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)

Medullary colon carcinoma with microsatellite instability: case report / Carcinoma medular do cólon com instabilidade de microssatélites: relato de caso

Colorectal cancer is the third most common neoplasm and the second most lethal worldwide. The most common histological type is adenocarcinoma, characterized by its glandular pattern. Medullary colon carcinoma is a rare histological variant of colorectal cancer, characterized by a predominantly solid architecture, poorly di?erentiated or undifferentiated morphology, often associated with an anomalous immunophenotype and microsatellite instability. The present study reports a case in an academic service of general surgery of a 74-year-old patient who presented with a tumor of the ascending colon, histologically with an exuberant lymphocytic in?ltrate, suggestive of large cell lymphoma, but which was revealed by subsequent immunohistochemistry to be medullary carcinoma of the colon with microsatellite instability.

O câncer colorretal é a terceira neoplasia mais comum e a segunda mais letal no mundo. O adenocarcinoma é o tipo histológico mais comum, caracterizado pelo seu padrão glandular. O carcinoma medular do cólon é uma variante histológica rara do câncer colorretal, caracterizada por uma arquitetura predominantemente sólida, morfologia pouco diferenciada ou indiferenciada, frequentemente associada a um imunofenótipo anômalo e instabilidade de microssatélites. O presente estudo relata um caso em um serviço acadêmico de cirurgia geral de um paciente de 74 anos que apresentou tumor de cólon ascendente, histologicamente com infiltrado linfocitário exuberante, sugestivo de linfoma de grandes células, mas que foi revelado através de exame subsequente imunohistoquímico como carcinoma medular do cólon com instabilidade de microssatélites.

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Fiebre prolongada, síndrome de Good y cáncer de colon: una asociación poco frecuente / Prolonged fever, Good syndrome and colon cancer: a rare association

Se define «síndrome febril prolongado¼ a todo cuadro de hipertermia que persiste al menos 10 días sin ser diagnosticado. El síndrome de Good es una inmunodeficiencia primaria del adulto que se caracteriza por presentar hipogammaglobulinemia, disminución de linfocitos B y anormalidades en los linfocitos T. Entre el 15 y el 20% de los casos de «fiebre de origen desconocido¼ ocurren debido a neoplasias, y el cáncer de colon representa menos del 1% de todos estos casos. Se presenta una paciente de 49 años admitida en el hospital por presentar síndrome febril con un mes de evolución, con antecedentes de síndrome de Good. Se le diagnostica cáncer de colon. (AU)

A prolonged febrile syndrome (PFS) is defined as any episode of hyperthermia that persists for at least 10 days without being diagnosed. Good's syndrome is a primary immunodeficiency in adults characterized by hypogammaglobulinemia, decreased B lymphocytes, and abnormalities in T lymphocytes. Between 15 to 20% of fever of unknown origin (FOD) cases are due to neoplasms, and colon cancer represents less than 1% of all these cases. A 49-year-old patient with a history of Good's syndrome was admitted to the hospital due to a febrile syndrome lasting for a month. She was diagnosed with colon cancer. (AU)

Variaciones anatómicas en la vascularización del colon derecho y su implicancia en la escisión completa del mesocolon con linfadenectomía D3. Estudio de corte transversal / Anatomical variations in right colon vascularization: its implication in complete mesocolic excision with D3 lymphadenectomy. A cross-sectional study

Introducción: La escisión completa del mesocolon con linfadenectomía D3 (CME-D3) mejora los resultados de los pacientes operados por cáncer del colon. Reconocer adecuadamente la anatomía vascular es fundamental para evitar complicaciones. Objetivo: El objetivo primario fue determinar la prevalencia de las variaciones anatómicas de la arteria mesentérica superior (AMS) y sus ramas en relación a la vena mesentérica superior (VMS). El objetivo secundario fue evaluar la asociación entre las distintas variantes anatómicas y el sexo y la etnia de lo pacientes. Diseño: Estudio de corte transversal. Material y métodos: Se incluyeron 225 pacientes con cáncer del colon derecho diagnosticados entre enero 2017 y diciembre de 2020. Dos radiólogos independientes describieron la anatomía vascular observada en las tomografías computadas. Según la relación de las ramas de la AMS con la VMS, la población fue dividida en 2 grupos y subdividida en 6 (1a-c, 2a-c). Resultados: La arteria ileocólica fue constante, transcurriendo en el 58,7% de los casos por la cara posterior de la VMS. La arteria cólica derecha, presente en el 39,6% de los pacientes, cruzó la VMS por su cara anterior en el 95,5% de los casos. La variante de subgrupo más frecuente fue la 2a seguida por la 1a (36,4 y 24%, respectivamente). No se encontró asociación entre las variantes anatómicas y el sexo u origen étnico. Conclusión: Las variaciones anatómicas de la AMS y sus ramas son frecuentes y no presentan un patrón predominante. No hubo asociación entre las mismas y el sexo u origen étnico en nuestra cohorte. El reconocimiento preoperatorio de estas variantes mediante angiotomografía resulta útil para evitar lesiones vasculares durante la CME-D3. (AU)

Background: Complete mesocolic excision with D3 lymphadenectomy (CME-D3) improves the outcomes of patients operated on for colon cancer. Proper recognition of vascular anatomy is essential to avoid complications. Aim: Primary outcome was to determine the prevalence of anatomical variations of the superior mesenteric artery (SMA) and its branches in relation to the superior mesenteric vein (SMV). Secondary outcome was to evaluate the association between these anatomical variations and sex and ethnicity of the patients. Design: Cross-sectional study. Material and methods: Two hundred twenty-fivepatients with right colon cancer diagnosed between January 2017 and December 2020 were included. Two independent radiologists described the vascular anatomy of computed tomography scans. The population was divided into 2 groups and subdivided into 6 groups (1a-c, 2a-c), according to the relationship of the SMA and its branches with the SMV. Results: The ileocolic artery was constant, crossing the SMV posteriorly in 58.7% of the cases. The right colic artery, present in 39.6% of the patients, crossed the SMV on its anterior aspect in 95.5% of the cases. The most frequent subgroup variant was 2a followed by 1a (36.4 and 24%, respectively). No association was found between anatomical variants and gender or ethnic origin. Conclusions: The anatomical variations of the SMA and its branches are common, with no predominant pattern. There was no association between anatomical variations and gender or ethnic origin in our cohort. Preoperative evaluation of these variations by computed tomography angi-ography is useful to avoid vascular injuries during CME-D3. (AU)

Identification of potential urinary protein biomarkers in colorectal cancer: a pilot study using a proteomic approach

Colorectal cancer (CRC) is among the most diagnosed malignancies worldwide, and it is also the second leading cause of cancer-related deaths. Despite recent progress in screening programs, noninvasive accurate biomarkers are still needed in the CRC field. In this study, we evaluated and compared the urinary proteomic profiles of patients with colorectal adenocarcinoma and patients without cancer, aiming to identify potential biomarker proteins. Urine samples were collected from 9 patients with CRC and 9 patients with normal colonoscopy results. Mass spectrometry (label-free LC—MS/MS) was used to characterize the proteomic profile of the groups. Ten proteins that were differentially regulated were identified between patients in the experimental group and in the control group, with statistical significance with a p value ≤ 0.05. The only protein that presented upregulation in the CRC group was beta-2-microglobulin (B2M). Subsequent studies are needed to evaluate patients through different analysis approaches to independently verify and validate these biomarker candidates in a larger cohort sample. (AU)

Prognostic roles and survival benefits of endoscopic resection versus surgical resection in the management of malignant colon polyps

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)

Risk factors and outcomes of occurrence of anastomotic leakage and reoperations for its management after colorectal surgery

Background: Anastomotic leakage (AL) is still the most annoying postsurgery complication after colorectal resection due to its serious complications up to death. Limited data were available regarding differences in AL incidence, management, and consequences for different types of colorectal resection. The aim of the present work was to evaluate differences in incidence of AL, incidence of postoperative complications, and length of hospital stay in a large number of patients who underwent elective colorectal resection for management of colorectal lesions. In addition to detect when and what type of reoperation for management of AL occur after colorectal resection. Patients: All 250 included patients underwent elective surgeries for colorectal resection with performance of primary anastomosis for management of colorectal neoplastic and non-neoplastic diseases in the period between May 2016 and July 31, 2021. We followed the patients for 90 days; we registered the follow-up findings. Results: the rates of AL occurrence were variable after the different procedures. The lowest rate of AL occurrence was found in patients who underwent right hemicolectomy, then in patients who underwent sigmoidectomy, left hemicolectomy, transversectomy and anterior resection (p= 0.004). A stoma was frequently performed during reoperation (79.5%) which was significantly different between different procedures: 65.5% in right hemicolectomy, 75.0% in transversectomy, 85.7% in left hemicolectomy, and 93.0% in sigmoid resection (p< 0.001). Conclusion Rates, types, time of occurrence and severity of AL vary according to the type of colectomy performed and selective construction of stoma during AL reoperation is currently safely applied with comparable mortality rates for patients who did and who did not have a stoma after reoperation. (AU)

Fulminant endogenous panophthalmitis caused by Clostridium septicum infection / Panoftalmite endógena fulminante por infecção por Clostridium septicum

ABSTRACT We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.

RESUMO Este é o relato de um caso incomum de panoftalmite endógena fulminante por Clostridium septicum. Um paciente do sexo masculino, 74 anos, apresentou amaurose súbita no olho direito, que em poucas horas evoluiu para celulite orbitária, endoftalmite, isquemia do segmento anterior e perfuração secundária do olho. Foi realizado um estudo diagnóstico completo, que incluiu uma tomografia computadorizada com contraste cranial e orbital, um exame de ressonância magnética, hemocultura e hemograma completo. Nenhum agente causal foi identificado. A infecção por Clostridium septicum causou uma panoftalmite gasosa fulminante. Apesar do tratamento com antibióticos de amplo espectro, foi necessário eviscerar o globo ocular. O estudo de seguimento mostrou um adenocarcinoma de cólon como a origem da infecção. A panoftalmite por Clostridium septicum é um tipo raro, mas muito agressivo de infecção orbitária. Essa infecção deve sugerir a busca por um processo neoplásico no trato gastrointestinal, em muitos casos não diagnosticado anteriormente.

Self-Management Program in Adults with Colorectal Cancer: A Pilot Study / Programa de automanejo en adultos con cáncer colorrectal: estudio piloto / Programa de autogestão em adultos com câncer colorretal: estudo-piloto

Objective: To design and validate a nursing intervention and its effect on improving self-management behaviors in patients with colorectal cancer following surgery within eight weeks after discharge. Method: Pilot study using Sidane and Braden's intervention design proposal, which included determining the guiding theoretical model, characterization of the intervention, validation with eight experts through content validity, and a pilot test with ten patients during the second semester of 2020. Results: The intervention obtained, called the Program for Self-Management Training in Colorectal Cancer (PEACCR, by its acronym in Spanish), is based on the theory of individual and family self-management in the dimensions proposed by Ryan and Sawin. The validity with experts indicates that it meets the criteria of clarity, precision, comprehension, relevance, and pertinence. The pilot reports an increase in self-management behaviors and the dimensions of knowledge, coping, and health personnel-patient alliance in months 1 and 2, with statistical significance. Conclusions: The designed and validated intervention increases the self-management behaviors of patients with colorectal cancer. The proposed scheme is highly acceptable to participants.

Objetivo: diseñar y validar una intervención de enfermería y su efecto para mejorar los comportamientos de automanejo en pacientes con cáncer colorrectal, después de una intervención quirúrgica dentro de las ocho semanas posteriores al alta. Método: estudio piloto que acoge la propuesta de diseño de intervenciones de Sidane y Braden, lo que incluyó determinar el modelo teórico orientador, la caracterización de la intervención, la validación con ocho expertos a través de la validez de contenido, y una prueba piloto con diez pacientes, durante el segundo semestre del año 2020. Resultados: la intervención obtenida, denominada Programa para el Entrenamiento en Automanejo en Cáncer Colorrectal (PEACCR), se basa en la teoría de automanejo individual y familiar en las dimensiones planteadas por Ryan y Sawin. La validez con expertos indica que cumple con los criterios de claridad, precisión, comprensión, relevancia y pertinencia. El piloto reporta un aumento en los comportamientos de automanejo y en las dimensiones de conocimiento, afrontamiento y alianza personal de salud-paciente en el mes 1 y en el mes 2, con significancia estadística. Conclusiones: la intervención diseñada y validada aumenta los comportamientos de automanejo de pacientes con cáncer colorrectal. El esquema propuesto es de alta aceptabilidad para los participantes.

Objetivo: desenhar e validar uma intervenção de enfermagem e seu efeito para melhorar os comportamentos de autogestão em pacientes com câncer colorretal, depois de uma intervenção cirúrgica dentro das oito semanas posteriores à alta. Materiais e método: estudo-piloto que utiliza a proposta de desenho de intervenções de Sidane e Braden, o que inclui determinar o modelo teórico orientador, a caracterização da intervenção, a validação com oitos especialistas por meio da validade de conteúdo e um teste-piloto com dez pacientes, durante o segundo semestre de 2020. Resultados: a intervenção obtida, denominada "Programa para o Treinamento em Autogestão em Câncer Colorretal", está baseada na teoria de autogestão individual e familiar nas dimensões propostas por Ryan e Sawin. A validade com especialistas indica que cumpre com os critérios de clareza, precisão, compreensão, relevância e pertinência. O piloto relata um aumento nos comportamentos de autogestão e nas dimensões de conhecimento, enfrentamento e parceria pessoal de saúde-paciente no mês 1 e no mês 2, com significância estatística. Conclusões: a intervenção desenhada e validada aumenta os comportamentos de autogestão de pacientes com câncer colorretal. O esquema proposto é de alta aceitabilidade para os participantes.

Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology.@*METHODS@#TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice.@*RESULTS@#Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05).@*CONCLUSION@#LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

NKD1 promotes glucose uptake in colon cancer cells by activating YWHAE transcription / 南方医科大学学报

OBJECTIVE@#Bo investigate the regulatory relationship between NKD1 and YWHAE and the mechanism of NKD1 for promoting tumor cell proliferation.@*METHODS@#HCT116 cells transfected with pcDNA3.0-NKD1 plasmid, SW620 cells transfected with NKD1 siRNA, HCT116 cells with stable NKD1 overexpression (HCT116-NKD1 cells), SW620 cells with nkd1knockout (SW620-nkd1-/- cells), and SW620-nkd1-/- cells transfected with pcDNA3.0-YWHAE plasmid were examined for changes in mRNA and protein expression levels of YWHAE using qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NKD1 to the promoter region of YWHAE gene. The regulatory effect of NKD1 on YWHAE gene promoter activity was analyzed by dual-luciferase reporter gene assay, and the interaction between NKD1 and YWHAE was analyzed with immunofluorescence assay. The regulatory effect of NKD1 on glucose uptake was examined in the tumor cells.@*RESULTS@#In HCT116 cells, overexpression of NKD1 significantly enhanced the expression of YWHAE at both the mRNA and protein levels, while NKD1 knockout decreased its expression in SW620 cells (P < 0.001). ChIP assay showed that NKD1 protein was capable of binding to the YWHAE promoter sequence; dual luciferase reporter gene assay showed that NKD1 overexpression (or knockdown) in the colon cancer cells significantly enhanced (or reduced) the transcriptional activity of YWHAE promoter (P < 0.05). Immunofluorescence assay demonstrated the binding of NKD1 and YWHAE proteins in colon cancer cells. NKD1 knockout significantly reduced glucose uptake in colon cancer cells (P < 0.01), while YWHAE overexpression restored the glucose uptake in NKD1-knockout cells (P < 0.05).@*CONCLUSION@#NKD1 protein activates the transcriptional activity of YWHAE gene to promote glucose uptake in colon cancer cells.

Identification of immune-related prognostic signature for colon adenocarcinoma based on weighted gene co-expression network analysis / 细胞与分子免疫学杂志

Objective To identify immune-related molecular markers in an attempt to predict prognosis of colon adenocarcinoma (COAD). Methods Immune related genes (IREGs) was analyzed based on the TCGA database. Weighted gene co-expression network analysis (WGCNA) and Cox regression analysis were used to establish risk models. According to the median risk score, COAD patients were divided into high risk and low risk groups. The prognostic difference were compared between the two groups. The function of the model was validated using GEO. Results A total of 1015 IREGs was obtained. The established model consisted of three genes: RAR related orphan receptor C (RORC), leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) and lectin galactoside-binding soluble galectin 4 (LGALS4). The high-risk group had significantly poorer prognosis than low-risk group in the GEO database, and it was validated using a GEO database. Further analysis via univariate and multivariate Cox regression analyses revealed that risk model could function as independent prognostic factor for COAD patients. Conclusion The risk model based on IREGs can predict the prognosis of patients with COAD.

Long non-coding RNA colon cancer-associated transcript 1-Vimentin axis promoting the migration and invasion of HeLa cells / 中华医学杂志(英文版)

BACKGROUND@#Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis.@*METHODS@#CCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells.@*RESULTS@#RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein.@*CONCLUSION@#CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.

Bletilla striata polysaccharide improves toxic and side effects induced by 5-FU: an untargeted metabolomics study / 中国中药杂志

This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.

Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Silenced ANP32A inhibits the growth, invasion and migration of colorectal cancer in vitro via the inactivation of AKT pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of ANP32A silencing on invasion and migration of colon cancer cells and the influence of the activity of AKT signaling pathway on this effect.@*METHODS@#Colorectal cancer HCT116 and SW480 were transfected with a small interfering RNA targeting ANP32A via a lentiviral vector. At 24, 48 and 72 h after the transfection, the changes in cell proliferation and AKT activity in the cells were detected using MTT assay and Western blotting, respectively. HCT116 and SW480 cells were treated with the AKT agonist SC79 or its inhibitor MK2206 for 24, 48, 72 and 96 h, and the changes in cell migration and invasion ability were analyzed using Transwell chamber assay and cell proliferation was assessed using MTT assay. The effects of SC79 and MK2206 on migration and invasion abilities of HCT116 and SW480 cells with or without ANP32A silencing were examined using wound healing and Transwell chamber assays, and the changes in the expression of metadherin (MTDH), a factor associated with cells invasion and migration, was detected with Western blotting.@*RESULTS@#Lentivirus-mediated ANP32A silencing significantly down-regulated the activity of AKT and inhibited the proliferation of both HCT116 and SW480 cells (P < 0.01). The application of AKT inhibitor MK2206 obviously inhibited the proliferation, invasion and migration of the colorectal cancer cells (P < 0.05), while the AKT agonist SC79 significantly promoted the invasion and migration of the cells (P < 0.01). In HCT116 and SW480 cells with ANP32A silencing, treatment with MK2206 strongly enhanced the inhibitory effects of ANP32A silencing on cell invasion and migration (P < 0.05) and the expression of MTDH, while SC79 partially reversed these inhibitory effects (P < 0.01).@*CONCLUSION@#ANP32A silencing inhibits invasion and migration of colorectal cancer cells possibly by inhibiting the activation of the AKT signaling pathway.