Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Nanomaterials-Involved Tumor-Associated Macrophages' Reprogramming for Antitumor Therapy.

Tumor-associated macrophages (TAMs) play pivotal roles in tumor development. As primary contents of tumor environment (TME), TAMs secrete inflammation-related substances to regulate tumoral occurrence and development. There are two kinds of TAMs: the tumoricidal M1-like TAMs and protumoral M2-like TAMs. Reprogramming TAMs from immunosuppressive M2 to immunocompetent M1 phenotype is considered a feasible way to improve immunotherapeutic efficiency. Notably, nanomaterials show great potential for biomedical fields due to their controllable structures and properties. There are many types of nanomaterials that exhibit great regulatory activities for TAMs' reprogramming. In this review, the recent progress of nanomaterials-involved TAMs' reprogramming is comprehensively discussed. The various nanomaterials for TAMs' reprogramming and the reprogramming strategies are summarized and introduced. Additionally, the challenges and perspectives of TAMs' reprogramming for efficient therapy are discussed, aiming to provide inspiration for TAMs' regulator design and promote the development of TAMs-mediated immunotherapy.

Metal-amplified sonodynamic therapy of Ti-based chitosan-polyvinyl alcohol hybrid hydrogel dressing against subcutaneous Staphylococcus aureus infection.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has received extensive attention in pathogen elimination for non-invasiveness and high spatial and temporal accuracy. Considering that hydrogel can provide a healing-friendly environment for wounds, in this work, hybrid hydrogels are constructed by embedding Ag doped TiO2 nanoparticles in chitosan-polyvinyl alcohol hydrogels for enhanced sonodynamic antibacterial therapy. With metal silver doped, TiO2 nanoparticles sonosensitivity is improved to generate more reactive oxygen species (ROS), which endows hybrid hydrogels with high-efficient antibacterial properties. In vivo results show that hybrid hydrogel dressing can prevent infection and promote wound closure within 2 days. The healing ratio excess 95 % with no pus produced at the end of treatment. The therapeutic mechanism was identified that heterojunction formed in Ag doped TiO2 facilitates the separation of charge carriers under US irradiation, leading to elevating ROS generation. The generated ROS promote hybrid hydrogels sonodynamic antibacterial therapeutic efficacy to thoroughly eliminate pathogen via disrupting bacterial cell membrane integrity, decreasing membrane fluidity and increasing membrane permeability. Besides, biofilm formation could be effectively inhibited. This work developed a hybrid hydrogel with amplified SDT effect for wound healing, which is expected to provide inspiration of hybrid hydrogels design and Ti-based nanomaterials sonosensitivity enhancement.

MiR-920 and LSP1 co-regulate the growth and migration of glioblastoma cells by modulation of JAK2/STAT5 pathway.

This study probes the function and mechanism of lymphocyte-specific protein 1 (LSP1) in glioblastoma pathogenesis. According to the data acquired from TCGA, Oncomine and GEO databases, the expression and prognostic value of LSP1 and miR-920 in glioblastoma patients were analyzed. The expression levels of LSP1 in U251 and A172 cell lines were analyzed by qRT-PCR and western blotting. CCK8, colony formation and transwell assays were utilized to test glioblastoma cell malignant abilities. Furthermore, the associations between LSP1 and miR-920 were indentified by bioinformatics analysis and rescue assays. Moreover, the protein expression levels of p-JAK2, JAK2, p-STAT5 and STAT5, as the hallmark of JAK/STAT5 signaling, were detected by western blotting. The observations showed that LSP1 was highly augmented in glioblastoma samples. Additionally, up-regulation of LSP1 was associated with a unfavorable prognosis in glioblastoma patients. Biological experiments revealed that depletion of LSP1 significantly suppressed the proliferation, invasion and migration of U251 and A172 cells. MiR-920, as an upstream regulator of LSP1, negatively modulated LSP1 expression and promoted U251 cells malignant behaviors after miR-920 inhibitor treatment. However, together knockdown LSP1 and miR-920 inhibited these effects. Moreover, the expression levels of p-JAK2 and p-STAT5 were increased or decreased in U251 cells after transfection of miR-920 inhibitor or si-LPS1. Taken together, miR-920 might blocked the malignant development of glioblastoma cells, which is possibly realized by targeting LSP1 and modulation of JAK/STAT5 pathway. These findings implied that miR-920/LSP1 was a potential therapeutic target for glioblastoma treatment.

A systematic review of risk factors for brain metastases and value of prophylactic cranial irradiation in non-small cell lung cancer.

BACKGROUND: The incidence of brain metastases (BM) varies in patients with non-small cell lung cancer (NSCLC), calls into question the value of prophylactic cranial irradiation (PCI). It is possible that clinicopathologic characteristics are associated with the development of BM, but these have yet to be identified in detail. Thus, we conducted the present meta-analysis on risk factors for BM and the value of PCI in patients with NSCLC. METHODS: Eligible data were extracted and the risk factors for BM and the value of PCI in patients with NSCLC were analyzed by calculating the pooled odds ratio (OR). Heterogeneity was detected using Q and I-squared statistics, and publication bias was tested by funnel plots and Egger's test. RESULTS: Six randomized controlled trials with a focus on the value of PCI and 13 eligible studies with a focus on risk factors for BM were included. PCI significantly reduced the incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.34, 95% confidence interval = 0.37-0.59). Compared with non-squamous cell carcinoma, squamous cell carcinoma was associated with a low incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.47, 95% confidence interval =0.34- 0.65). The funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis. CONCLUSIONS: This meta-analysis provides statistical evidence that compared with non-squamous cell carcinoma, squamous cell carcinoma can be used as a predictor for BM in patients with NSCLC, and PCI might reduce the incidence of BM in patients with NSCLC, but does not provide a survival benefit.

MUTYH association with esophageal adenocarcinoma in a Han Chinese population.

Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmental factors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in the pathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinese population. The objective of this study was to investigate this issue. A gene-based association study was conducted using three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463, rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results revealed that the genotype distribution of rs3219472 differed between the case and control groups (OR=1.66,95%CI=1.11-2.48, P=0.012 ), indicating that an association may exist between MUTYH and AE. These findings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population.