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SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.
Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.
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Introducción: Helicobacter pylori afecta a más de 50% de la población mundial, siendo más prevalente en poblaciones de nivel socioeconómico bajo; esta bacteria constituye la principal causa de cáncer gástrico a nivel global. Objetivo: Determinar la frecuencia y los factores asociados a la infección por H. pylori en personas adultas que viven en el centro histórico de la ciudad de Cajamarca, en el norte del Perú. Material y Método: Estudio descriptivo que incluyó 124 personas encuestadas mediante un cuestionario y evaluadas mediante endoscopía y cultivo de biopsia gástrica. Una biopsia por persona fue sometida a prueba de ureasa y los cultivos se confirmaron por reacción de polimerasa en cadena (RPC). Resultados: La frecuencia de infección fue de 60,5 % (IC 95% 51,3 - 69,2). El análisis univariado demostró asociación significativa entre la infección y la edad (p = 0,002), y entre la infección y el antecedente de patología gástrica (p = 0,015). El análisis multivariado reveló dos factores asociados: edad (OR = 0,94; IC95% 0,90-0,97) y antecedente de infección por H. pylori (OR = 0,23; IC95% 0,08 - 0,67). Conclusiones: Existe alta frecuencia de infección por H. pylori en esta población; la edad y el antecedente de infección constituyen factores asociados que deben evaluarse con mayor profundidad.
Background: Helicobacter pylori affects more than 50% of the world's population, being more prevalent in populations of low socioeconomic status. H. pylori is the main cause of gastric cancer globally. Aim: To establish the frequency and factors associated with H. pylori infection in adults living in the historic center of Cajamarca City, in northern Peru. Methods: This was a descriptive study that included 124 individuals surveyed through a questionnaire and evaluated through endoscopy and gastric biopsy culture. One biopsy per person underwent the urease test, and the cultures were confirmed by PCR. Results: The frequency of infection was 60.5% (95% CI 51.3 - 69.2). In the univariate analysis, there was a significant association between the infection and age (p = 0.002), and between the infection and a history of gastric pathology (p = 0.015). The multivariate analysis revealed two associated factors: age (OR = 0.94; 95% CI 0.90 - 0.97), and history of H. pylori infection (OR = 0.23; 95% CI 0.08 - 0.67). Conclusions: There is a high frequency of H. pylori infection in this population, and the age and history of H. pylori infection are factors that should be further evaluated.
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RESUMEN Antecedentes: el cáncer gástrico (CG) representa un problema de salud pública en Colombia y el mundo. Dado que la mayoría de los pacientes se encuentran en estadios avanzados en el momento del diagnóstico. desarrollar estrategias de manejo. como la terapia de conversión (TC). es una necesidad cada vez mayor en su tratamiento. Objetivo: estimar los resultados con la TC en el tratamiento de pacientes con CG avanzado en el Instituto Nacional de Cancerología de Colombia (INC). Material y métodos: serie de casos de pacientes con adenocarcinoma gástrico incurable llevados a quimioterapia de inducción y cirugía con intención curativa. entre los años 2010 y 2021. Se revisaron de forma retrospectiva los datos clínico-patológicos y de supervivencia. La supervivencia global (SG) se calculó desde la fecha de la primera quimioterapia hasta la muerte. Las funciones de supervivencia se estimaron con tablas de vida y por el método de Kaplan-Meier y se realizaron curvas de supervivencia a 3 y 5 años. Resultados: se analizaron los datos de 23 pacientes con edad promedio de 56 años. 17 (74%) fueron varones. El criterio de irresecabilidad más frecuente fue un tumor T4b en 13 casos (56.5%). Todos recibieron TC. La mediana de seguimiento fue de 28 meses. Se documentaron 11 recurrencias (52%). La mediana de supervivencia fue de 41.2 meses y la SG a 3 y 5 años de 57.7% y 38.5%. respectivamente. Conclusiones: la TC permitió obtener una SG aceptable de pacientes seleccionados con CG avanzado incurable. Esta estrategia requiere una cuidadosa selección y manejo multidisciplinario en centros oncológicos de referencia.
ABSTRACT Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis. it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods. and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years. and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months. and 3- and 5-year OS was 57.7% and 38.5%. respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires an adequate selection of patients and multidisciplinary management in reference oncology centers.
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ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.
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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.
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Humains , Mâle , Sujet âgé , Tumeurs de l'estomac/chirurgie , Tumeurs de l'estomac/anatomopathologie , Tumeurs primitives multiples , GastrectomieRésumé
RESUMEN Latinoamérica presenta una alta prevalencia de infección por Helicobacter pylori (Hp). Entre 1996-2003 la prevalencia en Santiago de Chile fue del 70%; estudios recientes presentan una disminución en esta infección. Actualizar la frecuencia de Hp es fundamental debido a su impacto en la salud asociado. Objetivo: Nuestro objetivo fue describir la tendencia de la infección por Hp en pacientes que asisten a endoscopía digestiva alta (EDA) ambulatoria en una población chilena. Materiales y métodos: Se realizó un estudio observacional retrospectivo de pacientes mayores de 18 años que asistieron a una primera EDA con test rápido de ureasa entre 2010-2020. La tendencia en el tiempo fue descrita mediante análisis de series de tiempo. Se construyó un modelo Poisson para estimar el riesgo de infección, ajustado por edad y sexo. Resultados: Se incluyeron 11 355 pacientes [66,9% mujeres; edad media 52 años; Hp 41,6%]. El sexo masculino presentó una mayor frecuencia de infección por Hp [RR 1,13; (IC95%:1,08-1,18)]. La frecuencia de Hp disminuyó significativamente desde 45,1% en 2010 hasta 29% en 2020, con 36% menor probabilidad de presentar infección por Hp en 2020 con respecto al 2010 [RR 0,64; (IC95%:0,55-0,74)]. Se proyectó un descenso progresivo en la tendencia de infección por Hp hasta valores cercanos al 25% para el año 2025. Conclusión: Se observó una reducción significativa en la infección por Hp entre los años 2010-2020. Esta disminución pudiese ser explicada mediante la incorporación de políticas públicas de salud en la última década asociadas a cambios sociosanitarios.
ABSTRACT Latin America presents a high prevalence of Helicobacter pylori (Hp) infection. Between 1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decrease in this infection. Updating the frequency of Hp is crucial due to its associated health impact. Objective: Our objective was to describe the trend in Hp infection in patients undergoing ambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. Materials and methods: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trends were described through time series analysis. A Poisson model was constructed to estimate the risk of infection, adjusted for age and gender. Results: 11,355 patients were included [66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequency of Hp infection [RR 1.13; (95% CI: 1.08-1.18)]. Hp frequency infection decreased significantly from 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64; (95% CI: 0.55-0.74)]. A progressive decline in Hp infection trend was projected, reaching values close to 25% by year 2025. Conclusion: A significant reduction in Hp infection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.
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Gastric cancer （GC） is a common malignant tumor of the digestive tract. T helper cells 17 （Th17） and T regulatory cells （Treg） are differentiated subsets of CD4+T cells. Th17/Treg imbalance has been shown to be closely related to the progression of GC. Traditional Chinese medicine （TCM） can not only improve the survival prognosis of GC patients， but also play a role in enhancing the efficacy and reducing the toxicity of postoperative chemotherapy for GC. This paper systematically sorted out the action rules of TCM in the intervention of GC by regulating Th17/Treg balance. The results showed that the TCM compound could regulate the balance of GC Th17/Treg by invigorating the spleen and invigorating Qi， warming Yang， removing blood stasis and detoxifying. The mechanism of regulating Th17/Treg balance in the intervention of GC is mainly to inhibit the excessive differentiation of Th17 and Treg and the overexpression of transcription factors and cytokines， reverse the excessive drift of GC Th17/Treg balance to Th17 or Treg， and thus restore the immune balance of GC Th17/Treg.
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ObjectiveTo observe the effect of Banxia Xiexintang （BXT） on the proliferation of human gastric cancer HGC-27， MKN-45， and AGS cells and its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the effects of different concentrations of BXT-containing serum （5%， 10%， and 20%） on the proliferation of HGC-27， MKN-45， and AGS cells. A mitochondrial membrane potential probe （TMRE） was used to detect the expression of mitochondrial membrane potential in cells. A kit was used to detect iron ion （Fe2+） content， lipid peroxide （LPO）， and superoxide dismutase （SOD） activity. Western blot was used to detect the protein expression levels of glycogen synthase3β （GSK3β）， phosphorylated GSK3β （p-GSK3β）， nuclear factor E2 related factor 2 （Nrf2）， and glutathione peroxidase 4 （GPX4）. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of member 11 of the cystine/glutamic acid reverse transporter solute vector family 7 （SLC7A11）， member 2 of the heavy chain solute vector family 3 （SLC3A2）， transferrin receptor 3 （TFRC）， and tumor protein （TP）53. ResultCCK-8 results showed that BXT and capecitabine could significantly reduce the survival rate of three kinds of gastric cancer cells after treatment with drug-containing serum for 24 h （P<0.01）. After 48 h of intervention with drug-containing serum， the survival rate of three kinds of gastric cancer cells was significantly decreased in both the capecitabine group and the BXT group compared with the blank group. The BXT group was dose-dependent， with 20% BXT having the most significant effect （P<0.01）. In terms of biochemical indicators of ferroptosis， compared with the blank group， BXT and capecitabine significantly decreased the expression of mitochondrial membrane potential （P<0.01） and SOD activity （P<0.01） and significantly increased the contents of LPO and Fe2+ （P<0.01）， so as to improve the sensitivity of gastric cancer cells to ferroptosis. In terms of the Nrf2/GPX4 pathway， compared with the blank group， the BXT group could reduce the protein expressions of p-GSK3β， Nrf2， and GPX4 （P<0.01） in gastric cancer cells and increase mRNA expressions of SLC7A11 and SLC3A2 （P<0.05）. It could also increase the protein expression of GSK3β （P<0.01） and mRNA expression of TP53 and TFRC （P<0.05， P<0.01） in gastric cancer cells. Inhibition of the Nrf2/GPX4 pathway induces ferroptosis in gastric cancer cells. Compared with the capecitabine group， the 20% BXT group showed a more obvious effect. ConclusionBanxia Xiexintang can induce ferroptosis in gastric cancer cells HGC-27， MKN-45， and AGS by inhibiting the Nrf2/GPX4 pathway.
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AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.
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Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.
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OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.
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Gastric cancer is one of the major types of cancer threatening human health worldwide. Its pathogenesis has not been fully elucidated, and patients are often diagnosed at an advanced stage. The oral cavity is the second largest microbial pool after the intestine in the human body, and thus the relationship between oral bacteria and human health is attracting increasing interest. Oral bacteria are closely related to gastric cancer and potentially serve as noninvasive diagnostic screening biomarkers for the disease. Imbalance in and displacement of these bacteria can promote the occurrence and development of gastric cancer. Hence, this article reviews the association between oral bacteria and gastric cancer, aiming to provide a basis for further elucidating the pathogenesis of gastric cancer and screening it early through noninvasive methods and serve as a reference for subsequent related research.
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Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.
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ABSTRACT BACKGROUND: Curative treatment for gastric cancer involves tumor resection, followed by transit reconstruction, with Roux-en-Y being the main technique employed. To permit food transit to the duodenum, which is absent in Roux-en-Y, double transit reconstruction has been used, whose theoretical advantages seem to surpass the previous technique. AIMS: To compare the clinical evolution of gastric cancer patients who underwent total gastrectomy with Roux-en-Y and double tract reconstruction. METHODS: A systematic review was carried out on Web of Science, Scopus, EmbasE, SciELO, Virtual Health Library, PubMed, Cochrane, and Google Scholar databases. Data were collected until June 11, 2022. Observational studies or clinical trials evaluating patients submitted to double tract (DT) and Roux-en-Y (RY) reconstructions were included. There was no temporal or language restriction. Review articles, case reports, case series, and incomplete texts were excluded. The risk of bias was calculated using the Cochrane tool designed for randomized clinical trials. RESULTS: Four studies of good methodological quality were included, encompassing 209 participants. In the RY group, there was a greater reduction in food intake. In the DT group, the decrease in body mass index was less pronounced compared to preoperative values. CONCLUSIONS: The double tract reconstruction had better outcomes concerning body mass index and the time until starting a light diet; however, it did not present any advantages in relation to nutritional deficits, quality of life, and post-surgical complications.
RESUMO RACIONAL: O tratamento curativo do câncer gástrico envolve a ressecção do tumor, seguida de reconstrução do trânsito, sendo o Y-de-Roux a principal técnica empregada. Para permitir o trânsito alimentar para o duodeno, ausente em Y-de-Roux, tem-se utilizado a reconstrução de duplo trânsito, cujas vantagens teóricas parecem superar a técnica anterior. OBJETIVOS: Comparar a evolução clínica de pacientes com câncer gástrico submetidos à gastrectomia total com Y-de-Roux e reconstrução de duplo trânsito. MÉTODOS: Foi realizada uma revisão sistemática nas bases de dados: Web of Science, Scopus, Embase, Scielo, Biblioteca Virtual em Saúde, PubMed e Cochrane. Os dados foram coletados até 11 de junho de 2022. Foram incluídos estudos observacionais ou ensaios clínicos avaliando pacientes que utilizaram reconstruções de duplo trânsito (DT) e Y-de-Roux (RY). Não houve restrição temporal ou de idioma. Foram excluídos artigos de revisão, relatos de casos, séries de casos e aqueles com texto incompleto. O risco de viés foi calculado utilizando a ferramenta Cochrane desenvolvida para ensaios clínicos randomizados. RESULTADOS: Foram incluídos quatro estudos de boa qualidade metodológica, abrangendo 209 participantes. No grupo RY houve maior redução na ingestão alimentar. No grupo DT, a diminuição do índice de massa corporal (IMC) foi menos pronunciada em comparação aos valores pré-operatórios. CONCLUSÕES: A reconstrução de duplo trânsito apresentou melhores resultados em relação ao índice de massa corporal e ao tempo para início de dieta leve, porém não apresentou vantagens em relação aos déficits nutricionais, qualidade de vida e complicações pós-cirúrgicas.
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ABSTRACT Background: Gastric atrophy (GA) and intestinal metaplasia (IM) are early stages in the development of gastric cancer. Evaluations are based on the Updated Sydney System, which includes a biopsy of the incisura angularis (IA), and the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Assessment using Intestinal Metaplasia (OLGIM) gastric cancer risk staging systems. Objective: To compare the OLGA and OLGIM classifications with and without IA biopsy. In addition, to determine the prevalence of Helicobacter pylori (HP) and pre-neoplastic changes (GA and IM) in different biopsied regions and to identify the exclusive findings of IA. Methods: Observational, prospective, descriptive, unicentric study with 350 patients without a diagnosis of gastric cancer, who underwent upper digestive endoscopy with biopsies at Gastroclínica Itajaí, from March 2020 to May 2022. The histopathological classification of gastritis followed the Updated Sydney System, and the gastric cancer risk assessment followed the OLGA and OLGIM systems. The methodology applied evaluated the scores of the OLGA and OLGIM systems with and without the assessment of the IA biopsy. Statistical analysis was performed using descriptive measures (frequencies, percentages, mean, standard deviation, 95% confidence interval). Ranks were compared using the Kruskal-Wallis or Wilcoxon tests. To analyze the relationship between the frequencies, the bilateral Fisher's exact test was used. Wilson's score with continuity correction was applied to the confidence interval. Results: The median age was 54.7 years, with 52.57% female and 47.43% male patients. The comparison between the used biopsies protocol (corpus + antrum [CA] vs corpus + antrum + incisura angularis [CAI]) and the OLGA and OLGIM stages showed a significant decrease in both staging systems when the biopsy protocol restricted to the corpus and antrum was applied (OLGA CAI vs CA; P=0.008 / OLGIM CAI vs CA; P=0.002). The prevalence of pre-malignant lesions (GA, IM and dysplasia) of the gastric mucosa was (33.4%, 34% and 1.1%, respectively) in the total sample. The antrum region exhibited significantly higher numbers of alteration (P<0.001), except for HP infection, which was present in 24.8% of the patients. Conclusion: Incisura angularis biopsy is important because it increased the number of cases diagnosed in more advanced stages of intestinal metaplasia and atrophy. The study had limitations, with the main one being the relatively small sample size, consisting mostly of healthy individuals, although mostly elderly.
RESUMO Contexto: A atrofia gástrica (AG) e a metaplasia intestinal (MI) são estágios iniciais do desenvolvimento do câncer gástrico. As avaliações são baseadas no Sistema de Sydney Atualizado, que inclui uma biópsia da incisura angular (IA), e nos sistemas de estadiamento de risco de câncer gástrico Operative Link on Gastritis Assessment (OLGA) e Operative Link on Gastritis Assessment using Intestinal Metaplasia (OLGIM). Objetivo: Comparar as classificações OLGA e OLGIM com e sem biópsia da IA. Além disso, determinar a prevalência de Helicobacter pylori (HP) e alterações pré-neoplásicas (AG e MI) em diferentes regiões biopsiadas e identificar os achados exclusivos da IA. Métodos: Estudo observacional, prospectivo, descritivo, unicêntrico, com 350 pacientes sem diagnóstico de câncer gástrico, submetidos à endoscopia digestiva alta com biópsias na Gastroclínica Itajaí, no período de março de 2020 a maio de 2022. A classificação histopatológica da gastrite seguiu o Sistema de Sydney Atualizado, e a avaliação do risco de câncer gástrico seguiu os sistemas OLGA e OLGIM. A metodologia aplicada avaliou os escores dos sistemas OLGA e OLGIM com e sem a avaliação da biópsia da IA. A análise estatística foi realizada por meio de medidas descritivas (frequências, porcentagens, média, desvio padrão, intervalo de confiança de 95%). As classificações foram comparadas usando os testes de Kruskal-Wallis ou Wilcoxon. Para analisar a relação entre as frequências, foi usado o teste exato de Fisher bilateral. O escore de Wilson com correção de continuidade foi aplicado ao intervalo de confiança. Resultados: A idade média foi de 54.7 anos, com 52.57% de pacientes do sexo feminino e 47.43% do sexo masculino. A comparação entre o protocolo de biópsias utilizado (corpo + antro [CA] vs corpo + antro + incisura angular [CAI]) e os estágios OLGA e OLGIM mostrou uma diminuição significativa em ambos os sistemas de estadiamento quando o protocolo de biópsia restrito ao corpo e ao antro foi aplicado (OLGA CAI vs CA; P=0.008 / OLGIM CAI vs CA; P=0.002). A prevalência de lesões pré-malignas (GA, MI e displasia) da mucosa gástrica foi de (33.4%, 34% e 1.1%, respectivamente) na amostra total. A região do antro exibiu um número significativamente maior de alterações (P<0.001), com exceção da infecção por HP, que estava presente em 24.8% dos pacientes. Conclusão: A biópsia de IA é importante porque aumentou o número de casos diagnosticados em estágios mais avançados de MI e AG. O estudo teve limitações, sendo a principal delas o tamanho relativamente pequeno da amostra, composta principalmente por indivíduos saudáveis, embora em sua maioria idosos.
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Background: Neoadjuvant chemotherapy (NACT) in carcinoma stomach was introduced in an effort to eliminate micro-metastasis and to improve resectablity before surgery which improves R0 resection rates. The aim of the current study was to evaluate the effect of neoadjuvant chemotherapy on downstaging and resectability rate in locally advanced gastric cancer. Material & Methods: This was a single-center quasi-experimental study conducted in the Department of Surgical Oncology in collaboration with the Departments of Medical Oncology, Radiation oncology, and Pathology at the National Institute of Cancer Research and hospital, Dhaka, which is a tertiary care cancer hospital in Bangladesh, between January 2021 and June 2022.Patients with locally advanced adenocarcinoma stomach staged by contrast-enhanced computed tomography (CECT) were randomly included in this study by purposive sampling. Patients in Group I underwent upfront surgery Patients in Group II were started on neoadjuvant chemotherapy, either XELOX or FLOT regimen. Surgery was done following the response assessment CECT. We assessed R0 resection rate, age, sex, comorbidities, tumour size, TNM stage and complications were compared between the two groups. Response to NACT was assessed in Group II. Results: The mean age of patients in groups 1 & 2 was 56 ± 11.06 and 55.70 ± 10.46 years of age respectively (p > 0.05). Majority of the respondents (55/74) were male and 19 patients (26%) were female. Male to female ratio was (24/37 &31/37) in group 1 and (31/37 & 6/37) groups respectively (p > 0.05). Out of 37 patients who received NACT, in 9 patients (24.32%) complete response was noted. Partial response was found in 20 cases (54.05%), p-value (<.0001) while a stable disease was reported in three (8.1%) cases. 5 patients (13.51%) had progressive disease. In the upfront surgery group, R0 resection was feasible in 16 (43.2%) cases, and in the NACT plus surgery group, R0 resection was done in 29 (78.4%) cases. In group 1, R1 resection was done in considerable numbers (19/37) compared to group 2 (5/37), P=0.001. Three patients (8.1%) in group 2 and one (2.7) in group 1 had irresectable lesions. Conclusion: In this study it can be concluded that neoadjuvant chemotherapy could downstage tumour and increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma. However, further studies are necessary to confirm the effect of this modality on patients’ overall survival. We await survival analysis to further validate the role of NACT.
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Introduction: Gastric cancer (GC) is the first cause of death by neoplasm in Colombia, with 6,451 deaths in 2020. This pathology and its chronic manifestations pose a public health challenge. The objective is to estimate the disease burden of GC in Tunja, Boyacá, from 2010 to 2019. Materials and methods: An exploratory ecological study was conducted using disability-adjusted life years (DALYs) as the unit of measurement. The National Administrative Department of Statistics (DANE) mortality databases and prevalence information from the Integrated Social Protection Information System (SISPRO) records were used. Deaths and GC cases were pooled and then adjusted to control for bias. Results: In 2010-2019, 34.2 DALYs were lost for every 1,000 people secondary to GC in Tunja, 30.5 were due to years lost due to premature death, and 3.72 were due to years lived with disability. DALYs due to premature death were found to exceed DALYs due to disability. Conclusion: The morbidity burden of GC from 2010 to 2019 for Tunja was similar to that of other cancers because of years of life lost due to premature death, so public health efforts should be made to increase early detection.
Introducción: el cáncer gástrico (CG) es la primera causa de muerte por neoplasia en Colombia, con 6451 muertes durante el 2020. Esta patología y sus manifestaciones crónicas plantean un desafío en la salud pública. El objetivo fue estimar la carga de enfermedad por CG en Tunja, Boyacá, durante los años 2010 a 2019. Metodología: se realizó un estudio ecológico exploratorio en el que se utilizó como unidad de medida los años de vida ajustados por discapacidad (AVAD). Se emplearon las bases de datos de mortalidad del Departamento Administrativo Nacional de Estadística (DANE) e información de la prevalencia desde los registros del Sistema Integrado de Información de la Protección Social (SISPRO). Las muertes y los casos de CG se agruparon y luego se ajustaron para controlar sesgos. Resultados: en el período 2010-2019 se perdieron 34,2 AVAD por cada 1000 personas secundarios a CG en Tunja, de los cuales 30,5 fueron debido a años perdidos por muerte prematura y 3,72 por años vividos con discapacidad. Se encontró que los AVAD por muerte prematura superan a los AVAD por discapacidad. Conclusión: la carga de morbilidad por CG en el período 2010 a 2019 para la ciudad de Tunja fue similar a la carga de otros cánceres y fue debido a años de vida perdidos por muerte prematura, motivo por el cual se deben realizar esfuerzos de salud pública para aumentar la detección temprana.
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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.
Sujets)
Animaux , Souris , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/anatomopathologie , Gastrines/métabolisme , Annexine A2/métabolisme , Mitochondries/anatomopathologie , Spectrométrie de masse , Facteur de transcription NF-kappa B , Technique d'immunofluorescence , Espèces réactives de l'oxygène , Apoptose , Lignée cellulaire tumorale , Immunoprécipitation , Prolifération cellulaire , Carcinogenèse , Cytométrie en fluxRésumé
ABSTRACT Background Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. Objectives The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. Methods We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. Results We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds' ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. Conclusions In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.
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This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.