Macmillanbech9213

The receiver operator characteristics (ROC) curve analysis was performed to evaluate predictive clinical usefulness of 8 metabolites. RESULTS A total of 8 metabolites including taurocholic acid, glycochenodexycholic acid, glycocholic acid, L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine were identified and relatively quantified as differential metabolites for discriminating PC, BD and NC. The 8 metabolites and their combination discriminated PC from BD and NC with well-performed area under the curve (AUC) values, sensitivity and specificity. CONCLUSION Bile acids (especially taurocholic acid) performed to be potential biomarkers in PC diagnosis. Other amino acids (such as L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine) in serum samples from PC patients might provide a sensitive, blood-borne diagnostic signature for the presence of PC or its precursor lesions. Chronic obstructive pulmonary disease (COPD) and lung cancer are two major diseases of the lung with high rate of mortality, mostly among tobacco smokers. The glycosylation patterns of various plasma proteins show significant changes in COPD and subsequent hypoxia, inflammation and lung cancer, providing promising opportunities for screening aberrant glycan structures contribute to early detection of both diseases. Glycoproteins associated with COPD and lung cancer consist of highly sialylated N-glycans, which play an important role in inflammation whereby hypoxia leads to accumulation of sialyl Lewis A and X glycans. Although COPD is an inflammatory disease, it is an independent risk factor for lung cancer. Marked decrease in galactosylation of plasma immunoglobulin G (IgG) together with increased presence of sialic acids and more complex highly branched N-glycan structures are characteristic for COPD and lung cancer. Numerous glycan biomarkers have been discovered, and analysis of glycovariants associated with COPD and lung cancer has been carried out. In this paper we review fundamental glycosylation changes in COPD and lung cancer glycoproteins, focusing on IgG to provide an opportunity to distinguish between the two diseases at the glycoprotein level with diagnostic value. Nanotechnology-based combination therapies, especially chemo-gene therapy, have been spotlighted as promising alternatives for cancer therapy. However, only a small amount of systemically administered nanomedicines reach the tumor site by the enhanced permeability and retention (EPR) effect, resulting in the limited therapeutic efficacy. Furthermore, the design of ideal drug delivery system for chemo-gene therapy has been impeded by the chemical and physical differences between nucleic acids and chemotherapeutics. Herein, we report a precisely designed nanocomplex which exhibits a focused ultrasound (FU)-responsive release and enhanced accumulation of released therapeutics to tumor site. After the nanocomplex composed of siRNA nanoparticles (siRNA-NP) and chemotherapeutics-loaded microbubbles was systemically injected, the nanocomplex was collapsed around the tumor tissue by FU exposure, and both siRNA-NP and chemotherapeutics were penetrated the dense extracellular matrix (ECM) of tumor site, leading to the enhanced chemo-gene therapeutic efficacy. The two-in-one nanocomplex is expected as a promising platform for combination therapy that can enhance the therapeutic efficiency of combination drugs at the cell and/or tissue levels with high drug loading ratio. Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic subtype of breast cancer showing non-responsiveness to most available therapeutic options. Therefore, smart therapeutic approaches to selectively transport and target TNBCs are required. Herein, we developed thymoquinone (TQ)-loaded, hyaluronic acid (HA)-conjugated Pluronic® P123 and F127 copolymer nanoparticles (HA-TQ-Nps) as a selective drug-carrying vehicle to deliver anticancer phytochemical TQ to TNBC cells. The mean size of nanoparticles was around 19.3 ± 3.2 nm. and they were stable at room temperature up to 4 months. Selleck T3 activator HA-TQ-Nps were immensely cytotoxic towards TNBC cells but did not show the toxic effect on normal cells. Detailed investigations also demonstrated its pro-apoptotic, anti-metastatic and anti-angiogenic activity. In-depth mechanistic studies highlighted that HA-TQ-Nps retarded cell migration of TNBC cells through up-regulation of microRNA-361 which in turn down-regulated Rac1 and RhoA mediated cell migration and also perturbed the cancer cell migration under the influence of the autocrine effect of VEGF-A. Moreover, HA-TQ-Np-treatment also perturbed tumor-induced vascularization by reducing the secretion of VEGF-A. The anti-metastatic and anti-angiogenic activity of HA-TQ-Nps was found to be evident in both MDA-MB-231 xenograft chick embryos and 4T1-mammary solid tumor model in syngeneic mice. Thus, an innovative targeted nano-therapeutic approach is being established to reduce the tumor burden and inhibit metastasis and angiogenesis simultaneously for better management of TNBC. Chemotherapy is the standard of care for bladder cancer after transurethral resection of the tumor. However, the rapid excretion of clinically used formulations of anticancer drugs make the common intravesical instillation chemotherapy far from efficient. Therefore, improving the muco-adhesion and penetrability of chemotherapeutic drugs became the key factors in the post-surgery treatment of superficial bladder cancers. Here, a reduction sensitive vehicle was developed to deliver the reactive oxygen species activated prodrug of gambogic acid for treatment of orthotopic bladder cancer. The positively charged chitosan can significantly enhance the adhesion and permeability of prodrug within the bladder wall. Moreover, by utilizing the different glutathione and ROS level between cancer cells and normal cells, the dual responsive nanoparticle can selectively and rapidly deliver drug in bladder cancer cells, and thus can significantly inhibit the proliferation of bladder cancer cells in an orthotopic superficial bladder cancer model without causing damage to normal cells. This work demonstrates that the smart prodrug nanomedicine may act as a promising drug-delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits. V.