Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.922
Filter
1.
J. coloproctol. (Rio J., Impr.) ; 43(3): 171-178, July-sept. 2023. tab, graf, ilus
Article in English | LILACS | ID: biblio-1521147

ABSTRACT

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)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Rectal Neoplasms/diagnosis , Biomarkers, Tumor/urine , Colonic Neoplasms/diagnosis , Proteomics , Neoplasm Staging
2.
J. coloproctol. (Rio J., Impr.) ; 43(2): 82-92, Apr.-June 2023. tab, graf
Article in English | LILACS | ID: biblio-1514426

ABSTRACT

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)


Subject(s)
Humans , Male , Female , Postoperative Complications , Colonic Neoplasms/surgery , Anastomotic Leak/epidemiology , Reoperation , Health Profile , Risk Factors , Treatment Outcome , Neoplasm Staging
3.
J. coloproctol. (Rio J., Impr.) ; 43(2): 126-132, Apr.-June 2023. tab, graf, ilus
Article in English | LILACS | ID: biblio-1514430

ABSTRACT

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)


Subject(s)
Digestive System Surgical Procedures/methods , Colonic Polyps/surgery , Colonic Neoplasms/mortality , Laparoscopy , Endoscopy , Neoplasm Recurrence, Local , Neoplasm Staging
4.
Arq. bras. oftalmol ; 86(1): 71-73, Jan.-Feb. 2023. graf
Article in English | LILACS | ID: biblio-1403476

ABSTRACT

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.


Subject(s)
Humans , Aged , Adenocarcinoma , Colonic Neoplasms , Clostridium septicum , Adenocarcinoma/complications , Adenocarcinoma/diagnostic imaging
5.
Aquichan ; 23(1): e2317, 13 ene 2023.
Article in English, Spanish | LILACS, BDENF, COLNAL | ID: biblio-1436430

ABSTRACT

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.


Subject(s)
Patient Discharge , Treatment Outcome , Colonic Neoplasms , Evaluation of the Efficacy-Effectiveness of Interventions , Self-Management , Nursing
7.
Chinese Journal of Cellular and Molecular Immunology ; (12): 509-515, 2023.
Article in Chinese | WPRIM | ID: wpr-981893

ABSTRACT

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.


Subject(s)
Humans , Prognosis , Adenocarcinoma/genetics , Colonic Neoplasms/genetics , Gene Expression Profiling , Lectins
8.
Chinese Journal of Gastrointestinal Surgery ; (12): 58-67, 2023.
Article in Chinese | WPRIM | ID: wpr-971234

ABSTRACT

Immunotherapy has been one of the hot topics in the field of colorectal cancer research in recent years. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) are the main beneficiaries of immunotherapy. The response rate of patients with dMMR/MSI-H colorectal cancer receiving neoadjuvant immunotherapy is nearly 100%, of which the pathological complete response rate approximately accounts for 60%-67%. The prospect of neoadjuvant immunotherapy in dMMR or MSI-H colorectal cancer patients, especially in the rectal cancer patients, lies in achieving sustainable clinical complete response so as to achieve organ preservation and avoid adverse effects on reproductive, sexual, bowel and bladder function after surgery and radiotherapy. Studies have shown that part of the colorectal cancer patients of microsatellite stability (MSS) or mismatch repair proficient (pMMR) can respond to neoadjuvant immunotherapy in combination with other treatment methods such as radiotherapy and chemotherapy. In pMMR or MSS colorectal cancer, optimizing neoadjuvant immunotherapy regimens and finding effective efficacy prediction biomarkers are important research directions. In neoadjuvant immunotherapy, overcoming primary and secondary resistance and identifying the pseudoprogression and hyperprogression of neoadjuvant immunotherapy are clinical challenges that require attention. This paper comprehensively reviews the research progress, controversies,challenges and future research directions of neoadjuvant immunotherapy (mainly immune checkpoint inhibitors) in colorectal cancer.


Subject(s)
Humans , Neoadjuvant Therapy/methods , Colorectal Neoplasms/drug therapy , Colonic Neoplasms/pathology , Immunotherapy/methods , DNA Mismatch Repair , Microsatellite Instability
9.
Chinese Journal of Gastrointestinal Surgery ; (12): 44-50, 2023.
Article in Chinese | WPRIM | ID: wpr-971232

ABSTRACT

Obstructive colorectal cancer is a common malignant bowel obstruction. Colostomy or colostomy following tumor resection may be the first choice for emergency surgery. The intestinal and systemic conditions of patients undergoing emergency surgery are often poor, and patients need to undergo multiple operations, which increase the surgical risk and economic burden and reduce the quality of life of patients. Poor intraoperative visualization may also affect the radical operation of emergency surgery. Transanal decompression tube (TDT) can rapidly decompress and drain the obstructed bowel, effectively relieve obstruction symptoms, and improve the success rate of primary radical resection. The TDT squeeze the tumor lightly, causing no spread of tumor cells, and is cheap, but the cavity of transanal decompression tube is small and easily blocked, and requires tedious flushing or regular replacement. Self-expanding metallic stents (SEMS) can relieve intestinal obstruction effectively, provide sufficient preparation time for preoperative examination and improvement of nutritional status. By improving patient's tolerance to radical surgery, SEMS might be used as an important treatment strategy choice for obstructive colorectal cancer. However, SEMS may squeeze the tumor, leading to the spread of tumor cells, increase the recurrence rate and metastasis rate, and reduce the survival rate. Moreover, intestinal wall edema still existed during the operation following SEMS, and the rate of ostomy after anastomosis was as high as 34%. We hypothesized that prolonging the interval between stent insertion and surgery to 2 months, with neoadjuvant chemotherapy administered during this interval (SEMS-neoadjuvant chemotherapy strategy), would help improve outcomes. The SEMS-neoadjuvant chemotherapy strategy is a safe, effective, and well tolerated treatment approach with a high laparoscopic resection rate, low stoma formation rate and improvement in the overall survival for patients with left-sided colon cancer obstruction. The patient physical status is improved, the primary tumor is downstaged, and intestinal wall edema is relieved during the relatively longer interval between SEMS placement and surgery. The SEMS-neoadjuvant chemotherapy strategy may be a preferred therapeutic strategy for obstructive left colon cancer.


Subject(s)
Humans , Quality of Life , Self Expandable Metallic Stents/adverse effects , Colonic Neoplasms/surgery , Stents/adverse effects , Intestinal Obstruction/surgery , Treatment Outcome , Colorectal Neoplasms/complications , Retrospective Studies
10.
Journal of Southern Medical University ; (12): 1051-1062, 2023.
Article in Chinese | WPRIM | ID: wpr-987022

ABSTRACT

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.


Subject(s)
Mice , Animals , Toll-Like Receptor 4 , Colitis-Associated Neoplasms , Network Pharmacology , Mice, Inbred C57BL , Colonic Neoplasms/pathology
11.
Journal of Southern Medical University ; (12): 585-589, 2023.
Article in Chinese | WPRIM | ID: wpr-986965

ABSTRACT

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.


Subject(s)
Humans , Colonic Neoplasms , HCT116 Cells , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , RNA, Messenger , Glucose , Calcium-Binding Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , 14-3-3 Proteins/metabolism
12.
Chinese Journal of Gastrointestinal Surgery ; (12): 701-706, 2023.
Article in Chinese | WPRIM | ID: wpr-986840

ABSTRACT

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.


Subject(s)
Humans , Laparoscopy/methods , Colonic Neoplasms/pathology , Lymph Node Excision/methods , Colectomy/methods , Dissection
13.
Chinese Journal of Gastrointestinal Surgery ; (12): 650-655, 2023.
Article in Chinese | WPRIM | ID: wpr-986834

ABSTRACT

The theory of membrane anatomy has been widely used in the field of colorectal surgery. The key point to perform high quality total mesorectal excision (TME) and complete mesocolic excision (CME) is to identify the correct anatomical plane. Intraoperative identification of the various fasciae and fascial spaces is the key to accessing the correct surgical plane and surgical success. The landmark vessels refer to the small vessels that originate from the original peritoneum on the surface of the abdominal viscera during embryonic development and are produced by the fusion of the fascial space. From the point of view of embryonic development, the abdominopelvic fascial structure is a continuous unit, and the landmark vessels on its surface do not change morphologically with the fusion of fasciae and have a specific pattern. Drawing on previous literature and clinical surgical observations, we believe that tiny vessels could be used to identify various fused fasciae and anatomical planes. This is a specific example of membrane anatomical surgery.


Subject(s)
Humans , Mesentery/surgery , Colonic Neoplasms/surgery , Colorectal Surgery , Digestive System Surgical Procedures , Peritoneum/surgery , Rectal Neoplasms/surgery , Laparoscopy
14.
Chinese Journal of Gastrointestinal Surgery ; (12): 639-643, 2023.
Article in Chinese | WPRIM | ID: wpr-986832

ABSTRACT

Complete mesocolic excision (CME) and D3 resection of right colon cancer have been widely implemented, but the definition and identification of the completeness of the mesentery have not been fully agreed, especially the dorsal and medial borders. In this paper, we proposed the dorsal fascia of the colonic mesentery as the dorsal border of the mesocolon and the line connecting the roots of the ileocolic artery and the middle colic artery (ICA-MCA line) as the medial border of the CME by systematically studying the relationship between the mesentery and the mesenteric bed from the theory of membrane anatomy, combined with surgical experience and in-depth review of ontogenetic anatomy. We also proposed the visible "superior mesenteric vein notch" and "middle colic artery triangle" on surgical specimens as identifiers of mesocolic completeness.


Subject(s)
Humans , Mesocolon/surgery , Lymph Node Excision , Colectomy , Laparoscopy , Colonic Neoplasms/surgery
15.
Chinese Journal of Gastrointestinal Surgery ; (12): 423-428, 2023.
Article in Chinese | WPRIM | ID: wpr-986809

ABSTRACT

Peritoneal metastatic colorectal cancer (pmCRC) is common and has been considered as the terminal stage. The theory of "seed and soil" and "oligometastasis" are the acknowledged hypotheses of pathogenesis of pmCRC. In recent years, the molecular mechanism related to pmCRC has been deeply researched. We realize that the formation of peritoneal metastasis, from detachment of cells from primary tumor to mesothelial adhesion and invasion, depends on the interplay of multiple molecules. Various components of tumor microenvironment also work as regulators in this process. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been widely used in clinical practice as an established treatment for pmCRC. Besides systemic chemotherapy, targeted and immunotherapeutic drugs are also increasingly used to improve prognosis. This article reviews the molecular mechanisms and treatment strategies related to pmCRC.


Subject(s)
Humans , Colorectal Neoplasms/pathology , Combined Modality Therapy , Peritoneal Neoplasms/secondary , Hyperthermia, Induced , Colonic Neoplasms/therapy , Rectal Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Cytoreduction Surgical Procedures , Survival Rate , Tumor Microenvironment
16.
Journal of Southern Medical University ; (12): 52-59, 2023.
Article in Chinese | WPRIM | ID: wpr-971494

ABSTRACT

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.


Subject(s)
Humans , Proto-Oncogene Proteins c-akt , Cell Proliferation , Blotting, Western , Cell Movement , Colonic Neoplasms , Membrane Proteins , RNA-Binding Proteins/genetics , Nuclear Proteins
17.
Journal of Zhejiang University. Science. B ; (12): 221-231, 2023.
Article in English | WPRIM | ID: wpr-971482

ABSTRACT

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.


Subject(s)
Humans , Glycolysis , Colonic Neoplasms/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Phosphopyruvate Hydratase/metabolism , Flavanones/pharmacology , Cell Line, Tumor , Databases, Genetic , Cell Proliferation/drug effects , Transfection , Warburg Effect, Oncologic
18.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 333-345, 2023.
Article in English | WPRIM | ID: wpr-982705

ABSTRACT

The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment (TIME). This study aimed to mechanistically assess whether Chang Wei Qing (CWQ) Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy. PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), rather than those with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Hence, immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients. Flow cytometry was used to analyze T-lymphocytes in tumors from mice. Western blot was used to measure the expression of PD-L1 protein in mouse tumors. The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry. 16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice. Subsequently, Spearmanapos;s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes. The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins. In vivo, CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+ and PD-1+CD8+ T cells in tumors. Additionally, the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone. CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes, andActinobacteria. Additionally, the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells were found to be positively correlated with the abundance of Akkermansia. Accordingly, CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.


Subject(s)
Animals , Mice , Immune Checkpoint Inhibitors/therapeutic use , Gastrointestinal Microbiome , CD8-Positive T-Lymphocytes , B7-H1 Antigen , RNA, Ribosomal, 16S , Colorectal Neoplasms/metabolism , Colonic Neoplasms , Tumor Microenvironment
19.
China Journal of Chinese Materia Medica ; (24): 3612-3622, 2023.
Article in Chinese | WPRIM | ID: wpr-981492

ABSTRACT

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.


Subject(s)
Animals , Male , Mice , Colonic Neoplasms/drug therapy , Diarrhea , Fluorouracil/adverse effects , Hormones , Metabolomics , Mice, Inbred BALB C , Polysaccharides/pharmacology
20.
China Journal of Chinese Materia Medica ; (24): 2325-2333, 2023.
Article in Chinese | WPRIM | ID: wpr-981308

ABSTRACT

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.


Subject(s)
Mice , Animals , Sterol Regulatory Element Binding Protein 1 , Colitis-Associated Neoplasms , PPAR alpha/genetics , Colonic Neoplasms/genetics , Colon , Azoxymethane , RNA, Messenger , Dextran Sulfate , Colitis/drug therapy , Mice, Inbred C57BL , Disease Models, Animal
SELECTION OF CITATIONS
SEARCH DETAIL