ABSTRACT
RATIONALE: This study used proteomics-based data-independent acquisition (DIA) technology with the aim of screening for differential expression proteins in type I gastric neuroendocrine neoplasm (g-NEN). METHODS: Differential expression proteins in type I g-NEN and peritumoral tissues were screened using DIA with liquid chromatography/tandem mass spectrometry (DIA-LC/MS/MS). The identified proteins were then functionally analysed using bioinformatics methods. We selected the three most highly expressed proteins, combined with patients' clinical data, for prognostic analysis. RESULTS: Compared with peritumoral tissues, 224 proteins were up-regulated, and 70 were down-regulated. The most significantly enriched biological processes and pathways were vacuolar proton-transporting V-type ATPase complex assembly and metabolism-related pathways. PCSK1, FBXO2, ACSL1, IRS2, and PTPRZ1 expression was markedly up-regulated in type I g-NENs. High IRS2 expression significantly correlated with a shorter time to recurrence. CONCLUSIONS: Our study provides a comprehensive proteomic signature based on DIA-LC/MS/MS and highlights high IRS2 expression as a potential prognostic marker for type I gNENs.
Subject(s)
Biomarkers, Tumor , Neuroendocrine Tumors , Proteomics , Stomach Neoplasms , Tandem Mass Spectrometry , Humans , Stomach Neoplasms/metabolism , Stomach Neoplasms/chemistry , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Tandem Mass Spectrometry/methods , Male , Female , Chromatography, Liquid/methods , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/chemistry , Prognosis , Proteomics/methods , Middle Aged , Adult , Aged , Proteome/analysis , Proteome/metabolism , Liquid Chromatography-Mass SpectrometryABSTRACT
ABSTRACT Background : It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. Aim : To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. Method : The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3β, axin, CK1, ubiquitin, cyclin D1 and c-myc. Results : There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. Conclusion: The canonical WNT pathway is involved in gastric carcinoma.
RESUMO Racional : Acredita-se que a via Wnt é uma das mais importantes da sinalização envolvidas na carcinogênese gástrica. Objetivos : Analisar a expressão das proteínas das vias Wnt canônicas e não-canônicas no carcinoma gástrico e relacionar sua expressão com as variáveisclinicopatológicas. Método : Foram coletadas 72 amostras de carcinoma gástrico, e áreas representativas do tumor foram selecionadas para o Tissue Microarray. Imunoistoquímica foi realizada para avaliar a expressão de Wnt-5a, FZD5, GSK3β, axina, CK1, ubiquitina, ciclina D1 e c-myc. Resultados : Houve diferenças significativas para a expressão de ubiquitina no citoplasma e núcleo para tumores moderadamente e bem diferenciados (p=0,03) e para aqueles do tipo intestinal da classificação de Lauren (p=0,03). A expressão negativa da proteína c-myc no citoplasma foi relacionada aos tumores intestinais de Lauren (p=0,028). A expressão positiva de CK1 no citoplasma das células neoplásicas foi relacionada a tumores com margens cirúrgicas livre de envolvimento neoplásico (p=0,03). A expressão positiva da proteína ciclina D1 foi maior nos tumores dos homens (p=0,03). Não houve relação da expressão positiva ou negativa das proteínas Wnt-5a e FZD5 no citoplasma ou núcleo com quaisquer variáveis clinicopatológicas. O mesmo foi observado para GSK3β e Axin. Conclusões : A relação da expressão das proteínas da via canônica com as variáveis epidemiológicas e tumorais sugere sua participação na carcinogênese gástrica. Por outro lado, a ausência da relação das expressões das proteínas da via não-canônica sugere sua não participação na carcinogênese gástrica.
Subject(s)
Humans , Male , Female , Stomach Neoplasms/chemistry , Carcinoma/chemistry , Wnt Signaling Pathway , Neoplasm Proteins/analysis , Reference Values , Stomach Neoplasms/pathology , Immunohistochemistry , Carcinoma/pathology , Proto-Oncogene Proteins c-myc/analysis , Cyclin D1/analysis , Ubiquitin/analysis , Casein Kinase I/analysis , Frizzled Receptors/analysis , Axin Protein/analysis , Carcinogenesis , Glycogen Synthase Kinase 3 beta/analysis , Wnt-5a Protein/analysis , Neoplasm StagingABSTRACT
El coriocarcinoma gástrico primario (CGP) es un tumor extremadamente raro, altamente invasivo y de rápida diseminación hematógena. Presentamos el caso de una paciente de 57 años que inicia con cuadro de hematemesis y, progresivamente, se le suman episodios de melena, baja de peso y epigastralgia. Es derivada al Instituto Nacional de Enfermedades Neoplásicas en donde se le realizan gastroscopía y biopsia. Así, el análisis histológico reportó patrón sugestivo para CGP; el cual se confirmó al realizarle a la paciente los estudios por imágenes necesarios y llevar a cabo el análisis inmunohistoquímico para gonadotrofina coriónica humana y alfa feto proteína. Posteriormente, a la paciente se le realiza una gastrectomía radical D2 con preservación esplénica y de cola de páncreas. Lamentablemente, su evolución no fue favorable y fallece por la progresión de la enfermedad.
Primary gastric choriocarcinoma (PGC) is an extremely rare and highly invasive tumor with rapid hematogenous spread. We present the case of a 57-year-old female patient who started with hematemesis and progressive episodes of melena, weight loss and epigastralgia. It is derived from the National Institute of Neoplastic Diseases where gastroscopy and biopsy are performed. Histological analysis reported pattern suggestive of PGC; that was confirmed by immunohistochemical analysis for human chorionic gonadotrophin and fetal alpha protein. Subsequently, the patient underwent a radical D2 gastrectomy with splenic preservation and tail of the pancreas preservation. Unfortunately, her evolution was not favorable and died due to the progression of the disease.
Subject(s)
Female , Humans , Middle Aged , Stomach Neoplasms/pathology , Choriocarcinoma/pathology , Polyps/diagnosis , Polyps/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/diagnosis , Stomach Neoplasms/chemistry , Stomach Ulcer/etiology , Weight Loss , Adenocarcinoma/diagnosis , alpha-Fetoproteins/analysis , Choriocarcinoma/surgery , Choriocarcinoma/diagnosis , Choriocarcinoma/chemistry , Biomarkers, Tumor/analysis , Hematemesis/etiology , Melena/etiology , Gastroscopy , Fatal Outcome , Diagnosis, Differential , Gastrectomy/methods , Chorionic Gonadotropin/analysisABSTRACT
Este artículo analiza las principales campañas promovidas por agencias internacionales y organismos nacionales de salud dirigidas a erradicar enfermedad infecciosas en el ámbito rural latinoamericano de los años 1940 y 1950. Las dimensiones políticas del periodo han sido estudiadas pero todavía se ha prestado poca atención a sus dimensiones sanitarias. Este trabajo propone el concepto de "cultura de la sobrevivencia" para explicar los problemas de la salud pública oficial de Estados con políticas sociales limitadas que no permitieron el ejercicio de la ciudadanía. La salud pública, como parte de esta cultura de la sobrevivencia, buscaba ser una solución temporal sin enfrentarse a los problemas sociales que originaban las infecciones y dejó un legado en la salud pública de la región.
This article analyzes the main campaigns run by international agencies and national health bodies to eradicate infectious diseases in rural Latin America in the 1940s and 1950s. The political dimensions of the period have been studied but there has been little attention as yet to the health dimensions. This article proposes the concept of a "culture of survival" to explain the official public health problems of states with limited social policies that did not allow the exercise of citizenship. Public health, as part of this culture of survival, sought a temporary solution without confronting the social problems that led to infections and left a public health legacy in the region.
Subject(s)
Humans , Male , Aged , Adenocarcinoma/genetics , DNA Mutational Analysis , Duodenal Neoplasms/genetics , Gene Expression Profiling , Gastrointestinal Neoplasms/genetics , Mutation , MicroRNAs/genetics , Neoplasms, Multiple Primary , Proto-Oncogene Proteins c-kit/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Stomach Neoplasms/genetics , Biomarkers, Tumor/genetics , Adenocarcinoma/chemistry , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Duodenal Neoplasms/chemistry , Duodenal Neoplasms/pathology , Duodenal Neoplasms/surgery , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Gastrointestinal Neoplasms/chemistry , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/surgery , Immunohistochemistry , Neoplasm Staging , Phenotype , Predictive Value of Tests , Prognosis , Stomach Neoplasms/chemistry , Stomach Neoplasms/pathology , Stomach Neoplasms/surgeryABSTRACT
Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Gastric Mucosa/chemistry , Helicobacter pylori , Precancerous Conditions/chemistry , Receptors, Immunologic/analysis , Stomach Neoplasms/chemistry , Biomarkers/analysis , Biopsy , Cyclin D1/analysis , Gastric Mucosa/microbiology , /analysis , Helicobacter Infections/metabolism , Immunohistochemistry , Mucin-1/analysis , beta Catenin/analysisABSTRACT
PURPOSE: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. METHODS: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. RESULTS: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. CONCLUSIONS: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal).
OBJETIVO: Os marcadores tumorais são substâncias encontradas no sangue e outros fluidos biológicos em pacientes com doenças oncológicas. São produzidos pelo próprio tumor ou ser resultado da interação entre o tumor e o organismo. Podem ser usados no seguimento de pacientes com câncer para identificar recidiva tumoral. Os níveis pré-tratamento têm valor prognóstico e podem sinalizar persistência de doença residual mínima após cirurgia radical.. MÉTODOS: Foram operados 52 pacientes com tumores do trato gastroinstestinal superior (32 com câncer do estômago e 20 do pâncreas). Amostras sanguineas foram colhidas no préoperatório e amostras peritoneais imediatamente após a laparotomia, antes de qualquer manipulação do tumor. Todas as amostras foram examinadas bioquímicamente e os resultados foram comparados entre si e em face ao progresso da doença. RESULTADOS: Os pacientes com câncer de estômago nos estadios I e II apresentaram níveis sanguineos mais elevados de ambos os marcadores tumorais do que no peritônio, mas a maioria dos valores encontrava-se dentro dos limites fisiológicos. Já nos estadios III e IV os níveis dos marcadores tumorais foram mais elevados no peritônio do que no sangue. O número de exames positivos aumentou de acordo com o estadio da doença. Nos estádios avançados, observou-se elevada variabilidade nos níveis de ambos os marcadores analisados no peritônio. Os doentes com carcinoma de pâncreas tiveram níveis de CEA semelhantes no sangue e no peritônio, mas os níveis peritoneais foram ligeiramente mais elevados nos estadios III e IV. Ca 19 - 9 foi muito mais sensível para o câncer do pâncreas. A porcentagem de exames positivos foi mais elevada no sangue, mas o níveis do Ca19-9 foram mais elevados no peritônio.A porcentagem de exames positivos também teve correlação com o estadio da doença. CONCLUSÕES: Os níveis de marcadores tumorais no sangue podem indicar inoperabilidade do tumor. No peritônio podem indicar o tipo de ressecção, especialmente nos doentes com câncer gástrico, e o risco de recidiva peritoneal precoce. A diferença entre os níveis no peritônio e sangue podem sinalizar a via de disseminação, hematogênica ou intra-peritoneal.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , /analysis , Carcinoembryonic Antigen/analysis , Pancreatic Neoplasms/chemistry , Peritoneal Neoplasms/chemistry , Stomach Neoplasms/chemistry , /blood , Carcinoembryonic Antigen/blood , Neoplasm Recurrence, Local , Neoplasm Staging , Peritoneal Cavity , Peritoneal Lavage , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Peritoneal Neoplasms/blood , Peritoneal Neoplasms/secondary , Stomach Neoplasms/bloodABSTRACT
Objectives: To determine the prevalence of Her-2/Neu-cerbb-2 in the gastric mucosa of patients with gastric adenocarcinoma in a brazilian patient group. Methods: The immunohistochemical expression of Her-2/Neu was studied in 37 formalin-fixed paraffinembedded tissue sections. Results: The immunohistochemical reaction produced by the anti-HER- 2/Neu antibody was positive in two cases (5.4%). Conclusion: The low prevalence of Her-2/Neu observed in these southern brazilian cases is probably due to the great number of poorly differentiated cancers in this serie.
Objetivo: Determinar a prevalência do Her-2/Neu-CerbB-2 na mucosa de pacientes com adenocarcinoma de estômago em um grupo de doentes brasileiros. Métodos: A expressão imunoistoquímica do Her-2/Neu foi estudada em 37 amostras de tecidosfixados em formalina e embebidos em parafina. Resultados: A reação imunoistoquímica produzida pelo anticorpo HER-2/Neu foi positiva em dois pacientes (5.4%). Conclusão: A baixa prevalência Her-2/Neu observada neste grupo de pacientes é provavelmente devida ao grande número de tumores pouco diferenciados encontrados nesta série.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma/genetics , /biosynthesis , /genetics , Stomach Neoplasms/genetics , Adenocarcinoma/chemistry , Immunohistochemistry , Retrospective Studies , /analysis , Stomach Neoplasms/chemistryABSTRACT
The concomitant presence of a primary gastric adenocarcinoma and a gastrointestinal stromal tumor in the stomach is uncommon. We report a 68-year-old male with an advanced gastric adenocarcinoma. During gastrectomy, a nodular intramural lesion was found. The pathological study, revealed a gastrointestinal stromal tumor, positive form CD117. After six months of follow up, there is no evidence of recurrence of either tumor.
Subject(s)
Aged , Humans , Male , Adenocarcinoma/pathology , Gastrointestinal Stromal Tumors/pathology , Neoplasms, Multiple Primary/pathology , Stomach Neoplasms/pathology , Gastrointestinal Stromal Tumors/chemistry , Neoplasms, Multiple Primary/chemistry , Proto-Oncogene Proteins c-kit/analysis , Stomach Neoplasms/chemistryABSTRACT
BACKGROUND: Early peritoneal recurrence of gastric carcinoma following curative resection remains a great challenge in the treatment and prevention of this disease. AIM: To analyze the relationship between levels of tumor markers, carcinoembryonic antigen (CEA) and CA 19-9 in the sera and peritoneal washing, and anatomopathological aspects of the gastric carcinoma. METHODS: Of the 46 patients in the study, 29 (63.0 percent) were males and 17 (37.0 percent) females. Mean age was 63.6 ± 11.7 years (31 to 91 years). Peripheral venous blood samples were collected from the upper limb vein from both patient groups after anesthetic induction, in order to determine serum levels of CEA and CA 19-9. After the end of the procedure, 50 mL of physiologic solution was introduced into the bottom of the Douglas sack and a portion aspirated to determine CEA and CA 19-9 levels in the peritoneal washing. Levels of CEA and CA 19-9 in the sera and peritoneal washing were compared to the following variables: lesion diameter ≤4 cm or >4 cm, lymph node involvement, angiolymphatic invasion, depth of invasion into gastric wall, and initial or late stage. RESULTS: Sera CEA levels were significantly higher in patients with lesions >5 cm. CEA levels in the sera and peritoneal washing were significantly greater in patients with signet ring cell gastric carcinoma. In addition, levels of CEA in peripheral blood and peritoneal washing showed significant association with the degree of carcinoma penetration into the gastric wall, while sera CEA was significantly higher in patients at more advanced stages. There was no significant difference between sera and peritoneal CEA values regarding grade of differentiation. Patients with gastric lesions measuring > 5cm and more differentiated lesions had significantly higher sera CA 19-9 values. In patients with lymph nodes invasion by gastric carcinoma, CA 19-9 levels in peritoneal washing were significantly higher than in ...
RACIONAL: A recidiva peritonial precoce do carcinoma gástrico operado com intenção curativa continua sendo um grande desafio do seu tratamento e prevenção. OBJETIVO: Analisar a relação entre os níveis do marcador tumoral antígeno carcinoembriônico (CEA) e CA 19-9 no sangue e no lavado peritonial e os aspectos anatomopatológicos do carcinoma gástrico. MÉTODO: Dos 46 doentes do estudo, 29 (63,0 por cento) eram do sexo masculino e 17 (37,0 por cento) do feminino. A média de idade foi de 63,6 ± 11,7 anos (31 a 91 anos). Após a indução anestésica, o sangue venoso periférico foi coletado de veia do membro superior para a determinação do nível sérico do CEA e CA 19-9. Após o término do procedimento operatório foram derramados 50 mL de solução fisiológica no fundo de saco de Douglas, aspirada alíquota que foi encaminhada para a determinação do nível no lavado peritonial do CEA e CA 19-9. O nível do CEA e do CA 19-9 sérico e no lavado peritonial foram relacionados às seguintes variáveis: diâmetro da lesão ≤4 cm ou >4 cm, comprometimento linfonodal, invasão angiolifática, profundidade de invasão na parede gástrica e estádio inicial ou tardio. RESULTADOS: Em relação ao CEA, o nível sérico foi significantemente maior nos doentes com o diâmetro da lesão >5 cm. O nível de CEA sérico e no lavado peritonial foi significantemente maior nos doentes com carcinoma gástrico com células em anel de sinete. O nível de CEA no sangue periférico e no lavado peritonial mostrou relação significante com o nível de penetração do carcinoma na parede gástrica, e o CEA sérico foi significantemente mais elevado nos doentes com estádio mais avançados. Não houve diferença significante entre os valores do CEA sérico e peritonial nos carcinomas mais diferenciados em relação aos menos diferenciados. No tocante ao CA 19-9, os enfermos com lesões gástricas com diâmetro >5 cm e mais diferenciadas exibiram valores séricos de CA 19-9 significantemente maiores. Nos doentes ...