Qi-Jing Wang

Sun Yat-Sen University Cancer Center, Shengcheng, Guangdong, China

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Publications (23)43.38 Total impact

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    ABSTRACT: Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such breast cancer patients although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in TNBC patients. In this study, we investigated the efficacy of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for post-mastectomy TNBC patients. From 2008 to 2012, 90 post-mastectomy TNBC patients were included in this retrospective study: 45 cases received chemotherapy alone or with sequential radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy and sequential CIK infusion. Survival analysis showed significantly higher disease-free survival (DFS) rate and overall survival (OS) rates in the CIK treatment group compared with the control group (p = 0.0382, p = 0.0046, respectively; log-rank test). Multivariate survival analysis showed that CIK adjuvant treatment was an independent prognostic factor for OS of TNBC patients. In subgroup analyses, CIK adjuvant treatment significantly increased the DFS rate of patients with pathological grade III, and significantly increased the OS rate of patients in N1, N2, N3-stage, IIB, III TNM stage and with pathological grade III. These data indicate that adjuvant CIK treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of TNBC patients, particularly those with lymph node metastasis, advanced TNM-stage and poor pathological grade.
    Clinical Cancer Research 03/2014; · 7.84 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro. Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion. The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis.
    PLoS ONE 01/2014; 9(4):e93073. · 3.73 Impact Factor
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    ABSTRACT: The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC) clinical specimens, we found the expression of IL-37 was decreased in tumor tissues, and the expression level was negatively correlated with tumor size. High expression of IL-37 in HCC tumor tissues was associated with better overall survival (OS) and disease-free survival (DFS). IL-37 expression in tumor tissues was positively associated with the density of tumor-infiltrating CD57+ natural killer (NK) cells, but not with the CD3+ and CD8+ T cells. Consistently, in vitro chemotaxis analysis showed that IL-37- overexpressing HCC cells could recruit more NK cells. The in vivo mouse model experiments also revealed that overexpression IL-37 in HCC cells significantly delayed tumor growth and recruited more NK cells into tumors tissues. Our finding suggested that IL-37 might play an important role for the prognosis of HCC patients via regulating innate immune-action.
    Scientific reports. 01/2014; 4:5177.
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    ABSTRACT: Cytokine-induced killer (CIK) cells are ex vivo generated heterogeneous NK-like T lymphocytes. It is not very clear whether the phenotype of CIK cells is associated with their therapeutic efficacy to cancer patients. Thus, in this study, the association of phenotype of CIK cells and the overall survival of 121 patients with hepatocellular carcinoma (HCC), 74 patients with lung cancer and 42 patients with colorectal cancer, all of whom underwent surgical resection and received autogenous CIK cell therapy, was analyzed. We found that high ratio of the CD3+CD4+ subset was associated with poorer overall survival in colorectal cancer, but not HCC or lung cancer. A high ratio of the CD3+CD8+ subset was associated with improved overall survival in all three types of cancer. A high ratio of the CD3+CD56+ NK-like subset was associated with improved overall survival in lung and colorectal cancer, but not HCC. A high ratio of the CD3-CD56+ NK subset was associated with poorer overall survival in lung and colorectal cancer, but not HCC. In conclusion, the CD3+CD8+ and CD3+CD56+ subsets, especially the CD3+CD8+ subset, may be the major phenotypes responsible for anti-tumor immunity in vivo after autogenous CIK cell therapy.
    Tumor Biology 08/2013; · 2.52 Impact Factor
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    ABSTRACT: Even after surgery, hepatocellular carcinoma (HCC) has poor prognosis; adjuvant therapy is needed to improve effectively the outcome of HCC patients. We evaluated the efficacy of cytokine-induced killer (CIK) cell infusion as an adjuvant therapy for postoperative HCC patients. A total of 410 patients were studied retrospectively (January 2002 to January 2007): 206 received surgery alone; 204 received surgery and at least four cycles of CIK cell transfusion (CIK group). Kaplan-Meier and Cox regression analyses were used to explore differences in OS between two groups. The CIK group overall survival rates were significantly higher than that of the surgery-alone group (log-rank test; p = 0.0007). Multivariate survival analysis showed that CIK cell treatment was an independent prognostic factor. In subgroup analysis, patients who received ≥8 cycles of CIK cell transfusion exhibited significantly better survival than the <8 cycle group (p = 0.0272). There was no significant difference in overall survival in patients with ≤5-cm tumors between the CIK and surgery-alone groups (p = 0.7567). However, in patients with >5-cm tumors, the CIK group displayed significantly better overall survival than the surgery-alone group (p = 0.0002). Postoperative immunotherapy with CIK cell transfusion may be an effective adjuvant treatment for improving the outcomes of HCC patients; >8 cycles of CIK cell transfusion may ensure that patients derive maximal benefits. Moreover, patients with large tumors might benefit more from CIK cell adjuvant treatment than patients with small tumors.
    Annals of Surgical Oncology 07/2013; · 4.12 Impact Factor
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    ABSTRACT: In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children; therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6 x 10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.
    Ai zheng = Aizheng = Chinese journal of cancer 05/2013;
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    ABSTRACT: Chuankezhi (CKZ), a new Chinese medicine, plays an important role in immunoregulation. Cytokine-induced killer (CIK) cells have been commonly used for immunotherapy in recent years. In this study, we aimed to investigate the immunoregulatory effect of CKZ on CIK cells. Peripheral blood monocytes were isolated from healthy donors, and CIK cells were generated by culturing monocytes with IFN-γ, OKT3, and IL-2. Different concentrations of CKZ were added on day 2. After incubation for 14 days in culture, the anti-tumor effects of CIK cells were measured by cytotoxicity assay. Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype, intracellular cytokine production, and apoptosis. The effect of CKZ on the anti-tumor activity of CIK cells in nude mice was also investigated. CKZ increased the proportion of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ T cells. CKZ-conditioned CIK cells showed a greater ability to kill tumor cell lines, as well as a higher frequency of IFN-γ and TNF-α production, compared with the CIK cells in the control group. CKZ also suppressed the apoptosis of CIK cells in vitro. Furthermore, CKZ combined with CIK cells had a stronger suppressive effect on tumor growth than the CIK, CKZ, or normal saline control groups in vivo. Our results indicate that CKZ enhances the anti-tumor activity of CIK cells and is a potential medicine for tumor immunotherapy.
    Ai zheng = Aizheng = Chinese journal of cancer 03/2013;
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    ABSTRACT: FOXO3a, a member of the forkhead class 'O' (FOXO) transcription factor family, controls a wide spectrum of biological processes, such as DNA damage repair, apoptosis, and cell cycle regulation. FOXO3a has been shown to be a tumor suppressor in various cancers. This study investigated the expression of FOXO3a in primary gastric adenocarcinomas and its prognostic value for primary gastric adenocarcinoma patients. Real-time quantitative RT-PCR (qRT-PCR), western blotting, and immunohistochemical staining were used to detect FOXO3a expression in primary gastric cancerous surgical specimens and adjacent non-tumorous tissues. Our data showed that the expression of FOXO3a mRNA (p = 0.03) and protein (p = 0.019) was lower in cancerous tissues compared with their adjacent non-tumorous tissues. In addition, the chi-square test revealed that low FOXO3a expression was significantly correlated with larger tumor size (p = 0.007), poor histopathological classification (p = 0.029), depth of invasion (p = 0.049), local lymph node metastasis (p = 0.013), distant metastasis (p = 0.013) and AJCC staging (p<0.001). Kaplan-Meier survival analysis demonstrated that low expression of FOXO3a was significantly correlated with a poor prognosis for gastric cancer patients (p<0.001). The multivariate analysis showed that FOXO3a expression was an independent prognostic factor of the overall survival rate of patients with primary gastric adenocarcinoma. Our study suggested that decreased FOXO3a expression may play an important role in the progression of gastric cancer. FOXO3a could be a valuable prognostic marker as well as a potential molecular therapy target for gastric cancer patients.
    PLoS ONE 01/2013; 8(10):e78158. · 3.73 Impact Factor
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    ABSTRACT: The ARID1A gene encodes adenine-thymine (AT)-rich interactive domain-containing protein 1A, which participates in chromatin remodeling. ARID1A has been showed to function as a tumor suppressor in various cancer types. In the current study, we investigated the expression and prognosis value of ARID1A in primary gastric cancer. Meanwhile, the biological role of ARID1A was further investigated using cell model in vitro. To investigate the role of ARID1A gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were used to examine the ARID1A expression in paired cancerous and noncancerous tissues. Results revealed decreased ARID1A mRNA (P = 0.0029) and protein (P = 0.0015) expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues, and in gastric cancer cell lines. To further investigate the clinicopathological and prognostic roles of ARID1A expression, we performed immunohistochemical analyses of the 224 paraffin-embedded gastric cancer tissue blocks. Data revealed that the loss of ARID1A expression was significantly correlated with T stage (P = 0.001) and grade (P = 0.006). Consistent with these results, we found that loss of ARID1A expression was significantly correlated with poor survival in gastric cancer patients (P = 0.003). Cox regression analyses showed that ARID1A expression was an independent predictor of overall survival (P = 0.029). Furthermore, the functions of ARID1A in the proliferation and colony formation of gastric cell lines were analyzed by transfecting cells with full-length ARID1A expression vector or siRNA targeting ARID1A. Restoring ARID1A expression in gastric cancer cells significantly inhibited cell proliferation and colony formation. Silencing ARID1A expression in gastric epithelial cell line significantly enhanced cell growth rate. Our data suggest that ARID1A may play an important role in gastric cancer and may serve as a valuable prognostic marker and potential target for gene therapy in the treatment of gastric cancer.
    PLoS ONE 01/2012; 7(7):e40364. · 3.73 Impact Factor
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    ABSTRACT: Exportin 4 (XPO4) is a recently-discovered candidate tumor-suppressor gene identified in a liver cancer mouse model. To investigate the role of XPO4 in hepatocellular carcinoma (HCC) pathogenesis, we determined XPO4 expression and its correlation to prognosis in human primary HCC. The XPO4 mRNA transcription level in HCC cell lines and tissue samples were detected by real-time quantitative polymerase chain reaction (PCR). XPO4 protein expression in 123 primary HCC clinical surgical specimens were analyzed by immunohistochemical detection. Real-time quantitative PCR showed a decrease in XPO4 expression in HCC cell lines BEL-7402, Hep-G2, and SK-hep1 compared to the normal liver cell line LO2. Decreased XPO4 mRNA was also found in the majority of tumor tissues compared with matched non-tumor liver tissues (P = 0.004). Immunohistochemical detection revealed that XPO4 expression was reduced in 51 of 123 (41.5%) tumor resection samples compared with adjunct non-tumor tissues. We also found XPO4 expression to be significantly correlated with tumor size (P = 0.045) and histopathological classification (P = 0.004). Kaplan-Meier survival curves showed that the downregulation of XPO4 resulted in a significantly poor prognosis (P = 0.008, log-rank test), and multivariate Cox's analysis showed that XPO4 expression was an independent prognostic factor for overall survival of HCC patients (P = 0.013). Our data suggest that XPO4 could be involved in the progression of human HCC and could serve as a potential target for gene therapy in the treatment of HCC.
    Journal of Gastroenterology and Hepatology 03/2011; 26(3):544-9. · 3.33 Impact Factor
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    ABSTRACT: In this study, we characterized the intratumoral expression of IL-17 and CD8(+) TILs in gastric adenocarcinoma patients after resection and determined the correlation between the survival probability of gastric adenocarcinoma patients and the expression of IL-17 in tumor. Expression of IL-17 and CD8 was assessed by immunohistochemistry, and the prognostic effects of intratumoral IL-17 expression and CD8(+) TILs were evaluated by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection revealed the presence of IL-17 and CD8(+) cells in gastric adenocarcinoma tissue samples (90.6%, 174 out of 192 patients and 96.9%, 186 out of 192 patients, respectively). We have also found that intratumoral IL-17 expression was significantly correlated with age (p=0.004) and that the number of CD8(+)TILs was significantly correlated with UICC staging (p=0.012) and the depth of tumor invasion (p=0.022). The five-year overall survival probability among patients intratumorally expressing higher levels of IL-17 was significantly better than those expressing lower levels of IL-17 (p=0.036). Multivariate Cox proportional hazard analyses revealed that intratumoral IL-17 expression (HR: 0.521; 95% CI: 0.329-0.823; p=0.005) was an independent factor affecting the five-year overall survival probability. We conclude that low levels of intratumoral IL-17 expression may indicate poor prognosis in gastric adenocarcinoma patients.
    International journal of biological sciences 01/2011; 7(1):53-60. · 3.17 Impact Factor
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    ABSTRACT: Immunotherapy, especially using dendritic cells (DCs)-based vaccine, appears promising in the treatment of hepatocellular carcinoma (HCC) following surgery. However, the therapeutic efficacy of current DC vaccines loaded with HCC antigen is limited in clinical practice. One important reason might be that the DC vaccines for the treatment of HCC were not aimed at targeting the hepatocellular carcinoma cancer stem cells (HCCCSCs). Therefore, establishing an immunotherapy to kill HCC stem cells could be a novel therapeutic strategy. In this study, we have developed an immunotherapy to target CD133(+) HCC cells in the treatment of HCC. This study had three main findings; (1) CD133(+)HCC cells RNA loaded DCs could induce special CD8(+) cytotoxic T lymphocytes (CD133(+)Huh7-CTLs) response against CD133(+) Huh7 cells in vitro. (2) Huh7 cells-induced tumor growth in vivo was effectively inhibited by CD133(+)Huh7-CTLs. (3) the great inhibition potential of CD133(+)Huh7-CTLs to Huh7-induced tumor growth might not be only associated with anti-tumor cytokines such as IFNγ, but also to CD133(+)Huh7-DCs induced specific CTLs. This study shows an experimental proof that CD133(+)HCC cells RNA loaded DC vaccine has potential in treating HCC and may provide a new therapy for clinical post operative adjuvant therapy in future.
    Cancer biology & therapy 08/2010; 10(4):368-75. · 3.29 Impact Factor
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    ABSTRACT: Cytokine-induced killer (CIK) cells and autologous dendritic cells-CIK (DC-CIK) cells co-cultured with autologous dendritic cells (DCs) and CIK cells are commonly used for immunotherapy recently. We compared the anti-tumor immune response of CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach. Peripheral monocytes were isolated from patients with renal carcinoma, lung cancer, or maxillary squamous cell carcinoma and their healthy adult children. Isolated cells were cultured and induced as DCs and CIK cells in vitro. CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively, generating DC-CIK cells and semi-allogeneic DC-CIK cells. The anti-tumor activities of autologous CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells were measured by LDH assay. Intracellular staining was used to test the secretion of cytokines. Flow cytometry was applied for detecting the phonotype changes of these three types of cells. Cell proliferation and cell apoptosis were detected by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and Annexin V/PI respectively. Compared with autologous CIK cells and DC-CIK cells, semi-allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN-gamma secretion, reduced IL-4 secretion, increased the ratio of CD3(+)CD56(+) cells and CD3(+)CD8(+) cells, decreased the number of CD4(+)CD25(+) cells, promoted cell proliferation, and lessened cell apoptosis. Semi-allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells. Our results provided experimental evidence for clinical application of DC-CIK cells.
    Chinese journal of cancer 07/2010; 29(7):641-8.
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    ABSTRACT: Our previous studies have shown that dendritic cell (DC)-tumor cell fusion vaccine can induce specific antitumor response against esophageal carcinoma cells. This study was to investigate the inhibitory effect of intratumor injection of the antigen-specific cytotoxic T lymphocytes (CTLs) induced by DC-tumor cell fusion vaccine against subcutaneously transplanted esophageal carcinoma cells in nude mice, and to analyze the influence of DC/tumor cell fusion vaccine on proliferation and apoptosis of esophageal carcinoma cells. Fusion cell vaccine of mature DCs with EC109 cells were generated by the polyethylene glycol (PEG) protocol and the antigen-specific CTLs were induced. The models of transplanted human esophageal carcinoma in nude mouse were established using EC-109 cell line. Thirty-three nude mice with subcutaneous tumors were randomly divided into three groups. Subcutaneous tumors of group A (n=11), group B (n=11) and group C (n=11) were intratumorally injected with the CTLs induced by DC/tumor fusion vaccine, T lymphocytes and RPMI 1,640 medium respectively once a week. After four weeks of intratumor injection, the nude mice were killed and the nodules were anatomized. The mean volume and weight of tumors of each group were measured, and the tumor inhibitory rates of the Group A and the Group B were calculated and compared. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (S-P method). The mean PCNA-label index (LI) of three groups was compared. The cell cycle and cell apoptosis of the xenograft tumor cells were analyzed by flow cytometry. The mean S-phase fraction (SPF) and the mean rate of cell apoptosis of three groups was compared respectively. Both the mean volume and the mean weight of xenograft tumors in group A (881.45+/-31.14 mm3 and 0.88+/-0.04 g) were significantly smaller than those of group B (1493.37+/-51.67 mm3 and 1.38+/-0.07 g) and group C (2065.77+/-87.55 mm3 and 2.04+/-0.11 g). The tumor inhibitory rates of Group A was significantly higher than that of group B (56.86% vs. 32.35%, F=1218.08, P=0.001). The mean PCNA-LI of xenograft tumors was less in the group A (26.83+/-0.95)% than in the group B (51.82+/-1.51)% and group C (68.93+/-2.40)% (F=1528.39, P=0.000). The mean SPF of xenograft tumors was less in the group A (12.46+/-0.36)% than in the group B (29.39+/-0.96)% and the group C (42.25+/-1.43)% (P<0.05). The mean apoptotic rate of xenograft tumors was less in the group A (38.03+/-1.21)% than in the group B (17.75+/-0.56)% and the group C (6.59+/-0.22)% (P<0.05). The model of subcutaneous xenograft tumors in nude mice using human esophageal carcinoma cell line EC-109 has been successfully established. CTLs induced by DC/tumor fusion vaccine has specific antitumor immunity efficacy in vivo. CTLs can inhibit the proliferation of tumor cells and induce apoptosis of tumor cells in local tumors.
    Ai zheng = Aizheng = Chinese journal of cancer 10/2009; 28(10):1067-71.
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    ABSTRACT: Suppressor of cytokine signaling 1 (SOCS1) plays a critical role in antitumor immunity. Down-regulating SOCS1 in antigen-presenting dendritic cells (DCs) could enhance antigen-specific antitumor immunity. This study was to investigate the antigen-specific antitumor effect and mechanism of DCs with siRNA-mediated inhibition of SOCS1, stimulated by OK-432 and pulsed with hepatocellular carcinoma cell line HepG2 antigens. The expression of SOCS1 in immature DCs was down-regulated by RNA interference (RNAi). DCs were pulsed with lysate of HepG2 cells and stimulated with OK-432. The morphology of DCs was observed under converted phase microscopy. Phenotypic changes in cells after stimulation were characterized by flow cytometry (FCM). The Alamar Blue assay was adopted to evaluate the activation and proliferation of autologous lymphocytes induced by mature DCs. The cytotoxicity of cytotoxic T lymphocytes (CTLs) elicited by modified DCs to HepG2, EC109 and K562 cells was tested by the lactate dehydrogenase (LDH) assay. Cells displaying a typical morphology and phenotypic properties of mature DCs were obtained successfully. The expression of SOCS1 in DCs was down-regulated by SOCS1 RNAi. Mature DCs showed high expressions of CD80, CD83, CD86, and HLA-DR. Pulsing of DCs with lysate of HepG2 had no influence on the phenotypic properties of DCs. Down-regulating SOCS1 expression enhanced the maturation of DCs. The modified DC tumor vaccine stimulated the proliferation of autologous lymphocytes effectively, and the proliferation rate of T cells was (110.7+/-22.2)%. After being activated by modified DCs, TCLs exerted a specific and effective killing effect on HepG2 cells, but not on EC109 and K562 cells. Mature DCs could induce antigen-specific antitumor immunity against hepatocellular carcinoma after silencing of SOCS1 by siRNA, stimulation by OK-432 and pulsing of DCs with HepG2 cell antigens.
    Ai zheng = Aizheng = Chinese journal of cancer 07/2008; 27(7):685-91.
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    ABSTRACT: The recurrence of hepatocellular carcinoma (HCC) after minimally invasive therapy is frequent. Adoptive immunotherapy is thought to be an effective method to lower recurrence and metastasis rates of malignant tumors. Therefore, 85 HCC patients after transcatheter arterial chemoembolization and radiofrequency ablation therapy were randomized to immunotherapy group and no adjuvant therapy group. Autologous cytokine-induced killer (CIK) cells were transfused via hepatic artery to the patients. The alteration of levels of lymphocyte subsets in peripheral blood of patients was examined by flow cytometry. All patients were screened by computed tomography every 2 months to observe the tumor recurrent conditions. After CIK cell infusions, the percentages of CD3+, CD4+, CD56+, CD3+CD56+ cells, and CD4+/CD8+ ratio increased from 68.6+/-11.0%, 31.1+/-9.0%, 15.6+/-7.9%, 5.2+/-3.1%, and 1.1+/-0.5 to 70.7+/-10.1%, 33.5+/-8.0%, 18.4+/-9.4%, 5.9+/-2.8%, and 1.3+/-0.7, respectively (P<0.05); whereas the percentage of CD8 cells decreased from 31.1+/-7.8% to 28.6+/-8.3% (P<0.05). The 1-year and 18-month recurrence rates of the study group were 8.9% and 15.6%, compared with 30.0% and 40.0% of the control group (both P value<0.05). The data suggest that CIK cell transfusion is an effective treatment. It can boost the immunologic function in HCC patients and plays an important role in reducing the recurrence rate of HCC.
    Journla of Immunotherapy 02/2008; 31(1):63-71. · 3.46 Impact Factor
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    ABSTRACT: Mucin-1 (MUC1), a tumor-associated antigen, is an optional molecular target for antitumor immunotherapy protocols. This study was to establish a subcutaneous human esophageal cancer transplantation model with MUC1 high expression in nude mice that closely resembles the biological features of human esophageal cancer, and provide a in vivo model for MUC1-targeting immunotherapy of esophageal cancer. Human esophageal carcinoma cell line EC-109 with MUC1 high expression was cultured, and subcutaneously transplanted into BALB/c athymic nude mice (4-5 weeks old). The growth status of transplanted tumor was observed. These subcutaneous tumors were examined histologically. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Cell cycle and MUC1 expression of the transplanted tumor cells were analyzed by flow cytometry. Human esophageal carcinoma transplantation models with MUC1 high expression were successfully established in 6 of the 7 nude mice. The histological and biological characteristics of subcutaneous transplanted tumors were similar to those of human esophageal carcinoma. The mean PCNA label index of subcutaneous transplanted tumor cells was (63.5+/-3.6)%. The mean S-phase fraction of cell cycle was (37.6+/-3.7)%. The positive rate of MUC1 in subcutaneous transplanted tumor cells was 97.5%. Human esophageal carcinoma transplantation model with MUC1 high expression in nude mice is similar to human malignant tumors in biological characteristics, and can be used to investigate the biological characteristics of esophageal carcinoma, as well as provides an applicable animal model for research on MUC1-targeting immunotherapy of esophageal cancer.
    Ai zheng = Aizheng = Chinese journal of cancer 08/2007; 26(7):693-7.
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    ABSTRACT: To investigate whether dendritic cells fused with tumor cells could elicit in vitro antitumor responses against renal cell carcinoma (RCC) cells. Renal carcinoma cells were purified from tumor tissue excised from patients with metastatic RCC through tumor cell purifying technique and cultured in RPMI-1640 medium containing 10% FCS. Monocyte-derived DCs generated from peripheral blood mononuclear cell of RCC patients were cultured in the presence of human recombinant granulocyte-macrophage colony stimulating factor and interleukin-4. Tumor cells and DCs were cocultured in the presence of polyethylene glycol (PEG) to generate cell fusion. The phenotype of tumor cells, DCs and fusion cells were detected by flow cytometry. MTT was used to measure the ability of fusion cells to stimulate T cell proliferation. T cell-mediated antitumor responses were measured by lactate dehydrogenase release (LDH) assay for lysis of autologous tumor cells. The DCs expressed MHC class I, MHC class II and costimulatary molecules (CD80 and CD86), while the renal carcinoma cells expressed a high molecular glycoprotein MUC-1. The DC/tumor fusion cells coexpressed MUC-1 and the phenotype of DCs, and could stimulate T cell proliferation effectively. CTLs stimulated by the fusion vaccine showed distinct lytie activity in vitro to autologous tumor cells. Dendritic cells fused with tumor cells can elicit distinct antitumor responses in vitro against tumor cells from patients with metastatic RCC, providing a basis for further research on the clinical application of fusion vaccine in treatment for renal cancers.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 07/2007; 29(6):411-4.
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    ABSTRACT: Dendritic cells (DCs) are antigen-presenting cells, and DC-based fusion vaccine of DCs with tumor cells can induce specific immune response against tumor cells effectively. This study was to investigate the antitumor immunity efficacy of fusion vaccine of DCs with human esophageal carcinoma EC109 cells in vitro. Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated, and cultured with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and interleukin-4 (IL-4) to generate DCs. Fusion cells of DCs with EC109 cells were generated by polyethylene glycol (PEG) protocol. The T-cell proliferation response stimulated by DC/EC109 cells was detected by MTT assay. The killing efficacy of cytotoxic T lymphocytes (CTLs), activated by DC/EC109 cells, on EC109 cells was evaluated by LDH assay in vitro, and compared with the killing efficacy on human gastric carcinoma SGC7901 cells and human breast cancer MCF7 cells. The highest fusion efficiency of DCs with EC109 cells was 22.25%. The stimulating efficacy of DC/EC109 cells on the proliferation of T cells was significantly higher than those of DCs and EC109 cells (P<0.05). DC/EC109 cells induced specific CTLs against EC109 cells, and the killing efficacy of the CTLs was significantly higher for EC109 cells than for SGC7901 cells or MCF7 cells (P<0.05). C/EC109 fusion vaccine can induce specific antitumor response against EC109 cells effectively.
    Ai zheng = Aizheng = Chinese journal of cancer 03/2007; 26(2):137-41.
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    ABSTRACT: Recently, micro-invasive treatments showed well application prospective in treating primary hepatocellular carcinoma (HCC), while tumor immunotherapy is a hot topic in tumor treatment. This study was to investigate the efficacy of cytokine-induced killer cells (CIK) combined micro-invasive treatments (transcatheter arterial chemoembolization and radiofrequency ablation) on the recurrence of HCC. A total of 85 HCC patients without active lesions and metastasis, which were displayed by imaging examination after transcatheter arterial chemoembolization and radiofrequency ablation therapy, were divided randomly into 2 groups: 45 in study group, and 40 in control group. The patients in study group were transfused with CIK cells through hepatic artery after micro-invasive treatments, while the patients in control group were not. The levels of T lymphocyte subsets and native killer (NK) cells in peripheral blood of HCC patients before and after CIK cell transfusion were detected by flow cytometry (FCM). Tumor condition was observed by CT scanning every 2-3 months. The percentages of CD3+, CD4+, and CD56+ effect cells and the proportion of CD4+/CD8+ were increased from (68.6+/-11.0)%, (31.0+/-9.0)%, (15.6+/-7.8)%, and 1.1+/-0.5 to (70.7+/-10.1)% (P<0.05), (33.5+/-8.0)% (P<0.05), (18.4+/-9.4)% (P<0.05), and 1.3+/-0.6 (P<0.05) after CIK cell transfusion; while the percentages of CD8+ and CD3+ CD56+ cells were decreased from (31.1+/-7.8)% and (6.4+/-3.5)% to (28.6+/-8.3)% (P<0.05) and (5.2+/-3.3)% (P<0.05). The 1- and 1.5-year recurrence rates were 8.89% and 15.56% in study group, and 30.00% and 40.00% in control group (Chi(2) = 4.87 and 6.41, P <0.05). CIK cell transfusion after micro-invasive treatments may improve the immunologic function in HCC patients, and play an important role in reducing the recurrence rate of HCC.
    Ai zheng = Aizheng = Chinese journal of cancer 12/2006; 25(11):1414-8.

Publication Stats

95 Citations
43.38 Total Impact Points

Institutions

  • 2012–2013
    • Sun Yat-Sen University Cancer Center
      Shengcheng, Guangdong, China
  • 2008–2013
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Shengcheng, Guangdong, China
  • 2010
    • State Key Laboratory of Medical Genetics of China
      Ch’ang-sha-shih, Hunan, China
  • 2006
    • Zhongshan University
      Shengcheng, Guangdong, China