1.Study on the single nucleotide polymorphisms of peptidylarginine deiminase 4 in patients with rheumatoid arthritis in Chinese Han population in Hebei province
Zhongjun FENG ; Haifeng WEN ; Yun LIANG ; Naining YIN ; Jinhua ZHANG ; Ying PANG ; Lijie ZHANG
Chinese Journal of Rheumatology 2012;16(5):346-349
Objective To elucidate the association of the susceptibility for rheumatoid arthritis ( RA )and peptidylarginine deiminase 4(PADI4) genetic single nucleotide polymorphism (SNP) in Han population in Hebei province.Methods This hospital-based ease-control study included 105 untreated RA patients and 96 healthy controls.The genotypes and allele frequencies of padi4_92 gene polymorphisms were analyzed by PCR-RFLP method,and the analysis of linkage disequilibrium and haplotype construction were performed for padi4_92,padi4_94 and padi4_104 SNPs.The Peason Chi-square test and Woolf statistic method were used to analyze the odds ration (OR) and 95% confidence interval (95%CI).Results Significant differences in the frequency of PADI4 alleles and genotypes between the cases and controls were observed.The combined effect of padi4_92,padi4_94 and padi4_104 SNPs was analyzed by SHEsis snd Genehunter software,and got three haplotypes,CCC,GTT and GCC.There was significant difference in haplotypes distribution of 3 SNPs of padi4 between the two groups.This analysis of haplotypes revealed that haplotype of PADI4 was a risk factor for RA The ORs for these three haplotypes for RA susceptibility were 0.634 (95%CI=0.425-0.946),1.306 (95%CI=0.864-1.975),4.286 (95%CI=1.274-14.424),respectively.Conclnsion The SNPs of PADI4 may contribute to genetic susceptibility to RA in Han population in Hebei Province.
2.Clinicalefficacy of activated-HLA haploidentical peripheral blood stem cells in treatment of advanced solid tumors
Ying HAN ; Jinpu YU ; Hui LI ; Baozhu REN ; Shui CAO ; Naining ZHANG ; Xiumei AN ; Xiubao REN
Chinese Journal of Cancer Biotherapy 2010;17(1):7-12
Objective: To evaluate the anti-tumor and side effects of activated-HLA haploidentical peripheral blood tem cells (haplo PBSCs) in the treatment of advanced refractory solid tumor patients. Methods: Forty-two patients with advanced refractory tumor, who were diagnosed in our hospital from Oct. 2004 to Oct. 2007, were enrolled in this study (all patients signed informed consent), including 12 with ovarian cancer, 9 with renal cancer, 8 with lung cancer, 8 with breast cancer, 2 with colon cancer, 2 with gastric cancer, and 1 with melanoma. The donors were healthy direct relatives of the patients; the donors' haplo-PBSCs were mobilized, collected, and activated by rhIL-2 in vitro. The clinical efficacy and side effects of haplo-PBSCs therapy were assessed by CT/PET-CT scanning, RESIST standard, KPS score, and clinical response rates, etc. Results: All 42 patients received one episode of haplo-PBSCs treatment. The progression-free survivals (PFS) were 6 months and the clinical beneficial rate (CR+PR+SD) was 73.8%. The beneficial rate of life quality was 76.2% and the KPS increased by 20 (0-30) points on average after haplo-PBSCs treatment. The patients with KIR unmatched in GVH direction had better outcomes than those with KIR matched or KIR unmatched in HVG direction (P<0.05), and the clinical beneficial rate, PFS and total beneficial rate were 94.1% vs 60.0%, (13.4±1.3) vs (8.0±0.9) months, and 89.5% vs 65.2%, respectively (all P<0.05). The donor/recipient relation as the mother/child had a better outcome than that as the father/child (P<0.05). Patients with renal cancer or ovarian cancer had better outcomes than those with other cancers, with clinical beneficial rates being 90.0% and 81.8%, respectively. Conclusion: Activated haplo-PBSCs therapy can induce non-specific anti-tumor effect, and improve the clinical symptom and life quality of advanced tumor patients.
3.Effect of RetroNectin on the Proliferation of CIK Cells and the Possible Mechanisms
Ying HAN ; Jinpu YU ; Hui LI ; Shui CAO ; Baozhu REN ; Jing QI ; Xiumei AN ; Naining ZHANG ; Xiubao REN ; Xishan HAO
Chinese Journal of Clinical Oncology 2010;37(2):71-75
Objective: To investigate the effect of RetroNectin on CIKs cells and the related mechanisms. Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients and divided into two groups: group Ⅰ and group Ⅱ. Samples in group Ⅰ were seeded into culture flask precoated with RetreNec-tin and CD3mAb to induce CIKs. While samples in group Ⅱ were seeded into common culture flask. The pro-liferation of CIKs was detected by cytometric analysis. The cytotoxic activity of CIKs was determined by LDH assays. The phenotype changes and cell cycle of CIKs were identified by flow cytometry. The apoptosis of cells was detected by Annexin V/PI. Western blot was employed to detect the level of protein Vav1. The CD49d and CD49e were blocked by anti-CD49d and anti-CD49e and the proliferation of cells was tested by cytometric analysis after the blockage. The phenotype changes of cells were identified by flow cytometry after the blockage. Results: RetroNectin enhanced the proliferation of CIKs (P<0.05). Flow cytometric analysis showed that RetroNectin significantly increased the number of CD25+ T cells (P<0.05). RN-CIK was more ac-tive than CIK in killing HCT-8 cell lines in vitro (P<0.05). RetroNectin could block the CIKs at G_1 phase (P<0.05) and resist apoptosis. There was no significant difference in the proliferation between the two groups af-ter the blockage with CD49d and CD49e (P>0.05). The expression of protein Vavl was associated with CD25+T cells. Conclusion: RetroNectin enhances the proliferation of CIKs by influencing the cell cycle, resist-ing apoptosis possibly through the site of CD49d and CD49e, and inducing T cell activation as the second sig-naling through Vav1.
4.Efficiency of Cytokine-Induced Killer Cells in Combination with Chemotherapy for Triple-Negative Breast Cancer.
Man LI ; Yang WANG ; Feng WEI ; Xiumei AN ; Naining ZHANG ; Shui CAO ; Baozhu REN ; Xinwei ZHANG ; Xiubao REN
Journal of Breast Cancer 2018;21(2):150-157
PURPOSE: The treatment of triple-negative breast cancer (TNBC) remains challenging, due to the absence of estrogen, progesterone, and human epidermal growth factor receptors. This study was designed to evaluate the efficiency and safety of cytokine-induced killer (CIK) cell immunotherapy, following regular chemotherapy, for patients with TNBC. METHODS: A total of 340 patients with postmastectomy TNBC, from January 1, 2010 to June 30, 2014, were included in this retrospective study. Seventy-seven patients received CIK cell immunotherapy, following regular chemotherapy (arm 1), and 263 patients received regular chemotherapy alone (arm 2). The primary aim was overall survival (OS) and disease-free survival (DFS), and the treatment responses and adverse events were also evaluated. RESULTS: The 5-year DFS and OS rates in arm 1 were 77.9% and 94.3%, compared with 69.8% and 85.6% in arm 2, respectively (p=0.159 and p=0.035, respectively). This clearly shows that there was no statistical difference in the 5-year DFS between the two groups. Multivariate analyses of arm 1 indicated that a Karnofsky performance score (KPS) ≥90 and stage I/IIA disease were significantly associated with a prolonged DFS period (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.09–0.74; p=0.012; and HR 0.21; 95% CI, 0.06–0.82; p=0.024, respectively), but a KPS ≥90 and stage I/IIA disease were not independent prognostic factors for OS. Toxicity was mild in patients who received the CIK therapy. CONCLUSION: The data suggested that CIK cell immunotherapy improved the efficiency of regular chemotherapy in patients with TNBC, and the side effects of CIK cell immunotherapy were mild.
Arm
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Cytokine-Induced Killer Cells*
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Disease-Free Survival
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Drug Therapy*
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Estrogens
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Humans
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Immunotherapy
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Multivariate Analysis
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Progesterone
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Prognosis
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Receptor, Epidermal Growth Factor
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Retrospective Studies
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Triple Negative Breast Neoplasms*