ABSTRACT
PURPOSE: The incidence of linezolid-induced thrombocytopenia (LIT) has been reported to vary widely across studies. We performed a meta-analysis to identify the risk factors for thrombocytopenia among patients who received linezolid treatment. METHODS: The PubMed, Embase and Cochrane Library databases were searched from inception to November 2022 to identify eligible studies. Data on the potential predictors of incidence in LIT were pooled using a random effects model. Sensitivity analyses were performed to determine the robustness of the results when significant heterogeneity was observed. RESULTS: Forty observational studies involving 6454 patients treated with linezolid were included in the analysis. LIT was estimated to occur in 37% of patients. The following important factors were associated with the incidence of LIT: advanced age, body mass index, concurrent renal impairment or liver disease, abnormal laboratory parameters (including white blood cell count, serum creatinine, baseline platelet count, albumin, creatinine clearance rate, and estimated glomerular filtration rate), treatment duration and renal replacement therapy. CONCLUSIONS: A variety of risk factors related to the occurrence of LIT were revealed in our analysis. Early identification of these factors could help patients improve clinical outcomes.
Subject(s)
Anemia , Renal Insufficiency , Thrombocytopenia , Humans , Linezolid/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Platelet Count/methods , Risk Factors , Anemia/chemically induced , Anti-Bacterial Agents/adverse effectsABSTRACT
BACKGROUND: Gastric cancer (GC) is the most aggressive malignant tumor with limited treatment alternatives post metastasis. Vernodalin (VN) induced apoptosis has been reported in various types of human cancer cells. However, the precise molecular mechanisms underlying the anti-metastasis action of VN on GC cells are yet to be elucidated. OBJECTIVE: In this study, we investigated the anti-metastatic and apoptotic effects of VN on SGC- 7901 and AGS cells, with a purpose of gaining a deeper understanding of the anti-metastatic mechanisms of VN on gastric carcinoma. To attenuate the activation of PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by VN in GC cells. METHODS: We employed VN and gastric cancer cells in experiments such as MTT assay, apoptosis, MMP, DAPI, Rh-123, cell adhesion assay, and western blot analysis on GC SGC-7901 and AGS cells. RESULTS: Our results revealed that VN inhibits cell proliferation, adhesion, and metastasis and induces apoptosis of both GC cells. VN potentially reduced the protein expressions of MMP-2, MMP-9, and uPA, whereas intensified expressions of TIMP-1 and TIMP-2. Also, VN attenuates the expression of FAK, p-PI3K, p-AKT, p-mTOR, p-JNK, p-p38MAPK, and p-ERK. Thus, it is inferred that VN treatment reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/ mTOR, and MAPKs signaling pathways. Our results confirm that VN prevented GC growth, invasion and metastasis and induce apoptosis in GC cells. CONCLUSION: Our findings suggest that VN is a potential natural therapeutic compound as a new remedy for GC chemotherapy treatment.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Phosphatidylinositol 3-Kinases/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/therapeutic use , Apoptosis , Cell Proliferation , Cell Line, Tumor , Cell MovementABSTRACT
FGFR1 is well known as a molecular target in anticancer drug design. TKI258 plays an important role in RTK inhibitors. Utilizing TKI258 as a lead compound that contains a quinazolinone nucleus, we synthesized four series of 3-vinyl-quinoxalin-2(1H)-one derivatives, a total of 27 compounds. We further evaluated these compounds for FGFR1 inhibition ability as well as cytotoxicity against four cancer cell lines (H460, B16-F10, Hela229, and Hct116) in vitro. Some compounds displayed good-to-excellent potency against the four tested cancer cell lines compared with TKI258. Structure-activity relationship analyses indicated that small substituents at the side chain of the 3-vinyl-quinoxalin-2(1H)-one were more effective than large substituents. Lastly, we used molecular docking to obtain further insight into the interactions between the compounds and FGFR1.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Quinolones/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 1/chemistry , Vinyl Compounds/chemical synthesis , Vinyl Compounds/pharmacology , Antineoplastic Agents/chemistry , Benzimidazoles/chemistry , Biological Phenomena , Cell Line, Tumor , Drug Design , HeLa Cells , Humans , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemistry , Quinolones/chemistry , Quinoxalines/chemistry , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Structure-Activity Relationship , Vinyl Compounds/chemistryABSTRACT
Hepatitis B virus (HBV) infection causes major public health problems worldwide. Acyclovir (ACV) is mainly used to inhibit herpes simplex virus (HSV) rather than HBV. In this study, we used the combination principle to design and synthesize nucleoside analogues that contain silatrane on the basis of the structure of ACV. We found that the compounds were effective inhibitors of HBV, both in vitro and in vivo. All of the compounds showed suppressive activity on the expression of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the HepG2.2.15 cell line with low cytotoxicity. One of compounds was studied in HBV transgenic mice model, and the test results showed its ability to reduce the levels of HBsAg, HBeAg and HBV DNA by ELASE and qPCR. Furthermore, significant improvement of T lymphocyte was observed after treatment, as evaluated by flow cytometry (FCM).
