ObjectiveTo systematically review the efficacy and safety of autologous natural killer cells (NK) cells for the treatment of malignant tumors. MethodsThe PubMed, Web of Science, and Embase databases were electronically searched to collect clinical studies on autologous NK cells for the treatment of malignant tumors from inception to July 1, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Descriptive analysis of the results were conducted. ResultsA total of 15 studies were included. The most common tumor type was non-small cell lung cancer. The dose of NK cell injections usually ranged from 7.0×107 to 7.0×109 cells, with a treatment interval of 14-21 days and a frequency of 3-6 injections. The overall response rate for NK cell therapy ranged from 0% to 77.78%. The main adverse effects were fever (3.98%), fatigue (1.99%), rash (0.4%), and dizziness (1.20%). ConclusionCurrent evidence shows that autologous NK cell therapy is safe for treating malignant tumors, and some studies have shown that NK cell therapy has a relieving effect. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify above conclusion.
Objective To observe the effects of bevacizumab on aquaporin 4 (AQP4) expression in human retinal Muuml;ller cells in vitro under hypoxia. To explored the mechanism of treating retinal edema with bevacizumab. Methods Human Muuml;ller cells were cultured using the enzymatic digestion method. Transmission electron microscopic analysis and immunofluorescence staining identified Muuml;ller cells. With semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), the expression of AQP4 mRNA and vascular endothelial growth factor （VEGF） mRNA in Muuml;ller cells cultured under different concentration of COCl2 for different hours were observed. The expression of AQP4 mRNA in Muuml;ller cells cultured using CoCl2 precultured with 200 mu;g/ml bevacizumab was measured. Results More than 95% of primary cells showed positive reaction to glial fibrillary acidic protein, glutamine synthetase, vimentin and alpha;-smooth muscle actin with immunofluorescence staining. Characteristic 8-10 nm intracellular filaments could be seen in the cytoplasm viewed with transmission electron microscopy. The results using RT-PCR showed that CoCl2 increased the AQP4 and VEGF mRNA expression in Muuml;ller cells in a dose and time dependent manner (r=0.952, 0.954;P＜0.05). The expression of AQP4 mRNA in Muuml;ller cells was increased by VEGF (F=12.43,P＜0.05). The expression of AQP4 mRNA was significantly decreased by bevacizumab (F=2 370.37，P＜0.05). Conclusion Bevacizumab can down-regulate the expression of AQP4 mRNA in human Muuml;ller cells under hypoxic conditions partially by VEGF path, which may be a mechanism for treating retinal edema with bevacizumab.
Müller cells are glial cells of the retina, whose major processes cross the internal and external limiting membranes of the retina, maintaining the function and metabolism of retinal photoreceptors and neurons. Their structure and function are closely related to the development of macular hole (MH). Müller cells are involved in the formation and recovery of MH from the aspect of traction and protein, and their morphology and biological function also influence the regression of MH. The current treatment modality for MH is vitrectomy combined with internal limiting membrane (ILM) peeling, in which Müller cells play a dual role after ILM peeling in different stages of MH. And its potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons making it a current research hot topic, which can be a reference and inspiration for clinical treatment.
ObjectiveTo observe the protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy.MethodsSeventy-five C57BL/6J mice were randomly divided into the normal control group, diabetes mellitus (DM) group, low concentrations group, medium concentrations group and high concentrations group, with 16 mice in each group. The diabetes model of mice in all groups except the normal control group were established by intraperitoneal injection of STZ (60 mg/kg). Four weeks after the successful modeling, the Zhicao Tea Mixture with low (30 ml/kg), medium (60 ml/kg) and high concentrations (120 ml/kg) were respectively administered by gavage. Weight and blood glucose of mice in each group were measured every two weeks. After 8 weeks, Western blot method was used to detect the mice retina Müller cells activation marker gelatinous fibrous acidic protein (GFAP). Immunofluorescence was performed to detect the expression GFAP and glutamine synthetase (GS). Real-time quantitative PCR (RT-qPCR) and ELISA were used to determine the mRNA and protein expression levels of mouse retinal VEGF, TNF-α, IL-1β and IL-6 respectively.ResultsThe weight of mice in the DM group was lower than that of the normal control group, and the blood glucose was increased. Zhicao Tea Mixture had no effect on the weight of DM mice, but had a significant hypoglycemic effect. The GFAP expression (t=38.318, P＜0.001) in the retina of mice in the DM group was increased and GS expression (t=29.737, P＜0.001) was decreased compared with the control group. The GFAP expression (t=13.677, 19.387, 16.305; P＜0.05) in the retina of mice in the low, medium and high concentrations group were decreased and GS expression (t=5.170, 19.399, 6.705; P＜0.05) were increased compared with the DM group. The expressions of retinal inflammatory factors VEGF, TNF-α, IL-1β and IL-6 in DM group all increased, while the expressions of the above-mentioned inflammatory factors in the retina of mice decreased in the low, medium and high concentrations group.ConclusionZhicao Tea Mixture can decrease the blood glucose of DM mice and reduces the diabetic retinal inflammatory response.
Objective To investigate the effect of long-term intraocular retention of domestic perfluorocarbon liquid (PFCL) on morphology and histology of ocular tissues. Methods A total of 18 New-Zealand rabbits were randomly divided into 3 experimental groups, whose left eyes underwent intraocular injection with 0.3, 0.6, and 1.0 ml PFCL, respectively. All of the right eyes of the rabbits were in the control group. The morphological, electrophysiological and histological changes of the ocular tissue were observed 4, 8, and 12 weeks after the injection. Results No clinically significant retinopathy but only mild morphological changes were found in group 1 and 2, while obvious morphological and histological changes were found in group 3. Mild morphological and histological changes were found in all of the rabbits 4-8 weeks after the injection while significant ones were found 8-12 weeks after the injection. The results of electroretinography indicated a statistically significant decline of amplitude of b wave in group 3. Conclusions Long-term intraocular retention of few PFCL may cause mild histological changes but not affect the clinical function. Plentiful PFCL remains in eyes may lead to toxic reaction to the ocular tissue. (Chin J Ocul Fundus Dis, 2006, 22: 128-130)
31 case of advanced primary liver cancer were treated by using IL-2 and LAK cells in which 15 cases were combined with surgery (group A) and 16 cases were combined with chemotherpy (Group B). 7～14 months follow-up showed: In group A there was no recurence and metastasis, and the cell-mediated immunity was obviously improved. In group B, the average life time was more than 5.84 months, the tumor average diameter dicreased in 10 cases ,and the cee-mediated immunity was also improved. The role of immunotherapy combined with surgery or chemotherapy was discussed.
Objective To investigate the effect of hypoxia on expressions of erythropoietin（EPO）mRNA and protein in retinal Muuml;ller cells cultured in vitro. Methods Retina tissues from the new-born Wistar rats were dissected into cell suspension after digested by pancreatin.Muuml;ller cells were separated and purified by mechanical concussion and blowing and striking method.The expression of EPO mRNA and protein under the condition of hypoxia was detected by semi-quantitative reverse transcriptase（RT）-polymerase chain reaction（PCR）and immunocytochemical method. Results Retinal Muuml;ller cells were cultured successfully，95% of which were positively stained by glial fibrillary acidic protein（GFAP）.Positively stained EPO protein was located in the cytoplasm and protuberance.The expression of EPO mRNA and protein was faint in the normal retinal Muuml;ller cells，but increased obviously and time-dependently after hypoxia. Conclusion Expression of EPO mRNA and protein increases in Muuml;ller cells after hypoxia，which may be one of the protective factors for the nerves in anoxic retinopathy. (Chin J Ocul Fundus Dis, 2006, 22: 196-199)
Objective To observe the different effect such as high concentration of glucose and high concentration of insulin on GLUT1 of Rabbit Retinal Muuml;ller Cell in vitro. Methods Rabbit retinal Muuml;ller cells were cultured in vitro with suspended constitution，which were divided as the following groups: common control group，high glucose group，insulin group，high glucose combined insulin group. Laser confocal microscope combined with immunocytochemical and fluorescence staining method to quantitatively analyze the expression condition of GLUT1. Results The expression of GLUT1 has been enhanced obviously by high glucose and high insulin，which locates mainly in the cytoplasm that near to the nucleus. Conclusion Rabbit retinal Muuml;ller cells can express GLUT1，and the expression of GLUT1 can be reinforced by high glucose and high insulin. （Chin J Ocul Fundus Dis，2008，24：265-267）
Abstract: Objective To investigate the effect of cytokineinduced killer (CIK) cells immunotherapy on immunity function of non-small cell lung cancer (NSCLC) patients after operation. Methods Fifty patients with histological or cytological diagnosis of NSCLC on Ⅰstage,Ⅱstage andⅢa stage of tumor, nodes, metastasisclassification were randomly divided CIK cells therapy group and conventional therapy group, 25 cases each group. The immunity function of patients with NSCLC, including the levels of CD3+, CD4+ T cells, ratio of CD4+/CD8+, natural killer(NK) cells, and the levels of Th1/Th2 cytokine were detected before treatment, and the 2nd, 4th, 8th week after treatment. Results The levels of CD3+, CD4+ T cells, NK cells, ratio of CD4+/CD8+, interleukin-2(IL-2), interferon-γ(INF-γ) in CIK cells therapy group at the 2nd week after treatment were more higher than those before treatment (Plt;0.01), their levels reached the peak at 4th week, from then on, it began to decrease. Meanwhile, the levels of Th2 of CIK cells therapy group began to decrease at the 2nd week after treatment, a low ebb at 4th week. At the 2nd, 4th and 8th week,the levels of CD3+,CD4+ T cells, ratio of CD4+/CD8+, NK cells,IL-2, INF-γ, interleukin-4(IL-4), interleukin-10(IL-10) of CIK cells therapy group compared with those inconventional therapy group,there were statistical significance difference［(Plt;0.05),at 4th week after treatment, CD3+ 70.2%±9.1% vs.46.3%±5.8%; CD4+40.2%±7.1% vs.22.9%±4.5%; CD4+/CD8+ 1.82±0.43 vs. 1.09±0.34; NK 15.7%±5.4% vs.10.5%±2.5%; IL-2 34.8±11.7 ng/L vs. 19.8±12.1 ng/L; INF-γ63.7±23.3 ng/Lvs. 30.8±10.6 ng/L; IL-4 10.2±8.6 ng/L vs. 25.8±6.3 ng/L; IL-10 10.6±3.4 ng/L vs. 21.4±8.6 ng/L］. Conclusion The results indicate that CIK cells immunotherapy can enhance the immune function of NSCLC patients after operation.
Objective To observe the influence of interleukin-1beta; (IL-1beta;) on the expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT 3) in rat retinal Muuml;ller cells.Methods For in vitro study cultured Muuml;ller cells were treated with IL-1beta; of different concentrations (0, 0.1, 1, 5 and 10 ng/ml) for 24 hours. For in vivo study, 32 Sprague-Dawley（SD）rats were divided into 4 groups randomly (control group，100，500 and 1000 ng/ml group) with 8 rats in each group. After 24 hours of injection with phosphate buffered solution (PBS), or 100,500,1000 ng/ml IL-1beta; into the vitreous cavities of the above rats, retinas were harvested. The expressions of pSTAT3 in cultured Muuml;ller cells or treated retinas were evaluated by indirect immunofluorescence and western blotting.Results After 24 hours of incubation without IL-1beta;, pSTAT3 has little expression in cultured Muuml;ller cells, but was upregulated by 1 ng/ml or higher IL-1beta; in a dosagedependent manner (F=46.64, 43.78;P＜0.01). pSTAT3 was not expressed in adult rat retina, but was upregulated by vitreous injection of 100 ng/ml or higher IL-1beta; in a dosagedependent manner (F=73.53,43.70;P＜0.01).pSTAT3 expressed mainly in inner nuclear layer and ganglion cell layer. Doublelabeling showed that there was no costaining of pSTAT3 and glial fibrillary acidic protein (GFAP) in retina of control group, but there were many costained Muuml;ller cells in retinas treated with IL-1beta;.Conclusions Expression of pSTAT3 in Muuml;ller cells could be activated by IL-1beta; which may represent one pathway link to reactive gliosis.