Progress of programmed death factor-1 and its ligand 1 inhibitors in immunotherapy of advanced non-small cell lung cancer / 肿瘤研究与临床

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, with the rapid development of immunotherapy, checkpoint inhibitors, especially programmed death factor-1 (PD-1)/programmed death factor ligand-1 (PD-L1) inhibitors, have made breakthrough progress in the treatment of NSCLC, breaking the pattern of low efficiency and extensive resistance to targeted therapy of traditional chemoradiotherapy, bringing survival benefits to patients. This article reviews the clinical research progress of PD-1/PD-L1 inhibitors in advanced NSCLC.

Research progress of the mechanism for PD-1 molecule regulating pulmonary fibrosis and its research prospects in silicosis / 公共卫生与预防医学

Programmed death factor-1 (PD-1) is a promising target molecule for clinical tumor immunotherapy in recent years. Recent studies suggest that PD-1 and related signaling pathways (PI3K/AKT, JAK/STAT3, p38MAPK, ERK, etc.) played a key regulatory role in the process of pulmonary fibrosis. Silicosis is a systemic disease caused by inhalation of free silicon dioxide dust, which is mainly characterized by extensive pulmonary nodular fibrosis and seriously endangers the health of patients. Dissecting the role of PD-1 in the pathogenesis of silicosis may be of great significance in the mechanism research and clinical diagnosis and treatment of silicosis. This paper reviews the regulation of PD-1 molecule on related signaling pathways and its role in pulmonary fibrosis, and looks forward to the potential application of these mechanistic studies in silicosis research.

miR-21 regulates the proliferation and migration of non-small cell lung cancer A549 cells by targeting PDCD4 gene / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the effects of miR-21 targeting PDCD4 (programmed cell death factor 4) on proliferation and migration of non-small cell lung cancer (NSCLC) A549 cells and the possible mechanism. Methods: The miR-21 mimics, miR-21 inhibitors and miR-NC plasmids were transfected into A549 cells in logarithmic growth phase by liposome transfection technology. Forty-eight hours after transfection, the transfection efficiency was observed under a fluorescence microscope, and the mRNA expression levels of miR-21 and PDCD4 in A549 cells were detected by qPCR. Dual luciferase reporter gene experiment was used to detect the targeting relationship between miR-21 and PDCD4, MTT method was used to detect cell proliferation, Transwell chamber method was used to detect cell migration ability, and ELISA was used to detect the content of TNF-α in each group of cell culture fluids. WB was used to detect the protein expression levels of PDCD4, NF-κB p65 and p-NF-κB p65 in cells. Results: The A549 cell line with miR-21 over-expression or knockdown was successfully constructed. Dual luciferase reporter gene assay confirmed that miR-21 targetedly inhibited PDCD4 expression. Over-expression of miR-21 could significantly inhibit the mRNA expression of PDCD4 in A549 cells (P<0.01), promote cell proliferation and migration (P<0.05 or P<0.01), increase the secretion level of TNF-α (P<0.01), down-regulate the expression of PDCD4 protein (P<0.01), and up-regulate p-NF-κB p65 protein level (P<0.05). The effect of silencing miR-21 on cells was opposite to the effect of miR-21 over-expression. Conclusion: Over-expression of miR-21 can promote the proliferation and migration ability of A549 cells, which may be related to its targeted inhibition of PDCD4 and activating the NF-κB/TNF-α pathway.

Immunotherapy with PD-1 and PD-L1 inhibitors for prostate cancer / 中华男科学杂志

Prostate cancer (PCa) has become one of the common malignant diseases in elderly men, and its incidence is increasing year by year. Apart from surgery, radiotherapy and chemotherapy, immunotherapy, as with the programmed death receptor-1 (PD-1) or the programmed death ligand-1 (PD-L1) inhibitor, is a most promising new strategy for the treatment of PCa. PD-1 and PD-L1 inhibitors restore the activity of T cells by blocking the PD-1/PD-L1 signaling pathway in tumor cells, reverse the mechanism of tumor immune escape, recover the immune system and directly kill tumor cells. This review focuses on the current progress in the studies of PD-1 and PD-L1 inhibitors in the treatment of PCa.

The expressions and clinical significance of PD-L1 and PD-1 in peripheral T-cell lymphoma / 天津医药

Objective To investigate the expression levels and clinical significance of programmed cell death 1 ligand (PD-L1) and programmed cell death factor-1 (PD-1) in peripheral T-cell lymphoma (PTCL). Methods Immunohistochem?istry was used to detect expression levels of PD-L1 and PD-1 in PTCL (test group, n=51) and benign proliferative lesions of lymph node tissues (control group, n=20). The correlations of PD-L1 and PD-1 expressions with clinical pathological param?eters and prognosis were analyzed between two groups. Results The expression level of PD-L1 was significantly higher in PTCL group than that in control group (74.51%vs 35.00%,χ2=9.662, P<0.05). The positive expression of PD-1 was signifi?cantly higher in PTCL group than that in control group (66.67%vs 25.00%,χ2=10.074, P<0.05). There were significant dif?ferences in PD-L1 and PD-1 expressions between different peripheral lactate dehydrogenase (LDH) levels of PTCL group (P<0.05). After two cycles of CHOP or ECHOP treatments, the response rate (RR) was higher in PD-L1 negative group than that in positive group (84.6%vs 47.4%,χ2=5.478, P<0.05), and RR was higher in PD-1 negative group than that in positive group(82.4%vs 44.1%,χ2=6.755, P<0.05). The median overall survival (OS) time was higher in PD-L1 negative group than that in positive group (29.8 months vs 17.6 months,χ2=4.413, P<0.05) and the median OS time was higher in PD-1 negative group than that in positive group (29.8 months vs 17.6 months,χ2=8.293, P<0.05). Conclusion There are high expression levels of PD-L1 and PD-1 in peripheral T-cell lymphoma, which is closely related with the elevated LDH in peripheral blood, poor response rate and shorter OS. Therefore, the expression levels of PD-L1 and PD-1 can be used as factors of worse effect of chemotherapy and poor prognosis.

Expression and significance of MRG15 in human age-reIated cataract Iens epitheIiaI ceIIs / 国际眼科杂志(Guoji Yanke Zazhi)

·AlM:To study the MRG15 (death factor related gene) in age-related cataract ( ARC ) , differential expression of normal lens epithelial cells. · METHODS: Forty mature healthy female SD rats were randomly divided into study group and control group, 20 rats in each group, the study group were ovariectomized, low concentration of naphthalene long interval of administration, the establishment of perimenopausal ARC model, the control group of conventional farming.ln the subtractive hybridization cloning by MRG15, and make the probe of the cDNA fragment using digoxigenin labeled. Access to the two groups of rats anterior lens capsule after slicing, and then through the differential expression in situ hybridization clear lens epithelial cells. · RESULTS: The cloned MRG15 through BamH1, EcoR1 enzyme digestion and agarose gel electrophoresis, available for 639bp long cDNA fragment. GeneBank display contrast, their homology was 99.0%. ln situ hybridization, ARC patients and normal lens epithelial cells were observed in the expression of MRG15.Study group the percentage of positive cells compared with control group, showed a significant difference (P<0.05). lntegral index study group and the control group compared with, was significantly difference (P<0.05). · CONCLUSlON: ARC, MRG15 in normal lens epithelial cells expressed ARC, and compared with the normal expression of lens epithelial cells, which may produce inhibitory effects are associated with MRG15 transcription in human lens epithelial cells in the part of key genes, by reducing the lens epithelial cell fu nction, make its appear aging, and the formation of cataract, clinical response to this should further study.

Apoptosis of Surrounding Neurons by Brain tumor

BACKGROUND: As brain tumor cells are immunologically active, they release various factors like a cytokine, growth factor and express a death domain on their surfaces. Accordingly they support proliferation, vascularity, invasiveness and maintain immune privileged sites. However, the relationship between tumor cells and surrounding neuron cells have been rarely reported in tumor patients with epilepsy that inhibitory neuron cells have been lost around peritumoral sites. This study was designed to address that tumor cells directly damage neuron cells. METHODS: Using LDH assay and special stain, we investigated whether or not cultured supernatants of astrocytoma cells induce the damage of neuron cells. RESULTS: The neuron cells were killed by tumor cells supernatant and increased by pretreatment of neuron cells supernatant and lysates. Protein extracted tumor cells supernatant also damage neuron cells. It was proved by Annexin-PI stain and DNA fragmentation that neuronal death by tumor cells was apoptosis. The more malignant tumor cells, the more neuronal death was induced and the more their cytokines were expressed. In comparison with various cytokine expressions in tumor cells, it can be assumed that the released protein from tumor cells was associated with TNF (tumor necrosis factor)-alpha. CONCLUSIONS: Brain tumor cells are active processing cells that they recognize surrounding normal neuron cells, release death factors and induce apoptosis of neuron cells. Released death factors are related toTNF-alpha. (J Korean Neurol Assoc 19(3):266~277, 2001)