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1.
Future Sci OA ; 10(1): 2340327, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817359

RESUMO

Aim: Statins are associated with lower risk of gallstones due to anti-inflammatory effects. We assessed whether statins impact circulating inflammation among Chilean women with gallstones. Materials & methods: 200 Mapuche women were matched on statin use and age to 200 non-Mapuche women in the Chile Biliary Longitudinal Study. We analyzed 92 inflammatory biomarkers using multivariable-adjusted regression models, random forests and pathway analyses. Results: Statins were not significantly associated with any inflammation marker when women were analyzed jointly or stratified by ancestry. No significant associations were found through random forest methods and pathway analyses. Discussion: We did not find significant associations between statin use and inflammation markers in women with gallstones, suggesting that statins do not reduce inflammation once gallstones have formed.


Statins are prescribed to lower cholesterol and can also decrease the risk of gallstone formation by reducing inflammation. We assessed whether statin use reduces inflammation among women who have already developed gallstones. We analyzed 92 inflammation markers among 400 women in Chile, including 200 women with Mapuche Amerindian ancestry and 200 women of Latina/European ancestry. We found that statin use was not correlated with inflammation in this group of women overall nor by ancestry. This may mean that statin use does not reduce inflammation in women who already were diagnosed with gallstones.

2.
Gastroenterol Hepatol ; 46(6): 411-418, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35580739

RESUMO

BACKGROUND: Adenocarcinoma is preceded by chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Trefoil factor 3 (TFF3) is a peptide secreted by goblet cells, which is abundantly present in intestinal metaplasia. AIM: To evaluate the utility of serum TFF3 as a non-invasive biomarker for the diagnosis of intestinal metaplasia and gastric cancer. METHODS: Single-center, cross-sectional study of 274 patients who consecutively underwent upper gastrointestinal endoscopy with gastric biopsies (updated Sydney system). TFF3 levels were measured in serum by a commercial ELISA kit. Patients with normal histology or chronic atrophic gastritis without intestinal metaplasia comprised the control group. In addition, 14 patients with invasive gastric cancer were included as a reference group. The association between TFF3 levels and intestinal metaplasia was assessed by logistic regression. RESULTS: Patients with intestinal metaplasia (n=110) had a higher median TFF3 level as compared to controls (n=164), 13.1 vs. 11.9ng/mL, respectively (p=0.024). Multivariable logistic regression showed a no significant association between TFF3 levels and intestinal metaplasia (OR=1.20; 95%CI: 0.87-1.65; p-trend=0.273). The gastric cancer group had a median TFF3 level of 20.5ng/mL, and a significant association was found (OR=3.26; 95%CI: 1.29-8.27; p-trend=0.013). CONCLUSION: Serum levels of TFF3 do not discriminate intestinal metaplasia in this high-risk Latin American population. Nevertheless, we confirmed an association between TFF3 levels and invasive gastric cancer.


Assuntos
Gastrite Atrófica , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Fator Trefoil-3 , Estudos Transversais , Biomarcadores , Metaplasia/patologia , Mucosa Gástrica , Lesões Pré-Cancerosas/patologia
3.
Am J Epidemiol ; 190(2): 196-206, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524121

RESUMO

Gallbladder cancer (GBC) is a highly fatal cancer that can be cured through cholecystectomy if identified early. The presence of gallstones is the primary risk factor for GBC, but few people with gallstones develop GBC. A key question is what drives the development of GBC among persons with gallstones. We initiated the Chile Biliary Longitudinal Study (Chile BiLS) to address this question. From 2016 to 2019, Chile BiLS enrolled 4,726 women aged 50-74 years with ultrasound-detected gallstones from southern-central Chile, accounting for an estimated 36% of eligible women with gallstones in the study area. The median age was 59 years; 25% of the women were Amerindian (Mapuche), 60% were obese, 25% had diabetes, and 6% had cardiovascular disease. Participants will be followed for gallbladder dysplasia or cancer for 6 years. As of April 30, 2020, over 91% of those eligible completed the year 2 follow-up visit. Data being collected include epidemiologic and sociodemographic information, anthropometric measurements, blood pressure, and tooth counts. Biosamples being taken include baseline plasma, buffy coat, red blood cells, serum, blood clot from serum, and PAXgene whole blood (PreAnalytiX GmbH, Hombrechtikon, Switzerland). Complete gallbladder sampling is conducted for most participants undergoing cholecystectomy. The Chile BiLS cohort study will increase our understanding of GBC etiology and could identify potential risk stratification and early detection strategies in high-risk areas.


Assuntos
Neoplasias da Vesícula Biliar/epidemiologia , Cálculos Biliares/epidemiologia , Idoso , Pressão Sanguínea , Pesos e Medidas Corporais , Doenças Cardiovasculares/epidemiologia , Chile , Diabetes Mellitus/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/etnologia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/etnologia , Humanos , Mediadores da Inflamação/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/epidemiologia , Projetos de Pesquisa , Fatores de Risco , Fatores Socioeconômicos , Perda de Dente/epidemiologia
4.
Sci Rep ; 11(1): 3686, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574564

RESUMO

Chile has high incidence rates of gallbladder cancer globally, particularly among Amerindian women, who also have a high prevalence of gallstones. We examined differences in inflammatory biomarkers between Mapuche and non-Mapuche women from the Chile Biliary Longitudinal Study, a cohort of women with ultrasound-detected gallstones. We randomly selected 200 Mapuche women frequency matched to non-Mapuche women on age and statin use Inflammatory biomarkers were analyzed using a multiplex assay and linear regression to assess associations of a priori markers (CCL20, CXCL10, IL-6, and IL-8) with ethnicity. Novel biomarkers were analyzed using exploratory factor analysis (EFA) and sufficient dimension reduction (SDR) to identify correlated marker groups, followed by linear regression to examine their association with ethnicity. The mean values of IL-8 were higher in Mapuche than non-Mapuche women (P = 0.04), while CCL20, CXCL10, and IL-6 did not differ significantly by ethnicity. EFA revealed two marker groups associated with ethnicity (P = 0.03 and P < 0.001). SDR analysis confirmed correlation between the biomarkers and ethnicity. We found higher IL-8 levels among Mapuche than non-Mapuche women. Novel inflammatory biomarkers were correlated with ethnicity and should be studied further for their role in gallbladder disease. These findings may elucidate underlying ethnic disparities in gallstones and carcinogenesis among Amerindians.


Assuntos
Quimiocina CCL20/genética , Quimiocina CXCL10/genética , Neoplasias da Vesícula Biliar/sangue , Interleucina-6/genética , Interleucina-8/genética , Idoso , Carcinogênese/genética , Quimiocina CCL20/sangue , Quimiocina CXCL10/sangue , Chile , Etnicidade/genética , Feminino , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/metabolismo , Cálculos Biliares/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Indígenas Sul-Americanos/genética , Inflamação/diagnóstico por imagem , Inflamação/genética , Inflamação/patologia , Interleucina-6/sangue , Interleucina-8/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Ultrassonografia
5.
Virchows Arch ; 478(5): 875-884, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33411027

RESUMO

Published data on survival of T2 gallbladder carcinoma (GBC) from different countries show a wide range of 5-year survival rates from 30-> 70%. Recently, studies have demonstrated substantial variation between countries in terms of their approach to sampling gallbladders, and furthermore, that pathologists from different continents apply highly variable criteria in determining stage of invasion in this organ. These findings raised the question of whether these variations in pathologic evaluation could account for the vastly different survival rates of T2 GBC reported in the literature. In this study, survival of 316 GBCs from three countries (Chile n = 137, South Korea n = 105, USA n = 74), all adequately sampled (with a minimum of five tumor sections examined) and histopathologically verified as pT2 (after consensus examination by expert pathologists from three continents), was analyzed. Chilean patients had a significantly worse prognosis based on 5-year all-cause mortality (HR: 1.89, 95% CI: 1.27-2.83, p = 0.002) and disease-specific mortality (HR: 2.41, 95% CI: 1.51-3.84, p < 0.001), compared to their South Korean counterparts, even when controlled for age and sex. Comparing the USA to South Korea, the survival differences in all-cause mortality (HR: 1.75, 95% CI: 1.12-2.75, p = 0.015) and disease-specific mortality (HR: 1.94, 95% CI: 1.14-3.31, p = 0.015) were also pronounced. The 3-year disease-specific survival rates in South Korea, the USA, and Chile were 75%, 65%, and 55%, respectively, the 5-year disease-specific survival rates were 60%, 50%, and 50%, respectively, and the overall 5-year survival rates were 55%, 45%, and 35%, respectively. In conclusion, the survival of true T2 GBC in properly classified cases is neither as good nor as bad as previously documented in the literature and shows notable geographic differences even in well-sampled cases with consensus histopathologic criteria. Future studies should focus on other potential reasons including biologic, etiopathogenetic, management-related, populational, or healthcare practice-related factors that may influence the survival differences of T2 GBC in different regions.


Assuntos
Neoplasias da Vesícula Biliar/patologia , Estadiamento de Neoplasias , Idoso , Causas de Morte , Chile , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/terapia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , República da Coreia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
7.
Rev. méd. Chile ; 147(11): 1382-1389, nov. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1094167

RESUMO

Background Chile has one of the highest mortality rates by gastric cancer (GC) worldwide. Primary prevention of GC and detection of pre-neoplastic and early neoplastic lesions should be a national priority. Aim To assess the impact of the protocolization of endoscopy referral and the use of H. pylori stool antigen test (HPSA) in the management of dyspepsia to decrease the waiting list for endoscopy and increase the detection of gastric pre-neoplastic and early neoplastic lesions. Material and Methods We included all patients referred to the Endoscopy Unit of a regional hospital, from January 2015 to December 2017. We also included patients with known pre-neoplastic lesions and all those with first degree relatives with GC. We implemented protocols for referral of patients with dyspepsia considering the use of HPSA test, prioritizing to endoscopy those with a higher risk of GC. Results A total of 4,641 endoscopies and 2,631 HPSA tests were carried out. After the adoption of these protocols, we observed a 52% decrease in the waiting time for endoscopy. The GC detection rate in this period was 1.8 to 3.1 cases per 100 endoscopies. After the adoption of the protocols, we observed a significant increase in early GC detection rate (from none in 2015 to 13% in 2017, p = 0.03). Conclusions The protocolization of the referral for endoscopy associated with widespread use of HPSA test in the management of patients with dyspepsia, are successful strategies to decrease waiting lists for endoscopy and optimize the detection rate of pre-neoplastic lesions and early GC.


Assuntos
Humanos , Lesões Pré-Cancerosas/diagnóstico , Listas de Espera , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Dispepsia/diagnóstico , Fezes/microbiologia , Antígenos de Bactérias/análise , Lesões Pré-Cancerosas/microbiologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Sensibilidade e Especificidade , Diagnóstico Precoce , Dispepsia/microbiologia , Endoscopia/estatística & dados numéricos
8.
Rev Med Chil ; 147(11): 1382-1389, 2019 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-32186598

RESUMO

Background Chile has one of the highest mortality rates by gastric cancer (GC) worldwide. Primary prevention of GC and detection of pre-neoplastic and early neoplastic lesions should be a national priority. Aim To assess the impact of the protocolization of endoscopy referral and the use of H. pylori stool antigen test (HPSA) in the management of dyspepsia to decrease the waiting list for endoscopy and increase the detection of gastric pre-neoplastic and early neoplastic lesions. Material and Methods We included all patients referred to the Endoscopy Unit of a regional hospital, from January 2015 to December 2017. We also included patients with known pre-neoplastic lesions and all those with first degree relatives with GC. We implemented protocols for referral of patients with dyspepsia considering the use of HPSA test, prioritizing to endoscopy those with a higher risk of GC. Results A total of 4,641 endoscopies and 2,631 HPSA tests were carried out. After the adoption of these protocols, we observed a 52% decrease in the waiting time for endoscopy. The GC detection rate in this period was 1.8 to 3.1 cases per 100 endoscopies. After the adoption of the protocols, we observed a significant increase in early GC detection rate (from none in 2015 to 13% in 2017, p = 0.03). Conclusions The protocolization of the referral for endoscopy associated with widespread use of HPSA test in the management of patients with dyspepsia, are successful strategies to decrease waiting lists for endoscopy and optimize the detection rate of pre-neoplastic lesions and early GC.


Assuntos
Antígenos de Bactérias/análise , Dispepsia/diagnóstico , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Lesões Pré-Cancerosas/diagnóstico , Listas de Espera , Dispepsia/microbiologia , Diagnóstico Precoce , Endoscopia/estatística & dados numéricos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Lesões Pré-Cancerosas/microbiologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Sensibilidade e Especificidade
9.
Pathol Oncol Res ; 25(3): 1135-1142, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30467699

RESUMO

Gastric cancer (GC) is the first cancer-related cause of death in Chile; however, no plan for GC early detection has been implemented in this country. The OLGA system characterizes gastritis from stages 0 to IV according to the risk of developing GC based on H. pylori infection, atrophy, metaplasia and GC. In this study, the performance of the OLGA system was evaluated in 485 Chilean patients receiving routine endoscopy to improve the detection of early GC or preneoplastic lesions. The results showed that OLGA scores, atrophy, metaplasia and GC increased significantly with age (p < 0.001). Conversely, H. pylori infection was higher in younger groups (p < 0.05). All gastric lesions were more frequent in men than women. The majority of patients with atrophy also had metaplasia (99%, p < 0.0001). Patients with H. pylori infection had more gastric atrophy and metaplasia than those without infection (p < 0.05). Of the 485 patients, 21 (4.3%) had GC, being 2.3 times more frequent among men than women and about 2/3 (14) were in OLGA stage ≥2. In addition, 19 (90%) GC patients had atrophy and 18 (85%) had metaplasia (p < 0.001). In conclusion, the OLGA system facilitated the evaluation of GC precursor lesions particularly in patients with an OLGA score > 2 between 45 and 56 years old, because this group showed atrophy and intestinal metaplasia more frequently. Therefore, biennial endoscopic surveillance of patients with an OLGA >2 can be an important health policy in Chile for diagnosing GC in its early stages and reducing mortality over the next two decades.


Assuntos
Detecção Precoce de Câncer/métodos , Gastrite/diagnóstico , Infecções por Helicobacter/complicações , Metaplasia/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Índice de Gravidade de Doença , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Seguimentos , Gastrite/etiologia , Gastrite/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metaplasia/etiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Prognóstico , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Adulto Jovem
10.
Hum Pathol ; 82: 87-94, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30036595

RESUMO

Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking owing to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women. Three cases (2%) revealed incidental invasive carcinoma, all T2, along with high-grade dysplasia (HGD). The surface areas covered by dysplasia or cancer in these cases were 9%, 37%, and 87%. Although the first longitudinal ("diagnostic") section of the whole gallbladder captured HGD or cancer in all 3 cases, the deepest focus of invasive carcinoma was not present in this section. Fourteen additional cases (10%) had low-grade dysplasia (LGD), which was typically very focal (covering <5% of the surface) and most often occurred in the fundus. LGD was not present in the diagnostic section of 5 cases (38%) and would have been missed without additional sampling. None of the cancers or dysplasias were grossly visible. Although HGD and carcinoma are likely to be identified in "diagnostic" sections, accurate staging requires total sampling. LGD is typically very focal and would often be missed in routine practice. To identify cancer precursors, additional sampling, particularly of the fundus, may be warranted. The predominance of LGD in the fundus also provides etiologic insight, supporting the contribution of gallstones and chronic inflammation.


Assuntos
Carcinoma/patologia , Neoplasias da Vesícula Biliar/patologia , Vesícula Biliar/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Biópsia , Carcinoma/epidemiologia , Carcinoma/cirurgia , Chile/epidemiologia , Colecistectomia , Feminino , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco
11.
Pathol Res Pract ; 213(5): 476-482, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28285962

RESUMO

Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues. In addition, protein expression analysis by western blot for ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3 were performed in seven GBC cell lines (GB-d1, G415, NOZ, OCUG-1, TGBC-1, TGBC-2 and TGBC-24). A higher ERK1/2 and p-ERK1/2 expression was found in GBC tissues compared to chronic cholecystitis (CC) tissues (P<0.001). However, neither significant differences in overall survival nor significant associations with any of the clinicopathological features were found by comparing low and high expression of both ERK1/2 and p-ERK1/2. Western blot analysis of seven GBC cell lines showed that, in general, GB-d1, G415 and NOZ cells evidenced a strong expression of ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3. Therefore, ERK1/2 and p-ERK1/2 seem to be important in the development of GBC and GB-d1, G415 and NOZ cell lines may be used as experimental models for further in vitro and in vivo studies that help to decipher the role of MAPK/ERK pathway in gallbladder carcinogenesis.


Assuntos
Neoplasias da Vesícula Biliar/metabolismo , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Serial de Tecidos , Adulto Jovem
12.
Pathol Oncol Res ; 22(4): 797-805, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27156070

RESUMO

The PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism and angiogenesis. Emerging evidence has shown that deregulation of this pathway has a role promoting gastric cancer (GC). The aim was to assess the expression of genes involved in this pathway by qPCR in 23 tumor and 23 non-tumor gastric mucosa samples from advanced GC patients, and in AGS, MKN28 and MKN45 gastric cancer cell lines. Results showed a slight overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1, EIF4EBP1 and EIF4E genes, and a slightly decreased PTEN and TSC1 expression. In AGS, MKN28 and MKN45 cells a significant gene overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1 and EIF4E, and a significant repression of PTEN gene expression were observed. Immunoblotting showed that PI3K-ß, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E and p-eIF4E proteins were present in cell lines at different levels, confirming activation of this pathway in vitro. This is the first time this extensive panel of 9 genes within PI3K/AKT/mTOR pathway has been studied in GC to clarify the biological role of this pathway in GC and develop new strategies for this malignancy.


Assuntos
Expressão Gênica/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , Humanos , PTEN Fosfo-Hidrolase/genética , Fosfoproteínas/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Transdução de Sinais/genética
13.
Cell Oncol (Dordr) ; 39(1): 23-33, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26458815

RESUMO

BACKGROUND: Gastric cancer (GC) is a deadly malignancy worldwide. In the past, it has been shown that cellular signaling pathway alterations play a crucial role in the development of GC. In particular, deregulation of the PI3K/AKT/mTOR pathway seems to affect multiple GC functions including growth, proliferation, metabolism, motility and angiogenesis. Targeting alterations in this pathway by microRNAs (miRNAs) represents a potential therapeutic strategy, especially in inhibitor-resistant tumors. The objective of this study was to evaluate the expression of 3 pre-selected miRNAs, miR-101-2, miR-125b-2 and miR-451a, in a series of primary GC tissues and matched non-GC tissues and in several GC-derived cell lines, and to subsequently evaluate the functional role of these miRNAs. METHODS: Twenty-five primary GC samples, 25 matched non-GC samples and 3 GC-derived cell lines, i.e., AGS, MKN28 and MKN45, were included in this study. miRNA and target gene expression levels were assessed by quantitative RT-PCR and western blotting, respectively. Subsequently, cell viability, clone formation, cell death, migration and invasion assays were performed on AGS cells. RESULTS: miR-101-2, miR-125b-2 and miR-451a were found to be down-regulated in the primary GC tissues and the GC-derived cell lines tested. MiRNA mimic transfections significantly reduced cell viability and colony formation, increased cell death and reduced cell migration and invasion in AGS cells. We also found that exogenous expression of miR-101-2, miR-125b-2 and miR-451a decreased the expression of their putative targets MTOR, PIK3CB and TSC1, respectively. CONCLUSIONS: Our expression analyses and in vitro functional assays suggest that miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in primary GCs as well as in GC-derived AGS cells.


Assuntos
Genes Supressores de Tumor , MicroRNAs/metabolismo , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Sequência de Bases , Morte Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Sobrevivência Celular/genética , Classe I de Fosfatidilinositol 3-Quinases , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Modelos Biológicos , Dados de Sequência Molecular , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/metabolismo , Transfecção , Proteína 1 do Complexo Esclerose Tuberosa , Ensaio Tumoral de Célula-Tronco , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
14.
Rev. méd. Chile ; 143(12): 1533-1538, dic. 2015. graf, tab
Artigo em Espanhol | LILACS | ID: lil-774438

RESUMO

Background: To validate the BIRADS in mammography, the calculation of its predictive value in each center is required, as recommended by the American College of Radiology. Aim: To determine the predictive value of the BIRADS system in our center. Material and Methods: All ultrasound guided needle percutaneous biopsies, performed at our center between 2006 and 2010 were reviewed. Predictive value, sensitivity, specificity and diagnostic accuracy of BIRADS were calculated, with a confidence interval of 95%. Results: Of 1,313 biopsies available, 1,058 met the inclusion criteria. Fifty eight percent of biopsies were performed to women with mammographies classified as BIRADS 4 or 5. The presence of cancer in mammographies classified as BIRADS 0 was 4%. The prevalence of cancer for mammographies BIRADS 1, 2, 3, 4 and 5 were 0, 3, 2.7, 17.7 and 72.4% respectively. The positive and negative predictive values of BIRADS classification were 55 and 92 % respectively. Conclusions: In our institution BIRADS classification 4 and 5 has a high positive predictive value for detecting cancer as in developed countries.


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias da Mama/patologia , Neoplasias da Mama , Biópsia por Agulha , Estudos Transversais , Biópsia Guiada por Imagem , Mamografia , Valor Preditivo dos Testes , Sensibilidade e Especificidade
15.
Rev Med Chil ; 143(12): 1533-8, 2015 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-26928614

RESUMO

BACKGROUND: To validate the BIRADS in mammography, the calculation of its predictive value in each center is required, as recommended by the American College of Radiology. AIM: To determine the predictive value of the BIRADS system in our center. MATERIAL AND METHODS: All ultrasound guided needle percutaneous biopsies, performed at our center between 2006 and 2010 were reviewed. Predictive value, sensitivity, specificity and diagnostic accuracy of BIRADS were calculated, with a confidence interval of 95%. RESULTS: Of 1,313 biopsies available, 1,058 met the inclusion criteria. Fifty eight percent of biopsies were performed to women with mammographies classified as BIRADS 4 or 5. The presence of cancer in mammographies classified as BIRADS 0 was 4%. The prevalence of cancer for mammographies BIRADS 1, 2, 3, 4 and 5 were 0, 3, 2.7, 17.7 and 72.4% respectively. The positive and negative predictive values of BIRADS classification were 55 and 92 % respectively. CONCLUSIONS: In our institution BIRADS classification 4 and 5 has a high positive predictive value for detecting cancer as in developed countries.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Estudos Transversais , Feminino , Humanos , Biópsia Guiada por Imagem , Mamografia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
Rev. chil. tecnol. méd ; 32(1): 1671-1677, jul. 2012. ilus
Artigo em Espanhol | LILACS | ID: lil-680422

RESUMO

El cáncer de mama es una de las enfermedades importantes en la mujer y se le dedican grandes esfuerzos científicos y económicos existiendo el propósito de la búsqueda constante de vías de mejor precocidad en el diagnóstico y con ello, mejoramiento del pronóstico. En los rangos etarios de mayor riesgo de presentar esta patología se han descrito varios factores desencadenantes como son los receptores de estrógenos (RE), progesterona (RP) y de la proteína c-erbB-2. Se utilizaron biopsias de cáncer mamario ductal y lobulillar de diagnóstico de rutina, sometidas a reacciones inmunohisto químicas con anticuerpos anti RE, anti RP y específicamente para anti c-erbB-2. El revelado fue a través de kit comercial HRP con AEC y DAB. Las imágenes fueron capturadas con microscopio Olympus CX31, cámara fotográfica digital incorporada y software Micrometrics SE Premium 2011. Los resultados permiten observar reacción positiva en color rojo intenso en las muestras reveladas con AEC y pardo cuando se utilizó DAB, en las células que expresan la marcación y que se distribuyen indistintamente en el sitio del tejido afectado por la patología. Estas técnicas son de uso clínico protocolizado en el diagnóstico de cáncer de mama, por lo cual su estandarización y visualización son de extrema importancia para el laboratorio de histopatología integrado a unidades de patologia mamaria.


Breast cancer is one of the major diseases in women and devote great economic and scientific eforts. The intention of continuing to find ways of better and early diagnosis, and improved prognosis. In the age ranges of increased risk for this disease have been described several triggers such as receptors: estrogen (ER), progesterone (PR), and protein c-erbB-2. Biopses were used ductal and lobular breast cancer diagnostic routine, subjected to immunohistochemical antibodies to ER, PR and specifically anti c-erbB-2. The development was through HRP AEC and DAB commercial kit. Images were captured with Olympus CX31 microscope and digital camera and software built Micrometrics SE Premium 2011. The results allow observed positive reaction in red color in the samples developed with AEC and brown when used DAB in cells expressing the bearing and which are distributed equally at the site of pathology tissue affected. These techniques are protocolized by clinical use in diagnosing breast cancer, so its standardization and visualization are of extreme importance to the histopathology laboratory of integrated units of breast disease.


Assuntos
Humanos , Feminino , Carcinoma Lobular/metabolismo , Neoplasias da Mama/metabolismo , Receptores de Estrogênio , /metabolismo , Carcinoma Lobular/patologia , Imuno-Histoquímica , Neoplasias da Mama/patologia , Receptores de Progesterona
17.
Rev Med Chil ; 139(4): 432-8, 2011 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-21879180

RESUMO

BACKGROUND: The absence of lymph node involvement (N0) in gastric cancer is associated with a better survival. However some N0 gastric tumors still have a bad prognosis. AIM: To study demographic and morphological variables associated with prognosis in N0 gastric carcinoma. MATERIAL AND METHODS: Review of pathological records of a regional general hospital, identifying patients with a N0 gastric cancer surgically excised between 1986 and 2003. RESULTS: In the study period, 459 gastrectomies were performed for gastric cancer and in 32%, the tumor was devoid of lymph node involvement. These later patients were followed for a median of 64 months with a 71% five years actuarial survival. Bivariate analysis identified age, tumor size, gastric wall infiltration, pathological type according to Lauren and Ming, lymphovascular involvement, number of lymph nodes excised and TNM stage as prognostic values Multivariate analysis disclosed the level of gastric wall infiltration, the presence of a poorly differentiated tumor, lymphatic vascular involvement, number of excise lymph nodes and tumor size as independent prognostic factors. CONCLUSIONS: N0 gastric tumors are found in 32% of gastrectomies for gastric cancer and have a 71% five years actuarial survival. Gastric wall infiltration, pathological degree of differentiation tumor size and lymphovascular involvement are independent prognostic factors.


Assuntos
Neoplasias Gástricas/patologia , Estudos de Coortes , Feminino , Gastrectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/secundário , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
18.
Rev Med Chil ; 139(2): 171-6, 2011 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-21773653

RESUMO

BACKGROUND: Gleason pathological score in prostate cancer is an important prognostic indicator. However, the concordance between the score of trans rectal needle biopsies and the final score of the surgical piece may be variable. AIM: To analyze the concordance between Gleason scores of trans rectal prostate biopsies and those of the surgical piece obtained after prostatectomy. MATERIAL AND METHODS: Retrospective analysis of 168 pathological records of radical prostatectomies, performed between 1993 and 2009. All these patients had also a trans rectal biopsy performed previously. Patients with less than 12 tissue cylinders obtained during the trans rectal biopsy or incomplete data were not included in this analysis. RESULTS: Sixty eight percent of trans rectal biopsies had Gleason scores that were concordant with those of the surgical piece. The score was higher or lower in 27 and 10% of biopsies, respectively. CONCLUSIONS: Gleason scores of trans rectal biopsies and those of the surgical piece were concordant in 68% of cases in this series of pathological records.


Assuntos
Adenocarcinoma/patologia , Carcinoma/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma/cirurgia , Humanos , Masculino , Gradação de Tumores , Prognóstico , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/cirurgia
19.
Rev. chil. tecnol. méd ; 31(1): 1607-1612, jul. 2011. ilus
Artigo em Espanhol | LILACS | ID: lil-609919

RESUMO

En Chile, el cáncer es la segunda causa de muerte después de las enfermedades cardiovasculares. Los principales cánceres asociados a muerte en mujeres fueron mama, estómago, vesícula biliar, broncopulmonar y cérvico uterino. Alteraciones de las E-cadherinas han sido relacionadas con varios tipos de cáncer, ya que uno de los principales eventos involucrados con su disfunción es el gatillar la invasión y metástasis del tumor. La inactivación del gen CDH1 ha sido demostrada en el cáncer gástrico difuso y el cáncer de mama lobulillar. Asimismo, la inactivación del gen FHIT parece estar asociado con la progresión a neoplasias más agresivas. Se realizaron determinaciones inmunohistoquímicas (IHQ) en fibroadenomas mamarios y cánceres previamente diagnosticados por RE, RPg y Her2, mostrando positividad en todos los casos. La detección (IHQ) de la expresión de FHIT y E-cadherina en tejidos con patologías benignas y malignizados, puede aportar una importante información diagnóstica y pronóstica en el cáncer de mama.


In Chile, cancer is the second leading cause of death after cardiovascular diseases. The major death-related cancers in women were breast, stomach, gallbladder, lung and cervical cancer. Alterations of E-cadherin have been linked to various cancers, as one of the main events involved in its dysfunction is the trigger of tumor invasion and metastasis. CDH1 gene inactivation has been demonstrated in diffuse gastric cancer and lobular breast cancer. Furthermore, inactivation of the FHIT gene to be associated with progression to more aggressive tumors. Immunohistochemistry (IHC) determinations were performed in fibroadenomas and breast cancers previously diagnosed by ER, PgR and Her2, showing positivity in all cases. Immunohistochemical detection of FHIT and E-cadherin expression in tissues with benign disease and malignant, may provide an important diagnostic and prognostic information in breast cancer.


Assuntos
Humanos , Feminino , Hidrolases Anidrido Ácido/metabolismo , Caderinas/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/metabolismo , Fibroadenoma/diagnóstico , Fibroadenoma/metabolismo , Imuno-Histoquímica
20.
Rev Med Chil ; 138(12): 1535-8, 2010 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-21526303

RESUMO

Cryptococcosis is an invasive mycotic infection caused by Cryptococcus neoformans, an encapsulated, yeast-like fungus. It is considered an opportunist infection, since it mainly affects immunocompromised subjects. However there are isolated reports of the infection in immunocompetent subjects. Cryptococcal infection of intra-abdominal organs or tissues is extremely rare. We report a 21-year-old HIV positive male that, during the treatment of a meningeal cryptococcosis, presented a clinical picture of an acute abdomen suggesting acute appendicitis. The patient was operated, finding enlarged mesenteric lymph nodes forming conglomerates and a macroscopically normal appendix. The conglomerated lymph nodes and the appendix were excised. The pathological study of the surgical piece revealed an intra abdominal cryptococcal lymphadenitis and a normal appendix.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Abdome Agudo/microbiologia , Apendicite/patologia , Criptococose/patologia , Linfadenite Mesentérica/patologia , Apendicite/microbiologia , Humanos , Masculino , Adulto Jovem
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