Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer

BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery.METHODS We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People’s Hospital from December 2019 to December 2022.Patients were divided into liver metastasis and non-liver metastasis groups.Sex,age,and other general and clinicopathological data(preoperative blood routine and biochemical test indexes)were compared.The risk factors for liver metastasis were analyzed using singlefactor and multifactorial logistic regression.A predictive model was then constructed and evaluated for efficacy.RESULTS Systemic inflammatory index(SII),C-reactive protein/albumin ratio(CAR),red blood cell distribution width(RDW),alanine aminotransferase,preoperative carcinoembryonic antigen level,and lymphatic metastasis were different between groups(P<0.05).SII,CAR,and RDW were risk factors for liver metastasis after colon cancer surgery(P<0.05).The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively.The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve,with good agreement.The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases,indicating that the model is safer.CONCLUSION Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII,CAR,and RDW.

Inhibiting effects of ^(131)I-labeled anti-CEA monoclonal antibodies injected intrasplenically on liver metastasis from human colonic adenocarcinoma

I-labeled anti-CEA monoclonal antibody injected intrasplenically has better effects on inhibiting liver metastasis from human colonic adenocarcinoma than that through tail vein in nu/nu mice model.

Advances in liver transplantation for unresectable colon cancer liver metastasis

It is estimated that 50%of patients with colorectal cancer will develop liver metastasis.Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metastasis(CRLM).Increasing the resectability of primary unresectable liver metastasis provides more survival benefit for those patients.Considerable surgical innovations have been made to increase the resection rate and decrease the potential risk of hepatic failure postoperation.Liver transplantation(LT)has been explored as a potential curative treatment for unresectable CRLM.However,candidate selection criteria,chemotherapy strategies,refined immunity regimens and resolution for the shortage of grafts are lacking.This manuscript discusses views on surgical indication,peritransplantation anti-tumor and anti-immunity therapy and updated advances in LT for unresectable CRLM.A literature review of published articles and registered clinical trials in PubMed,Google Scholar,and Clinicaltrials.gov was performed to identify studies related to LT for CRLM.Some research topics were identified,including indications for LT for CRLM,oncological risk,antitumor regimens,graft loss,administration of anti-immunity drugs and solutions for graft deficiency.The main candidate selection criteria are good patient performance,good tumor biological behavior and chemosensitivity.Chemotherapy should be administered before transplantation but is not commonly administered posttransplantation for preventive purposes.Mammalian target of rapamycin regimens are recommended for their potential oncological benefit,although there are limited cases.In addition to extended criterion grafts,living donor grafts and small grafts combined with two-stage hepatectomy are efficient means to resolve organ deficiency.LT has been proven to be an effective treatment for selected patients with liver-only CRLM.Due to limited donor grafts,high cost and poorly clarified oncological risks,LT for unresectable CRLM should be strictly performed under a well-organized study plan in selected patients.Some vital factors,like LT indication and anti-tumor and anti-immune treatment,remain to be confirmed.Ongoing clinical trials are expected to delineate these topics.

Needle track seeding:A real hazard after percutaneous radiofrequency ablation for colorectal liver metastasis

Neoplastic needle track seeding following percutaneous radiofrequency ablation(RFA)of secondary liver tumors is exceedingly rare.Reports on cutaneous tumor seeding after percutaneous RFA for colorectal liver metastasis are even rarer in the literature.Here we report a case of a 46-year-old female who developed an ulcerating skin lesion along the needle track of a previous percutaneous RFA site around 6 mo after the procedure.The previous RFA was performed by the LeVeen needle for a secondary liver tumor from a primary rectal cancer.The diagnosis of secondary skin metastasis was confirmed by fine needle aspiration cytology.The lesion was successfully treated with wide local excision.We believe that tumor seeding after percutaneous RFA in our patient was possibly related to its unfavorable subcapsular location and the use of an expansion-type needle.Hence,prophylactic ablation of the needle track should be performed whenever possible.Otherwise,alternative routes of tumor ablation such as laparoscopic or open RFA should be considered.

Serological Diagnosis of Liver Metastasis in Patients with Breast Cancer

Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011. Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Results Liver metastasis was more likely to occur in patients with stage Ill cancer or c-erbB-2-positive expression. Alanine aminotransferase, aspartate aminotransferase, ~/-glutamyltransferase （GGT）, alkaline phosphatase, lactate dehvdrogenase （LDH）, and carbohydrate antigen 1153 （CA153） levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH, GGT, and CA153 were 174 U/L, 32 U/L, and 26.48 Dg/L, respectively. The areas under the curves of LDH, GGT, and CEA were 0.795, 0.784, and 0.661, respectively, and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6% and 85.7 %, respectively. The specificity of serial tests for both pairs of enzymes was 97.7%. Conclusions Tile sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.

Fascioliasis presenting as colon cancer liver metastasis on 18Ffluorodeoxyglucose positron emission tomography/computed tomography: A case report

BACKGROUND Fascioliasis is caused by watercress and similar freshwater plants or drinking water or beverages contaminated with metacercariae. Fascioliasis can radiologically mimic many primary or metastatic liver tumors. Herein, we aimed to present the treatment process of a patient with fascioliasis mimicking colon cancer liver metastasis. CASE SUMMARY A 35-year-old woman who underwent right hemicolectomy due to cecum cancer was referred to our clinic for management of colon cancer liver metastasis. Both computed tomography and 18F-fluorodeoxyglucose positron emission tomography revealed several tumoral lesions localized in the right lobe of the liver. After a 6-course FOLFOX (folinic acid, fluorouracil, oxaliplatin) and bevacizumab regimen, the hypermetabolic state on both liver and abdominal lymph nodes continued, and chemotherapy was extended to a 12-course regimen. The patient was referred to our institute when the liver lesions were detected to be larger on dynamic liver magnetic resonance imaging 6 weeks after completion of chemotherapy. Right hepatectomy was performed, and histopathological examination was compatible with fascioliasis. Fasciola hepatica IgG enzyme-linked immunosorbent assay was positive. The patient was administered two doses of triclabendazole (10 mg/kg/dose) 24 h apart. During the follow-up period, dilatation was detected in the common bile duct, and Fasciola parasites were extracted from the common bile duct by endoscopic retrograde cholangiopancreatography (ERCP). Triclabendazole was administered to the patient after ERCP. CONCLUSION Parasitic diseases, such as those caused by Fasciola hepatica, should be kept in mind in the differential diagnosis of primary or metastatic liver tumors, such as colorectal cancer liver metastasis, in patients living in endemic areas.

Identification of liver metastasis-associated genes in human colon carcinoma by mRNA profiling

Objective: Liver metastasis,which contributes substantially to high mortality,is the most common recurrent mode of colon carcinoma.Thus,it is necessary to identify genes implicated in metastatic colonization of the liver in colon carcinoma.Methods: We compared mRNA profiling in 18 normal colon mucosa(N),20 primary tumors(T) and 19 liver metastases(M) samples from the dataset GSE49355 and GSE62321 of Gene Expression Omnibus(GEO) database.Gene ontology(GO) and pathways of the identified genes were analyzed.Co-expression network and proteinprotein interaction(PPI) network were employed to identify the interaction relationship.Survival analyses based on The Cancer Genome Atlas(TCGA) database were used to further screening.Then,the candidate genes were validated by our data.Results: We identified 22 specific genes related to liver metastasis and they were strongly associated with cell migration,adhesion,proliferation and immune response.Simultaneously,the results showed that C-X-C motif chemokine ligand 14(CXCL14) might be a favorable prediction factor for survival of patients with colon carcinoma.Importantly,our validated data further suggested that lower CXCL14 represented poorer outcome and contributed to metastasis.Gene set enrichment analysis(GSEA) showed that CXCL14 was negatively related to the regulation of stem cell proliferation and epithelial to mesenchymal transition(EMT).Conclusions: CXCL14 was identified as a crucial anti-metastasis regulator of colon carcinoma for the first time,and might provide novel therapeutic strategies for colon carcinoma patients to improve prognosis and prevent metastasis.

Rational Operation for Primary Gastric Carcinoma with Liver Metastasis

OBJECTIVE To investigate the prognosis of advanced gastric carcinoma patients with liver metastasis, and provide a foundation for rational operations. METHODS The operations and prognosis of 102 primary gastric carcinoma patients with liver metastasis were studied retrospectively. RESULTS In gastric carcinoma patients with H1 metastasis who underwent a resection operation, the 6-month, 1- and 2-year post-operative survival rates were 61%, 42% and 7%. There was a statistically significant difference in survival between resected and non-resected patients （P=0.000） in gastric carcinoma cases with H2 metastasis, resection operations resulted in 54%, 16% and 8% respective survival rates, with no significant difference compared to patients not receiving a resection （P=0.132）. Gastric carcinoma patients with H3 metastasis who received a resection operation showed 25%, 13% and 0% respective survivals with no significantly better prognosis compared to the non-resected cases （P=0.135）. There was no statistically significant difference in survival between the cases with or without peritoneal metastasis （P=0.152）. CONCLUSION A resection operation provides a better prognosis for gastric carcinoma patients with H1 metastasis independent of peritoneal metastasis, but resection has no benefit for gastric carcinoma cases with H2 or H3 metastasis. Peritoneal metastases are not the significant influencing factor for the prognosis of gastric cancer with liver metastasis.

Risk factors,prognostic predictors,and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis

BACKGROUND Liver metastasis(LM)remains a major cause of cancer-related death in patients with pancreatic cancer(PC)and is associated with a poor prognosis.Therefore,identifying the risk and prognostic factors in PC patients with LM(PCLM)is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients.However,there are limited data on risk and prognostic factors in PCLM patients.AIM To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms.METHODS Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance,Epidemiology,and Results Database.Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode.The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model.The performance of the two nomogram models was evaluated using receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA),and risk subgroup classification.The Kaplan-Meier method with a logrank test was used for survival analysis.RESULTS We enrolled 33459 patients with PC in this study.Of them,11458(34.2%)patients had LM at initial diagnosis.Age at diagnosis,primary site,lymph node metastasis,pathological type,tumor size,and pathological grade were identified as independent risk factors for LM in patients with PC.Age>70 years,adenocarcinoma,poor or anaplastic differentiation,lung metastases,no surgery,and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM.The C-index of diagnostic and prognostic nomograms were 0.731 and 0.753,respectively.The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves,calibration plots,and DCA curves.The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation.CONCLUSION Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention.External validation is required to confirm these results.

Interaction between Colon Cancer Cells and Human Liver Sinusoidal Endothelial Cells Promotes Liver Metastasis of Tumor Cells

OBJECTIVE To investigate the effect of co-culture between colon cancer cells （SW1116） and human liver sinusoidal endothelial cells （HLSECs） on cancer cell metastasis, and to provide a novel model for studying the mechanism of colon cancer liver metastasis. METHODS HLSECs and SW1116 were co-cultured for 21 rounds in vitro. Transwell migration, gelatin-zymography, CCK-8 proliferation and colony formation assays were used to examine the invasion, proliferation, and colony forming ability of cancer cells. Assays were carried out to examine tumor growth ability and liver metastasis. The associated molecular change was examined by western blotting. RESULTS After 21 selection rounds, colon cancer cells SWl 1161）21 displayed a clear boundary. Compared with the 5W1116 cells, SW1116P21 cells had a greater invasive ability, cell proliferation and colony formation in soft agar. A gelatin-zymography assay showed that the ability of SW1116P21 cells to secrete matrix metalloproteinase-2/9 was significantly greater than that of SWl116 cells. Additionally, the capacity for subcutaneous tumor formation of SW1116P21 was significantly increased. It was found that mice injected with SW1116P21 cells developed significantly more visually observable liver nodules than mice injected with SW1116 cells. Western blotting showed increased vimentin expression and decreased E-cadherin expression in the SW1116P21 cells, compared with the SWl 116 cells. CONCLUSION The interaction between SW1116 and HLSECs may promote tumor cell invasion, proliferation and colony formation in vitro, and tumor formation and liver metastasis in vivo. An epithelial-mesenchymal transition occurs in SWl 116P21 cells, which contributes to the change in the characteristics of tumor cells.

Diagnostic value of bile CEA assay for the detection of liver metastasis from colorectal cancer

Objective： We measured CEA （carcinoembryonic antigen） levels in both serum and bile from patients with coloroctal cancer （CRC） to evaluate the relationship between bile CEA levels and liver metastasis （LM）. Methods： Throe groups were enrolled in our study. Primary CRC group： 27 patients with CRC but without LM; LM group： 14 patients with LM from CRC; Controlled group： 20 patients with benign biliary diseases （cholelithiasis or cholecystitis）. Both serum and bile were collected to measure CEA levels in all groups but only bile CEA was measured in controlled group. Results： Bile CEA level in LM group was significantly higher than that of the primary CRC group （314.27 and 13.07 ng/mL respectively; P 〈 0.05）. In LM group bile CEA level was significantly higher than serum CEA level （314.27 and 43.51 ng/mL respectively; P 〈 0.05）. Bile CEA level was more relevant to the number and size of LM than the primary tumor factors. Conclusion： In confirmed CRC liver metastasis, the bile CEA level is significantly elevated. Bile CEA assay may be of potential value in diagnosis of liver metastasis,especially for the occult LM.

Curative resection of leiomyosarcoma of the descending colon with metachronous liver metastasis: A case report

BACKGROUND Leiomyosarcoma(LMS)has a poor prognosis and rarely originates from the colon.If resection is possible,surgery is the first treatment most commonly considered.Unfortunately,no standard treatment exists for hepatic metastasis of LMS;although,several treatments,such as chemotherapy,radiotherapy,and surgery,have been used.Subsequently,the management of liver metastases remains controversial.CASE SUMMARY We present a rare case of metachronous liver metastasis in a patient with LMS originating from the descending colon.A 38-year-old man initially reported abdominal pain and diarrhea over the previous two months.Colonoscopy revealed a 4-cm diameter mass in the descending colon,40 cm from the anal verge.Computed tomography revealed intussusception of the descending colon due to the 4-cm mass.The patient underwent a left hemicolectomy.Immunohistochemical analysis of the tumor revealed that it was positive for smooth muscle actin and desmin,and negative for cluster of differentiation 34(CD34),CD117,and discovered on gastrointestinal stromal tumor(GIST)-1,which are characteristic of gastrointestinal LMS.A single liver metastasis developed 11 mo postoperatively;the patient subsequently underwent curative resection thereof.The patient remained disease-free after six cycles of adjuvant chemotherapy(doxorubicin and ifosfamide),and 40 and 52 mo after liver resection and primary surgery,respectively.Similar cases were obtained from a search of Embase,PubMed,MEDLINE,and Google Scholar.CONCLUSION Early diagnosis and surgical resection may be the only potential curative options for liver metastasis of gastrointestinal LMS.

Prevention of metastasis to liver by using 5-FU intraperitoneal chemotherapy in nude mice inoculated with human colonic cancer cells

AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristics

AIM To establish a liver metastasis model of human colorectal carcinoma in nude mice.METHODS Orthotopic transplantation of histologically intact colorectal tissues from patients into colorectal mucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electron microscopy and immunohistochemistry.RESULTS Liver metastasis models of human colon carcinoma (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after screening from 34 colorectal carcinomas. They had been passaged in vivo for 18 and 21 generations respectively. There were lymphatic, hemotogenous and implanting metastasesis. CEA secretion was maintained after transplantation. The primary and liver metastatic tumors were similar to the original human carcinoma in histopathological and ultrastructural features, DNA content and chromosomal karyotype.CONCLUSION The liver metastasis models provide useful tools for the study of mechanism of metastasis and its treatment of human colorectal cancer.INTRUDUCTIONSome models of nude mice that fresh human colorectal carcinoma tissue or cells were successfully transplanted subcuteneously have been reported at home and abroad[1,2]. But until now there has been no report on a liver metastasis model of human colorectal carcinoma established by orthotopic transplantation in nude mice in China. Based on our previous models of human liver and pancreas carcinoma by orthotopic transplantation[3,4], we established liver metastasis models of colon and rectum carcinoma with a spontaneous metastasis rate of 100%.

Colonic metastasis after resection of primary squamous cell carcinoma of the lung:A case report and literature review

Lung cancer is a common malignancy in the world; however symptomatic colonic metastasis from primary lung cancer is rare. A 64-year-old man was originally found poorly differentiated squamous cell carcinoma of right lung and received right lower lobectomy and lymph node dissection. Three years later, the patient presented to our emergency room with the symptom of upper abdominal pain and weight loss. Abdominal palpation and computed tomography scan of the abdomen revealed a large mass measuring 7.6 cm &#x000d7; 8.5 cm in the ascending colon. Colonoscopy and biopsy revealed poorly differentiated squamous cell carcinoma with similar morphological pattern to that of the previous lung cancer. Chemotherapy was given and the patient died 5 mo later. Lung cancer metastatic to the colon confers a poor prognosis: overall survival ranged from 5 wk to 1 year, with a median survival of 3 mo after the diagnosis of the colonic metastasis.

Neuroendocrine neoplasms of liver-A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification

AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) NEN.METHODS Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were collected.RESULTS Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients.CONCLUSION Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.

Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as

Cancer stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system

Aim: We have recently identified a cancer stem cell (CSC) subpopulations within the tumor nests (TNs) and another within the peritumoral stroma (PTS) in liver metastasis from colon adenocarcinoma (LMCA). This study investigated the expression of components of the renin-angiotensin (RAS): pro-renin receptor (PRR), angiotensin converting enzyme (ACE), and angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) in LMCA. Methods: 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining was performed on 16 LMCA samples for PRR, ACE, ATIIR1 and ATIIR2. Immunofluorescence (IF) IHC staining was performed to investigate co-expression of these components of the RAS with SOX2 or OCT4. NanoString analysis (n = 6) and Western blotting (WB,n = 3) were performed on snap-frozen LMCA samples to confirm mRNA and protein expression, respectively. Results: DAB IHC staining showed the expression of PRR, ACE, ATIIR1 and ATIIR2 within all LMCA samples. NanoString analysis and WB confirmed gene and protein expression of these components of the RAS. IF IHC staining demonstrated expression of PRR, ATIIR1 and ATIIR2 by the SOX2+ CSCs within the TNs and the OCT4+ CSCs within the PTS. ACE was expressed on the endothelium of the microvessels within the PTS. ;Conclusion: These finding suggests the CSCs within LMCA maybe a novel therapeutic target by manipulation of the RAS.

Antitumor immunity of low-dose cyclophosphamide:changes in T cells and cytokines TGF-beta and IL-10 in mice with colon-cancer liver metastasis

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.

Inhibitory effects of two oligosaccharideson murine melanoma experimental liver metastasis

AIM To observe the effects of a chemically synthesized tetrose and a natural yeast mannan on experimental liver metastasis of mouse melanoma. METHODS After treated with 4mg tetrose (tetrose group) or 4mg mannan (mannan group) for 30 minutes at 37℃, 0 5ml 1×10 6 B16 MBK melanoma cells were injected into the spleen of mice. Fifty five days later, melanoma metastatic nodes on the surface of the liver and in other organs as well as mouse survival time were observed. RESULTS Of the 6 mice in control (B16 cell+PBS) group, 4 died naturally within 55 days, and 2 were killed on the 55th day. All of the 6 mice had metastases in livers, the total number of the melanoma nodes on each liver surface ranged from 2 to 30, with the largest one merging into the whole liver. One mouse had a neoplasm in the remnant site of injection, and 3 had metastases in lungs. In contrast, of the 6 mice in tetrose group, only one died on the 50th day after injection, with 3 metastases in the liver, the largest being 10mm in diameter, the other 5 mice survived until being dissected on the 55th day after injection and had no liver metastasis, but 3 of them had neoplasms in their remnant sites of injection. In mannan group, all of the 6 mice survived and no metastasis was seen except for 2 liver nodes in one mouse with the largest diameter of 1mm. Neither tetrose nor mannan group had metastasis out of the liver, and the weight of liver in the two groups was significantly lower than those in the control group. CONCLUSION Both tetrose and mannan had the effects of preventing melanoma cells from experimental metastasis to and out of the liver, and prolonging the survival time of the mouse.