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1.
Int. j. morphol ; 42(1): 111-116, feb. 2024. ilus, tab, mapas
Article in Spanish | LILACS | ID: biblio-1528817

ABSTRACT

El cáncer gástrico (CG), es la primera causa de muerte por cáncer, en hombres, y la tercera en mujeres, en Chile. No obstante ello, el CG bifocal (CGB) es una situación poco frecuente. El objetivo de este manuscrito fue reportar un caso de CGB, con linfonodos negativos en un paciente con cirrosis hepática, que fue intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Caso clínico: Hombre de 74 años diabético, hipertenso, insuficiente cardíaco y cirrótico; portador de CGB (subcardial y antro-pilórico), diagnosticado por endoscopia y con confirmación histológica de ambas lesiones; operado en Clínica RedSalud Mayor Temuco en septiembre de 2023. En el intraoperatorio se verificó además la coexistencia de una lesión de aspecto metastásico en el segmento III del hígado, y adhesión de la región antro-pilórica a la vesícula biliar. Se realizó gastrectomía total, linfadenectomía D2, esófago-yeyuno anastomosis término-lateral, resección segmentaria hepática (segmento III) y colecistectomía. El paciente permaneció 6 días en la UCI debido a que desarrolló insuficiencia hepática (encefalopatía leve y ascitis). Se alimentó vía enteral por sonda naso-yeyunal. Posteriormente inició alimentación oral progresiva, la que fue bien tolerada. Completó 11 días de hospitalización en servicio médico-quirúrgico, donde mejoró actividad neurológica, hasta su alta domiciliaria. Actualmente, lleva dos meses desde su operación, se encuentra en buenas condiciones generales, y el Comité Oncológico decidió no dar quimioterapia adyuvante. Se presenta un caso inusual de CG de tipo bifocal, respecto de lo cual hay escasa información disponible. Se logró realizar cirugía con intención curativa en un paciente de alto riesgo, con un resultado exitoso.


SUMMARY: Gastric cancer (GC) is the first cause of death from cancer in men, and the third one in women, in Chile. However, a bifocal GC (BGC) is uncommon. The aim of this study was to report a case of CGB, with negative-lymph nodes in a patient with liver cirrhosis, who underwent surgery; and review the existing evidence regarding its morphological, therapeutic and prognostic characteristics. Clinical case: A 74-year-old male patient with a medical history of diabetes, hypertension, congestive heart failure, and cirrhosis underwent surgical intervention for GC located in subcardial and antro- pyloric regions. The diagnosis was established via endoscopy and confirmed histologically. Surgery was performed at the RedSalud Mayor Temuco Clinic in September 2023. During intraoperative assessment, the coexistence of a lesion with metastatic-like characteristics in segment III of the liver was also verified, along with adhesions between the antro-pyloric region and the gallbladder. Surgical approach encompassed total gastrectomy, D2 lymphadenectomy, esophago-jejunostomy, segmental hepatic resection, and cholecystectomy. Subsequently, the patient required a six-day stay in ICU due to the development of hepatic insufficiency, characterized by mild encephalopathy and ascites. Enteral nutrition was administered via a naso-jejunal tube, followed by a gradual transition to oral feeding, which was well-tolerated. The patient completed an 11-day hospitalization period in the medical-surgical ward, during which his neurological function improved significantly, resulting in his discharge. At present, 2 months post-surgery, the patient remains in satisfactory general health, and the Oncology Committee decided not to proceed with adjuvant chemotherapy. This case represents a rare instance of bifocal GC, for which there is limited available literature. Surgical intervention with curative intent was successfully carried out in a high-risk patient, yielding a positive outcome.


Subject(s)
Humans , Male , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Neoplasms, Multiple Primary , Gastrectomy
2.
Int. j. morphol ; 42(1): 173-184, feb. 2024.
Article in English | LILACS | ID: biblio-1528836

ABSTRACT

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.


El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.


Subject(s)
Humans , Stomach Neoplasms/metabolism , Adenocarcinoma/metabolism , Chloride Channels/metabolism , Prognosis , Stomach Neoplasms/immunology , Immunohistochemistry , Adenocarcinoma/immunology , Biomarkers, Tumor , Survival Analysis , Chloride Channels/genetics , Chloride Channels/immunology , Computational Biology , Mutation
3.
Rev. colomb. cir ; 39(1): 94-99, 20240102. fig, tab
Article in Spanish | LILACS | ID: biblio-1526827

ABSTRACT

Introducción. La gastrectomía y disección ganglionar es el estándar de manejo para los pacientes con cáncer gástrico. Factores como la identificación de ganglios por el patólogo, pueden tener un impacto negativo en la estadificación y el tratamiento. El objetivo de este estudio fue comparar el recuento ganglionar de un espécimen quirúrgico después de una gastrectomía completa (grupo A) y de un espécimen con un fraccionamiento por grupos ganglionares (grupo B). Métodos. Estudio de una base de datos retrospectiva de pacientes sometidos a gastrectomía D2 en el Servicio de Cirugía gastrointestinal de la Liga Contra el Cáncer seccional Risaralda, Pereira, Colombia. Se comparó el recuento ganglionar en especímenes quirúrgicos con y sin división ganglionar por regiones anatómicas previo a su envío a patología. Resultados. De los 94 pacientes intervenidos, 65 pertenecían al grupo A y 29 pacientes al grupo B. El promedio de ganglios fue de 24,4±8,6 y 32,4±14,4 respectivamente (p=0,004). El porcentaje de pacientes con más de 15 y de 25 ganglios fue menor en el grupo A que en el grupo B (27 vs 57, p=0,432 y 19 vs 24, p=0,014). El promedio de pacientes con una relación ganglionar menor 0,2 fue mayor en el grupo B (72,4 % vs 55,4 %, p=0,119). Conclusiones. Los resultados de nuestro estudio mostraron que una división por grupos ganglionares previo a la valoración del espécimen por el servicio de patología incrementa el recuento ganglionar y permite establecer de manera certera el pronóstico de los pacientes, teniendo un impacto positivo en su estadificación, para evitar el sobretratamiento


Introduction. A gastrectomy and lymph node dissection is the standard of management for patients with gastric cancer. Factors such as the identification of nodes by the pathologist can have a negative impact on staging and treatment. The objective of this study was to compare the lymph node count of a surgical specimen after a complete gastrectomy (group A) and of a specimen with lymph node by groups (group B). Methods. Study of a retrospective database of patients undergoing D2 gastrectomy in the Risaralda section of the Liga Contra el Cancer Gastrointestinal surgical service, Pereira, Colombia. The lymph node count was compared in surgical specimens with and without lymph node division by anatomical regions, prior to sending them to pathology. Results. Of the 94 patients who underwent surgery, 65 were from group A and 29 patients were from group B. The average number of nodes was 24.4±8.6 and 32.4±14.4, respectively (p=0.004). The percentage of patients with more than 15 and 25 nodes was lower in group A than in group B (27 vs 57, p=0.432 and 19 vs 24, p=0.014). The average number of patients with a nodal ratio less than 0.2 was higher in group B (72.4% vs 55.4%, p=0.119). Conclusions. The results of our study showed that a division by lymph node groups prior to the evaluation of the specimen by the pathology service increases the lymph node count and allows the prognosis of patients to be accurately established, having a positive impact on their staging, to avoid overtreatment.


Subject(s)
Humans , Stomach Neoplasms , Lymph Node Excision , Neoplasm Staging , Gastrectomy , Lymph Nodes , Lymphatic Metastasis
4.
Rev. Ciênc. Méd. Biol. (Impr.) ; 22(2): 181-187, set 2023. tab
Article in Portuguese | LILACS | ID: biblio-1516183

ABSTRACT

Introdução: o câncer é um grave problema de saúde pública, considerado a segunda causa de óbitos no Brasil. Devido à sua relevância, é indispensável um controle eficiente dos casos através do acompanhamento da taxa de mortalidade. Dessa forma, o trabalho analisou a evolução da mortalidade por câncer para as localizações primárias mais frequentes, segundo sexo, durante o período de 2010 a 2020. Metodologia: trata-se de um estudo observacional descritivo, no qual os dados foram obtidos através do Atlas On-line de Mortalidade por Câncer. Os dados colhidos correspondem ao número de óbitos estratificados por tipo de câncer mais frequente, por ano estudado e por sexo, além das taxas de mortalidade específica bruta e a taxa de mortalidade ajustada por idade para o sexo masculino e feminino, para cada tipo de câncer em estudo, considerando a população padrão mundial, sendo avaliado por regressão linear a significância da tendência temporal. Resultados: no Brasil, no período de 2010 a 2020, as neoplasias mais frequentes em mulheres foram câncer de mama, câncer nos brônquios e pulmões, câncer no colo do útero, câncer no cólon e no pâncreas e em homens foram brônquios e pulmões, câncer de próstata, câncer de estômago, de esôfago e no fígado e vias biliares, sendo observado uma tendência crescente na taxa de mortalidade em mulheres e decrescente na taxa de mortalidade em homens. Conclusão: os resultados demonstram um possível comprometimento com a notificação durante o período de pandemia por Covid-19 e um possível rastreamento ainda deficiente de câncer na população masculina.


Introduction: cancer is a severe public health problem, considered the second cause of death in Brazil. Due to its relevance, efficient control of cases by monitoring the mortality rate is essential. Thus, the work analysed the evolution of cancer mortality for the most frequent primary locations, according to sex, from 2010 to 2020. Methodology: this is a descriptive observational study in which data were obtained through the Atlas Online Cancer Mortality Report. The data collected correspond to the number of deaths stratified by the most frequent type of cancer, by year studied and by sex, in addition to the crude specific mortality rates and the age-adjusted mortality rate for males and females, for each type of cancer. Understudy, considering the standard world population, the significance of the temporal trend is evaluated by linear regression. Results: in Brazil, from 2010 to 2020, the most frequent neoplasms in women were breast cancer, bronchial and lung cancer, cervical cancer, colon and pancreas cancer and in men, they were bronchial and lung cancer, cancer prostate, stomach, oesophagal and liver and biliary tract cancer, with an increasing trend in the mortality rate in women and a decreasing trend in the mortality rate in men. Conclusion: the results demonstrate a possible compromise with notification during the Covid-19 pandemic and a possible still poor screening of cancer in the male population.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Death , Neoplasms , Pancreatic Neoplasms , Prostatic Neoplasms , Stomach Neoplasms , Breast Neoplasms , Esophageal Neoplasms , Uterine Cervical Neoplasms , Epidemiology, Descriptive , Liver Neoplasms , Lung Neoplasms
5.
Rev. colomb. cir ; 38(3): 447-458, Mayo 8, 2023. tab, fig
Article in Spanish | LILACS | ID: biblio-1438422

ABSTRACT

Introducción. El diagnóstico adecuado de los tumores de la unión esofagogástrica es esencial para el tratamiento de estos pacientes. La clasificación propuesta por Siewert-Stein define las características propias, factores de riesgo y estrategias quirúrgicas según la localización. El objetivo de este estudio fue describir las características de los pacientes con adenocarcinoma de la unión esofagogástrica tratados en nuestra institución. Métodos. Estudio retrospectivo, descriptivo, de corte longitudinal, que incluyó los pacientes con diagnóstico de adenocarcinoma de la unión esofagogástrica intervenidos quirúrgicamente en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre enero de 2012 y mayo de 2017. Resultados. Se operaron 59 pacientes (84,7 % hombres), con una edad media de 62,5 años. En su orden de frecuencia los tumores fueron tipo II (57,6 %), tipo III (30,7 %) y tipo I (11,9 %). El 74,6 % recibieron neoadyuvancia y se realizó gastrectomía total en el 73 % de los pacientes. La concordancia diagnóstica moderada con índice Kappa fue de 0,56, difiriendo con la endoscópica en 33,9 %. El 10,2 % de los pacientes presentó algún tipo de complicación intraoperatoria. La supervivencia a tres años en los tumores tipo II fue del 89,6 % y del 100 % en aquellos con respuesta patológica completa. Conclusión. Es necesario el uso de diferentes estrategias para un proceso diagnóstico adecuado en los tumores de la unión esofagogástrica. En esta serie, los pacientes Siewert II, aquellos que recibieron neoadyuvancia y los que obtuvieron una respuesta patológica completa, tuvieron una mejor supervivencia a tres años


Introduction: Proper diagnosis of gastroesophageal junction tumors is essential for the treatment of these patients. The classification proposed by Siewert-Stein defines its own characteristics, risk factors and surgical strategies according to the location. This study describes the characteristics of patients with adenocarcinoma of the esophagogastric junction treated at our institution. Methods. Retrospective, descriptive, longitudinal study, which includes patients diagnosed with adenocarcinoma of the esophagogastric junction who underwent surgery at the National Cancer Institute in Bogotá, Colombia, between January 2012 and May 2017. Results. Fifty-nine patients (84.7% men) were operated on, with a mean age of 62.5 years. In their order of frequency, the tumors were type II (57.6%), type III (30.7%) and type I (11.9%). 74.6% received neoadjuvant therapy and total gastrectomy was performed in 73% of the cases. The moderate diagnostic concordance with the Kappa index was 0.56, differing from the endoscopic one in 33.9%. 10.2% of the patients presented some type of intraoperative complication. Three-year survival in type II tumors was 89.6% and 100% in those with complete pathologic response. Conclusion. The use of different strategies is necessary for an adequate diagnostic process in tumors of the esophagogastric junction. In this series, Siewert II patients, those who received neoadjuvant therapy, and those who obtained a complete pathological response had a better three-year survival


Subject(s)
Humans , Esophageal Neoplasms , Esophagogastric Junction , Stomach Neoplasms , Survival , Classification
6.
Rev. colomb. cir ; 38(3): 459-467, Mayo 8, 2023. tab, fig
Article in Spanish | LILACS | ID: biblio-1438423

ABSTRACT

Introducción. El cáncer gástrico es la cuarta causa de muerte por cáncer a nivel mundial, con más de un millón de casos diagnosticados cada año. La cirugía con intención curativa sigue siendo el pilar del manejo para los pacientes resecables. La identificación de pacientes con mayor riesgo de morbimortalidad es importante para el proceso de toma de decisiones, sin existir hasta el momento una herramienta ideal. La revisión y el análisis de la experiencia de un centro oncológico de referencia pueden generar información útil. Métodos. Estudio observacional de cohorte histórica, en el que se incluyeron los pacientes llevados a gastrectomía por adenocarcinoma gástrico en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre el 1° de enero del 2010 y el 31 de diciembre del 2017. Resultados. Se evaluaron 332 pacientes, de los cuales el 57,2 % eran hombres con edad promedio de 61 años. La mortalidad en esta serie fue del 4,5 % y la morbilidad de 34,9 %. El factor asociado con mayor riesgo de muerte fue la edad, con un HR de 1,05 (p=0,021). Se encontró un mayor riesgo en el grupo de pacientes con ASA mayor a II (p=0,009).El 17,4 % presentaron complicaciones mayores a IIIA de la clasificación de Clavien-Dindo. Conclusiones. En el presente trabajo las cifras de morbilidad y mortalidad son similares a las reportadas en la literatura. Solo la edad y la clasificación de ASA mostraron asociación con valor estadístico significativo para complicaciones postoperatorias


Introduction. Gastric cancer is the fourth leading cause of cancer death worldwide with more than one million cases diagnosed each year. Surgery with curative intent remains the mainstay of management for resectable patients. Identify patients at increased risk of morbidity and mortality is important for the decision making process, with no ideal tool available yet. Review and analysis of the experience of a referral cancer center may generate useful information. Methods. Historical cohort observational study. Patients undergoing gastrectomy for gastric adenocarcinoma at the National Cancer Institute in Bogotá, Colombia, between January 1, 2010 and December 31, 2017 were included. Results. We included 332 patients of which 57.2% were men with mean age of 61 years. Mortality in this series was 4.5% and morbidity was 34.9%. The factor associated with higher risk of death was age with a HR of 1.05 statistically significant value (p=0.021). A higher risk was found in the group of patients with ASA greater than II (p=0.009). The 17.4% presented complications greater than IIIA of the Clavien Dindo classification. Conclusions. In this study morbidity and mortality seem similar to those reported in the literature. Only age and ASA score showed an association with significant statistical value for postoperative complications


Subject(s)
Humans , Stomach Neoplasms , Gastrectomy , Postoperative Complications , Prognosis , Morbidity , Mortality
7.
Rev. colomb. cir ; 38(3): 468-473, Mayo 8, 2023. tab, fig
Article in Spanish | LILACS | ID: biblio-1438424

ABSTRACT

Introducción. El tratamiento oncológico perioperatorio en pacientes con cáncer gástrico localmente avanzado está indicado; aun así, no siempre es posible. El objetivo de este estudio fue evaluar la supervivencia de los pacientes según la administración de quimioterapia perioperatoria. Métodos. Estudio observacional, tipo cohorte ambispectivo, incluyendo pacientes con cáncer gástrico localmente avanzado quienes recibieron o no quimioterapia perioperatoria. Resultados. Se incluyeron 33 pacientes, 90,9 % pertenecían al régimen subsidiado de salud y el 78,8 % en estadio T4. El grupo que recibió quimioterapia perioperatoria, que solo tuvo 5 pacientes (15,1 %), presentó mayor supervivencia global a 2 años (100 %), seguido del grupo de quimioterapia postoperatoria (58,8 %) y del grupo sin quimioterapia, que alcanzó una supervivencia global a 2 años de 54,5 %. Discusión. La supervivencia global fue mayor en el grupo de quimioterapia perioperatoria, consonante a lo descrito a nivel internacional, aunque los pacientes se encontraban en un estadío localmente más avanzado, la mayoría con T4 y N+ según AJCC VIII edición. Conclusiones. El estadío clínico es un factor pronóstico importante y, en nuestro medio, la mayoría de los pacientes consultan en estadíos localmente más avanzados. A eso se suman las dificultades en el acceso a la atención en salud. Aun así, la quimioterapia perioperatoria mostró una supervivencia mayor en pacientes con cáncer gástrico localmente avanzado


Introduction. Perioperative cancer treatment in patients with locally advanced gastric cancer is indicated; even so, it is not always possible. The objective was to evaluate survival according to time and receipt of perioperative chemotherapy. Methods. Observational study, ambispective cohort type, including patients with locally advanced gastric cancer who received or did not receive perioperative chemotherapy. Results. Thirty-three patients were included, 90.9% belonged to the subsidized regimen and 78.8% with TNM T4. The perioperative chemotherapy group, which only had five patients (15.1%), had a higher overall survival at 2 years (100%), followed by the postoperative chemotherapy group and by the group without chemotherapy, with an overall survival at 2 years of 58.8% and 54.5%, respectively. Discussion. Overall survival was higher in the perioperative chemotherapy group, consistent with what has been described internationally, although the patients were in a more advanced stage, most being with T4 and N+ according to the AJCC VIII edition. Conclusions. The clinical stage is an important prognostic factor and in our environment, most patients consult in more advanced stages, coupled with difficulties in accessing health care. Even so, perioperative chemotherapy showed a longer survival in patients with locally advanced gastric cancer, the data should not be extrapolated since the number of patients in each group is significantly different


Subject(s)
Humans , Stomach Neoplasms , Survival Analysis , Prognosis , Mortality , Chemotherapy, Adjuvant
8.
Int. j. morphol ; 41(2): 491-500, abr. 2023. ilus, tab
Article in Spanish | LILACS | ID: biblio-1440341

ABSTRACT

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.


SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.


Subject(s)
Humans , Precancerous Conditions/pathology , Stomach Neoplasms/pathology , Gastric Mucosa/pathology , Precancerous Conditions/genetics , Precancerous Conditions/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Immunohistochemistry , Biomarkers, Tumor , Mass Screening , Risk Factors , Genes, p53 , Mucin-2 , CDX2 Transcription Factor , Gastric Mucosa/metabolism , Metaplasia
9.
Univ. salud ; 25(1): A1-A6, ene.-abr. 2023. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1424733

ABSTRACT

Introducción: El riesgo de desarrollar cáncer gástrico varía entre continentes, países y regiones. A pesar de que existe una alta prevalencia de Helicobacter pylori su rol como patógeno o mutualista define el riesgo de cáncer gástrico en las regiones de Colombia. Objetivo: Discutir el rol de Helicobacter pylori en el riesgo de cáncer gástrico en Colombia. Materiales y métodos: Revisión de literatura mediante la búsqueda, en las bases de datos LILACS, SciELO, PubMed. Resultados: La coevolución del humano y de Helicobacter pylori; la virulencia de genes cagA, vacA; el tipo de respuesta inmune inflamatoria a Helicobacter pylori (Th1) o antinflamatoria (Th2) y la susceptibilidad humana a cáncer gástrico (IL1β, IL10), junto a la dieta y factores ambientales explican el papel de Helicobacter pylori como patógeno o mutualista asociado al riesgo de cáncer gástrico en Colombia. Conclusiones: Helicobacter pylori tiene un rol mutualista principalmente en poblaciones de bajo riesgo de cáncer gástrico (costas), no obstante, en poblaciones con alto riesgo de cáncer gástrico (andes), su papel como patógeno amerita la erradicación; única estrategia para mitigar la alta incidencia de este cáncer en Colombia.


Introduction: The risk to develop gastric cancer varies between continents, countries and regions. Although there is a high prevalence of Helicobater pylori, its role as either pathogen or mutualistic bacteria defines the risk of gastric cancer in Colombian regions. Objective: To discuss the role of Helicobacter pylori in the risk of gastric cancer in Colombia. Materials and methods: A literature review based on searching LILACS, SciELO, and PubMed databases. Results: Helicobacter pylori role as either a pathogen or mutualistic microorganism associated with gastric cancer risk in Colombia can be explained by analyzing elements such as: human and Helicobacter pylori coevolution; cagA and vacA gene virulence; inflammatory (Th1) or anti-inflammatory (Th2) responses induced by Helicobacter pylori; human susceptibility to gastric cancer (IL1β, IL10); diet; and environmental factors. Conclusions: Even though Helicobacter pylori has a mutualistic role in populations at low gastric cancer risk (coastal regions), its role as a pathogen in populations at higher risk (Andean regions) justifies its eradication as a key strategy to mitigate the incidence of this cancer in Colombia.


Introdução: O risco de desenvolver câncer gástrico varia entre continentes, países e regiões. Embora haja uma alta prevalência de Helicobacter pylori, seu papel como patógeno ou mutualista define o risco de câncer gástrico nas regiões da Colômbia. Objetivo: Discutir o papel do Helicobacter pylori no risco de câncer gástrico na Colômbia. Materiais e métodos: Revisão da literatura por meio da busca, nas bases de dados LILACS, SciELO e PubMed. Resultados: A coevolução de humanos e Helicobacter pylori; a virulência dos genes cagA, vacA; o tipo de resposta imune inflamatória ao Helicobacter pylori (Th1) ou anti-inflamatório (Th2) e a suscetibilidade humana ao câncer gástrico (IL1β, IL10), juntamente com a dieta e fatores ambientais explicam o papel do Helicobacter pylori como patógeno ou mutualista associado ao risco de câncer gástrico na Colômbia. Conclusões: Helicobacter pylori tem um papel mutualista principalmente em populações de baixo risco de câncer gástrico (litoral), porém, em populações com alto risco de câncer gástrico (andes), seu papel como patógeno justifica a erradicação; única estratégia para mitigar a alta incidência deste câncer na Colômbia.


Subject(s)
Humans , Bacteria , Neoplasms , Stomach Neoplasms , Carcinogens , Risk Factors , Helicobacter pylori
10.
Oncología (Guayaquil) ; 33(1): 58-69, 4 de Abril 2023.
Article in Spanish | LILACS | ID: biblio-1427643

ABSTRACT

Introducción: El cáncer gástrico constituye como una de las enfermedades de mayor morbimortalidad a nivel mundial; no obstante, la mortalidad se puede reducir con intervenciones tempranas. El objetivo del presente estudio fue determinar la relación entre la edad y la sobrevida tras cirugía con intención curativa por cáncer gástrico en pacientes atendidos en el Instituto del cáncer SOLCA, Cuenca, en el periodo 2012-2017. Métodos: El presente estudio analítico, retrospectivo fue realizado con la base de datos del Instituto del Cáncer SOLCA-Cuenca. Los datos fueron presentados en tablas de frecuencia y porcentajes. Se aplicó Chi-cuadrado (X2), análisis de Kaplan Meier y regresión de Cox, para relacionar las variables edad y años de sobrevida, considerándose estadísticamente significativo cuando P<0.05. Resultados: De los 603 pacientes con cáncer gástrico registrado durante el periodo de evaluación, el 35.3% fueron intervenidos quirúrgicamente, lográndose el seguimiento del 45.1%. Un total de 96 pacientes fueron incluidos, el 70.8% fueron intervenidos quirúrgicamente con intención curativa. En la muestra predominaba los hombres (52.9%) y el grupo etario de 70 a 79 años (30.2%). La tasa de sobrevida a los 5 años fue de 69.1% con un tiempo promedio de supervivencia de 7.24±0.49 años. La edad no se relacionó significativamente con la sobrevida de los pacientes (X2=3.15; P=0.667). Conclusión: existe una elevada tasa de sobrevida a los 5 años en los pacientes con cáncer gástrico intervenidos quirúrgicamente con intención curativa, la cual no asoció con la edad.


Introduction: Gastric cancer is one of the diseases with the highest morbidity and mortality worldwide; however, early interventions can reduce mortality. This study aimed to determine the relationship between age and survival after surgery with curative intent for gastric cancer in patients treated at the SOLCA Cancer Institute, Cuenca, in 2012-2017. Methods: The present analytical, retrospective study was carried out with the database of the SOLCA-Cuenca Cancer Institute. Data were presented in frequency and percentage tables. Chi-square (X2), Kaplan Meier analysis, and Cox regression were applied to relate the variables age and years of survival, being considered statistically significant when P<0.05. Results: Of the 603 patients with gastric cancer registered during the evaluation period, 35.3% underwent surgery, achieving a follow-up of 45.1%. A total of 96 patients were included, 70.8% underwent surgery with curative intent. The sample was dominated by men (52.9%) and the age group of 70 to 79 (30.2%). The 5-year survival rate was 69.1%, with a median survival time of 7.24±0.49 years. Age was not significantly related to patient survival (X2=3.15; P=0.667). Conclusion: there is a high 5-year survival rate in patients with gastric cancer who underwent surgery with curative intent, which was not associated with age. Keywords:


Subject(s)
Humans , Adult , Middle Aged , Stomach Neoplasms , Survivorship , Survival Analysis , Mortality Registries , Gastrectomy
11.
ABCS health sci ; 48: e023227, 14 fev. 2023.
Article in English | LILACS | ID: biblio-1518568

ABSTRACT

INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.


Subject(s)
Stomach Neoplasms/diagnosis , Biomarkers, Tumor , Computational Biology , Prognosis , Computer Simulation , Gene Expression , Tissue Array Analysis
12.
Int. j. morphol ; 41(1): 308-318, feb. 2023. ilus, tab, graf
Article in English | LILACS | ID: biblio-1430503

ABSTRACT

SUMMARY: Gastrin plays a vital role in the development and progression of gastric cancer (GC). Its expression is up-regulated in GC tissues and several GC cell lines. Yet, the underlying mechanism remains to be investigated. Here, we aim to investigate the role and mechanism of gastrin in GC proliferation. Gastrin-overexpressing GC cell model was constructed using SGC7901 cells. Then the differentially expressed proteins were identified by iTRAQ analysis. Next, we use flow cytometry and immunofluorescence to study the effect of gastrin on the mitochondrial potential and mitochondria-derived ROS production. Finally, we studied the underlying mechanism of gastrin regulating mitochondrial function using Co-IP, mass spectrometry and immunofluorescence. Overexpression of gastrin promoted GC cell proliferation in vitro and in vivo. A total of 173 proteins were expressed differently between the controls and gastrin- overexpression cells and most of these proteins were involved in tumorigenesis and cell proliferation. Among them, Cox17, Cox5B and ATP5J that were all localized to the mitochondrial respiratory chain were down-regulated in gastrin-overexpression cells. Furthermore, gastrin overexpression led to mitochondrial potential decrease and mitochondria-derived ROS increase. Additionally, gastrin-induced ROS generation resulted in the inhibition of cell apoptosis via activating NF-kB, inhibiting Bax expression and promoting Bcl-2 expression. Finally, we found gastrin interacted with mitochondrial membrane protein Annexin A2 using Co-IP and mass spectrometry. Overexpr ession of gastrin inhibits GC cell apoptosis by inducing mitochondrial dysfunction through interacting with mitochondrial protein Annexin A2, then up-regulating ROS production to activate NF-kB and further leading to Bax/Bcl-2 ratio decrease.


La gastrina juega un papel vital en el desarrollo y progresión del cáncer gástrico (CG). Su expresión está regulada al alza en tejidos de CG y en varias líneas celulares de CG. Sin embargo, el mecanismo subyacente aun no se ha investigado. El objetivo de este estudio fue investigar el papel y el mecanismo de la gastrina en la proliferación de CG. El modelo de células CG que sobre expresan gastrina se construyó usando células SGC7901. Luego, las proteínas expresadas diferencialmente se identificaron mediante análisis iTRAQ. A continuación, utilizamos la citometría de flujo y la inmunofluorescencia para estudiar el efecto de la gastrina en el potencial mitocondrial y la producción de ROS derivada de las mitocondrias. Finalmente, estudiamos el mecanismo subyacente de la gastrina que regula la función mitocondrial utilizando Co-IP, espectrometría de masas e inmunofluorescencia. La sobreexpresión de gastrina promovió la proliferación de células CG in vitro e in vivo. Un total de 173 proteínas se expresaron de manera diferente entre los controles y las células con sobreexpresión de gastrina y la mayoría de estas proteínas estaban implicadas en la tumorigenesis y la proliferación celular. Entre estas, Cox17, Cox5B y ATP5J, todas localizadas en la cadena respiratoria mitocondrial, estaban reguladas a la baja en las células con sobreexpresión de gastrina. Además, la sobreexpresión de gastrina provocó una disminución del potencial mitocondrial y un aumento de las ROS derivadas de las mitocondrias. Por otra parte, la generación de ROS inducida por gastrina resultó en la inhibición de la apoptosis celular mediante la activación de NF-kB, inhibiendo la expresión de Bax y promoviendo la expresión de Bcl-2. Finalmente, encontramos que la gastrina interactuaba con la proteína de membrana mitocondrial Anexina A2 usando Co-IP y espectrometría de masas. La sobreexpresión de gastrina inhibe la apoptosis de las células CG al inducir la disfunción mitocondrial a través de la interacción con la proteína mitocondrial Anexina A2, luego regula el aumento de la producción de ROS para activar NF-kB y conduce aún más a la disminución de la relación Bax/Bcl-2.


Subject(s)
Animals , Mice , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Gastrins/metabolism , Annexin A2/metabolism , Mitochondria/pathology , Mass Spectrometry , NF-kappa B , Fluorescent Antibody Technique , Reactive Oxygen Species , Apoptosis , Cell Line, Tumor , Immunoprecipitation , Cell Proliferation , Carcinogenesis , Flow Cytometry
13.
An. Facultad Med. (Univ. Repúb. Urug., En línea) ; 10(2): e302, 2023. ilus
Article in Spanish | BNUY, UY-BNMED, LILACS | ID: biblio-1513565

ABSTRACT

El carcinoma de células en anillo de sello es una variante histopatológica de cáncer gástrico que se encuentra en aumento, se caracteriza por un mal pronóstico. Se presenta el caso de un hombre joven al que se le hizo este diagnóstico en el contexto de una complicación rara como es el síndrome de estenosis gastroduodenal.


Signet ring cell carcinoma is a histopathological variant of gastric cancer that is increasing and is characterized by a poor prognosis. We present the case of a young man who underwent this diagnosis in the context of a rare complication such as upper gastrointestinal stenosis syndrome.


O carcinoma de células em anel de sinete é uma variante histopatológica do câncer gástrico que está aumentando e é caracterizado por um mau prognóstico. É apresentado o caso de um jovem que recebeu este diagnóstico no contexto de uma complicação rara como a síndrome de estenose gastroduodenal.


Subject(s)
Humans , Male , Adult , Stomach Neoplasms/diagnosis , Carcinoma, Signet Ring Cell/diagnosis , Stomach Neoplasms/surgery , Stomach Neoplasms/complications , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/complications , Constriction, Pathologic/etiology , Gastrectomy
14.
ABCD (São Paulo, Online) ; 36: e1745, 2023. tab, graf
Article in English | LILACS | ID: biblio-1447011

ABSTRACT

ABSTRACT BACKGROUND: There are no information in the literature associating the volume of gastrectomies with survival and costs for the health system in the treatment of patients with gastric cancer in Colombia. AIMS: The aim of this study was to analyze how gastrectomy for gastric cancer is associated with hospital volume, 30-day and 180-day postoperative mortality, and healthcare costs in Bogotá, Colombia. METHODS: A retrospective cohort study based on hospital data of all adult patients with gastric cancer who underwent gastrectomy between 2014 and 2016 using a paired propensity score. The surgical volume was identified as the average annual number of gastrectomies performed by the hospital. RESULTS: A total of 743 patients were included in the study. Hospital mortality at 30 and 180 days postoperatively was 36 (4.85%) and 127 (17.09%) patients, respectively. The average health care cost was USD 3,200. A total of 26 or more surgeries were determined to be the high surgical volume cutoff. Patients operated on in hospitals with a high surgical volume had lower 6-month mortality (HR 0.44; 95%CI 0.27-0.71; p=0.001), and no differences were found in health costs (mean difference 398.38; 95%CI-418.93-1,215.69; p=0.339). CONCLUSIONS: This study concluded that in Bogotá (Colombia), surgery in a high-volume hospital is associated with better 6-month survival and no additional costs to the health system.


RESUMO RACIONAL: Não há informações na literatura relacionando o volume de gastrectomias bem como a sobrevida e os custos para o sistema de saúde, no tratamento de pacientes com câncer gástrico na Colômbia. OBJETIVOS: analisar como a gastrectomia para câncer gástrico está associada ao volume hospitalar, mortalidade pós-operatória de 30 e 180 dias e custos de saúde em Bogotá, Colômbia. MÉTODOS: Estudo de coorte retrospectivo baseado em dados hospitalares de todos os pacientes adultos com câncer gástrico submetidos à gastrectomia entre 2014 e 2016, utilizando um escore de propensão pareado. O volume cirúrgico foi identificado como o número médio anual de gastrectomias realizadas pelo hospital. RESULTADOS: Foram incluídos no estudo 743 pacientes. A mortalidade hospitalar aos 30 e 180 dias de pós-operatório, foram respectivamente, 36 (4,85%) e 127 (17,09%) pacientes. O custo médio de saúde foi de US$ 3.200. Vinte e seis ou mais cirurgias foram determinadas como ponto de corte de alto volume cirúrgico. Pacientes operados em hospitais de alto volume cirúrgico tiveram menor mortalidade em seis meses (HR 0,44; IC95% 0,27-0,71; p=0,001) e não foram encontradas diferenças nos custos com saúde (diferença média 398,38; IC95% −418,93-1215,69; p=0,339). CONCLUSÕES: Este estudo concluiu que em Bogotá (Colômbia), a cirurgia em um hospital com alto volume cirúrgico está associada a uma melhor sobrevida de seis meses e não há custos adicionais para o sistema de saúde.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Stomach Neoplasms/surgery , Gastrectomy/economics , Gastrectomy/mortality , Postoperative Complications/mortality , Stomach Neoplasms/mortality , Survival Analysis , Retrospective Studies , Hospital Mortality , Colombia/epidemiology , Gastrectomy/statistics & numerical data
15.
Journal of Southern Medical University ; (12): 183-190, 2023.
Article in Chinese | WPRIM | ID: wpr-971513

ABSTRACT

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Nomograms , Retrospective Studies , Prognosis , Neoplasm Staging , Stomach Neoplasms/pathology
16.
Journal of Zhejiang University. Science. B ; (12): 232-247, 2023.
Article in English | WPRIM | ID: wpr-971483

ABSTRACT

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.


Subject(s)
Humans , Signal Transduction , Stomach Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Apoptosis , Proto-Oncogene Proteins c-bcl-2 , Cell Line, Tumor
17.
Journal of Central South University(Medical Sciences) ; (12): 260-267, 2023.
Article in English | WPRIM | ID: wpr-971393

ABSTRACT

Gastric cancer (GC) is one of the most common malignant tumors worldwide, and most of the patients are diagnosed at the advanced stage. Most of the treating options are comprehensive treatment, in which immunotherapy plays more and more important role. Melanoma antigen-associated gene-A (MAGE-A) family is a kind of cancer testis antigens. Except in germ cells of testis and trophoblast cells of placenta, MAGE-A family is highly expressed in cancerous tissues and participates in a variety of biological processes, such as cancer cell proliferation, differentiation and metastasis. In addition, cancer testis antigen also possesses good immunogenicity, which can induce humoral and cellular immune responses, is a good target for immunotherapy, and has good application value in the diagnosis, treatment and prognosis of GC. A variety of targeted therapeutic drugs based on MAGE-A are in phase I or II clinical trials, it has good safety and potential clinical application value. With the continuous progress of clinical trials and basic research on MAGE-A targets in GC, it is expected to provide a theoretical basis for clinical transformation and immunotherapy of MAGE-A in the future.


Subject(s)
Male , Humans , Stomach Neoplasms/therapy , Antigens, Neoplasm/genetics , Melanoma , Immunotherapy , Prognosis
18.
Journal of Central South University(Medical Sciences) ; (12): 157-164, 2023.
Article in English | WPRIM | ID: wpr-971381

ABSTRACT

OBJECTIVES@#Gastric cancer is a common cancer of the digestive system. Long non-coding RNA (lncRNA) plays an important role in the formation and development of gastric cancer. This study aims to investigate the effect of long non-coding lncRNA 114227 on biologic behaviors in gastric cancer cells.@*METHODS@#The experiment was divided into 4 groups: a negative control (NC) group, a lncRNA 114227 small interference (si-lncRNA 114227) group, an empty vector (Vector) group, and an overexpression vector (OE-lncRNA 114227) group. The expressions of lncRNA 114227 in gastric mucosa and gastric cancer tissues, gastric mucosal epithelial cells and different gastric cancer strains were determined by real-time reverse transcription PCR (real-time RT-PCR).The proliferation were detected by CCK-8 assay in gastric cancer cells. The epithelial-mesenchymal transformation (EMT) was utilized by Transwell assay, scratch healing assay, and Western blotting in gastric cancer cells. The effect of lncRNA 114227 on proliferation of gastric cancer cells was detected by tumor bearing experiment in nude mice in vivo.@*RESULTS@#The expression level of lncRNA 114227 in the gastric cancer tissues was significantly lower than that in the gastric mucosa tissues, and in 4 kinds of gastric cancer strains was all significantly lower than that in gastric mucosal epithelial cells (all P<0.01). In vitro, the proliferation and migration abilities of gastric cells were significantly reduced after overexpressing lncRNA 114227, and cell proliferation and migration were enhanced after silencing lncRNA 114227 (all P<0.05). The results of in vivo subcutaneous tumorigenesis in nude mice showed that the tumorigenic volume of the tumor-bearing mice in the OE-lncRNA 114227 group was significantly smaller than that of the Vector group, and the tumorigenic quality was lower than that of the Vector group (P<0.05), indicating that lncRNA 114227 inhibited tumorigenesis.@*CONCLUSIONS@#The expression of lncRNA 114227 is downregulated in gastric cancer gastric cancer tissues and cell lines. LncRNA 114227 may inhibit the proliferation and migration of gastric cancer cells through EMT process.


Subject(s)
Animals , Mice , RNA, Long Noncoding/metabolism , Stomach Neoplasms/pathology , Mice, Nude , Cell Line, Tumor , Cell Proliferation/genetics , Carcinogenesis/genetics , Cell Movement/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Apoptosis/genetics
19.
Chinese journal of integrative medicine ; (12): 213-223, 2023.
Article in English | WPRIM | ID: wpr-971328

ABSTRACT

OBJECTIVE@#To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer.@*METHODS@#Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay.@*RESULTS@#Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G1/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05).@*CONCLUSION@#Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.


Subject(s)
Humans , Animals , Mice , Oldenlandia/metabolism , Proliferating Cell Nuclear Antigen , Stomach Neoplasms , Flavonoids/pharmacology , Reactive Oxygen Species/metabolism , Mice, Nude , Ki-67 Antigen , Cell Line, Tumor , Apoptosis , Plant Extracts/pharmacology , Caspases , Cell Proliferation
20.
China Journal of Chinese Materia Medica ; (24): 2368-2378, 2023.
Article in Chinese | WPRIM | ID: wpr-981313

ABSTRACT

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.


Subject(s)
Humans , Stomach Neoplasms/metabolism , Medicine, Chinese Traditional , Molecular Docking Simulation , Prognosis , Computational Biology
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