; Payão, Spencer Luiz Marques [UNIFESP]; Assumpcao, Paulo Pimentel; Lourenço, Laércio Gomes [UNIFESP]; Demachki, Samia; Artigiani, Ricardo [UNIFESP]; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Sagrado Coracao; Fac Med Marilia; Fed Univ Para
    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.
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    DNA and histone methylation in gastric carcinogenesis
    (Baishideng Publishing Group Inc, 2013-02-28) Calcagno, Danielle Queiroz [UNIFESP]; Gigek, Carolina Oliveira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Burbano, Rommel Rodriguez; Cardoso Smith, Marilia de Arruda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para
    Epigenetic alterations contribute significantly to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches that target DNA methylation and histone modifications have emerged. A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment. Here, we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome. (C) 2013 Baishideng. All rights reserved.
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    Establishment and Partial Characterization of an Epirubicin-Resistant Gastric Cancer Cell Line with Upregulated ABCB1
    (Asian Pacific Organization Cancer Prevention, 2014-01-01) Felipe, Aledson Vitor [UNIFESP]; Moraes, Andrea Aparecida Fátima Souza [UNIFESP]; Oliveira, Juliana de [UNIFESP]; Silva, Tiago Donizetti da [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Nove de Julho
    Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. the AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.
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    The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray
    (Elsevier B.V., 2011-01-01) Gomes, Thiago Simao [UNIFESP]; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Segreto, Helena Regina Comodo [UNIFESP]; Barrezueta, Luis Fernando Mesias [UNIFESP]; Costa, Henrique de Oliveira [UNIFESP]; Lima, Flavio de Oliveira [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue microarray by immunohistochemistry. the tumor and the adjacent normal tissues were positive for FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%, for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and 8.3%, respectively. FasL and the FADD from tumor were statistically different in relation to the histological type. Cleaved caspase 8 was statistically different in relation to clinical stage (p = 0.031). the FADD from normal tissue was statistically different in relation to age (p = 0.039), sex (p = 0.055), clinical stage (p = 0.019), and Fas was different in relation to tumor size (p = 0.012). in the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and FasL and cleaved caspase 3. in the adjacent normal tissue, a correlation was observed between FasL and Fas, FasL and FADD. There was no association of another marker with sex, age, clinical stage, and survival. Our results suggest that these proteins mediate the early extrinsic apoptotic pathway in gastric cancer and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently binds to death receptor FADD signaling activation of the extrinsic apoptotic pathway. in this phase, there was inhibition of caspase 8 and, consequently, decreased apoptosis. (C) 2011 Elsevier GmbH. All rights reserved.
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    Gastrectomy and Lymphadenectomy for Gastric Cancer: is the Pancreas Safe?
    (Springer, 2008-11-01) Herbella, Fernando A. [UNIFESP]; Tineli, Ana C. [UNIFESP]; Wilson, Jorge L. [UNIFESP]; Del Grande, Jose C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction Resection of the capsule of the pancreas is part of the radical operation proposed by oriental authors for the treatment of gastric cancer. It is unclear; however, if resection of the capsule is a safe procedure or even if it is necessary. This study aims to assess in patients treated for gastric cancer the occurrence of: (a) pancreatic fistula and (b) metastasis to the pancreatic capsule.Methods We studied 80 patients (mean age 61 years, 42 males) submitted to gastrectomy with resection of the pancreatic capsule by hydrodissection. Patients with pancreatic disease, tumoral invasion of the pancreas, submitted to concomitant splenectomy, or anastomotic leakage were excluded. the tumor was located in the distal third of the stomach in 60% of the patients, in the middle third in 27%, and proximally in 12%. Total gastrectomy was performed in 27% of the cases and partial gastrectomy in 73%. in all patients, amylase activity in the drainage fluid was measured on day 2. If initial measurement was abnormal, subsequent measurements were performed in alternated days until normalization. Pancreatic fistula was defined as amylase levels greater than 600. in 25 of these patients (mean age 53 years, 16 males), the pancreatic capsule was histologically analyzed for metastasis.Results Pancreatic fistula was diagnosed in eight (10%) patients. the mean amylase level was 5,863. Normalization of amylase levels was achieved within 7 days in all patients. No patient developed clinical signs of fistula besides abnormal amylase levels in the drainage fluid, such as intra-abdominal abscesses. Pancreatic fistula was associated to younger age (p = 0.03) but not to gender (p = 0.1), tumor location (p = 0.6), and type of gastrectomy (p = 0.8). Metastasis to the pancreatic capsule was not identified.Conclusion in conclusion, resection of the pancreatic capsule must be discouraged due to subclinical pancreatic fistula in a significant number of the cases and absence of metastasis.
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    Genetic variants in gastric cancer: Risks and clinical implications
    (Academic Press Inc Elsevier Science, 2017) Gigek, Carolina Oliveira [UNIFESP]; Calcagno, Danielle Queiroz; Rasmussen, Lucas Trevizani; Santos, Leonardo Caires [UNIFESP]; Leal, Mariana Ferreira [UNIFESP]; Wisnieski, Fernanda [UNIFESP]; Burbano, Rommel Rodriguez; Lourenco, Laercio Gomes [UNIFESP]; Lopes-Filho, Gaspar Jesus [UNIFESP]; Cardoso Smith, Marilia Arruda [UNIFESP]
    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.
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    HNF4A expression as a potential diagnostic tool to discriminate primary gastric cancer from breast cancer metastasis in a Brazilian cohort
    (Biomed Central Ltd, 2017) de Freitas Campos Juca, Patricia Chaves; Correa, Stephany; Vignal, Giselle Maria; de Souza Accioly, Maria Theresa; Silva Lustosa, Suzana Angelica [UNIFESP]; Abdelhay, Eliana; Matos, Delcio [UNIFESP]
    Background: Among the many challenges in cancer diagnosis is the early distinction between metastatic cancer and a secondary tumor. This difficulty stems from the lack of markers that offer high sensitivity and specificity and can be easily applied in routine laboratory work. An example of this challenge is distinguishing gastric metastases originating from breast cancer from a gastric primary tumor. Hepatocyte nuclear factor 4 alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of this study was to analyze the expression of HNF4A, estrogen receptor (ER), progesterone receptor (PR) and gross cystic disease fluid protein 15 (GCDFP-15) in a Brazilian cohort. Methods: We performed immunohistochemistry analysis of HNF4A, ER, PR and GCDFP-15 in 126 patients divided into three cohorts: primary breast cancer, primary gastric cancer and both types of tumors. Results: Our data confirmed the sensitivity and specificity of the HNF4A marker compared to other currently used clinical markers. Conclusion: HNF4A alone could be a gold standard marker for distinguishing primary gastric cancer from breast metastasis, thus validating its potential clinical use, especially in populations with high genetic diversity.
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    How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis
    (Springer, 2012-09-01) Seevaratnam, Rajini; Cardoso, Roberta; Mcgregor, Caitlin; Lourenço, Laércio Gomes [UNIFESP]; Mahar, Alyson; Sutradhar, Rinku; Law, Calvin; Paszat, Lawrence; Coburn, Natalie; Sunnybrook Hlth Sci Ctr; Universidade Federal de São Paulo (UNIFESP); Queens Univ; Univ Toronto; Inst Clin Evaluat Sci
    Background Surgery is the fundamental curative option for gastric cancer patients. Imaging scans are routinely prescribed in an attempt to stage the disease prior to surgery. Consequently, the correlation between radiology exams and pathology is crucial for appropriate treatment planning.Methods Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009. We calculated the accuracy, overstaging rate, understaging rate, Kappa statistic, sensitivity, and specificity for abdominal ultrasound (AUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) with respect to the gold standard (pathology). We also compared the performance of CT by detector number and image type. A meta-analysis was performed.Results for pre-operative T staging MRI scans had better performance accuracy than CT and AUS; CT scanners using >= 4 detectors and multi-planar reformatted (MPR) images had higher staging performances than scanners with <4 detectors and axial images only. for pre-operative N staging PET had the lowest sensitivity, but the highest specificity among modalities; CT performance did not significantly differ by detector number or addition of MPR images. for pre-operative M staging performance did not significantly differ by modality, detector number, or MPR images.Conclusions the agreement between pre-operative TNM staging by imaging scans and post-operative staging by pathology is not perfect and may affect treatment decisions. Operator dependence and heterogeneity of data may account for the variations in staging performance. Physicians should consider this discrepancy when creating their treatment plans.
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    hTERT methylation and expression in gastric cancer
    (Taylor & Francis Ltd, 2009-01-01) Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Oliveira Silva, Patricia Natalia; Frias Lisboa, Luara Carolina; Lima, Eleonidas Moura; Calcagno, Danielle Queiroz; Assumpcao, Paulo Pimentel; Burbano, Rommel Rodriguez; Cardoso Smith, Marilia de Arruda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para
    Gastric cancer is the second most prevalent cause of cancer death worldwide. DNA methylation is a common event in gastric carcinogenesis. hTERT seems to be the rate-limiting determinant of telomerase activation, which is responsible for stability and life span. hTERT hypermethylation has been associated with telomerase expression. in the present study, we investigated the promoter methylation status and hTERT protein expression in gastric cancer and normal mucosa samples. One hundred and nine gastric cancer and 53 normal mucosa samples were investigated through methylation-specific PCR. Immunohistochemistry was analysed using peroxidase in 55 gastric cancer and 18 normal gastric mucosa samples. This is the first study evaluating hTERT methylation status in gastric carcinogenesis. We did not observe hTERT protein expression in normal gastric mucosa. Moreover, hTERT expression was observed in 80% of tumours and was associated with gastric cancer (p < 0.0001). Partial methylation was the most frequent pattern in gastric samples, even in normal mucosa. the frequency of specimens presenting hypermethylation was significantly higher in tumours than in normal mucosa samples (p = 0.0002), although the presence of hypermethylated promoter was not associated with a higher frequency of hTERT expression. A low correlation between hTERT protein expression and methylation was verified in gastric cancer samples. There was a clear difference in the frequency of hTERT expression and methylation within tumoral and non-tumoral tissues. Methylation status and telomerase expression may be useful for the diagnosis of gastric cancer and may have an impact on the anti-telomerase strategy for cancer therapy.
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    Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines
    (Baishideng Publishing Group Inc, 2016) Calcagno, Danielle Queiroz [UNIFESP]; Takeno, Sylvia Santomi [UNIFESP]; Gigek, Carolina Oliveira [UNIFESP]; Leal, Mariana Ferreira [UNIFESP]; Wisnieski, Fernanda [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Araújo, Taíssa Maíra Thomaz [UNIFESP]; Lima, Eleonidas Moura [UNIFESP]; Melaragno, Maria Isabel [UNIFESP]; Demachki, Samia [UNIFESP]; Assumpção, Paulo Pimentel [UNIFESP]; Burbano, Rommel Rodríguez [UNIFESP]; Smith, Marilia de Arruda Cardoso [UNIFESP]
    AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.