MGMT gene promoter methylation in humoral tissue as biomarker for lung cancer diagnosis: An update meta-analysis.

OBJECTIVE: To investigate O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation in humoral tissue as biomarker for lung cancer diagnosis by pooling relevant open published data. METHODS: Clinical studies relevant to MGMT gene promoter methylation and lung cancer were systematic electronic searched in the databases of Medline, EMBASE, Ovid, Web of Science, and CNKI. Data of true positive (tp), false positive (fp), false negative (fn), and true negative (tn) were extracted from the included studies and made combination. The diagnostic sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) of MGMT gene methylation for lung cancer diagnosis were pooled. RESULTS: Twelve studies were included in the meta-analysis. The diagnostic sensitivity, specificity, DOR were 0.39 (95% CI = 0.31-0.49) 0.92 (95% CI = 0.77-0.97), and 4.20 (95% CI = 2.09-8.44), respectively under random effect model. The SROC of MGMT gene methylation for lung cancer diagnosis was 0.58 (95% CI = 0.53-0.62). CONCLUSION: MGMT methylation rate was higher in plasma and bronchoalveolar lavage fluid (BLAF) of lung cancer cases compared to controls. High diagnostic specificity indicated that MGMT methylation in plasma and BLAF can be applied as lung cancer confirmation test.

Multiple metachronous rare primary malignant tumors: A case report.

Multiple primary malignant tumors (MPMTs) are rarely seen among the patients with malignant neoplasms. Moreover, the existence of five MPMTs in the same patient is an extremely rare phenomenon. In this case, a 42-year-old male patient developed five metachronous MPMTs within 16 years and the duration between each malignant tumor shortened with the progression of the disease. Multidisciplinary treatments were used on this patient and he fought against the cancers until the end of his life. Our report provides us with a new awareness of MPMTs, which should be considered when we come across with cancer patients who develop various unexplainable symptoms after the diagnosis of the first neoplasm.

A 3,2-Hydroxypyridinone-based Decorporation Agent that Removes Uranium from Bones In Vivo.

Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.

Real-time monitoring of a controlled drug delivery system in vivo: construction of a near infrared fluorescence monomer conjugated with pH-responsive polymeric micelles.

Real-time monitoring of drug delivery systems has attracted growing interest for potential applications in biomedical therapy. Fluorescence imaging is a highly sensitive technique for illuminating the pathways of such systems. In this work, we designed and synthesized a new near infrared (NIR) fluorescent dye monomer (NFM). The NFM monomer was covalently attached to a pH-responsive amphiphilic block copolymer by reversible addition-fragmentation chain transfer (RAFT) copolymerization using hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) as the macro-RAFT agent and pH-responsive 2-(4-(dodecyloxy)phenyl)-1,3-dioxan-5-yl methacrylate (DBAM) and NFM as the comonomer, to synthesize the multifunctional amphiphilic block copolymer PPEGMA-b-P(DBAM-co-NFM) with NIR moieties and pH-sensitive groups. The PPEGMA-b-P(DBAM-co-NFM) could be self-assembled easily into stable micelles with doxorubicin (DOX) with an average diameter of 66 nm in water. The nano-size of the micelles is suitable for cycling through the body and carrying drugs to tumor sites safely via the enhanced permeability and retention (EPR) effect. Confocal laser scanning microscopy (CLSM) results indicated cells' uptake and the intracellular distribution. In vivo imaging of the micelles was observed in real time and the fluorescent signals clearly demonstrated the dynamic process of tumor treatment. This versatile and effective strategy is a potential tool for monitoring controlled drug delivery for tumor treatment.

Self-assembly of BODIPY based pH-sensitive near-infrared polymeric micelles for drug controlled delivery and fluorescence imaging applications.

Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR fluorescence enhancement induced by the phenol/phenolate interconversion equilibrium works as a switch in response to the intracellular pH fluctuations. DOX-loaded PMAA-b-P(PEGMA-co-BODIPY) micelles can detect the physiological pH fluctuations with a pKa near physiological conditions (∼7.52), and showed pH-responsive collapse and an obvious acid promoted anticancer drug release behavior (over 58.8-62.8% in 10 h). Real-time imaging of intracellular pH variations was performed and a significant chemotherapy effect was demonstrated against HeLa cells.