ABSTRACT
ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity （FVC） from the baseline， and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity （FVC%pred）， percentage of forced expiratory volume in first second to predicted value （FEV1%pred）， King's Brief Interstitial Lung Disease （K-BILD） total score， 6 minute walking distance （6MWD）， hydroxyproline （HYP）， matrix metalloproteinase （MMP）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， and transforming growth factor-β （TGF-β） from baseline. Patients in line with the inclusion criteria were included in the primary analysis， and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients （included in the sensitivity analysis） meeting the inclusion criteria included 34 in the observation group and 32 in the control group， and 60 patients finally received the whole trial intervention （included for primary analysis）. Compared with the baseline， the FVC increased in the observation group and decreased in the control group after intervention （P<0.01）， which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred， FEV1%pred， 6MWD， and K-BILD total score from baseline in the observation group were superior to those in the control group （P<0.01）， with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline （P<0.05）， while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP， MMP-9， and TGF-β from baseline （P<0.05）. The common adverse events were cough， diarrhea， nausea， rash， and upper gastrointestinal tract infection， the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function， motor function， and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β， MMP-9， and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.
ABSTRACT
One of the main mechanisms of tumorigenesis and development is silencing of the patient's immune response to cancer-specific antigens.The defect of cancer immune surveillance may occur at any stage of tumor progression.In the tumor micro-environment,the abnormal expression of the immune checkpoint molecules that have an activation or inhibition effect on T lymphocytes can cause immune tolerance or escape of tumor cells.Targeted immune checkpoint molecules such as PD-1(programmed cell death protein 1)and its ligand PD-L1,have been shown to be new directions for the treatment of many types of cancer.microRNAs(miR-NAs)play an important role in tumor microenvironment.Studies have shown that miRNAs are highly expressed in some tumors and play an important role in immune response,especially in early regulation.Therefore,miRNAs may be ideal candidates for the regula-tion of immune checkpoints in cancer therapy.The abnormal expression of multiple miRNAs in cancer cells provides new opportunities for cancer therapy,but the exact function of these miRNAs and their interaction with immune checkpoints are still in the exploratory phase.This review summarizes the recent findings regarding the use of miRNAs as molecular regulators of immune checkpoints and their potential applications in the treatment of cancer in clinical practice.
ABSTRACT
Objective The objective of this study were to investigate the effects of miR-219 on cell proliferation,invasion and metastasis and the correlation between PRKCI and miR-219 expression in tongue squamous cell carcinoma. Methods The lu-ciferase reporter gene assay was used to verify the predicted target gene. The expression of PRKCI in tongue squamous cell carcinoma cells overexpressed exogenous miR-219 was detected by qRT-PCR and Western blot. Finally,the reverse effects of PRKCI on the proliferation,clone formation,migration and invasion ability were examined in stable overexpressing miR-219 tongue squamous cell carcinoma(TSCC)cells by MTT assay,cell plate cloning assay,scratch assay and Transwell chamber assays. qRT-PCR assay was used to determine the expression of PRKCI gene and miR-219 in tongue squamous cell carcinoma tissues,and the relationship be-tween PRKCI and miR-219 was further analyzed. Results The bioinformatics analysis predicted that the downstream target gene of miR-219 was PRKCI. The double luciferase reporter gene assay showed that miR-219 was able to reduce the fluorescence activity of the wild type PRKCI reporter vector. In addition,qRT-PCR and Western blot also showed that miR-219 could down-regulate the expression of PRKCI in TSCC cells. MTT results showed that overexpression of PRKCI could reverse the inhibitory effect of miR-219 on the proliferation of TSCC cells,and further demonstrated that the overexpression of PRKCI could reverse the inhibitory effect of miR-219 on the proliferation, invasion and metastasis of TSCC cells by cell plate cloning, scratch and Transwell experiments. Conclusion MiR-219 plays a role in inhibiting tumor by directly targeting PRKCI and negatively regulating the expression of PRK-CI. miR-219 was negatively correlated with PRKCI expression in tongue squamous cell carcinoma.
ABSTRACT
Despite recent advances in surgical techniques and radiotherapy and chemotherapy ,the prog-nosis of laryngeal carcinoma is still poor ,especially patients with in the stage ⅢandⅣ.Hence,there needs a no-vel therapy to improve the treatment of laryngeal carcinoma .Molecular targeted therapy represents an exciting field in the treatment of cancer .This review focuses on the relationship between the laryngeal carcinoma and some promising targets,including EGFR,VEGF,COX-2,mTOR,Nm23-H1 and iNOS,and related inhibitors in la-ryngeal carcinoma research .