Objective:To explore the therapeutic effect of laparoscopic radical colorectal cancer treatment in colorectal cancer patients.Methods:A total of 50 colorectal cancer patients treated between August 2018 and August 202...Objective:To explore the therapeutic effect of laparoscopic radical colorectal cancer treatment in colorectal cancer patients.Methods:A total of 50 colorectal cancer patients treated between August 2018 and August 2023 were randomly divided into two groups:Group A underwent laparoscopic radical colorectal cancer surgery,while Group B received open surgery.Clinical indicators,inflammatory factors,immune function indicators,and complications were compared between the two groups.Results:Group A showed significantly shorter operation times,faster recovery times,and reduced hospital stays compared to Group B.Additionally,Group A had less abdominal drainage and intraoperative bleeding(P<0.05).Levels of interleukin(IL)-4,IL-6,ultrasensitive C-reactive protein(hs-CRP),and tumor necrosis factor-alpha(TNF-α)were lower in Group A compared to Group B(P<0.05).Furthermore,immune function indicators,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were better in Group A(P<0.05).The complication rate in Group A was also lower than in Group B(P<0.05).Conclusion:Laparoscopic radical treatment for colorectal cancer is efficient and feasible,causing minimal immune function impairment and inflammatory response.It also shortens postoperative recovery time.展开更多
The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the tre...The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.展开更多
Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of adv...Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.展开更多
Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D ma...Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.展开更多
Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molec...Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molecular character-istics of tumor cells(mucinous,ring-cell carcinomas,etc.),analysis of mechanisms of carcinogenesis involved(chromosomal instability,microsatellite instability,CpG island methylator phenotype)and mutational statuses of commonly altered genes(KRAS,NRAS,BRAF,APC,etc.),as well as expression signatures(CMS 1-4).It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.According to the latest data,the immune microenvironment can also be predictive of the response to immune checkpoint inhibitors.In this review,we highlight how the immune environment influences CRC prognosis and sensitivity to systemic therapy.展开更多
The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the tre...The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.展开更多
BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing t...BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.展开更多
BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of...BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery;and(5)Physical status:One month after surgery,the Karnofsky performance score in the observation group was higher than that in the control group.CONCLUSION Laparoscopic radical resection of CRC has significant benefits,such as reducing postoperative pain and postoperative inflammatory response,avoiding excessive immune inhibition,and contributing to postoperative recovery.展开更多
BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with ...BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune function.Buzhong Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related inflammation.Moreover,it is widely used in the treatment of spleen and stomach qi deficiency syndrome.AIM To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer.METHODS One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed.The patients were divided equally into control and observation groups.Both groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi decoction.SPSS 26.0 was used for statistical analyses.Theχ2 test was used for univariate analysis;independent sample t-tests were used in all cases.RESULTS No significant differences were observed preoperatively in the general characteristics of the two groups.Fourteen days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly higher than that of the patients in the control group(P<0.05).CONCLUSION Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function,thereby promoting overall immune nutrition and restoring the body’s balance.展开更多
BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[de...BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[dendritic cell-cytokine-induced killer(DC-CIK)cell immunotherapy]on patients after CRC surgery and to explore the mediating variables.METHODS A total cohort of 121 patients who underwent CRC surgery between January 2019 and April 2022 were selected.The sample comprised a control group of 55 pa-tients who received the XELOX chemotherapy regimen and a research group of 66 patients who received XELOX+DC-CIK immunotherapy.We performed compa-rative analyses of the clinical and pathological data of the two groups,including efficacy(2-year disease-free survival[DFS]rate),the incidence of adverse events(diarrhea,myelosuppression,gastrointestinal reactions,and peripheral neuritis),serum levels of tumor markers[carcinoembryonic antigens and carbohydrate an-tigens(CA)19-9 and CA242],and T-cell subsets[cluster of differentiation(CD)3+,CD3+CD4+,CD3+CD8+,natural killer(NK),and NK T cells].We also conducted preliminary univariate and mul-tivariate analyses of the variables that affected the efficacy of the treatments.RESULTS We found a significantly higher 2-year DFS rate of treatment efficacy in the research group than in the control group,with a statistically lower incidence of adverse events.Both groups showed a reduction in serum tumor markers after treatment but there was no marked intergroup difference.After treatment,the various T-cell subgroup indicators in the control group were significantly lower than those in the research group.The indices of T-cell subsets in the research group showed no significant change from preoperative levels.Univariate analysis revealed a significant correlation between TNM staging,tumor differentiation,and the rates of nonresponse to treatment in CRC patients after surgery.Multivariate results indicated that the treatment approach significantly affected the efficacy of postoperative CRC treatment.CONCLUSION We concluded that XELOX+DC-CIK immunotherapy for postsurgical CRC patients offers reduced rates of treatment-induced adverse events,extended 2-year DFS,enhanced immunity,and increased physiological antitumor responses.展开更多
Objective:To investigate the effect of dexmedetomidine on inflammatory factors and immune function in elderly patients undergoing laparoscopic radical resection of colorectal cancer. Methods: From April 2016 to April ...Objective:To investigate the effect of dexmedetomidine on inflammatory factors and immune function in elderly patients undergoing laparoscopic radical resection of colorectal cancer. Methods: From April 2016 to April 2017, 86 cases of elderly laparoscopic radical resection of colorectal cancer in our hospital were selected and randomly divided into the observation group and the control group. 2 groups of patients were open venous access, oxygen mask, monitoring heart rate (HR), blood pressure (BP), electrocardiogram (ECG), oxygen saturation (SpO2), bispectral index (BIS), after induction of anesthesia, the observation group was given dexmedetomidine 0.4 g/kg to 20 mL of normal saline control. Group of 20 mL saline, 15 min infusion is completed, and the observation group of dexmedetomidine in 0.4 g/kg - h continuous infusion of normal saline control group, continuous infusion, until the end of surgery. Before induction of anesthesia (T0), 2 h after operation beginning (T1), at the end of operation (T2), 24 h after operation (T3) in venous blood, using ELISA method for the determination of serum interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6), tumor necrosis factor alpha (the level of TNF-alpha);on preoperative and postoperative 4 h, 12 h, 24 h after operation in venous blood serum epinephrine ELISA method (E), norepinephrine (NE), endothelin-1 (ET-1) level;on preoperative and postoperative 4 h, 12 h after surgery, 24 h venous blood flow cytometry determination of CD3+, CD4+, CD8+, CD4+/CD8+.Results:compared with before operation, the observation group after 4 h, 12 h, 24 h NE, and the lower control group E, NE and ET-1 increased, the observation group after 4 h, 12 h, 24 h E, NE, ET-1 lower than that of the control group;compared with T0, 2 patients in group T2, T3 sIL-2R, IL-6, TNF-alpha were increased, the observation group T2, T3 sIL-2R, IL-6, TNF- were lower than that of the control group;compared with the preoperative, 2 group after 4 h, 12 h, 24 h CD3+, CD4+, CD8+ and CD4+/CD8+ decreased, the observation group after 4 h, 12 h, 24 h CD3+, CD4+, CD8+, CD4+/CD8+ higher than those in the control group.Conclusion: Dexmedetomidine has a good analgesic effect on elderly patients undergoing laparoscopic radical resection of colorectal cancer. It can effectively relieve the stress reaction and inflammatory reaction during perioperative period, and effectively improve the immune function of the patients.展开更多
Objective:To investigate the effects of propofol on immune function, stress response and hemodynamics in patients undergoing colorectal cancer surgery.Methods: 90 patients who were undergoing laparoscopic radical rese...Objective:To investigate the effects of propofol on immune function, stress response and hemodynamics in patients undergoing colorectal cancer surgery.Methods: 90 patients who were undergoing laparoscopic radical resection of colorectal cancer were randomly divided into propofol group (n=45) and sevoflurane group (n=45). The propofol group was anesthetized with propofol and the control group was given the same dose of sevoflurane. Changes in HR, SBP and DBP were observed before anesthesia, 1 h after induction, and at the end of surgery. The levels of CD19+, NK cells, MDA, SOD, insulin and cortisol were measured before anesthesia, at the end of operation and 24 h after operation.Results: Compared with before anesthesia, the levels of HR, SBP and DBP decreased at 1 h after induction (allP<0.05). At the end of the surgery, HR, SBP, and DBP returned to pre-anesthesia levels in both groups. The levels of HR, SBP and DBP in the propofol group were (74.56±7.55) times/min, (108.34±10.71) mmHg and (76.35±7.65) mmHg were higher than those in the sevoflurane group (allP<0.05). Compared with before anesthesia, CD19+ and NK cell ratio decreased at the end of surgery and 24 h after surgery, while MDA level increased at the end of surgery and 24 h after surgery (P<0.05). At the end of the propofol group, the proportion of CD19+and NK cells were (7.23±0.83)% and (15.17±1.21)% ,which were higher than the sevoflurane group (allP<0.05). At 24 h after surgery, the proportions of CD19+ and NK cells in the propofol group were (9.68±0.96) % and (19.58±1.86)%, which were higher than those in the sevoflurane group (all P<0.05). Compared with before anesthesia, MDA levels increased and SOD levels decreased at the end of surgery (P<0.05). At the end of the propofol group, the MDA level was (6.15±0.62) mmol/L, which was lower than that of the sevoflurane group (P<0.05). And the SOD level was (98.75±9.78) nU/mL, which was higher than the sevoflurane group (P<0.05). Compared with before anesthesia, the levels of insulin and cortisol increased at the end of surgery and 24 h after surgery (P<0.05). At the end of the operation, the propofol group insulin (22.69±2.28) mIU/mL was higher than the sevoflurane group, and the propofol group cortisol were (171.59±17.12) ng/mL, which were lower than sevoflurane group (allP<0.05).Conclusion:The patients undergoing radicalresection of colorectal cancer received propofol intravenous anesthesia preoperativel, which can effectively alleviate oxidative stress, and has little effect on hemodynamic parameters and stress response.展开更多
Objective: To study the effect of dietary fiber enteral nutrition on inflammatory response and anti-tumor immune response after colorectal cancer surgery. Methods: A total of 162 patients who underwent radical operati...Objective: To study the effect of dietary fiber enteral nutrition on inflammatory response and anti-tumor immune response after colorectal cancer surgery. Methods: A total of 162 patients who underwent radical operation for colorectal cancer in West China Hospital, Sichuan University between March 2015 and August 2017 were selected as the research subjects and randomly divided into the dietary fiber group who accepted dietary fiber enteral nutrition intervention and the control group who accepted conventional nutrition intervention. The number of intestinal flora was determined before surgery and at the first defecation after surgery;the inflammatory response indexes and immune response indexes were measured before surgery as well as 3 d and 5 d after surgery. Results: At the first defecation after surgery, the bifidobacteria, lactobacillus, Escherichia coli and enterococcus contents in the feces of both groups were lower than those before surgery, and the bifidobacterium and lactobacillus contents in feces of dietary fiber group were higher than those of control group whereas Escherichia coli and enterococcus contents were lower than those of control group;3 d and 5 d after surgery, NF-κB, IL-1, TNF-α and IL-8 contents in serum as well as Treg, Th17, Th22, TGF-β, IL-17 and IL-22 contents in peripheral blood of both groups of patients were significantly higher than those before surgery, and NF-κB, IL-1, TNF-α and IL-8 contents in serum as well as Treg, Th17, Th22, TGF-β, IL-17 and IL-22 contents in peripheral blood of dietary fiber group were lower than those of control group. Conclusion: The dietary fiber enteral nutrition intervention after colorectal cancer surgery can inhibit the inflammatory response and improve the anti-tumor immune response.展开更多
BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their assoc...BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.展开更多
Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(...Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR CRC.In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients.Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC.Herein,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies.In addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.展开更多
Objective: To investigate the effect of laparoscopic radical resection of colorectal cancer on the immune status and CRP. Methods: A total of 90 patients with colorectal cancer treated in our hospital from January 201...Objective: To investigate the effect of laparoscopic radical resection of colorectal cancer on the immune status and CRP. Methods: A total of 90 patients with colorectal cancer treated in our hospital from January 2017 to June 2017 were randomly divided into the observation group and the control group, each with 45 cases. The observation group received laparoscopic surgery, while the control group was given open surgery. The changes of immune indexes and CRP in two groups before and after 3 d and after 7 d were compared. Results: (1) In the control group, the postoperative 3 d and postoperative 7 d, CRP index were (7.87±2.01) mg/dL, (2.81±1.03) mg/dL, the observation group postoperative 3 d and postoperative 7 d, CRP index were (7.01±1.33) mg/dL, (1.59±0.81) mg/dL, compared with before treatment, the difference was statistically significant. The CRP in the observation group postoperative 7 d were significantly lower than those in the control group at the same time period, the difference was significant. The IgM and IgG index level of control group postoperative 3 d respectively (137.04±23.46) IU/mL and (114.36±27.18) IU/mL, compared with preoperative and observation group postoperative 3 d index level (163.07±30.19) IU/mL, (130.24±31.16) IU/mL decreased significantly, the difference was significant. (2) The control group postoperative 3 d CD4+and CD8+index level were respectively (0.49±0.05)×109/L, (0.29±0.08)×109/L. CD8+index level of 7 d after operation was (0.31±0.10)×109/L, which were significantly decreased than 1 d before operation and significantly lower than the same period of observation group indicator level (0.59±0.09)×109/L, (0.35±0.11)×109/L, (0.37±0.12)×109/L, the differences were statistically significant. Conclusion: Compared with open surgery, laparoscopic surgery has less influence on the immune function of patients, and has less inflammatory and stress damage, so it is worthy of clinical application.展开更多
Objective: To investigate the effects of laparoscopic surgery on serum inflammatory factors, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), oxidative stress and immune function in patie...Objective: To investigate the effects of laparoscopic surgery on serum inflammatory factors, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), oxidative stress and immune function in patients with colorectal cancer. Methods: According to the random data table 103 cases of colorectal cancer patients were divided into the control group (n=52) and observation group (n=51), patients in the control group were treated with traditional open surgery, and observation group patients were given laparoscopic surgery, preoperative and postoperative 1 d, the levels of serum inflammatory factor, VEGF, MMP-9, oxidative stress and immune function of the two groups were compared. Results: There were no significant differences in TNF-α, IL-6, CRP, VEGF, MMP-9, MDA, SOD, CD4+, CD8+, CD4+/CD8+levels between the two groups before operation. Postoperative 1 d, the levels of TNF-α, IL-6, CRP, MDA and CD8+in the two groups were significantly higher than those in the same group preoperative, and the observation group was significantly lower than the control group, the difference was statistically significant;Two groups of VEGF, MMP-9, SOD, CD4+and CD4+/CD8+were significantly lower than those in the group before the operation, and the observation group VEGF, MMP-9 levels were significantly lower than those in the control group, SOD, CD4+, CD4+/CD8+levels of the observation group were significantly higher than the control group, the difference was statistically significant. Conclusion: Compared with open surgery, laparoscopic surgery for colorectal cancer, can effectively reduce the release of light inflammatory factors, decrease VEGF, MMP-9 levels, less influence on oxidative stress and immune function of patients, has a certain clinical value.展开更多
AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by...AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed.RESULTS: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with control.CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.展开更多
Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their...Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.展开更多
The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors.Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity rel...The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors.Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship.Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified,still no approved therapies based on host immunity intensification have so far been introduced in clinical practice.Moreover,a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach.The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.展开更多
文摘Objective:To explore the therapeutic effect of laparoscopic radical colorectal cancer treatment in colorectal cancer patients.Methods:A total of 50 colorectal cancer patients treated between August 2018 and August 2023 were randomly divided into two groups:Group A underwent laparoscopic radical colorectal cancer surgery,while Group B received open surgery.Clinical indicators,inflammatory factors,immune function indicators,and complications were compared between the two groups.Results:Group A showed significantly shorter operation times,faster recovery times,and reduced hospital stays compared to Group B.Additionally,Group A had less abdominal drainage and intraoperative bleeding(P<0.05).Levels of interleukin(IL)-4,IL-6,ultrasensitive C-reactive protein(hs-CRP),and tumor necrosis factor-alpha(TNF-α)were lower in Group A compared to Group B(P<0.05).Furthermore,immune function indicators,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were better in Group A(P<0.05).The complication rate in Group A was also lower than in Group B(P<0.05).Conclusion:Laparoscopic radical treatment for colorectal cancer is efficient and feasible,causing minimal immune function impairment and inflammatory response.It also shortens postoperative recovery time.
文摘The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.
基金Supported by IU Simon Comprehensive Cancer Center grant,No.5P30CA082709-24.
文摘Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.
文摘Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.
文摘Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molecular character-istics of tumor cells(mucinous,ring-cell carcinomas,etc.),analysis of mechanisms of carcinogenesis involved(chromosomal instability,microsatellite instability,CpG island methylator phenotype)and mutational statuses of commonly altered genes(KRAS,NRAS,BRAF,APC,etc.),as well as expression signatures(CMS 1-4).It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.According to the latest data,the immune microenvironment can also be predictive of the response to immune checkpoint inhibitors.In this review,we highlight how the immune environment influences CRC prognosis and sensitivity to systemic therapy.
文摘The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.
文摘BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.
基金Supported by Scientific Research Project of Hunan Provincial Health Commission,No.202204114103.
文摘BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery;and(5)Physical status:One month after surgery,the Karnofsky performance score in the observation group was higher than that in the control group.CONCLUSION Laparoscopic radical resection of CRC has significant benefits,such as reducing postoperative pain and postoperative inflammatory response,avoiding excessive immune inhibition,and contributing to postoperative recovery.
文摘BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune function.Buzhong Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related inflammation.Moreover,it is widely used in the treatment of spleen and stomach qi deficiency syndrome.AIM To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer.METHODS One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed.The patients were divided equally into control and observation groups.Both groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi decoction.SPSS 26.0 was used for statistical analyses.Theχ2 test was used for univariate analysis;independent sample t-tests were used in all cases.RESULTS No significant differences were observed preoperatively in the general characteristics of the two groups.Fourteen days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly higher than that of the patients in the control group(P<0.05).CONCLUSION Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function,thereby promoting overall immune nutrition and restoring the body’s balance.
文摘BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[dendritic cell-cytokine-induced killer(DC-CIK)cell immunotherapy]on patients after CRC surgery and to explore the mediating variables.METHODS A total cohort of 121 patients who underwent CRC surgery between January 2019 and April 2022 were selected.The sample comprised a control group of 55 pa-tients who received the XELOX chemotherapy regimen and a research group of 66 patients who received XELOX+DC-CIK immunotherapy.We performed compa-rative analyses of the clinical and pathological data of the two groups,including efficacy(2-year disease-free survival[DFS]rate),the incidence of adverse events(diarrhea,myelosuppression,gastrointestinal reactions,and peripheral neuritis),serum levels of tumor markers[carcinoembryonic antigens and carbohydrate an-tigens(CA)19-9 and CA242],and T-cell subsets[cluster of differentiation(CD)3+,CD3+CD4+,CD3+CD8+,natural killer(NK),and NK T cells].We also conducted preliminary univariate and mul-tivariate analyses of the variables that affected the efficacy of the treatments.RESULTS We found a significantly higher 2-year DFS rate of treatment efficacy in the research group than in the control group,with a statistically lower incidence of adverse events.Both groups showed a reduction in serum tumor markers after treatment but there was no marked intergroup difference.After treatment,the various T-cell subgroup indicators in the control group were significantly lower than those in the research group.The indices of T-cell subsets in the research group showed no significant change from preoperative levels.Univariate analysis revealed a significant correlation between TNM staging,tumor differentiation,and the rates of nonresponse to treatment in CRC patients after surgery.Multivariate results indicated that the treatment approach significantly affected the efficacy of postoperative CRC treatment.CONCLUSION We concluded that XELOX+DC-CIK immunotherapy for postsurgical CRC patients offers reduced rates of treatment-induced adverse events,extended 2-year DFS,enhanced immunity,and increased physiological antitumor responses.
文摘Objective:To investigate the effect of dexmedetomidine on inflammatory factors and immune function in elderly patients undergoing laparoscopic radical resection of colorectal cancer. Methods: From April 2016 to April 2017, 86 cases of elderly laparoscopic radical resection of colorectal cancer in our hospital were selected and randomly divided into the observation group and the control group. 2 groups of patients were open venous access, oxygen mask, monitoring heart rate (HR), blood pressure (BP), electrocardiogram (ECG), oxygen saturation (SpO2), bispectral index (BIS), after induction of anesthesia, the observation group was given dexmedetomidine 0.4 g/kg to 20 mL of normal saline control. Group of 20 mL saline, 15 min infusion is completed, and the observation group of dexmedetomidine in 0.4 g/kg - h continuous infusion of normal saline control group, continuous infusion, until the end of surgery. Before induction of anesthesia (T0), 2 h after operation beginning (T1), at the end of operation (T2), 24 h after operation (T3) in venous blood, using ELISA method for the determination of serum interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6), tumor necrosis factor alpha (the level of TNF-alpha);on preoperative and postoperative 4 h, 12 h, 24 h after operation in venous blood serum epinephrine ELISA method (E), norepinephrine (NE), endothelin-1 (ET-1) level;on preoperative and postoperative 4 h, 12 h after surgery, 24 h venous blood flow cytometry determination of CD3+, CD4+, CD8+, CD4+/CD8+.Results:compared with before operation, the observation group after 4 h, 12 h, 24 h NE, and the lower control group E, NE and ET-1 increased, the observation group after 4 h, 12 h, 24 h E, NE, ET-1 lower than that of the control group;compared with T0, 2 patients in group T2, T3 sIL-2R, IL-6, TNF-alpha were increased, the observation group T2, T3 sIL-2R, IL-6, TNF- were lower than that of the control group;compared with the preoperative, 2 group after 4 h, 12 h, 24 h CD3+, CD4+, CD8+ and CD4+/CD8+ decreased, the observation group after 4 h, 12 h, 24 h CD3+, CD4+, CD8+, CD4+/CD8+ higher than those in the control group.Conclusion: Dexmedetomidine has a good analgesic effect on elderly patients undergoing laparoscopic radical resection of colorectal cancer. It can effectively relieve the stress reaction and inflammatory reaction during perioperative period, and effectively improve the immune function of the patients.
文摘Objective:To investigate the effects of propofol on immune function, stress response and hemodynamics in patients undergoing colorectal cancer surgery.Methods: 90 patients who were undergoing laparoscopic radical resection of colorectal cancer were randomly divided into propofol group (n=45) and sevoflurane group (n=45). The propofol group was anesthetized with propofol and the control group was given the same dose of sevoflurane. Changes in HR, SBP and DBP were observed before anesthesia, 1 h after induction, and at the end of surgery. The levels of CD19+, NK cells, MDA, SOD, insulin and cortisol were measured before anesthesia, at the end of operation and 24 h after operation.Results: Compared with before anesthesia, the levels of HR, SBP and DBP decreased at 1 h after induction (allP<0.05). At the end of the surgery, HR, SBP, and DBP returned to pre-anesthesia levels in both groups. The levels of HR, SBP and DBP in the propofol group were (74.56±7.55) times/min, (108.34±10.71) mmHg and (76.35±7.65) mmHg were higher than those in the sevoflurane group (allP<0.05). Compared with before anesthesia, CD19+ and NK cell ratio decreased at the end of surgery and 24 h after surgery, while MDA level increased at the end of surgery and 24 h after surgery (P<0.05). At the end of the propofol group, the proportion of CD19+and NK cells were (7.23±0.83)% and (15.17±1.21)% ,which were higher than the sevoflurane group (allP<0.05). At 24 h after surgery, the proportions of CD19+ and NK cells in the propofol group were (9.68±0.96) % and (19.58±1.86)%, which were higher than those in the sevoflurane group (all P<0.05). Compared with before anesthesia, MDA levels increased and SOD levels decreased at the end of surgery (P<0.05). At the end of the propofol group, the MDA level was (6.15±0.62) mmol/L, which was lower than that of the sevoflurane group (P<0.05). And the SOD level was (98.75±9.78) nU/mL, which was higher than the sevoflurane group (P<0.05). Compared with before anesthesia, the levels of insulin and cortisol increased at the end of surgery and 24 h after surgery (P<0.05). At the end of the operation, the propofol group insulin (22.69±2.28) mIU/mL was higher than the sevoflurane group, and the propofol group cortisol were (171.59±17.12) ng/mL, which were lower than sevoflurane group (allP<0.05).Conclusion:The patients undergoing radicalresection of colorectal cancer received propofol intravenous anesthesia preoperativel, which can effectively alleviate oxidative stress, and has little effect on hemodynamic parameters and stress response.
基金Natural Science Foundation of China,No:NSFC 81062341.
文摘Objective: To study the effect of dietary fiber enteral nutrition on inflammatory response and anti-tumor immune response after colorectal cancer surgery. Methods: A total of 162 patients who underwent radical operation for colorectal cancer in West China Hospital, Sichuan University between March 2015 and August 2017 were selected as the research subjects and randomly divided into the dietary fiber group who accepted dietary fiber enteral nutrition intervention and the control group who accepted conventional nutrition intervention. The number of intestinal flora was determined before surgery and at the first defecation after surgery;the inflammatory response indexes and immune response indexes were measured before surgery as well as 3 d and 5 d after surgery. Results: At the first defecation after surgery, the bifidobacteria, lactobacillus, Escherichia coli and enterococcus contents in the feces of both groups were lower than those before surgery, and the bifidobacterium and lactobacillus contents in feces of dietary fiber group were higher than those of control group whereas Escherichia coli and enterococcus contents were lower than those of control group;3 d and 5 d after surgery, NF-κB, IL-1, TNF-α and IL-8 contents in serum as well as Treg, Th17, Th22, TGF-β, IL-17 and IL-22 contents in peripheral blood of both groups of patients were significantly higher than those before surgery, and NF-κB, IL-1, TNF-α and IL-8 contents in serum as well as Treg, Th17, Th22, TGF-β, IL-17 and IL-22 contents in peripheral blood of dietary fiber group were lower than those of control group. Conclusion: The dietary fiber enteral nutrition intervention after colorectal cancer surgery can inhibit the inflammatory response and improve the anti-tumor immune response.
基金Supported by the National Natural Science Foundation of China,No.81960100Applied Basic Foundation of Yunnan Province,No.202001AY070001-192+2 种基金Young and Middle-aged Academic and Technical Leaders Reserve Talents Program in Yunnan Province,No.202305AC160018Yunnan Revitalization Talent Support Program,No.RLQB20200004 and No.RLMY20220013and Yunnan Health Training Project of High-Level Talents,No.H-2017002。
文摘BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.
基金supported by grants from National Cancer Center Climbing Fund(Grant No.NCC201916B03)Provincial-ministerial Co-construction Project of Henan Province Science and Technology Key Point Tackling Plan(Grant No.SBGJ202102064)Henan Provincial Scientific and Technological Project(Grant Nos.222102310363 and 222102310677)。
文摘Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR CRC.In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients.Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC.Herein,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies.In addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.
文摘Objective: To investigate the effect of laparoscopic radical resection of colorectal cancer on the immune status and CRP. Methods: A total of 90 patients with colorectal cancer treated in our hospital from January 2017 to June 2017 were randomly divided into the observation group and the control group, each with 45 cases. The observation group received laparoscopic surgery, while the control group was given open surgery. The changes of immune indexes and CRP in two groups before and after 3 d and after 7 d were compared. Results: (1) In the control group, the postoperative 3 d and postoperative 7 d, CRP index were (7.87±2.01) mg/dL, (2.81±1.03) mg/dL, the observation group postoperative 3 d and postoperative 7 d, CRP index were (7.01±1.33) mg/dL, (1.59±0.81) mg/dL, compared with before treatment, the difference was statistically significant. The CRP in the observation group postoperative 7 d were significantly lower than those in the control group at the same time period, the difference was significant. The IgM and IgG index level of control group postoperative 3 d respectively (137.04±23.46) IU/mL and (114.36±27.18) IU/mL, compared with preoperative and observation group postoperative 3 d index level (163.07±30.19) IU/mL, (130.24±31.16) IU/mL decreased significantly, the difference was significant. (2) The control group postoperative 3 d CD4+and CD8+index level were respectively (0.49±0.05)×109/L, (0.29±0.08)×109/L. CD8+index level of 7 d after operation was (0.31±0.10)×109/L, which were significantly decreased than 1 d before operation and significantly lower than the same period of observation group indicator level (0.59±0.09)×109/L, (0.35±0.11)×109/L, (0.37±0.12)×109/L, the differences were statistically significant. Conclusion: Compared with open surgery, laparoscopic surgery has less influence on the immune function of patients, and has less inflammatory and stress damage, so it is worthy of clinical application.
文摘Objective: To investigate the effects of laparoscopic surgery on serum inflammatory factors, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), oxidative stress and immune function in patients with colorectal cancer. Methods: According to the random data table 103 cases of colorectal cancer patients were divided into the control group (n=52) and observation group (n=51), patients in the control group were treated with traditional open surgery, and observation group patients were given laparoscopic surgery, preoperative and postoperative 1 d, the levels of serum inflammatory factor, VEGF, MMP-9, oxidative stress and immune function of the two groups were compared. Results: There were no significant differences in TNF-α, IL-6, CRP, VEGF, MMP-9, MDA, SOD, CD4+, CD8+, CD4+/CD8+levels between the two groups before operation. Postoperative 1 d, the levels of TNF-α, IL-6, CRP, MDA and CD8+in the two groups were significantly higher than those in the same group preoperative, and the observation group was significantly lower than the control group, the difference was statistically significant;Two groups of VEGF, MMP-9, SOD, CD4+and CD4+/CD8+were significantly lower than those in the group before the operation, and the observation group VEGF, MMP-9 levels were significantly lower than those in the control group, SOD, CD4+, CD4+/CD8+levels of the observation group were significantly higher than the control group, the difference was statistically significant. Conclusion: Compared with open surgery, laparoscopic surgery for colorectal cancer, can effectively reduce the release of light inflammatory factors, decrease VEGF, MMP-9 levels, less influence on oxidative stress and immune function of patients, has a certain clinical value.
文摘AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed.RESULTS: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with control.CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.
基金Supported by Associazione Italiana per la Ricerca sul Cancro(AIRC),Special Program Molecular Clinical Oncology,5X1000,No.12214(G.T.)European Research Council,Programme‘‘Ide-as’’,Proposal No.269051(G.T.,F.R.)
文摘Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.
文摘The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors.Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship.Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified,still no approved therapies based on host immunity intensification have so far been introduced in clinical practice.Moreover,a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach.The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.