ABSTRACT
Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs. .
Subject(s)
Humans , Myeloid-Derived Suppressor Cells , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms/drug therapy , T-Lymphocytes , Immunotherapy , Tumor MicroenvironmentABSTRACT
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR are effective in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. With the application and expansion of individualized and combined therapy, more and more studies have shown that combined administration of Metformin effectively solves the problem of acquired drug resistance to EGFR-TKIs in clinical treatment and prolongs the survival of patients with NSCLC. EGFR-TKIs combined with Metformin is expected to be the treatment method of choice for NSCLC patients with EGFR-TKIs resistance. This paper intends to summarize the research progress of EGFR-TKIs combined with Metformin in the treatment of EGFR-TKIs acquired resistance in NSCLC, in order to provide a new idea for the treatment of NSCLC patients with acquired resistance to EGFR-TKIs. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Metformin/therapeutic use , Protein Kinase Inhibitors/therapeutic use , ErbB Receptors/metabolism , Drug Resistance, Neoplasm , MutationABSTRACT
Background and purpose:The prognostic role of human epidermal growth factor receptor 2 (HER-2) remains controversial in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the expression of HER-2 and its prognostic implication in patients with NSCLC.Methods:Four hundred and twenty-ifve NSCLC patients’ specimens were obtained from Zhejiang Cancer Hospital. HER-2 protein expression was determined by immunohistochemistry (IHC). The relationship between HER-2 and clinicopathological parameters and patients’ prognosis was analyzed by Chi-square test and COX proportional hazards regression model.Results:Eighty-three patients were positive expression of HER-2 (83/425, 19.5%). The expression of HER-2 was closely related with histological type (P=0.051), most patients with HER-2 positive were adenocarcinoma, then were squamous carcinoma or other histological types. However, HER-2 was not an independent prognostic indicator for the overall survival of patients with NSCLC.Conclusion:We found that the expression of HER-2 was closely connected with histological type, but it was not a predictive marker for the prognosis in patients with NSCLC.
ABSTRACT
As a member of regenerating islet-derived family,regenerating islet-derived type Ⅳ(RegⅣ)is involved in cell proliferation and differentiation. RegⅣ is closely related to the occurrence and develop-ment of tumor,tumor cell proliferation and invasion and anti-apoptosis,and it may be a potential molecular tar-get of targeting therapy in cancer.
ABSTRACT
Objective To investigate the relationship of the metastasis-associated genes and its copy numbers variation in the highly metastatic human epithelial ovarian cancer cell line HO-8910PM. Methods The differentially expressed genes and its copy number variation between HO-8910PM cell line and normal ovarian tissues was detected by human genome UI33A 2.0 gene chip and human mapping 10K array 2.0 gene chip, and the data was analyzed by bioinformatics. Some of metastasis-associated genes were validated the results of single nucleotide polymorphism (SNP) and cDNA chips by fluorescence in situ hybridization (FISH) and real-time quantitative PCR. Results Integrate analysis of two gene chips data showed that there were 385 differentially expressed genes in the same and 379 SNP positional point (6 of them, included 2 genes) between HO-8910PM cell line and normal ovarian tissues, these copy number amplification of 379 SNP positional point of chromosome were ≥3, which had 240, deletion ≤ 1 had 139. Chromosome location analysis showed that there were 385 differentially expressed genes located at all chromosomes, and 261 of them ( 67.8%, 261/385 ) located at 10 chromosomes, included that 34 (8.8% ), 33 ( 8.6% ), 28 (7.3%), 27 (7.0%), 25 (6.5%), 24 (6.2%) of them located at chromosome 3, 2, 9, 10, 1 and 11 respectively, and 23 (6.0%) of them at chromosome 6 and 12 each, 22 (5.7%) of them at chromosome 4 and 5 each. For the function of differentially expressed genes, the results showed that 99 (25.7% ) genes belonged to the family of enzymes and their regulators, 54 ( 14.0% ) genes associated with signal transduction, 50 (13.0%) genes associated with nucleic acid binding, and 36 (9.4%) genes associated with protein binding. Conclusion We have demonstrated that there are 4 kinds of differentially expressed genes related to metastasis of ovarian cancer, which belonged to the families enzyme and its regulator, nucleic acid binding, signal transduction and protein binding, and located at chromosome 1, 2, 3, 4, 5, 6, 9, 10, 11 and 12.
ABSTRACT
Objective To detect the level of Tnl and T.2 type cytokines in the patients with lym-phoma in order to find out the laboratory evidence of tumor immunotherapy. Methods The levels of serum IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 were measured by cytometric bead array (CBA) in 92 patients with lymphoma, and 70 normal sera as control. Results The levels of TH1 type cytokincs in 92 patients with lymphoma were: IFN-γ (34.26 ± 33.48) pg/ml, TNF-α (8.17 ± 10. 09) pg/ml, IL-2 (3.74 ±1.72) pg/ml; and the levels of TH2 type cytokines were: IL-10 (6. 28±8.56) pg/ml, IL-5 (3.53 ±3.20) pg/ml, IL-4 (6.22±7.13) pg/ml. The levels of TH1 and TH2 cytokines in lymphoma patients were significantly higher than those in controls(P ＜ 0.01) except TNF-α. And the rate of IL-2/IL-4 was signifi-cantly decreased in lymphoma patients(P ＜0.01). The level of IL-10 in Ⅲ/Ⅳ stage lymphoma patients was much higher than that in Ⅰ/Ⅱ stage patients(P ＜0.01). The level of IFN-γ/was significantly decreased in aged patients with lymphoma (P ＜0. 05). Conclusion TH 1/TH2 is imbalance in lymphoma, which may provide clinical index for the evaluation of progrossien and prognosis. In the lymphoma patients TH1/TH2 shifts to TH2, which may be the mechanism of tumor arising and transferring by immune escape from immu-nosurveillance.