Therapeutic effect and mechanism of regulating cellular immune function of chemotherapy combined with PD-1 inhibitor in the first-line treatment of Lewis xenografts / 国际肿瘤学杂志

Objective To investigate the efficacy of chemotherapy combined with programmed death-1 (PD-1) inhibitor in the first-line treatment of Lewis xenografts and its possible mechanism of regulating cellular immune function.Methods Lewis xenografts mouse model was established.The mice were randomly divided into control,chemotherapy,immunotherapy and combination group according to the method of random number table (10 in each group),and each group separately received saline,cisplatinum,PD-1 inhibitor and cisplatinum combined with PD-1 inhibitor.The tumor growth and survival of each group were observed.Flow cytometry was used to detect and compare the proportion of CD8 + T cells and CD4 + CD25 + FOXP3 + regulatory T cells (Treg cells).Results On the second day after treatment,the tumor volume of Lewis xenografts in control group,chemotherapy group,immunotherapy group and combination group were (1 662.0 ± 209.0) mm3,(1 189.2 ±155.6) mm3,(991.1 ± 146.6) mm3 and (761.7-± 141.8) mm3,with statistically significant difference (F =29.78,P ＜ 0.001).The tumor volume in the three treatment groups were significantly smaller than that in control group,combination group was significantly smaller than chemotherapy group and immunotherapy group,and immunotherapy group was significantly smaller than chemotherapy group (all P ＜ 0.05).Three mice died during the experiment (two in control group and one in chemotherapy group).The median survival time of mice in the four groups were 10,12,14 and 18 days,with statistically significant difference (x2 =26.06,P ＜ 0.001).The median survival time of mice in the three treatment groups were significantly longer than that in control group,combination group was significantly longer than chemotherapy group and immunotherapy group,and immunotherapy group was significantly longer than chemotherapy group (all P ＜ 0.05).The proportions of CD8 + T cells in the peripheral blood of the four groups were (28.5 ± 1.2) ％,(33.9 ± 2.9) ％,(34.0 ± 2.5) ％ and (42.4 ± 1.5) ％,with statistically significant difference (F =21.32,P ＜ 0.001).The proportions of CD8 + T cells in the peripheral blood of the three treatment groups were significantly higher than that of control group,and combination group was significantly higher than chemotherapy group and immunotherapy group (all P ＜ 0.05).The proportions of CD8 + T cells in the tumor microenvironment of the four groups were (23.5 ±1.3)％,(26.7 ±1.4)％,(34.2 ±2.8)％ and (41.3 ±2.0)％,with statistically significant difference (F =61.65,P ＜ 0.001).The proportions of CD8 + T cells in the tumor microenvironment of the three treatment groups were significantly higher than that of control group,combination group was significantly higher than chemotherapy group and immunotherapy group,and immunotherapy group was significantly higher than chemotherapy group (all P ＜ 0.05).The proportions of CD4 + CD25 + FOXP3 + Treg cells in the spleen of the four groups were (8.6 ± 0.5) ％,(7.2 ± 0.3) ％,(6.3 ± 0.4) ％ and (5.4 ± 0.4) ％,with statistically significant difference (F =37.06,P ＜ 0.001).The proportions of CD4 + CD25 + FOXP3 + Treg cells in the spleen of the three treatment groups were significantly lower than that of control group,combination group was significantly lower than chemotherapy group and immunotherapy group,and immunotherapy group was significantly lower than chemotherapy group (all P ＜ 0.05).Conclusion Chemotherapy and PD-1 inhibitor can enhance the anti-tumor effect of the body immune system by down-regulating the proportion of Treg cells and upregulating the proportion of CD8 + T cells,etc.Chemotherapy combined with immunotherapy can improve the anti-tumor immune function,inhibit tumor growth and prolong the survival of mouse with xenograft,which were significantly better than chemotherapy and immunotherapy alone.

Application of controlled hypotension in cesarean section of pregnant women with high-risk hemorrhage

To explore the application of controlled hypotension in cesarean section of pregnant women with high-risk hemorrhage. 75 cases were randomly divided into three groups: controlled hypotension Group 1 [Group H1], controlled hypotension Group 2 [Group H2] and normal blood pressure Group [Group N]. The preoperative general data, intraoperative conditions, postpartum concurrent Symptoms and other indicators of all the cases in three groups were compared. The Apgar score, umbilical arterial blood gas and other indicators of the newborns were detected. There was no significant difference in the preoperative general data, Apgar score at 1 min and 5 min, the level of PH, PaO2, PaCO2 among the three groups [P>0.05]. The intraoperative blood transfusion volume in group H1 and group H2 decreased significantly than that in-group N [P<0.05], but there was no significant difference between group H1 and group H2 [P>0.05]. Compared with group H1, the red cell transfusion volume in-group H2 was significantly reduced [P<0.05]. There was no significant difference in other intra-operative indexes such as bleeding volume, infusion volume, patient urine volume and hospitalization days among the three groups [P>0.05]. Controlled hypotension [within 5 min of MAP down to 70% of basal blood pressure] can reduce the incidence of hemorrhage and postpartum hemorrhage during cesarean section in high-risk bleeding pregnant women and which had no bad effects on the incidence of complications and umbilical arterial blood gas indicators compared with control group

Effects of LncRNA MT1JP on migration and invasion of uveal melanoma cells / 眼科新进展

Objective To investigate the effects of LncRNA MT1JP on the migration and invasion of uveal melanoma cell,and explore its regulatory mechanism.Methods The expression level of LncRNA MT1JP in uveal melanoma cell line and normal retinal pigment epithelium cell line were measured by qRT-PCR.The SP6.5 cell line was divided into three groups,MT1JP group transfect with pcDNA3.1-MT1JP,siMT1JP group transfect with pcDNA3.1-siMT1JP and NC group transfect with negative pcDNA3.1 plasmid.The migration and invasion ability were measured by cell wound scratch assay and transwell assay.Western blot was used to measure the expression level of P53 protein.Results The expression level of LncRNA MT1JP in SP6.5 and M23 cell line was 0.20 ± 0.02 and 0.31 ± 0.01,respectively,which was significantly lower than 1.0 in ARPE-19 cell line (all P ＜0.01).The wound healing rate in siMT1JP group was 61.50 ± 3.70％.while,NC group was 20.0％ ± 2.10％,and MT1JP group was 10.6％ ± 1.7％,there was no statistical difference among three groups (all P ＜ 0.01).The invasion cell number was 75.6 ±6.8 in siMT1JP group,which was significantly more than 29.5 ± 3.9 in NC group,and 10.3 ±2.6 in MT1JP group,there was no statistical difference among three groups (all P ＜ 0.01).The expression level of P53 protein in siMT1JP group was 0.41 ± 0.04,which was significantly lower than 1.0 in NC group (P ＜ 0.01).However,the expression level of P53 protein in MT1JP group was 5.73 ±0.62,which was significantiy higher than 1.0 in NC group (P ＜ 0.01).Conclusion LncRNA MT1JP inhibits the migration and invasion of uveal melanoma cell,which may be associated with upregulation of P53 expression.

Studies on the preparation of docetaxel nano-liposomes and its treatment on liver cancer cells in vivo and in vitro / 中国生化药物杂志

Objective To prepared the docetaxel nano liposome (L-DOC) for the therapy of liver cancer HepG2 cells in vitro and in vivo. Methods The film-ultrasonic dispersion method was used to prepare the L-DOC.The diameter and Zeta potential of L-DOC were determined by Nanosizer and the encapsulation efficiency was further measured.CCK-8 method was used to determine the cell viability of HepG2 cell after treating with various concentration of DOC and L-DOC respectively and the cell death type was detected by Flow cytometer.Next, we have studied the relative tumor volume change of tumor-bearing mice and the toxicity in vivo.Results The average diameter of L-DOC was 104 nm and the Zeta potential was about -35.1 mV.The Zeta potential of L-DOC was almost unchanged after standing for 96 hours.The encapsulation efficiency of L-DOC was ( 71.2 ±1.6 )%.The CCK-8 results showed that the cell viability was decreased after treating with various concentration of DOC and L-DOC, but the inhibition effect of L-DOC was better than that of DOC after treating with the same dose, especially for 20μg/mL.It was found that the cell death was induced by apoptosis.The in vivo study results showed that 6mg/kg L-DOC could inhibit the tumor volume better than that of same dose of DOC.In addition, 6mg/kg L-DOC and DOC didn’ t induce in vivo toxicity.Conclusion The L-DOC is prepared by film-ultrasonic dispersion method which has small diameter, great biocompatibility.And it could inhibit the HepG2 cells in vitro and in vivo, especially for no in vivo toxicity.

CaMKIIγ promotes in vitro and in vivo growth of colorectal cancer cells by upregulating nuclear factor-κB signaling pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of the γ isoform of Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIγ) on colorectal cancer (CRC) cell growth in vitro and in vivo and explore the mechanisms.</p><p><b>METHODS</b>The mRNA levels of CaMKIIγ in 5 CRC cell lines, tumor tissues and matched adjacent tissues from 20 CRC patients were examined by semi-quantitative RT-PCR. The lentiviral vector pLenti6.3-MCS-IRES2-eGFP was used to generate the lentivirus particle Lenti-CaMKIIγ for transfecting SW620 cells. The proliferation ability of the transfected SW620-CaMKIIγ cells was assessed by growth curve and colony formation assay. The expression of IKKα, IKKβ, IKKγ, p-IKKα/β, p-IκB andIκB of the transfected cells were determined by Western blotting, and the expression and localization of nuclear factor-κB (NF-κB) p65 were detected by immunofluorescence. In nude mouse models bearing the transfected SW620-CaMKIIγ cell xenograft, the tumor volume was measured twice a week.</p><p><b>RESULTS</b>CaMKIIγ mRNA showed high expressions in the 5 colorectal cancer cell lines. Eighteen of the 20 tumor tissues showed higher expressions of CaMKIIγ than the adjacent non-tumor tissues. The proliferation of transfected SW620-CaMKIIγ cells was enhanced significantly. CaMKIIγ activated NF-κB signaling pathway and led to NF-κB p65 nuclear translocation. In the tumor-bearing mouse model, the volume of the tumors generated by the transfected SW620-CaMKIIγ cells was 1.46- and 1.68-fold higher than that of the tumors with the control cells at the 8th and 12th day, respectively.</p><p><b>CONCLUSION</b>CaMKIIγ can effectively promote the growth of colorectal cancer cells in vitro and in vivo by activating NF-κB signaling pathway.</p>

Long-term outcome of female orthotopic ileal neobladder / 中华泌尿外科杂志

Objective To evaluate the clinical application of female orthotopic ileal neobladder.Methods Modified radical cysteetomy plus orthotopic ileal neobladder was performed on 19 female pa-tients with bladder cancer from June 1999 to January 2008.The mean age of the patients was 52(45-66) years,mean course of disease was 4.4 months (16 days-1.9 years).Of all the patients,there were 10 cases with grade 1,7 cases with grade 2 and 2 cases grade 3.According to the UICC stage system,5 patients were T1 stage,12 T2 and 2 T3a.All the patients received modified radical cystecto-my without resection of uterus and anterior vagina,meanwhile the nerves around urethra were protec-ted.0.8-1.2 cm proximal end of the urethra was excised and 30 cm distal ileum was used for the re-construction of the neobladder.Results Sixteen cases were followed up for 6-102 months,mean 71 months.Fifteen patients survived without disease recurrence,1 patient died of myocardial infarc-tion 17 months postoperation.The daytime and night continent rate was 100$,93% at 9 months postoperative.The average voiding volume of the 15 patients was 519.0 ml.The average residual vol-ume was 29.2 ml,and Qmax was 18.6 ml/s.The average filling and voiding pressure was 16.7 cm H2O and 53.0 cm H2O.Intravenous urography showed slight hydronephrosis in 1 case.Conclusion Female orthotopic ileal neobladder could be a good choice because of the continence,fewer complica-tions,lower pressure and enough bladder capacity.