1.Efficacy Analysis on Arterial Interventional Therapy Combined with Erlotinib in Advanced Non-Small-Cell Lung Cancer with Brain Metastasis
Tianjin Medical Journal 2014;(3):271-274
Objective To analyse retrospectively the clinical efficacy and prognostic factors of arterial intervention-al therapy combined with epidermal growth factor receptor (EGFR) and tyrosine kinase inhibitors (TKI) erlotinib (erlotinib) on non-small cell lung cancer (NSCLC) patient with brain metastasis. Methods A total of 45 NSCLC patients with brain metastasis were underwent infusion chemotherapy two-six cycles by selective bronchial artery or intracranial arterial. Erlo-tinib (150 mg, 1/d) was used simultaneously or sequentially with the infusion chemotherapy. The clinical efficacy was as-sessed every two cycles or when the disease got progressed. The progression-free survival (PES) and overall survival (OS) were recorded from the follow up data. Results All the patients received at least two cycles of treatment. The median num-ber of cycles was 3 (range 2-6 cycles). The results were as follows:complete remission (CR) in 7 cases (15.56%), partial re-mission (PR) 12 cases (26.67%), stable (SD) 16 cases (35.56%) and progression (PD) 10 cases (22.22%). The objective re-sponse rate (ORR, CR+PR) and disease control rate (DCR, CR+PR+SD) were 42.22%and 77.78%respectively. Patients in this study were followed up for 19 months (6-45 months), with the median PFS time 11.00 months,the median OS time 17.00 months. The univariate analysis showed that patients with low PS score had longer PFS and OS than those of patients with higher PS score. There were 53 adverse events during the treatment. No serious adverse reactions of drugs were found in patients. Conclusion The arterial interventional therapy combined with erlotinib showed a better short-term effect and pro-longed survival time, and with mild side effects.
2.Myeloid derived suppressor cells mediated suppress immunity
Baohong YANG ; Jinpu YU ; Xiubao REN
Journal of International Oncology 2011;38(11):813-816
There exists a population of myeloid-origin cells that are associated with tumor immune escape in cancer patients,commonly termed as myeloid derived suppressor cells(MDSCs).M DSCs accumulate in the blood,lymph nodes,bone marrow,and inhibit both adptive and innate immunity.Different suppressive mechanisms are used by MDSCs to block tumor immunity.Reducing the numbers of MDSCs or inhibiting the suppressive pathway conducted by MDSCs will bring new highlight to biotherapy in tumor treatment.
3.Research progress of the application of immune checkpoints in tumor radiotherapy
Cihui YAN ; Xinmiao SONG ; Xiubao REN
Chinese Journal of Radiological Medicine and Protection 2016;36(10):785-789
Radiation could induce DNA damage,cell death,and changes of tumor phenotype and tumor microenvironment leading to the regulation of immune response.Immune checkpoint signaling pathways are involved in the immune tolerance of anti-microorganism responses and thus limit tissue damage.In the anti-tumor immune response,these pathways are associated with anti-functional activation of specific cytotoxic T cells and also enhance the inhibition effect of immune response,which always result in immune escape.Blockade of the immune checkpoint signaling pathways benefits to the anti-tumor inmune responses and could delay tumor progress.As a result,the combination treatment of radiotherapy and immune checkpoint biockade has attracted more attentions in clinical application.This paper reviews the recent research progresses in the radiation effect of immune system,the regulation of immune checkpoints and the combination treatment of radiotherapy and immune checkpoint blockade in tumor therapy,trying to arouse some new clues in cancer therapy.
4.Research progress of IL-17+Foxp3+T cells
Hua ZHAO ; Hui LI ; Xiubao REN
Tianjin Medical Journal 2015;(11):1342-1344
Recently, it is reported that regulatory T cells (Tregs) can be reprogrammed into a novel population [interleu?kin (IL)-17+Foxp3+T cells] phenotypically and functionally resembling Th17 cells under complicated cytokine circumstanc?es. IL-17+Foxp3+T cells are characterized by production of IL-17 and expression of retinoic acid receptor related orphan re?ceptor (ROR)γt, demonstrating dual functions in immune response and providing novel insight into the interconnection be?tween Tregs and Th17 cells. In this review, we lay emphasis on the phenotype features, origination, differentiation and the pleiotropic functions of IL-17+Foxp3+T cells. Furthermore, we summarized the functions of IL-17+Foxp3+T cells in inflam?matory disease and tumor microenvironment.
5.Mechanisms of STAT family mediated IDO regulation in dendritic cells
Yue WANG ; Jinpu YU ; Xiubao REN
Journal of International Oncology 2013;(3):163-165
Indoleamine 2,3-dioxygenase (IDO) is known as an endogenous immunosuppressive enzyme which plays a significant role in the process of tumor.IDO is not only found in tumor cells but also detected in dendritic cell (DC) in tumor microenvironment,which participates in the formation of tumor immune tolerance through expressing IDO enzyme.Signal transducer and activator of transcription (STAT) is the main signal protein family which participates in the IDO transcriptional regulation of DC.It is necessary to detail the signaling pathway in regulating IDO expression,which will help us develop high specific and more active IDO inhibitors and provide new options for anti-cancer targeted therapy.
6.Research development of Aurora-A kinase
Xiangqian ZHENG ; Ming GAO ; Xiubao REN ; Jin Q.CHENG
Chinese Journal of Clinical Oncology 2014;46(4):272-275
Aurora-A is a mitotic serine/threonine kinase that is evolutionally conserved and localized at the centrosome. Aurora-A activation is required for mitotic entry, centrosome maturation, and centrosome separation. Aurora-A is frequently amplified and/or over-expressed in breast, ovarian, esophageal, colon, lung, and bladder cancers. Aurora-A has recently become a new target of malignant tumors. The Aurora-A inhibitor can be combined with other chemotherapeutic drugs to provide a new way for cancer treatment. In this study, we review the function and inhibitor of Aurora-A kinase.
7.MiR-150 downregulation and its significance in mantle cell lymphoma
Xinwei ZHANG ; Fang WANG ; Xiubao REN ; Jianguo TAO
Chinese Journal of Clinical Oncology 2013;(13):763-766
Objective: This study explores the miR-150 expression and its clinical significance in mantle cell lymphoma (MCL). Methods: The miR-150 and c-Myc expression was measured in 29 primary MCL tissue samples and 7 normal donors through quantita-tive real-time polymerase chain reaction. MiR-150 expression was detected in Mino and HBL-2 cells after c-Myc was knocked down by small interfering RNAs. MiR-150 was analyzed in tet-treated P493-6 cells with Myc turned off. The number of tumor colonies in the BL-2 cells transfected with pre-miR-150 was determined through colony formation assay, and c-Myb was detected through Western blot. Results: Compared with the normal donors, miR-150 expression was significantly downregulated and c-Myc was considerably overexpressed in MCL. Moreover, MCLs with high Myc expression had a significantly low miR-29 expression. MiR-150 was upregu-lated in the Mino and HBL-2 cells with c-Myc knockdown. MiR-150 was evidently upregulated in P493-6 cells after c-Myc was turned off. MiR-150 overexpression suppressed colony formation and c-Myb expression of HBL-2. Conclusion: MiR-150 is downregulated in MCL, which may be related to c-Myc overexpression. The recovery of miR-150 suppresses MCL cell survival. These results indicate that miR-150 may be a potential therapeutic target of MCL.
8.Clinical significance of FoxP3 and the correlation of FoxP3 expression with epithelial-mesenchymal transition in breast cancer
Lili HUO ; Hui LI ; Feng WEI ; Hua ZHAO ; Xiubao REN
Chinese Journal of Clinical Oncology 2014;(3):158-161
Objective: This study aims to investigate the correlation between the expression of FoxP3, TGF-β1, and epitheli-al-mesenchymal transition (EMT) in breast cancer and to determine the clinical significance of FoxP3. Methods: The expression of FoxP3, TGF-β1, E-Cadherin, N-Cadherin, Vimentin, and Fibronectin protein were detected in the cancer cells of 74 cases with breast carcinoma via immunohistochemistry. The correlation of FoxP3 protein with clinico-pathologic features of breast carcinoma and the re-lationships among the expressions of FoxP3, TGF-β1, and epithelial-mesenchymal transition (EMT) were analyzed. Results:The ex-pression rates of FoxP3, TGF-β1, and EMT are 36.5%(27/74), 39.2%(29/74), and 40.5%(30/74), respectively. The FoxP3 protein ex-pression in breast cancer is correlated with lymph node metastasis (P<0.05) but not with other clinico-pathological features (P>0.05). The expression of FoxP3 is also correlated with the expression of TGF-β1. Furthermore, TGF-β1 can induce EMT (P<0.05). Conclu-sion:The expression of FoxP3 is correlated with lymph node metastasis and EMT in breast cancer. Therefore, FoxP3 may be a marker for predicting metastasis.
9.The clinical senses of MUC1/Y gene expressing in gastrointestinal cancer and MUC1/Y modified DC inducing anti-tumor response
Zhiwei YIN ; Hong LIU ; Xiubao REN ; Xishan HAO
Chinese Journal of Immunology 2001;0(07):-
Objective:For developing the study of MUC1/Y vaccine,constructed th eukaryotic expression vectors expressing MUC1/Y.Used it to modify the DC inducint CTL in order to treat the gastrointestinal cancers.Methods:Obtained the MCU1/Y cDNA full length cloned it into pIRES2 EGFP that expressing green fluorescence protein and pcDAN3 1+ respectively.Selected 8 cases of gastrointestinal cancer whose HLA phenotype was A2,inducing DC using rhIL 4 combined with GM CSF in vitro.Transfected DC with pcDAN3.1 MUC1/Y then co cultured DC with T cell to induce CTL (named as T pcDAN3 1 MUC1/Y).At the same time,used pIRES2 EGFP MUC1/Y to detect transfection efficiency.SW620 (HLA A2+,MUC1/Y+),the gastric cancer cell line was used as specific target cell;Lovo(HLA A2 ,MUC1/Y+)and Raji(HLA A2 ,MUC1/Y )were used as unspecific target cells.The cytolytic of specific CTL was measured by LDH releasing assay.The apoptosis of target cells were detected by ANNEXIN V FITC kit.The ability of IFN ? releasing of T cells was measured by ELISA.Results:The transfection efficiency of plasmid was about 8%.There was significant difference between the cytolytic activity of T pcDNA3 1 MUC1/Y to SW620,Lovo and Raji.The cytolytic activity was about (42 8?6 15),(27 26?1 96)% and (22 73?2 15)% respectively.Compared with T IL 2)CTL induced by PBMC stimulated of IL 2(100 U/ml)) and T pcDNA3 1(CTL induced by DC transfected by pcDNA3 1+),the cytolytic activity of T pcDNA3 1 MUC1/Y against SW620 cell line showed a significant increase.The results of ANNEXIN V-FITC experimences showed that T pcDNA3 1 MUC1/Y could induce apoptosis of specific target cell.Conclusion:The expressing of MUC1/Y mRNA has important sense in gastrointestinal cancer.Constructed eukaryotic vector pIRES2 EGFP MUC1/Y that contains full length MUC1/Y cDNA could be used to study the transfection efficiency and select the positive clone;pcDAN3 1 MYC1/Y could induce powerful CTL immunoresponse.
10.The influence of the peripheral hematopoietic stem cell mobilization on circulating endothelial cells
Xiubao REN ; Hui LI ; Hong LIU ; Peng ZHANG ; Xishan HAO
Chinese Journal of Immunology 1985;0(03):-
Objective:Analyze the influence of hematopoietic stem cell mobilization on circulating endothelial cells (CECs) and circulating endothelial precursors (CEPs).Methods:CECs and CEPs were enumerated in 68 tumor patients and 15 healthy controls by 3-color flow cytometry. 11 cases underwent PBSC (peripheral blood stem cell) mobilization by combination chemotherapy and G-CSF (granulocyte colony-stimulating factor).Results:CECs and CEPs in tumor patients were 0.378%?0.103% and 0.059%?0.013% respectively,which were higher than that of normal controls.CECs/CEPs in peripheral blood (PB) were increased after G-CSF mobilization.Conclusion:Hematopoietic and endothelial progenitors can be mobilized into the PB by treatment with growth factor G-CSF.