Jisheng Chen

Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer.

Expression of membrane-bound Fas ligand (mFasL) on colon cancer cells serves as a potential mechanism to inhibit host immune function by inducing apoptosis of host lymphocytes. Membrane-bound FasL can be cleaved and released as a soluble mediator (sFasL), which may spread the apoptosis induction effect. Our study examined whether colon adenocarcinoma cells release sFasL, and induce apoptosis of host lymphocytes without direct cell–cell contact. In 12 consecutive patients with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured in the sera and apoptosis identified in tumour-infiltrating and peripheral blood lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily cultured; sFasL was isolated from supernatants, measured, incubated with Fas-bearing Jurkat cells, and the resulting apoptosis was analysed. Serum levels of sFasL were significantly elevated in all colon cancer patients with mFasL expression in tumour tissues (n = 8). In these patients, the number of apoptotic lymphocytes was significantly increased within tumour and peripheral blood. Furthermore, sFasL was present in the corresponding supernatants and induced apoptosis of Jurkat cells in a dose-dependent manner. These findings suggest that mFasL-positive colon cancer cells release sFasL, and thus may induce apoptosis of host lymphocytes as a potential mechanism for immune evasion.

Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis

Metastasis of colorectal carcinomas rarely occurs in cirrhotic livers. Our study investigated the influence of activated Kupffer cells from cirrhotic rat livers on hepatic colonization and FasR-mediated apoptosis of colon cancer cells. A rat colon cancer cell line, RCN-9, was used to inoculate rat livers. Treatment with conditioned media of Kupffer cells isolated from CCl4-induced cirrhotic rat livers (cirrhotic KCM) significantly reduced the incidence of hepatic colonization of RCN-9 cells. In vitro cytotoxicity of Kupffer cells and tumour infiltrating lymphocytes (TILs) on RCN-9 cells was evaluated using [3H]-release assay. RCN-9 cells were resistant to cytotoxicity mediated by cirrhotic Kupffer cells, but were sensitized to TIL-mediated killing after treatment with cirrhotic KCM. The specific killing induced by TILs was FasR-mediated, as it was inhibited by ZB4, an antagonistic anti-FasR antibody. In agreement, cirrhotic KCM increased recombinant Fas ligand-induced apoptosis of RCN-9 cells, and up-regulated FasR expression on RCN-9 cells as evaluated by RT-PCR and flow cytometry. These findings suggest that Kupffer cells in cirrhotic livers sensitize metastatic colon cancer cells to FasR-mediated apoptosis by up-regulating the receptors, which thus prepare them to be eliminated by infiltrating lymphocytes.

Rare occurrence of metastatic colorectal cancers in livers with replicative hepatitis B infection

BACKGROUND It has been demonstrated that colorectal carcinomas rarely metastasize to diseased livers. However, this phenomenon has not been thoroughly evaluated in patients with various forms of chronic hepatitis B virus (HBV) infection. Therefore, the present study examined the relationship between the incidence of hepatic metastasis of colorectal carcinomas and chronic HBV infection, with emphasis on the influence of HBV viral replication and chronic liver damage. METHODS We analyzed the clinicopathological data of 512 patients undergoing surgical treatment of colorectal carcinomas at our department from 1992 to 1998. Among these cases, 74 had chronic HBV infection, including 28 cases with HBV replication and 21 with chronic liver damage. RESULTS The incidence of liver metastasis in the HBV infection group (13.5%) was significantly lower than that of the noninfection group (27.1%, P <0.05). In addition, patients with HBV infection survived longer than those without infection (P = 0.018). Furthermore, liver metastatic rate in patients with HBV replication (3.6%) was lower than those without virus replication (19.6%, P <0.05). In contrast, there was no significant difference in liver metastasis between HBV infected patients with or without chronic liver damage (P >0.05). CONCLUSIONS Chronic HBV infection with viral replication reduces hepatic metastasis of colorectal cancer, and thus prolongs the survival of patients.

Modification of N staging systems for penile cancer: a more precise prediction of prognosis

Background:The tumour-node-metastasis (TNM) classification is the most widely used tool for penile cancer. However, the current system is based on few studies and has been unchanged since 2009. We determined whether a modified pathological N staging system that incorporates the laterality and number of lymph node metastases (LNMs) increases the accuracy of the results in predicting survival compared with the 7th edition of the pathological N staging system of the American Joint Committee on Cancer (AJCC) for penile cancer.Methods:The clinical and histopathologic data from 111 patients with penile cancer with LNMs were analysed. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the impact of the clinical and pathological factors on disease-specific survival of these patients. The predictive accuracy was further assessed using the concordance index.Results:According to the 7th edition of the pathological N classification, the 3-year disease-specific survival (DSS) rates for patients with pN1, pN2, and pN3 disease are 89.6%, 65.9%, and 33.6%, respectively (PN1–N2=0.030, PN2–N3<0.001, P<0.001). Under the modified pathological N category criteria, the 3-year DSS rates for pN1, pN2, and pN3 patients were 90.7%, 60.5%, and 31.4%, respectively (PN1–N2=0.005, PN2–N3=0.004, P<0.001). In separate multivariate Cox regression models, only modified N stages (hazard ratio: 4.877, 10.895; P=0.018, P<0.001) exhibited independent effects on the outcome. The accuracy of the modified pathological N category was significantly increased.Conclusions:The modified pathological N staging system is a better reflection of the prognosis of patients with penile cancer. Our study should contribute to the improvement of prognostic stratification and systemic treatment to avoid overtreatment of patients.

The value of interferon combined with hepatic artery chemoembolization and portal vein chemotherapy in preventing a recurrence after radical resection for hepatocellular carcinoma

ObjectiveThe change of cell immune function after hepatectomy of patients suffering from hepatocellular carcinoma (HCC) is usually neglected. The aim of this study was to explore the change of T cell subsets in HCC patients after hepatectomy, and to study the value of treatment with interferon (INF) combined with hepatic artery chemoembolization (HACE) and portal vein chemotherapy (PVC) to prevent recurrence after radical resection of HCC.MethodsSeventy-five HCC patients were treated with PVC and HACE at the 2nd week and 4th week after radical tumor resection. In the 2nd week after surgery, 33 pationts received INF treatment for one week. Seventy-two patients were followed up over three years. The effect of INF combined with HACE and PVC on the postoperative recurrence rate was compared with that of HACE and PVC treatment. Changes of T cell subsets in the peripheral blood were examined with labeled monoclonal antibodies before and after hepatectomy or with use of interferon. Forty cholecystolithiasis patients who received a cholecystectomy were used as controls.ResultsCD3+ and CD4+ cells in the peripheral blood were reduced in patients with HCC. After hepatectomy, they declined further with a decrease in the CD4+/CD8+ ratio. The values returned to pre-operative level at the 4th week after surgery. The CD3+ and CD4+ cells and the CD4+/CD8+ ratio increased remarkably following the use of INF. The 1-, 2- and 3-year recurrent rates of patients treated with HACE, PVC and INF in combination were 0%, 6.2% and 15.6%, respectively, while those treated only with HACE and PVC were 5.0%, 12.5% and 27.5%, respectively.ConclusionPatients with HCC suffer from a marked immuno-suppression, which become ever more severe after hepatectomy. The combined use of HACE, PVC and INF is superior in decreasing the recurrent rate to the combination of only HACE and PVC.OBJECTIVE To explore the change of T cell subsets in patients suffered from hepatocellular carcinoma (HCC) before and after hepatectomy, and study the value of Roferon-A (interferon alpha-2a) combined with hepatic artery chemoembolization (HACE) and portal vein chemotherapy (PVC) after radical resection of HCC for preventing recurrence. METHODS On 75 HCC patients, PVC and HACE were respectively given at 2 weeks and 4 weeks after radical tumor resection. In 2nd week after surgery, 33 cases of them accepted Roferon-A treatment for 1 week. Seventy-two patients were followed up over 3 years. Effect of Roferon-A combined with HACE and PVC on postoperative recurrence rate was compared with that of HACE and PVC. Changes of T cell subsets in peripheral blood were examined with labeled monoclonal antibodies before and after hepatectomy or using interferon. Forty cholecystolithiasis patients received cholecystectomy were used as the controls. RESULTS CD(3)(+) and CD(4)(+) cells in peripheral blood were reduced in patients with HCC. After hepatectomy, they declined further with decrease in CD(4)(+)/CD(8)(+) ratio. The results returned to pre-operative level at the end of 4th week after surgery. The CD(3)(+), CD(4)(+) cells and the CD(4)(+)/CD(8)(+) ratio increased remarkably following the use of Roferon-A. The 1-, 2- and 3-year recurrence rates of patients treated with HACE, PVC and Roferon-A in combination were 0%, 6.2% and 15.6%, respectively, while those treated with HACE and PVC were 5.0%, 12.5% and 27.5%, respectively. CONCLUSION Patients with HCC suffer from marked immuno-suppression which became ever more severe after hepatectomy, combined use of HACE, PVC and Roferon-A is superior to only HACE and PVC by decreasing the recurrence rate.