Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Barreras y facilitadores del acceso al tamizaje de cáncer colorrectal / Barriers and facilitators of colorectal cancer screening access

Resumen Introducción : El cáncer colorrectal (CCR) es un pro blema de salud a nivel global. En el sector público de Bahía Blanca, el tamizaje de CCR es oportunista, por solicitud de sangre oculta en materia fecal (SOMF). El objetivo de este trabajo es describir el acceso al tamiza je de CCR de la población con cobertura pública exclu siva que reside en el área programática 2 de la ciudad entre 2019 y 2021, y relevar las barreras y facilitadores que lo determinan. Métodos : Se estimó la tasa de uso anual y acumula da de SOMF. Las barreras y facilitadores se relevaron a través de 41 entrevistas individuales semi-estructuradas al personal de salud del área programática, el Hospital Municipal, Secretaría de Salud y usuarios/no usuarios del sistema. Resultados : La tasa acumulada de uso de SOMF en el período fue 4.8%. Entre las barreras al tamizaje per cibidas se destacan: la dificultad en el acceso a estudios de mayor complejidad para pacientes con SOMF+, el desconocimiento y falta de percepción del CCR como un problema de salud por parte de la población y la baja adherencia de los profesionales a los lineamientos. La territorialidad y el vínculo de los centros de salud con la población, y la predisposición de usuarios y profesio nales a incorporar el tamizaje surgen como facilitadores del mismo. Conclusiones : El relevamiento de las barreras orien tará el diseño de estrategias adaptadas al contexto que permitan en el futuro reforzar el tamizaje.

Abstract Introduction : Colorectal cancer (CRC) is a global health problem. In the public sector of Bahía Blanca, CRC screening is opportunistic, through the request of fecal occult blood test (FOBT). The objective of this study is to describe access to CRC screening for the population with exclusive public coverage residing in the program matic area 2 of the city between 2019 and 2021, and to identify the barriers and facilitators that determine it. Methods : The annual and cumulative usage rate was estimated based on the number of patients who requested FOBT. The barriers and facilitators were studied through 41 semi-structured individual inter views to healthcare staff from the area, the Municipal Hospital, Health Secretariat and users/non-users of the system. Results : The cumulative usage rate of FOBT during the period was less than 5%. Among the perceived bar riers to screening, we found: the difficulties in accessing more complex studies for patients with positive FOBT, the lack of population awareness and perception of CRC as a health problem, the low adherence of professionals to guidelines. The territoriality and link of health centers with the population, as well as the willingness of users and professionals to incorporate screening, emerge as facilitators. Conclusion : The identification of barriers and facilita tors will allow the design of context-adapted strategies that will strengthen screening in the future.

Efectividad de estrategias para incrementar la adherencia al tamizaje de cáncer colorrectal: una revisión sistemática / Effectiveness of strategies to increase adherence to colorectal cancer screening: a systematic review

Resumen Introducción : En Argentina la cobertura al tamizaje de cáncer colorrectal (CCR) es muy baja. El objetivo de esta revisión fue relevar y sintetizar la evidencia sobre la efectividad de estrategias dirigidas a incrementar la adherencia al tamizaje de CCR del personal de salud y población con riesgo promedio. Métodos : Revisión de revisiones sistemáticas (RS) que evaluaron la efectividad de dichas estrategias. Bús queda en bases de datos electrónicas, meta-buscadores, biblioteca Cochrane y búsqueda manual. Aplicación de criterios de elegibilidad e inclusión; con evaluación de la calidad de las RS a través del AMSTAR-II y la certeza de la evidencia por el método GRADE. Síntesis temática sobre la base de la taxonomía de estrategias propuesta por Dougherty (dirigidas al paciente/comunidad; a pro fesionales; otro tipo de estrategias). Resultados : Se identificaron 635 estudios; 36 fueron elegibles y 11 se descartaron por no contar con cali dad suficiente, incluyéndose 10 RS. Se identificó una multiplicidad de estrategias de efectividad variada, la mayoría dirigida a la población. Entre estas, destacan la educación, el auto-test con recolección en lugares específicos y recordatorios. En el caso de profesionales, solo educación y recordatorios mostraron ser efectivas. La combinación de estrategias mostró tener mayor efec tividad que las estrategias aisladas. Conclusiones : Es mayor la evidencia sobre estrategias dirigidas a la población que a profesionales. Las estrate gias combinadas demostraron tener mayor efectividad, lo que destaca la necesidad de explorar, en cada con texto, las barreras en la población y en los profesionales para priorizar y combinar aquellas que demostraron ser efectivas y tendrían mayor impacto.

Abstract Introduction : Coverage for colorectal cancer screening in Argentina is very low. The objective of this review is to assess and synthesize the evidence on the effectiveness of strategies aimed at increasing adherence to colorectal cancer screening among healthcare personnel and the general population at average risk. Methods : A review of systematic reviews (SRs) that evaluated the effectiveness of these strategies was con ducted. Searches were performed in electronic data bases, meta-search engines, the Cochrane Library, and through manual searching. Eligibility and inclusion criteria were applied, with assessment of the quality of the SRs using AMSTAR II and the certainty of evidence using the GRADE approach. Thematic synthesis was con ducted based on the taxonomy of strategies proposed by Dougherty (patient/community-targeted, professional-targeted, and other types of strategies). Results : A total of 635 studies were identified, with 36 deemed eligible and 11 excluded due to insufficient quality, resulting in the inclusion of 10 SRs. A multi plicity of strategies with varying effectiveness were identified, with the majority targeting the population. Among these, education, self-testing with specimen collection at specific locations, and reminders stood out. For professionals, only education and reminders showed effectiveness. Combined strategies demonstrated greater effectiveness than isolated strategies. Conclusions : There is more evidence on strategies targeting the population than professionals. Combined strategies showed greater effectiveness, highlighting the need to explore barriers in both the population and professionals in each specific context in order to priori tize and combine those that have proven effective and would have a greater impact.

Resultados del uso de prótesis endoscópica colorrectal. 15 años de experiencia

Objetivo: Describir morbimortalidad asociada al uso de prótesis colorrectales (PC) e identificar factores asociados a sus complicaciones durante los años 2007 a 2022 en Clínica INDISA. Material y Método: Estudio transversal retrospectivo basado en registro clínico. Resultados: Se instalaron 49 PC con un 100% de éxito de desobstrucción. El 87,8% en colon izquierdo. La etiología principal fue la patología maligna 91,8% y el 85,7% de ellos fueron primarios colorrectales. Se instalaron 34 como tratamiento paliativo (TP), 12 como puente a cirugía electiva (PCE) y 3 por patología benigna. La tasa de complicaciones fue de 26,5% (7 estenosis, 4 perforaciones y 2 migraciones). La mortalidad asociada fue de 4,1% (2 pacientes). El grupo de complicados fue más joven, con etapas oncológicas más avanzadas y con estenosis en rectosigmoides(p < 0,005). Los menores de 50 años tuvieron 5 veces más riesgo de alguna complicación (OR = 5,0;IC95%:1,09-23,0; p = 0,039). Discusión: El uso de PC tiene baja morbimortalidad. Su uso principal es como TP o PCE en obstrucción colorrectal maligna, con alta tasa de desobstrucción. Está asociado con menor morbilidad que la cirugía de urgencia, menor tasa de ostomía y mayor cosecha ganglionar. La instalación como puente se asocia además a mayor tasa de anastomosis primaria. Nuestra serie mostró mayor tasa de complicación en aquellos con tumores avanzados y más jóvenes. Conclusión: El uso de PC es seguro y con baja morbimortalidad. La principal indicación es en neoplasia colorrectal obstructiva como TP. Tienen mayor riesgo de complicación los pacientes jóvenes y los tumores colorrectales avanzados con ganglios peri tumorales.

Objective: To describe morbidity and mortality associated with colorectal prostheses (CP) and identify factors associated with their complications during the 2007 to 2022 at INDISA Clinic. Material and Method: Retrospective cross-sectional study based on clinical registry. Results: 49 CPs were installed with 100% clearing success. 87.8% in left colon. The main etiology was malignant 91.8% and 85.7% were primary colorectal. 34 were installed with palliative intention, 12 as a bridge to elective surgery (BTS) and 3 for benign pathology. There were 13 (26.5%) patients with adverse effects (7 strictures, 4 perforations and 2 migrations). Associated mortality was 4.1% (2 patients). The complicated group was younger, with more advanced oncological stages and rectosigmoid stenosis (p < 0.005). Those under 50 years of age had 5 times higher risk of some complication (OR = 5.0; 95% CI: 1.09-23.0; p = 0.039). Discussion: The use of CPs has low short-term morbidity and mortality. Its main use is as palliative treatment or BTS in malignant colorectal obstruction. It's a high clearance rate. It is associated with less morbidity than emergency surgery, a lower ostomy rate, and a higher lymph node harvest. Installation as a bridge is also associated with a higher rate of primary anastomosis. Our group showed a higher complication rate in those with advanced and younger tumors. Conclusion: The use of CPs is safe, with low morbidity and mortality. The main indication is in obstructive colorectal neoplasia as palliative treatment. Young patients and advanced colorectal tumors with peritumoral nodes have a higher risk of complications.

Validación del cuestionario EORTC QLQ-CR29 para evaluación de la calidad de vida relacionada a la salud de personas adultas con cáncer colorrectal en Chile

Introducción: Personas con cáncer colorrectal (CCR) pueden presentar efectos adversos, perjudicando la calidad de vida relacionada a la salud (CVRS). Objetivo: Validar el módulo QLQ CR29 para evaluación de la CVRS, en Chile. Materiales y método: Estudio transversal que incluyó 170 personas con CCR. Se analizaron la consistencia interna y validez de constructo del instrumento con test de hipótesis. Resultados: 117 personas (68,8%) fueron evaluadas antes de la cirugía y 53 (31,2%) después de la cirugía. La consistencia interna del QLQ CR29 fue α = 0,838. Fueron comprobadas las hipótesis planteadas: Los pacientes evaluados antes de la cirugía se quejaron más de "sangre/mucosidad en las heces", "dolor abdominal", "pérdida de cabello" e "hinchazón abdominal", mientras que los pacientes evaluados después presentaron más "incontinencia fecal" (p < 0,05). Antes de la cirugía, los pacientes con cáncer de recto CCR presentaron mayores valores de "frecuencia urinaria", "frecuencia de deposiciones", "dolor en las nalgas", "problemas con el gusto" y "vergüenza"; mientras que aquellos con cáncer de colon que se quejaban más de "sangre/mucosidad en las heces" (p < 0,05). Después de la cirugía, los pacientes con cáncer de recto tenían mayor "frecuencia de deposiciones", "eliminación de gases" y "vergüenza" (p = 0,004) en comparación con los con cáncer de colon (p < 0,05). Los pacientes ostomizados presentaron más "incontinencia fecal" y "vergüenza" (p < 0,001). Fueron observadas correlaciones positivas y negativas bajas entre la mayoría de las dimensiones del QLQ CR29 con las dimensiones del QLQ C30. Conclusión: La versión chilena del módulo QLQ CR29 es adecuada para evaluar la CVRS en personas con CCR.

Introduction: People with colorectal cancer (CRC) can present adverse effects, impairing the quality of life related to health (HRQoL). Objective: To validate the QLQ-CR29 module for the assessment of HRQoL, in Chile. Materials and method: Cross-sectional study that included 170 people with CRC. The internal consistency and construct validity (hypothesis tests) were analyzed. Results: 117 patients (68.8%) were evaluated before surgery and 53 (31.2%) after tumor resection. The internal consistency of the QLQCR29 was α = 0.838. The proposed hypotheses were confirmed: The patients evaluated before surgery complained more of "blood/mucus in the stool", "abdominal pain", "hair loss" and "abdominal swelling", while the patients evaluated after presented more "fecal incontinence" (p < 0.05). Before surgery, patients with rectal cancer presented higher values of "urinary frequency", "frequency of stools", "pain in the buttocks", "taste problems" and "embarrassment"; while those with colon cancer complained more of "blood/mucus in stool" (p < 0.05). After surgery, patients with CCR had higher "stool frequency", "flatus" and "embarrassment" (p = 0.004) compared with those with colon cancer (p < 0.05). Ostomized patients presented more "fecal incontinence" and "embarrassment" (p < 0.001). Low significant correlations were observed between most of the dimensions of the QLQ CR29 with the dimensions of the QLQ C30. Conclusion: The Chilean version of the QLQ CR29 module is adequate to assess HRQoL in people with CRC.

Prótesis colónicas en el tratamiento paliativo del cáncer colónico. Nuestra evaluación tras 10 años de experiencia / Self-expanding metal stents in the palliative treatmentof coloncancer. Results of 10 years of experience

Introducción: la colocación de prótesis metálicas autoexpansibles (PAE) por vía endoscópica surge como opción terapéutica para la obstrucción colónica neoplásica en dos situaciones: como tratamiento paliativo y como puente a la cirugía curativa. Este procedimiento evita cirugías en dos tiempos y disminuye la probabilidad de colostomía definitiva y sus complicaciones con el consecuente deterioro de la calidad de vida. Objetivo: comunicar nuestra experiencia en la colocación de PAE para el tratamiento paliativo de la obstrucción colorrectal neoplásica. Diseño: retrospectivo, longitudinal, descriptivo y observacional. Material y métodos: se incluyeron todos los pacientes a quienes el mismo grupo de endoscopistas les colocó PAE con intención paliativa por cáncer colorrectal avanzado entre agosto de 2008 y diciembre de 2019. Fueron analizadas las variables demográficas y clínicas, el éxito técnico y clínico, las complicaciones tempranas y tardías y la supervivencia. Resultados: se colocó PAE en 54 pacientes. La media de edad fue 71 años. El 85% de las lesiones se localizó en el colon izquierdo. En el 57% de los pacientes se realizó en forma ambulatoria. El éxito técnico y clínico fue del 92 y 90%, respectivamente y la supervivencia media de 209 días. La tasa de complicaciones fue del 29,6%, incluyendo un 14,8% de obstrucción y un 5,6% de migración. La mortalidad tardía atribuible al procedimiento fue del 5,6%, ocasionada por 3 perforaciones tardías: 2 abiertas y 1 microperforación con formación de absceso localizado. Conclusiones: la colocación de PAE como tratamiento paliativo de la obstrucción neoplásica colónica es factible, eficaz y segura. Permitió el manejo ambulatorio o con internación breve y la realimentación temprana, mejorando las condiciones para afrontar un eventual tratamiento quimioterápico paliativo. Las mayoría de las complicaciones fueron tardías y resueltas endoscópicamente en forma ambulatoria. (AU)

Introduction: endoscopic placement of self-expanding metal stents (SEMS) emerges as a therapeutic option for neoplastic obstruction of the colon in two situations: as palliative treatment and as a bridge to curative surgery. This procedure avoids two-stage surgeries and reduces the probability of permanent colostomy and its complications with the consequent deterioration in quality of life. Objective: to report our experience in the placement of SEMS as palliative treatment in neoplastic colorectal obstruction. Design: retrospective, longitudinal, descriptive and observational study. Methods: all patients in whom the same group of endoscopists performed SEMS placement with palliative intent for advanced colorectal cancer between August 2008 and December 2019 were analyzed. Data collected were demographic and clinical variables, technical and clinical success, early and late complications, and survival. Results: SEMS were placed in 54 patients. The average age was 71 years. Eighty-five percent were left-sided tumors. In 57% of the patients the procedure was performed on an outpatient basis. Technical and clinical success was 92 and 90%, respectively, and median survival was 209 days. The complication rate was 29.6%, including 14.8% obstruction and 5.6% migration. Late mortality attributable to the procedure was 5.6%, caused by 3 late perforations: 2 open and 1 microperforation with localized abscess formation. Conclusions: The placement of SEMS as a palliative treatment for neoplastic colonic obstruction is feasible, effective and safe. It allowed outpa-tient management or brief hospitalization and early refeeding, improving the conditions to face an eventual palliative chemotherapy treatment. Most complications were late and resolved endoscopically on an outpatient basis. (AU)

Calidad asistencial y seguimiento de los pacientes operados por cáncer colorrectal en un Hospital de Paysandú, Uruguay / Quality of care and follow-up of patients operated on forcolorectal cancer at the Paysandú Hospital, Uruguay

Introducción: el cáncer colorrectal (CCR) es la segunda causa de muerte dentro de las enfermedades neoplásicas. El pronóstico individual está signado por el estadio de la enfermedad al momento del diagnóstico y la posibilidad de realizar un tratamiento curativo. Este también depende de la estratificación post quirúrgica y de la aparición de complicaciones ulteriores. El objetivo del seguimiento es diagnosticar la recidiva en un estadio potencialmente curable y detectar otros cánceres primarios. Objetivo: realizar una valoración de la calidad de la cirugía colorrectal y el seguimiento de los pacientes operados de CCR en nuestro hospital. Diseño: estudio descriptivo, observacional, retrospectivo. Material y métodos: se analizaron todos los pacientes con CCR operados en el servicio de cirugía del Hospital de Paysandú entre enero de 2017 y diciembre de 2020. Se describen diversas variables que influyen en la calidad quirúrgica y se analizan las relacionadas al seguimiento post operatorio dividiendo a los pacientes en 3 grupos, seguimiento completo, perdidos y sin datos de seguimiento. Resultados: se incluyeron 39 pacientes, con una edad media de 68 años. El 28% se diagnosticaron en estadio IV, con porcentajes bajos en estadios tempranos. Hubo 57% de cirugías de urgencia y 43% electivas. La causa más frecuente de urgencia fue la oclusión intestinal (36,6%). La tasa de dehiscencia anastomótica fue 16,6% y la de mortalidad 15,3%. Solo el 33% de los pacientes tuvieron seguimiento completo. Conclusión: existe un déficit en la atención y el seguimiento de los pacientes operados por CCR en nuestro hospital. Se impone la creación de un equipo específico en el área de coloproctología, así como un protocolo de seguimiento unificado para mejorar estos resultados. (AU)

Introduction: colorectal cancer (CRC) is the second cause of death among neoplastic diseases. The individual prognosis is determined by the stage of the disease at the time of diagnosis and the possibility of curative treatment. This also depends on the postsurgical stratification and the appearance of subsequent complications. The goal of follow-up is to diagnose recurrence at a potentially curable stage and detect other primary cancers. Objective: to carry out an evaluation of the quality of colorectal surgery and the follow-up of patients operated on for CRC in our hospital. Design: descriptive, retrospective observational study. Material and methods: all patients with CRC operated on in the surgery service of the Paysandú Hospital between January 2017 and December 2020 were analyzed. Variables that influence surgical quality are described and those related to postoperative follow-up are analyzed by dividing patients in 3 groups, complete follow-up, lost to follow-up and without follow-up data. Results: Thirty-nine patients were included, with a mean age of 68 years. Twenty-eight percent were diagnosed in stage IV, with low percentages in early stages. There were 57% emergency procedures and 43% elective proceduress. The most common cause of emergency was intestinal obstruction (36.6%). The anastomotic dehiscence rate was 16.6% and the mortality rate was 15.3%. Only 33% of patients had complete follow-up. Conclusion: there is a deficit in the care and follow-up of patients undergoing CRC surgery in our hospital. The creation of a specific team in the area of coloproctology is required, as well as a unified monitoring protocol to improve these results. (AU)

ALPPS en cáncer colorrectal sincrónico en tiempos de COVID-19 / ALPPS in synchronous colorectal cancer in times of COVID-19

RESUMEN Durante la pandemia por SARS-CoV-2 evidenciamos un aumento de la morbimortalidad secundario a procedimientos quirúrgicos. Se estima una mortalidad a los 30 días del 19,1% en cirugías programadas y del 26% en procedimientos quirúrgicos de emergencia, y alrededor de la mitad de los pacientes que se someten a cirugía estando infectados con SARS-CoV-2 experimentan complicaciones pulmonares posoperatorias. Los tratamientos oncológicos sufrieron deficiencias en nuestro país debido a las limitantes secundarias a la emergencia sanitaria, en cuanto a capacidad de internación e implementación de los tratamientos quimioterápicos. Informamos la primera cirugía de ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) realizada en el nordeste argentino en una paciente con metástasis colorrectales múltiples en contexto de la pandemia por SARS-CoV-2, con buenos resultados.

ABSTRACT During the SARS-CoV-2 pandemic, we observed an increase in morbidity and mortality secondary to surgical procedures. The mortality rate for elective surgery is estimated at 19.1% and is 26% for emergency procedures. Additionally, approximately half of patients who undergo surgery while infected with SARS-CoV-2 experience postoperative pulmonary complications. Due to limitations caused by the health emergency, cancer treatments in our country have been affected in terms of hospitalization capabilities and implementation of chemotherapy treatments. We report the first ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) procedure performed in northeastern Argentina on a patient with multiple colorectal metastases during the SARS-CoV-2 pandemic, with successful outcomes.

Modulación por Passiflora edulis de triglicéridos y colesterol intracelulares en líneas celulares de cáncer colorrectal SW480 y sus derivadas metastásicas (SW620) / Modulation by Passiflora edulis of intracellular triglycerides and cholesterol in SW480 col orectal cancer cell lines and their metastatic derivatives (SW620)

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.

Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Experiencia en cirugía colorrectal resectiva laparoscópica en pacientes mayores de 75 años

Objetivo: Describir la experiencia en cirugía colorrectal resectiva laparoscópica en mayores de 75 años durante los años 2004 a 2019 en Clínica INDISA. Material y Método: Estudio transversal de las cirugías electivas por vía laparoscópica en mayores de 75 años, en los que se realizó anastomosis colorrectal, basado en el registro clínico electrónico. Resultados: Un total de 48 cirugías completamente laparoscópicas, la mayoría por cáncer colorrectal (CCR) (89,6%), mostraron indicadores de calidad óptima en la cosecha ganglionar en el 73,2%. Con una mediana de estadía de 6 días y una mortalidad a 30 días de 2,1% (un caso), comparable a las series internacionales. Discusión: El abordaje laparoscópico en pacientes ancianos tiene beneficios por sobre la vía abierta y presenta morbimortalidad aceptable. El balance intraoperatorio entre riesgo/seguridad quirúrgica y pronóstico oncológico es un factor a tener en cuenta en la toma de decisiones, junto con las patologías inherentes al grupo etario y la reserva funcional de cada paciente en particular. Conclusión: Se trata de la primera serie nacional de pacientes sobre 75 años sometidos a cirugía colorrectal resectiva electiva vía laparoscópica. Es factible y seguro en estos pacientes realizar cirugía mínimamente invasiva con morbimortalidad aceptable. La edad por sí sola no representa una contraindicación para la cirugía colorrectal laparoscópica. Es necesario contar con estudios de mayor volumen para conocer mejor la realidad nacional y los resultados a largo plazo.

Objective: To describe the experience in laparoscopic resective colorectal surgery in older than 75 years old, during 2004 to 2019 in INDISA Clinic. Material and Methods: It's a transversal study about all the elective laparoscopic surgeries with colorectal anastomosis in elderly people, based on electronic clinical records. Results: 48 full laparoscopic surgeries, the majority by colorectal cancer (89.6%) shows optimal quality indicators about nodal harvest in 73.2%. The median duration of hospital stay after surgery was 6 days with 30 days mortality of 2.1%. These results are comparable to the international reports. Discussion: The laparoscopic approach in elderly patients has benefits over the open approach with acceptable morbility and mortality. The intraoperatory balance between surgical risk/security and oncologic prognostic it's a factor to consider in the decision-making process besides the morbility by the age and the own functional reserve. Conclusion. It's the first series in Chile about over 75 years patients with laparoscopic resective colorectal surgery. Is feasible and secure to do minimal invasive surgery with acceptable morbility and mortality. Only the age isn't a contraindication to laparoscopic colorectal surgery. It's necessary more studies with mayor number of patients to known better the national results and long-term results.

Biological Connotation of Pathogenesis of Colorectal Cancer Due to Damp-heat Accumulation Based on Immune Response-intestinal Microbial Axis / 中国实验方剂学杂志

Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Knowledge, attitudes, and practices in colorectal cancer screening in the Philippines

Background and Objective@#Colorectal cancer (CRC) has the third highest incidence in the Philippines. Currently, there is a paucity in literature that is focused on the knowledge, attitudes, and perceptions of Filipinos regarding CRC screening. This is the first study in the Philippines that describes this. @*Methods@#This is a cross-sectional study that validated a 52-item Filipino questionnaire on the knowledge on colorectal cancer, willingness to undergo CRC screening, and perceived benefits and barriers to fecal occult blood test (FOBT) and colonoscopy. The study enrolled household heads more than 20 years of age residing in both urban and rural communities in the Philippines. @*Results@#The UP-PGH CRC KAP (University of the Philippines – Philippine General Hospital Colorectal Cancer Knowledge, Attitudes, and Practices) and Rawl Questionnaire’s validity and internal consistency were established in a pilot study of 30 respondents. A total of 288 respondents were then enrolled to the main study group with a median age of 54.0. Knowledge scores for prognosis and utility of CRC screening were modest (6.3/12 and 8.4/20, respectively). Perceived benefit scores to FOBT and colonoscopy were high (9.9/12 and 13.9/16, respectively).Median scores to barriers to FOBT and colonoscopy were intermediate (22.5/36 and 35.8/60, respectively). Notably, a vast majority (86.1%) were willing to participate in CRC screening programs initiated by the government, and 46.9% agreed to undergo screening tests even as out-of-pocket expense. @*Conclusion@#The UP-PGH CRC KAP Questionnaire as well as the Filipino translation of the Rawl Questionnaire are reliable and valid tools in extensively assessing the knowledge of Filipinos on CRC and willingness to undergo screening, as well as the benefits of and barriers to FOBT and colonoscopy. Knowledge scores were modest suggesting that directed educational campaigns and awareness programs can aid in increasing awareness about CRC and its screening. Household income and highest educational attainment were significantly positively correlated with knowledge scores, and perceived benefits of and barriers to CRC screening. Scores were generally comparable between urban and rural communities.

Mechanism of Fucoidan Phlorofucofuroeckol A on Inhibit the Proliferation and Invasion of Colorectal Cancer Cells by Down-regulating TGF-β1/Smads Signaling Pathway / 医药导报

Objective To investigate the effect of phlorofucofuroeckol A(PFFE-A)on the proliferation and invasion of colorectal carcinoma cells and its regulation of transforming growth factor-β1(TGF-β1)and mothers against decapentaplegic hom-olog 2/3(Smad2/3)signaling pathway.Methods The cells were processed as follows:the cells were intervened with low,medium and high doses of 50,100,and 150 μmol·L-1 of PFFE-A,respectively and cells in the normal control group were also established.5-Ethynyl-2'-deoxyuridine(EdU)staining was used to detect the cell proliferation.The transwell chamber was used to detect the invasion ability.A xenograft colon cancer nude mice model was used to detect the growth and metastasis ability of the cells in vivo.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of epithelial-to-mes-enchymal transition(EMT)related genes.Western blotting was used to detect the expression levels of TGF-β1 and p-Smad2/3 in cells.Results Compared with normal control group,the proliferation rate,the number of invaded cells,the tumor mass,the pro-portion of tumor metastasis,the expression of N-cadherin mRNA,the expression of TGF-β1 and p-Smad2/3 were significantly de-creased(P＜0.05),and the mRNA expression of E-cadherin was significantly increased(P＜0.05).All were presented with a sig-nificant dose-dependent(P＜0.05).Conclusion PFFE-A could inhibit the EMT process of tumor cells,inhibit the prolifera-tion and invasion of HT29 cells in vitro,and down-regulate the growth and metastasis of HT29 cells in vivo,which may be achieved by down-regulating TGF-β1/Smad2/3 signaling pathway.

Application value of combined coagulation function indicators in monitoring hypercoagulable state of patients with colorectal cancer after chemotherapy / 中国癌症杂志

Background and purpose:The plasma used for routine coagulation test(CCT)can only reflect a single component at a certain coagulation time point/segment,while thromboelastography(TEG)can depict the overall dynamic process curve of coagulation and fibrinolysis,which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing.This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy,and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy,so as to provide reference for clinical monitoring of hypercoagulable state.Methods:A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group,and 80 healthy subjects were selected as the control group.Then the experimental group was divided into a group without thrombosis(82 cases)and a group with thrombosis(78 cases)according to whether they had thrombosis or not.The determinations of thromboelastography(TEG)[coagulation reaction time(R),coagulation formation time(K),blood clot formation rate(α-Angle),maximum amplitude(MA)and coagulation index(CI)],conventional coagulation tests(CCT)[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(Fib),D-dimer(DD),fibrinogen degradation products(FDP)]and platelet count(PLT)were studied among three groups.With or without thrombosis as the criterion of hypercoagulable state,statistically significant indicators were selected to be included in the binary logistic regression analysis,and the receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy.Basic information,tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer.Logistic regression analysis was performed to explore the risk factors of thrombosis.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:050432-4-2108*).Results:Compared with the control group,the R,TT and PLT of the group with thrombosis were decreased(P＜0.05),while APTT,PT,DD and FDP were increased(P＜0.05).The differences in various indicators between the group with thrombosis and the control group were statistically significant(P＜0.05).Compared with the group without thrombosis,the K in the group with thrombosis decreased(P＜0.05),while Angle,MA,CI,FIB,DD and FDP all increased(P＜0.05).ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy,the area under curve(AUC)of TEG was 0.756,sensitivity was 67.5%,and specificity was 73.8%.The AUC of CCT was 0.691,sensitivity was 78.8%,and specificity was 56.2%.The combined detection AUC was 0.840,sensitivity was 80.0%,and specificity was 77.5%.In the analysis of risk factors,tumor stage,distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy(P＜0.05),and the differences of the three risk factors in K,Angle,MA,CI,Fib,DD and FDP were statistically significant(P＜0.05).Conclusion:K,Angle,MA,CI,Fib,DD and FDP are the main indicators to reflect the hypercoagulable state,and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy.Tumor stage Ⅲ to Ⅳ,distant metastasis and high Autar score are risk factors for thrombosis.The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.

Effects of Nalbuphine combined with Sufentanil on postoperative analgesia and stress response in patients undergoing laparoscopic colorectal cancer surgery / 中国内镜杂志

Objective To investigate the impacts of Nalbuphine combined with Sufentanil on postoperative analgesia and stress response in patients undergoing laparoscopic colorectal cancer surgery.Methods 86 patients who underwent laparoscopic colorectal cancer surgery from August 2020 to April 2022 were collected and grouped into an experimental group and a control group according to the analgesic plan,with 43 patients in each group.The control group was given Sufentanil after surgery,and the experimental group was given Nalbuphine + Sufentanil.The analgesic and sedative effects at different time points after surgery(1,6,12,24 and 48 h),and the changes in serum pain mediator and stress response indicators were observed and compared.The time of getting out of bed after surgery,the number of patient-controlled analgesia,the number of cases of remedial analgesia,the recovery of gastrointestinal function,and the occurrence of adverse reactions within 48 hours after surgery were recorded in both groups.Results Compared with the control group,the experimental group had a shorter time to get out of bed for the first time after surgery(t = 3.29,P = 0.001),and had fewer instances of patient-controlled analgesia(Z = 4.53,P = 0.000)and cases of remedial analgesia(χ2 = 4.48,P = 0.034);Postoperative 12,24 and 48 h after surgery,the visual analogue scale(VAS)in the experimental group was obviously lower than that in the control group(t = 2.86,t = 2.55,t = 0.10,P<0.05);Postoperative 1 and 6 h,the Ramsay sedation score in the experimental group patients was lower than that in the control group(t = 2.10,t = 2.07,P<0.05);Postoperative 6,12 and 24 h,the serum substance P(SP)(t = 3.63,t = 5.51,t = 3.46,P<0.05)and prostaglandin E2(PGE2)(t = 2.34,t = 3.56,t = 0.33,P<0.05)levels in the experimental group were obviously lower than those in the control group;Postoperative 6,12 and 24 h,the serum cortisol(Cor)level in the experimental group was obviously lower than that in the control group(t = 4.65,t = 6.50,t = 6.52,P<0.05);Postoperative 6,12,24 and 48 h,the serum norepinephrine(NE)(t = 5.49,t = 7.85,t = 7.70,t = 2.18,P<0.05),tumor necrosis factor-α(TNF-α)(t = 5.43,t = 7.83,t = 5.27,t = 2.32,P<0.05),and hypersensitivity C-reactive protein(hs-CRP)(t = 3.39,t = 9.241,t = 4.87,t = 2.37,P<0.05)levels in the experimental group were obviously lower than those in the control group.There was no statistically obvious difference between the two groups in terms of postoperative exhaust time,defecation time,bowel sounds occurrence time,and incidence of adverse reactions(P>0.05).Conclusion Nalbuphine combined with Sufentanil is effective in postoperative analgesia of laparoscopic colorectal cancer patients,and can effectively regulate the post-traumatic stress response of the body after surgery.

Optimization of the azomethane oxide and dextran sodium sulfate model of colitis-associated colon cancer and changes in the intestinal microbiota / 中国实验动物学报

Objective To optimize the method of combining azomethane oxide(AOM)and dextran sodium sulfate(DSS)to create a colitis-associated colon cancer(CAC)model,and to explore the pathogenesis of the intestinal flora in CAC.Methods Model groups A and B were established by one and two injections of AOM,respectively,combined with free drinking of DSS,and a normal control group was injected intraperitoneally with normal saline combined with purified water(n=10 mice per group).The better modeling scheme was selected by comprehensive evaluation of the disease activity index score,colon length,tumor rate,and mortality.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and tumor markers CA199,CEA,and CA724 were detected by enzyme-linked immunosorbent assay.Colon lesions were evaluated by hematoxylin and eosin(HE)staining.Changes in the intestinal microbiota in CAC mice were detected by 16S rDNA high-throughput gene sequencing analysis of mouse feces.Results Both single and enhanced AOM injections combined with DSS induced CAC mice;however,colon growths were larger,more closely arranged,and their morphological size was more consistent in group B compared with group A,with a tumor-formation rate of 100％.IL-6 levels were increased in the model group compared with the normal group(P＜0.05).TNF-α levels were increased in the model group compared with the normal group(P＞0.05).The CA199 and CEA levels were also significantly increased(P＜0.05),but CA724 levels were not.Infiltration of inflammatory cells in the colon detected by HE pathology was accompanied by high-grade intraepithelial tumor-like changes on the surface of the lumen.The diversity and abundance of intestinal bacteria were decreased in CAC mice compared with normal mice:phyla Verrucomicrobiota and Actinobacteriota were significantly increased(P＜0.05),Bacteroidota and Campilobacterota were significantly decreased(P＜0.05).Akkermansia,Prevotellaceae,Ruminococcus,and Bifidobacterium were significantly increased(P＜0.05),and Roseburia,Rikenellaceae_RC9_gut_group,Anaeroplasma,and Muribaculaceae were significantly decreased(P＜0.05).Conclusions Two injections of AOM combined with 1.5％(1.5 g/100 mL)DSS induced CAC model mice with a high colon-tumorigenesis rate,uniform tumor morphology,and low mortality,and may thus be the preferred modeling scheme for pharmacodynamic experiments.Disorders or dysfunction of the intestinal flora may lead to increased permeability,loss of intestinal mucosal barrier function,and the release of enterogenic endotoxins,Resultsing in a sustained inflammatory response,as an indirect or direct cause of CAC pathogenesis.

Mechanism of dihydroartemisinin binding SERCA2b and inducing apoptosis in colorectal cell HCT-116 / 中国医科大学学报

Objective To investigate the binding sites of dihydroartemisinin(DHA)and sarcoplasmic/endoplasmic reticulum calcium ATPase(SERCA)and explore the mechanisms underlying apoptosis induction in HCT-116 colon cancer cells through the mitochondrial pathway.Methods HCT-116 cells were cultured in DHA concentrations of 0,10,20,40 μmol/L.After 24 h of culture,Western blot-ting assessed SERCA concentration,CCK-8 measured cell proliferation,Hoechst nuclear staining examined cell apoptosis,JC-1 probe evaluated mitochondrial membrane potential.LeDock molecular docking predicted DHA and SERCA binding sites.Synthetic SERCA2b mutated and non-mutated proteins at Ile315 and Thr316 sites were combined with small molecule DHA using biofilm interference tech-nology.Results Western blotting revealed a significant decrease in SERCA2 protein levels with increasing DHA concentration.CCK-8 demonstrated a statistically significant decrease in cell proliferation with increasing DHA concentration(P＜0.01).Hoechst nuclear staining illustrated DHA-induced rounding and pyknosis of HCT-116 cell nuclei compared to the control group.DHA gradually decreased mitochondrial membrane potential within the first 4 h of treatment,starting from 5 h,followed by a sustained reduction.Molecular docking predicted a hydrogen bond with Thr316 and a hydrophobic interaction with Ile315.Biofilm interference techniques indicated robust binding of DHA to non-mutated SERCA2b protein,while binding to the SERCA2b mutant protein at Ile315 and Thr316 sites was poor.Conclusion DHA directly binds to the Ile315 and Thr316 sites of SERCA2b,inducing apoptosis in colon cancer cells HCT-116 through the mitochondrial pathway.