Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they ra...Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they rarely involve the stomach.We report an unusual case of a patient with an ectopic adrenal cortical adenoma in the gastric wall.The patient was a 72-year old female admitted to our hospital with upper abdominal discomfort.Physical examination revealed tenderness below the xiphoid process.Both computed tomography and fibergastroscopy revealed a mass on the lesser curvature side of the gastric antrum;it was initially diagnosed as a gastric stromal tumor.After adequate preparation,the patient underwent surgery.During the procedure,we found a 30 mm×30 mm mass with medium density in the lesser curvature near the gastric antrum within the serosa.Following immunohistochemistry examination, we corrected the diagnosis to an ectopic adrenal cortical adenoma;the tumor was nonfunctional.展开更多
AIM:To determine the role of NOB1,a regulator of cell survival in yeast,in human colorectal cancer cells.METHODS:Lentivirus-mediated small interfering RNA(si RNA) was used to inhibit NOB1 expression in RKO human color...AIM:To determine the role of NOB1,a regulator of cell survival in yeast,in human colorectal cancer cells.METHODS:Lentivirus-mediated small interfering RNA(si RNA) was used to inhibit NOB1 expression in RKO human colorectal cancer cells in vitro and in vivo in a mouse xenograft model.The in vitro and in vivo knockdown efficacy was determined using both Western blot and quantitative reverse transcription polymerase chain reaction(q RT-PCR).q RT-PCR was also used to analyze the downstream signals following NOB1 knockdown.Cell growth and colony formation assays were used to determine the effect of NOB1 inhibition on RKO proliferation and their ability to form colonies.Endonuclease activity,as evaluated by terminal deoxytransferase-mediated d UTP nick end labeling(TUNEL),and annexin V staining were used to determine the presence of apoptotic cell death prior to and following NOB1 inhibition.Cell cycle analysis was used to determine the effect of NOB1 inhibition on RKO cell cycle.A c DNA microarray was used to determine global differential gene expression following NOB1 knockdown.RESULTS:Virus-mediated si RNA inhibition of NOB1 resulted in(1) the down-regulation of NOB1 expression in RKO cells for both the m RNA and protein;(2) inhibition of NOB1 expression both in vitro and in vivo experimental systems;(3) cell growth inhibition via significant induction of cell apoptosis,without alteration of the cell cycle distribution; and(4) a significant decrease in the average weight and volume of xenograft tumors in the NOB1-si RNA group compared to the control scr-si RNA group(P = 0.001,P < 0.05).Significantly more apoptosis was detected within tumors in the NOB1-si RNA group than in the control group.Microarray analysis detected 2336 genes potentially regulated by NOB1.Most of these genes are associated with the WNT,cell proliferation,apoptosis,fibroblast growth factor,and angiogenesis signaling pathways,of which BAX and WNT were validated by q RT-PCR.Among them,1451 probes,representing 963 unique genes,were upregulated; however,2308 probes,CONCLUSION:NOB1 gene silencing by lentivirusmediated RNA interference can inhibit tumor growth by inducing apoptosis of cancerous human colorectal cells.展开更多
BACKGROUND Complications of Crohn’s disease such as intestinal obstruction,fistula or perforation often need surgical treatment.Nearly 70%-80%patients with Crohn’s disease would receive surgical treatment during the...BACKGROUND Complications of Crohn’s disease such as intestinal obstruction,fistula or perforation often need surgical treatment.Nearly 70%-80%patients with Crohn’s disease would receive surgical treatment during the lifetime.However,surgical treatment is incurable for Crohn’s disease.The challenge of recurrence postoperatively troubles both doctors and patients.Over 50%patients would suffer recurrence postoperatively.Some certain risk factors are associated with recurrence of Crohn’s disease.AIM To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn’s disease.METHODS Patients diagnosed Crohn’s disease and received intestinal resection between April 2007 and December 2013 were included in this study.Data on the general demographic information,preoperative clinical characteristics,surgical information,postoperative clinical characteristics were collected.Continuous data are expressed as median(inter quartile range),and categorical data as frequencies and percentages.Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence,then log-rank test was applied to test the homogeneity of those clinical variables.Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence.RESULTS A total of 64 patients were included in this study.The median follow-up time for the patients was 17(9.25-25.75)mo.In this period,41 patients(64.1%)had endoscopic recurrence or clinical recurrence.Endoscopic recurrence occurred in 34(59.6%)patients while clinical recurrence occurred in 28(43.8%)patients,with the interval between the operation and recurrence of 13.0(8.0-24.5)months and 17.0(8.0-27.8)mo,respectively.In univariate analysis,diagnosis at younger age(P<0.001),disease behavior of penetrating(P=0.044)and preoperative use of anti-tumor necrosis factor(TNF)(P=0.020)were significantly correlated with endoscopic recurrence,while complication with perianal lesions(P=0.032)and preoperative use of immunomodulatory(P=0.031)were significantly correlated with clinical recurrence.As to multivariate analysis,diagnostic age(P=0.004),disease behavior(P=0.041)and preoperative use of anti-TNF(P=0.010)were independent prognostic factors for endoscopic recurrence,while complication with perianal lesions(P=0.023)was an independent prognostic factor for clinical recurrence.CONCLUSION Diagnostic age,disease behavior,preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn’s disease.展开更多
Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.How...Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.展开更多
Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the ...Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.展开更多
Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this stud...Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.展开更多
Background:The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer.Low-dose cyclophosphamide(CTX)is widely believed to be involved in the modulation...Background:The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer.Low-dose cyclophosphamide(CTX)is widely believed to be involved in the modulation of the immune system.However,the underlying mechanism of low-dose CTX remains unknown.This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis.Methods:Thirty mice were randomly divided into five groups.After liver metastasis was established in colon-cancer models,mice in the treatment groups were injected with low-dose CTX(20 mg/kg)at different time points.Liver and spleen tissues were examined for T-cell markers via flow cytometry.Interleukin(IL)-10 and transforming growth factor(TGF)-b1 expression levels in liver tissues were analysed by immunohistochemistry.Serum interferon(IFN)-c and IL-10 levels were detected by enzyme-linked immunosorbent assay.An additional 20 mice were randomly allocated into two groups and the survival times were recorded.Results:The expression levels of CD4^(+)T cells,CD8^(+)T cells,and IFN-c were down-regulated,whereas those of IL-10 and TGF-b1 were up-regulated in liver metastasis from colon cancer in mice.Furthermore,the local and systemic microenvironments of the liver were altered,which led to reduced antitumor immune responses and subsequently liver metastasis.However,treatment with low-dose CTX reversed these effects.The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups.Conclusions:Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation inmice.CTX could be used as a drug to prevent and treat livermetastasis from colon cancer.展开更多
文摘Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they rarely involve the stomach.We report an unusual case of a patient with an ectopic adrenal cortical adenoma in the gastric wall.The patient was a 72-year old female admitted to our hospital with upper abdominal discomfort.Physical examination revealed tenderness below the xiphoid process.Both computed tomography and fibergastroscopy revealed a mass on the lesser curvature side of the gastric antrum;it was initially diagnosed as a gastric stromal tumor.After adequate preparation,the patient underwent surgery.During the procedure,we found a 30 mm×30 mm mass with medium density in the lesser curvature near the gastric antrum within the serosa.Following immunohistochemistry examination, we corrected the diagnosis to an ectopic adrenal cortical adenoma;the tumor was nonfunctional.
基金Supported by National Natural Science Foundation of China,No.81272735Class A Medical and Health Technology Program Project from Zhejiang Province,No.2010KY178the Science and Technology Department of Hunan Province,No.2010Ck3013
文摘AIM:To determine the role of NOB1,a regulator of cell survival in yeast,in human colorectal cancer cells.METHODS:Lentivirus-mediated small interfering RNA(si RNA) was used to inhibit NOB1 expression in RKO human colorectal cancer cells in vitro and in vivo in a mouse xenograft model.The in vitro and in vivo knockdown efficacy was determined using both Western blot and quantitative reverse transcription polymerase chain reaction(q RT-PCR).q RT-PCR was also used to analyze the downstream signals following NOB1 knockdown.Cell growth and colony formation assays were used to determine the effect of NOB1 inhibition on RKO proliferation and their ability to form colonies.Endonuclease activity,as evaluated by terminal deoxytransferase-mediated d UTP nick end labeling(TUNEL),and annexin V staining were used to determine the presence of apoptotic cell death prior to and following NOB1 inhibition.Cell cycle analysis was used to determine the effect of NOB1 inhibition on RKO cell cycle.A c DNA microarray was used to determine global differential gene expression following NOB1 knockdown.RESULTS:Virus-mediated si RNA inhibition of NOB1 resulted in(1) the down-regulation of NOB1 expression in RKO cells for both the m RNA and protein;(2) inhibition of NOB1 expression both in vitro and in vivo experimental systems;(3) cell growth inhibition via significant induction of cell apoptosis,without alteration of the cell cycle distribution; and(4) a significant decrease in the average weight and volume of xenograft tumors in the NOB1-si RNA group compared to the control scr-si RNA group(P = 0.001,P < 0.05).Significantly more apoptosis was detected within tumors in the NOB1-si RNA group than in the control group.Microarray analysis detected 2336 genes potentially regulated by NOB1.Most of these genes are associated with the WNT,cell proliferation,apoptosis,fibroblast growth factor,and angiogenesis signaling pathways,of which BAX and WNT were validated by q RT-PCR.Among them,1451 probes,representing 963 unique genes,were upregulated; however,2308 probes,CONCLUSION:NOB1 gene silencing by lentivirusmediated RNA interference can inhibit tumor growth by inducing apoptosis of cancerous human colorectal cells.
基金Science and Technology Planning Project of Guangdong Province,No.20160916Medical Science Research Grant from the Health Department of Guangdong Province,No.A2018007
文摘BACKGROUND Complications of Crohn’s disease such as intestinal obstruction,fistula or perforation often need surgical treatment.Nearly 70%-80%patients with Crohn’s disease would receive surgical treatment during the lifetime.However,surgical treatment is incurable for Crohn’s disease.The challenge of recurrence postoperatively troubles both doctors and patients.Over 50%patients would suffer recurrence postoperatively.Some certain risk factors are associated with recurrence of Crohn’s disease.AIM To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn’s disease.METHODS Patients diagnosed Crohn’s disease and received intestinal resection between April 2007 and December 2013 were included in this study.Data on the general demographic information,preoperative clinical characteristics,surgical information,postoperative clinical characteristics were collected.Continuous data are expressed as median(inter quartile range),and categorical data as frequencies and percentages.Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence,then log-rank test was applied to test the homogeneity of those clinical variables.Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence.RESULTS A total of 64 patients were included in this study.The median follow-up time for the patients was 17(9.25-25.75)mo.In this period,41 patients(64.1%)had endoscopic recurrence or clinical recurrence.Endoscopic recurrence occurred in 34(59.6%)patients while clinical recurrence occurred in 28(43.8%)patients,with the interval between the operation and recurrence of 13.0(8.0-24.5)months and 17.0(8.0-27.8)mo,respectively.In univariate analysis,diagnosis at younger age(P<0.001),disease behavior of penetrating(P=0.044)and preoperative use of anti-tumor necrosis factor(TNF)(P=0.020)were significantly correlated with endoscopic recurrence,while complication with perianal lesions(P=0.032)and preoperative use of immunomodulatory(P=0.031)were significantly correlated with clinical recurrence.As to multivariate analysis,diagnostic age(P=0.004),disease behavior(P=0.041)and preoperative use of anti-TNF(P=0.010)were independent prognostic factors for endoscopic recurrence,while complication with perianal lesions(P=0.023)was an independent prognostic factor for clinical recurrence.CONCLUSION Diagnostic age,disease behavior,preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn’s disease.
基金This work is supported by grants from the National Key Clinical Discipline,National Natural Science Foundation of China(No.81300367 and No.81400604)Guangdong Natural Science Foundation(No.2015A030313108)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.
基金supported by National Natural Science Foundation of China(No.81400603)Guangdong Natural Science Foundation(No.2015A030310190)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.
基金supported by the National Key R&D Program of China[no.2017YFC1308800]the National Natural Science Foundation of China[no.81870383]+1 种基金the Clinical Innovation Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)[no.2018GZR0201005]the Science and Technology Planning Project of Guangzhou City[no.201804010014].
文摘Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.
基金This work was supported by National Key Clinical Discipline,the Fundamental Research Funds for the young teacher training program of Sun Yat-sen University[grant number 18ykpy02]Medical Scientific Research Foundation of Guangdong Province of China[grant number A2016198]‘5010 Clinical Research Programme’of Sun Yat-sen University[grant number 2010012].
文摘Background:The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer.Low-dose cyclophosphamide(CTX)is widely believed to be involved in the modulation of the immune system.However,the underlying mechanism of low-dose CTX remains unknown.This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis.Methods:Thirty mice were randomly divided into five groups.After liver metastasis was established in colon-cancer models,mice in the treatment groups were injected with low-dose CTX(20 mg/kg)at different time points.Liver and spleen tissues were examined for T-cell markers via flow cytometry.Interleukin(IL)-10 and transforming growth factor(TGF)-b1 expression levels in liver tissues were analysed by immunohistochemistry.Serum interferon(IFN)-c and IL-10 levels were detected by enzyme-linked immunosorbent assay.An additional 20 mice were randomly allocated into two groups and the survival times were recorded.Results:The expression levels of CD4^(+)T cells,CD8^(+)T cells,and IFN-c were down-regulated,whereas those of IL-10 and TGF-b1 were up-regulated in liver metastasis from colon cancer in mice.Furthermore,the local and systemic microenvironments of the liver were altered,which led to reduced antitumor immune responses and subsequently liver metastasis.However,treatment with low-dose CTX reversed these effects.The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups.Conclusions:Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation inmice.CTX could be used as a drug to prevent and treat livermetastasis from colon cancer.
