AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided ...AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided into two groups:ethanol-fed group (group E) and control group (group C). Group E was fed with ethanol(5-12 g x kg(-1) x d(-1)) and group C received dextrose instead of ethanol. Rats of the two groups were sacrificed at 4 weeks and 8 weeks. Levels of endotoxin and alanine transaminase (ALT) in blood were measured, and liver pathology was observed under light and electronic microscopy. Expressions of LBP and CD14 mRNA in liver tissues were determined by RT-PCR analysis. RESULTS: Plasma endotoxin levels were increased more significantly in group E(129+/-21) ng x L(-1) and (187+/-35) ng x L(-1) at 4 and 8 wk than in control rats(48+/-9) ng x L(-1) and (53+/-11) ng x L(-1), respectively (P【0.05). Mean values of plasma ALT levels were (1867+/-250) nkat x L(-1) and (2450+/-367) nkat x L(-1) in Group E. The values were increased more dramatically in ethanol-fed rats than in Group C after 4 and 8 weeks. In liver section from ethanol-fed rats, there were marked pathological changes (steatosis, cell infiltration and necrosis). In ethanol-fed rats, ethanol administration led to a significant increase in LBP and CD14 mRNA levels compared with the control group (P【0.05). CONCLUSION: Ethanol administration led to a significant increase in endotoxin levels in serum and LBP and CD14 mRNA expressions in liver tissues. The increase of LBP and CD14 mRNA expression might wake the liver more sensitive to endotoxin and liver injury.展开更多
AIM: To improve the immunogenicity of receptor binding site of hepatitis B virus (HBV) on preS1 antigen using HBV core antigen as an immuno-carrier. METHODS: One to 6 tandem copies of HBV preS1 (21-47) fragment were i...AIM: To improve the immunogenicity of receptor binding site of hepatitis B virus (HBV) on preS1 antigen using HBV core antigen as an immuno-carrier. METHODS: One to 6 tandem copies of HBV preS1 (21-47) fragment were inserted into HBcAg at the sites of aa 78 and 82, and expressed in E.coli. ELISA, Western blot and animal immunization were used to analyze the antigenicity and immmunogenicity of purified particulate antigens. The ability to capture HBV by antibodies elicited by chimeric particles was detected with immuno-capture PCR. RESULTS: Recombinant antigens CI, CII, CIII carrying 1-3 copies of HBV preSl (21-47) individually could form virus-like particles (VLPs), similar to HBcAg in morphology. But recombinant antigens carrying 4-6 copies of HBV preSl (21-47) were poorly expressed in E.coli. Chimeric antigens were lacking of immunoreactivity with anti-HBc monoclonal antibodies (McAbs), but still reserved good immunoreactivity with anti-HBe McAbs. CI, CII, CIII could strongly react with anti-preS1 McAb, suggesting that preS1 (21-47) fragment was well exposed on the surface of chimeric VLPs. Three chimeric VLP antigens (CI, CII and CIII) could stimulate mice to produce high-level antibody responses, and their immunogenicity was stronger than non-particulate antigen 21-47*6, containing 6 copies of preS1 (21-47). Mouse antibodies to CI, CII and CIII were able to capture HBV virions in immuno-capture PCR assay in vitro. CONCLUSION: Chimeric particulate antigens of receptor binding site-core antigen of HBV can elicit strong antibody responses to preS1. They have a potential to be developed into prophylactic or therapeutic vaccines against HBV infection.展开更多
The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievem...The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.展开更多
Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whethe...Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.展开更多
AIM: To investigate the levels of serum soluble intercellular adhesion molecules-1 (sICAM-1) and neutrophilic expression of CD18 in patients with various stages of diabetic retinopathy and to determine their different...AIM: To investigate the levels of serum soluble intercellular adhesion molecules-1 (sICAM-1) and neutrophilic expression of CD18 in patients with various stages of diabetic retinopathy and to determine their different expression pattern in the development of diabetic retinopathy(DR). METHODS: Levels of serum sICAM-1 and CD18 on the surface of neutrophile were measured in 41 DR patients, they were classified in three subgroups according to the stage of retinopathy as determined by fund's ophthalmoscopy; 10 control subjects were also studied. sICAM-1 were measured by enzyme-linked immunosorbent assay and CD18 by flow cytometry. RESULTS: The neutrophilic CD18 expression and serum sICAM-1 level were all significantly elevated in all diabetic subgroups compared to control subjects (P <0.01). The differences of CD18 and sICAM-1 among the diabetic subgroups were significant in CD18 but not in sICAM-1. The progression of retinopathy was associated with an increase both in CD18 and in sICAM-1 levels by simple correlation analysis (beta =0.74, P<0.001; beta =0.38, P<0.01, respectively). But stepwise multiple regression analysis revealed that only CD18 Was independent determinant of retinopathy (beta =1.04, P<0.01). CONCLUSION: Our results confirm the contribution of endothelial and neutrophilic activation in the development of DR as indicated by increased levels of CD18 and sICAM-1. However, a direct implication of CD18 and ICAM-1 in the progression of DR can be supported only in the CD18 but not ICAM-1. CD18 and ICAM-1 may play different role in the development of diabetic retinopathy.展开更多
AIM: Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factorβ1 (TGF-β1)and vascular endothelial growth factor (VEG...AIM: Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factorβ1 (TGF-β1)and vascular endothelial growth factor (VEGF). However,the roles of TGFβ1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-β1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-β1 and its receptor CD105 in gastric malignant tumors.METHODS: The expressions of TGF-β1 and CDL05 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-β1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Tmmunohistochemistry (DS-ABC).RESULTS: Among the 55 cases of gastric carcinoma tissues,30 were positive for TGF-β1 (54.55 %). The MVD of TGF-β1 strong positive group (++～+++ 23.22±5.8) was significantly higher than that of weak positive group (+17.56±7.2) and negative group (- 17.46±3.9) (q=4.5, q=5.3207, respectively,P＜0.01). In the areas of high expression of TGF-β1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of both VEGF and CD105 (MVD)were related with the depth of invasion (F=5.438, P＜0.05;F=4.168, P=0.05), lymph node metastasis (F=10.311, P＜0.01;F=20.282, P＜0.01) and Dukes stage (F=6.196, P＜0.01;F=10.274, P＜0.01), but not with histological grade (F=0.487,P＞0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P＜0.01).CONCLUSION: Over-expression of TGF-β1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors.CD105, as a receptor of TGF-β1, can regulate the biological effect of TGF-β1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.展开更多
Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe...Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.展开更多
CD151 is a member of the tetraspanin family that is implicated as a promoter of pathological or physiological angiogenesis. C-Met is expressed on a variety of cells including vascular endothelial cells（VECs） and up-...CD151 is a member of the tetraspanin family that is implicated as a promoter of pathological or physiological angiogenesis. C-Met is expressed on a variety of cells including vascular endothelial cells（VECs） and up-regulated during angiogenesis. In this study, we investigated whether CD151 regulated migration, proliferation, tube formation and angiogenesis of human umbilical VECs（HUVECs） with activation of C-Met. Moreover, we studied whether CD151 could affect the angiogenic molecules such as nitric oxide（NO）, vascular cell adhesion molecule-1（VCAM-1） and vascular endothelial growth factor（VEGF）. The expression of CD151 was determined by Western blotting. The cell proliferation assay was performed using the cell counting kit-8（CCK-8） method and cell migration was assessed in microchemotaxis chambers by using fetal bovine serum（FBS） as the chemotactic stimulus. The angiogenic molecules were evaluated using ELISA. The NO level was detected using NO detection kit. The potential involvement of various signaling pathways was explored using relevant antibodies. We found that proliferation, migration and tube formation of HUVECs were promoted by CD151 with activation of C-Met, FAK and CDC42, while they were suppressed with CD151 knockdown by RNAi. Similarly, the levels of NO, VCAM-1 and VEGF in HUVECs were increased by CD151, but they were inhibited with CD151 knockdown by RNAi. These data suggested that CD151 could promote migration, proliferation, tube formation and angiogenesis of HUVECs, which was possibly related to the C-Met signaling pathways.展开更多
Objective:To explore the possible association between polymorphisms in CD1 genes and both asymptomatic and mild Plasmodium falciparum infection.Methods:Two clusters of 85 school children,from the village of Dienga(Gab...Objective:To explore the possible association between polymorphisms in CD1 genes and both asymptomatic and mild Plasmodium falciparum infection.Methods:Two clusters of 85 school children,from the village of Dienga(Gabon) were investigated.The first group was analysed for the prevalence and the multiplicity of asymptomatic Plasmodium falciparum infection,whereas the second group was screened for the frequency of malarial attacks.Results:Our findings showed that homozygosity for the CD1E★02 allele was associated with a low frequency of malarial attacks.Furthermore,a strong association between CD1E★02 homozygotes and the resistance to multiple malarial attacks was identified.The CD1A★01 allele showed a weak association with a small number of malarial attacks.Conclusion:Our results suggest a possible role of CD1E polymorphisms in malaria protection among school children and that CD1e molecules are involved in anti-malarial immunity.展开更多
The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin an...The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin and VNTR genes into VR1012,respectively.The eukaryotic vector pEGFP expressing survivin and MUC1 VNTRs fusion gene pEGFP-MS was also constructed.Mouse melanoma cell line（B16） stably expressing survivin and MUC1 VNTRs（MS ＋ B16） was established by Lipofectamine-mediated transfection of pEGFP-MS into B16 cells.EGFP expression in MS ＋ B16 cells was observed using a fluorescent microscope and survivin and MUC1 VNTRs（MS） expression was confirmed by means of Western blot analysis.A syngenic graft tumor model was generated by subcutaneous injection of MS ＋ B16 cells into C57/BL6 mice and tumor size increased rapidly with time in a cell number dependent manner.After the third immunization,mice were challenged subcutaneously with 5×l0 5 MS ＋ B16 cells.Compared with that of the negative control immunized with phosphate-buffered saline（PBS）,a significant reduction of tumor growth was observed in groups immunized with survivin plasmid DNA and MUC1 VNTRs plasmid DNA.Thus,the suppression of subcutaneous tumor was antigen-specific.This model is useful for the development of tumor vaccines targeting survivin and MUCI VNTRs.展开更多
Aquaporins（AQPs） are molecular water channels that play important physiological roles in fluid trans-porting organs. The expression and function of AQPs in the immune system are largely unknown. CD 11 （a-d）/CD18 i...Aquaporins（AQPs） are molecular water channels that play important physiological roles in fluid trans-porting organs. The expression and function of AQPs in the immune system are largely unknown. CD 11 （a-d）/CD18 integrins are adhesion molecules expressed on leukocytes, which play a critical role in leukocyte adhesion, migration and host defense. In the present study, we discovered the expression of aquaporin-3（AQP3） on spleen CD1 lb positive cells, and the content of CDllb positive splenocytes in aquaporin 3-null mice is significantly decreased. Further analysis suggested remarkably decreased monocyte/macrophage subpopulation and significantly decreased granulocyte subpopulation. It is the first report suggesting an important role of AQP in the development and maturation of imrnunocytes.展开更多
T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for imm...T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.展开更多
BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of brea...BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of breast cancer.AIM To investigate the expression status of CD155 and the association with exhausted CD4+helper and CD8+cytotoxic tumor infiltrating lymphocytes(TILs)and PD-L1 in the breast cancer microenvironment.METHODS One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study.Immunohistochemistry was used to detect the expression CD155,PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment.RESULTS The proportion of patients with CD155 expression was higher in triple negative breast cancer(72.7%)than in Luminal A patients(22.2%,P<0.05).Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+helper TILs(30%)than patients with negative CD155 expression(21%,P<0.05).Patients with positive CD155 expression also had higher cell counts of exhausted CD4+TILs[47 vs 20/high-power fields(HPF)]and unexhausted CD8+TILs(30 vs 17/HPF)than patients with negative expression(P<0.05).CD155 expression was correlated with increased PD-L1 expression in immune cells,0.8%and 0.02%immune cells expressed PD-L1 in patients with positive and negative CD155 expression,respectively(P<0.05).CONCLUSION CD155 was related to an inhibitory immune breast cancer microenvironment.CD155 was associated with a high proportion of exhausted CD4+and unexhausted CD8+TILs and high PD-L1 expression in immune cells.展开更多
基金Supported by the National Natural Science Foundation of China(No.39970719).
文摘AIM: To evaluate the relationship between the expression of lipopolysaccharides (LPS) binding protein (LBP) and CD14 mRNA and the severity of liver injury in alcohol-fed rats. METHODS: Twenty Wistar rats were divided into two groups:ethanol-fed group (group E) and control group (group C). Group E was fed with ethanol(5-12 g x kg(-1) x d(-1)) and group C received dextrose instead of ethanol. Rats of the two groups were sacrificed at 4 weeks and 8 weeks. Levels of endotoxin and alanine transaminase (ALT) in blood were measured, and liver pathology was observed under light and electronic microscopy. Expressions of LBP and CD14 mRNA in liver tissues were determined by RT-PCR analysis. RESULTS: Plasma endotoxin levels were increased more significantly in group E(129+/-21) ng x L(-1) and (187+/-35) ng x L(-1) at 4 and 8 wk than in control rats(48+/-9) ng x L(-1) and (53+/-11) ng x L(-1), respectively (P【0.05). Mean values of plasma ALT levels were (1867+/-250) nkat x L(-1) and (2450+/-367) nkat x L(-1) in Group E. The values were increased more dramatically in ethanol-fed rats than in Group C after 4 and 8 weeks. In liver section from ethanol-fed rats, there were marked pathological changes (steatosis, cell infiltration and necrosis). In ethanol-fed rats, ethanol administration led to a significant increase in LBP and CD14 mRNA levels compared with the control group (P【0.05). CONCLUSION: Ethanol administration led to a significant increase in endotoxin levels in serum and LBP and CD14 mRNA expressions in liver tissues. The increase of LBP and CD14 mRNA expression might wake the liver more sensitive to endotoxin and liver injury.
基金Supported by the Excellent Scholar Incubation Plan of Ministry of Education, China
文摘AIM: To improve the immunogenicity of receptor binding site of hepatitis B virus (HBV) on preS1 antigen using HBV core antigen as an immuno-carrier. METHODS: One to 6 tandem copies of HBV preS1 (21-47) fragment were inserted into HBcAg at the sites of aa 78 and 82, and expressed in E.coli. ELISA, Western blot and animal immunization were used to analyze the antigenicity and immmunogenicity of purified particulate antigens. The ability to capture HBV by antibodies elicited by chimeric particles was detected with immuno-capture PCR. RESULTS: Recombinant antigens CI, CII, CIII carrying 1-3 copies of HBV preSl (21-47) individually could form virus-like particles (VLPs), similar to HBcAg in morphology. But recombinant antigens carrying 4-6 copies of HBV preSl (21-47) were poorly expressed in E.coli. Chimeric antigens were lacking of immunoreactivity with anti-HBc monoclonal antibodies (McAbs), but still reserved good immunoreactivity with anti-HBe McAbs. CI, CII, CIII could strongly react with anti-preS1 McAb, suggesting that preS1 (21-47) fragment was well exposed on the surface of chimeric VLPs. Three chimeric VLP antigens (CI, CII and CIII) could stimulate mice to produce high-level antibody responses, and their immunogenicity was stronger than non-particulate antigen 21-47*6, containing 6 copies of preS1 (21-47). Mouse antibodies to CI, CII and CIII were able to capture HBV virions in immuno-capture PCR assay in vitro. CONCLUSION: Chimeric particulate antigens of receptor binding site-core antigen of HBV can elicit strong antibody responses to preS1. They have a potential to be developed into prophylactic or therapeutic vaccines against HBV infection.
文摘The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.
基金supported by grants from the National Natural Science Foundation of China [grant number 81703003,Z.G.Fu and grant number 81700968,P.X]a China Postdoctoral Science Foundation Funded Project [Project No.:2017M623395 and Project No.:2018T111143]
文摘Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.
基金Supported by Natural Science Foundation of Shaanxi Province, China (No. 2011JM4048)
文摘AIM: To investigate the levels of serum soluble intercellular adhesion molecules-1 (sICAM-1) and neutrophilic expression of CD18 in patients with various stages of diabetic retinopathy and to determine their different expression pattern in the development of diabetic retinopathy(DR). METHODS: Levels of serum sICAM-1 and CD18 on the surface of neutrophile were measured in 41 DR patients, they were classified in three subgroups according to the stage of retinopathy as determined by fund's ophthalmoscopy; 10 control subjects were also studied. sICAM-1 were measured by enzyme-linked immunosorbent assay and CD18 by flow cytometry. RESULTS: The neutrophilic CD18 expression and serum sICAM-1 level were all significantly elevated in all diabetic subgroups compared to control subjects (P <0.01). The differences of CD18 and sICAM-1 among the diabetic subgroups were significant in CD18 but not in sICAM-1. The progression of retinopathy was associated with an increase both in CD18 and in sICAM-1 levels by simple correlation analysis (beta =0.74, P<0.001; beta =0.38, P<0.01, respectively). But stepwise multiple regression analysis revealed that only CD18 Was independent determinant of retinopathy (beta =1.04, P<0.01). CONCLUSION: Our results confirm the contribution of endothelial and neutrophilic activation in the development of DR as indicated by increased levels of CD18 and sICAM-1. However, a direct implication of CD18 and ICAM-1 in the progression of DR can be supported only in the CD18 but not ICAM-1. CD18 and ICAM-1 may play different role in the development of diabetic retinopathy.
文摘AIM: Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factorβ1 (TGF-β1)and vascular endothelial growth factor (VEGF). However,the roles of TGFβ1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-β1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-β1 and its receptor CD105 in gastric malignant tumors.METHODS: The expressions of TGF-β1 and CDL05 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-β1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Tmmunohistochemistry (DS-ABC).RESULTS: Among the 55 cases of gastric carcinoma tissues,30 were positive for TGF-β1 (54.55 %). The MVD of TGF-β1 strong positive group (++～+++ 23.22±5.8) was significantly higher than that of weak positive group (+17.56±7.2) and negative group (- 17.46±3.9) (q=4.5, q=5.3207, respectively,P＜0.01). In the areas of high expression of TGF-β1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of both VEGF and CD105 (MVD)were related with the depth of invasion (F=5.438, P＜0.05;F=4.168, P=0.05), lymph node metastasis (F=10.311, P＜0.01;F=20.282, P＜0.01) and Dukes stage (F=6.196, P＜0.01;F=10.274, P＜0.01), but not with histological grade (F=0.487,P＞0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P＜0.01).CONCLUSION: Over-expression of TGF-β1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors.CD105, as a receptor of TGF-β1, can regulate the biological effect of TGF-β1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.
基金supported by the Beijing Natural Science Foundation (No. 7202026)Capital’s Funds for Health Improvement and Research (No. 2020-2Z-2157)
文摘Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.
基金supported by the National Natural Science Foundation of China(No.81000047)Hubei Natural Science Foundation(No.2014CFB437)
文摘CD151 is a member of the tetraspanin family that is implicated as a promoter of pathological or physiological angiogenesis. C-Met is expressed on a variety of cells including vascular endothelial cells（VECs） and up-regulated during angiogenesis. In this study, we investigated whether CD151 regulated migration, proliferation, tube formation and angiogenesis of human umbilical VECs（HUVECs） with activation of C-Met. Moreover, we studied whether CD151 could affect the angiogenic molecules such as nitric oxide（NO）, vascular cell adhesion molecule-1（VCAM-1） and vascular endothelial growth factor（VEGF）. The expression of CD151 was determined by Western blotting. The cell proliferation assay was performed using the cell counting kit-8（CCK-8） method and cell migration was assessed in microchemotaxis chambers by using fetal bovine serum（FBS） as the chemotactic stimulus. The angiogenic molecules were evaluated using ELISA. The NO level was detected using NO detection kit. The potential involvement of various signaling pathways was explored using relevant antibodies. We found that proliferation, migration and tube formation of HUVECs were promoted by CD151 with activation of C-Met, FAK and CDC42, while they were suppressed with CD151 knockdown by RNAi. Similarly, the levels of NO, VCAM-1 and VEGF in HUVECs were increased by CD151, but they were inhibited with CD151 knockdown by RNAi. These data suggested that CD151 could promote migration, proliferation, tube formation and angiogenesis of HUVECs, which was possibly related to the C-Met signaling pathways.
基金International Centre of Medical Research(Franceville,Gabon)that is supported by the government of Gabon,Total-Gabonthe French Ministry of Foreign Affairs,Histocompatibility and Immunology Laboratory AP-HP,IUH and INSERM U662,Saint-Louis hospital(Paris,France)
文摘Objective:To explore the possible association between polymorphisms in CD1 genes and both asymptomatic and mild Plasmodium falciparum infection.Methods:Two clusters of 85 school children,from the village of Dienga(Gabon) were investigated.The first group was analysed for the prevalence and the multiplicity of asymptomatic Plasmodium falciparum infection,whereas the second group was screened for the frequency of malarial attacks.Results:Our findings showed that homozygosity for the CD1E★02 allele was associated with a low frequency of malarial attacks.Furthermore,a strong association between CD1E★02 homozygotes and the resistance to multiple malarial attacks was identified.The CD1A★01 allele showed a weak association with a small number of malarial attacks.Conclusion:Our results suggest a possible role of CD1E polymorphisms in malaria protection among school children and that CD1e molecules are involved in anti-malarial immunity.
基金Supported by the National Natural Science Foundation of China(No.30872396)the Scientific Research Foundation of Jilin Province,China(Nos.20080709,200905169)the Jilin University Basic Research Project,China(No.200903255)
文摘The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin and VNTR genes into VR1012,respectively.The eukaryotic vector pEGFP expressing survivin and MUC1 VNTRs fusion gene pEGFP-MS was also constructed.Mouse melanoma cell line（B16） stably expressing survivin and MUC1 VNTRs（MS ＋ B16） was established by Lipofectamine-mediated transfection of pEGFP-MS into B16 cells.EGFP expression in MS ＋ B16 cells was observed using a fluorescent microscope and survivin and MUC1 VNTRs（MS） expression was confirmed by means of Western blot analysis.A syngenic graft tumor model was generated by subcutaneous injection of MS ＋ B16 cells into C57/BL6 mice and tumor size increased rapidly with time in a cell number dependent manner.After the third immunization,mice were challenged subcutaneously with 5×l0 5 MS ＋ B16 cells.Compared with that of the negative control immunized with phosphate-buffered saline（PBS）,a significant reduction of tumor growth was observed in groups immunized with survivin plasmid DNA and MUC1 VNTRs plasmid DNA.Thus,the suppression of subcutaneous tumor was antigen-specific.This model is useful for the development of tumor vaccines targeting survivin and MUCI VNTRs.
基金Supported by the National Basic Research Program of China(No.2009CB521908)the National Natural Science Foundation of China(Nos.30470405, 30570864,30670477 and 30770493)the National Natural Science Fund for Distinguished Young Scholars of China(No.30325011)
文摘Aquaporins（AQPs） are molecular water channels that play important physiological roles in fluid trans-porting organs. The expression and function of AQPs in the immune system are largely unknown. CD 11 （a-d）/CD18 integrins are adhesion molecules expressed on leukocytes, which play a critical role in leukocyte adhesion, migration and host defense. In the present study, we discovered the expression of aquaporin-3（AQP3） on spleen CD1 lb positive cells, and the content of CDllb positive splenocytes in aquaporin 3-null mice is significantly decreased. Further analysis suggested remarkably decreased monocyte/macrophage subpopulation and significantly decreased granulocyte subpopulation. It is the first report suggesting an important role of AQP in the development and maturation of imrnunocytes.
文摘T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.
基金Supported by Beijing Municipal Committee of Science and Technology,No.Z181100001718090 and Z19110006619041Beijing Municipal Administration of Hospitals,No.PX2018029Beijing Shijitan Hospital,Capital Medical University,No.2017-KF01.
文摘BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of breast cancer.AIM To investigate the expression status of CD155 and the association with exhausted CD4+helper and CD8+cytotoxic tumor infiltrating lymphocytes(TILs)and PD-L1 in the breast cancer microenvironment.METHODS One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study.Immunohistochemistry was used to detect the expression CD155,PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment.RESULTS The proportion of patients with CD155 expression was higher in triple negative breast cancer(72.7%)than in Luminal A patients(22.2%,P<0.05).Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+helper TILs(30%)than patients with negative CD155 expression(21%,P<0.05).Patients with positive CD155 expression also had higher cell counts of exhausted CD4+TILs[47 vs 20/high-power fields(HPF)]and unexhausted CD8+TILs(30 vs 17/HPF)than patients with negative expression(P<0.05).CD155 expression was correlated with increased PD-L1 expression in immune cells,0.8%and 0.02%immune cells expressed PD-L1 in patients with positive and negative CD155 expression,respectively(P<0.05).CONCLUSION CD155 was related to an inhibitory immune breast cancer microenvironment.CD155 was associated with a high proportion of exhausted CD4+and unexhausted CD8+TILs and high PD-L1 expression in immune cells.
