Self-assembled iRGD-R7-LAHP-M nanoparticle induced sufficient singlet oxygen and enhanced tumor penetration immunological therapy.

The generation of singlet oxygen (1O2) using photodynamic therapy (PDT) is limited by the hypoxia of the tumor microenvironment and the depth of external light penetration because it depends on the precise cooperation between the photosensitizers, oxygen, and light. Herein, we report a self-sufficient 1O2 nanoreactor with enhanced penetration into deep tumors for cancer therapy. Linoleic acid hydroperoxide (LAHP) is coordinated with transition metal ions (Cu2+/Fe3+) to prepare linoleic acid hydroperoxide metal complex nanoparticles (LAHP-M NPs). iRGD combined with R7 decoration endows the nanoparticles with tumor targeting and penetration ability. We show that the polypeptide carries the nanoparticles into deep tumors, and thereafter the nanoparticles are disassembled into LAHP and catalytical metal ions to produce 1O2 based on the Russell mechanism under the stimulation of acidic pH. The elevated ROS induces necrotic cell death in vitro and in vivo, and further causes immunogenic cell death (ICD). This study demonstrates the effectiveness of exploiting biochemical reactions as a spatial-temporal strategy to overcome the current limitations of photodynamic therapy.

Silencing of perilipin by short hairpin RNA inhibits proliferation and induces apoptosis in liposarcoma cells.

Previous studies have identified that perilipin-1 (PLIN1) is a highly specific marker for liposarcoma. However, its functions have yet to be fully elucidated. The aim of the present study was to investigate the potential role of PLIN1 in the proliferation, migration and apoptosis of liposarcoma cells. Short hairpin RNA was designed to inhibit PLIN1 levels. Cell proliferation was monitored by Cell Counting Kit­8 assay and cell migration determined by wound healing assay. Flow cytometry was performed to assess the cell cycle distributions and apoptosis in liposarcoma cells. The results demonstrated that the expression of PLIN1 was significantly upregulated in liposarcoma tumor tissues compared with normal adipose tissues. Silencing of PLIN1 by short hairpin RNA significantly inhibited proliferation and migration and induced G1 phase cell cycle arrest and apoptosis in liposarcoma cell lines. It was identified that PLIN1 serves a crucial role in the pathogenesis and progression of liposarcoma and may be a potential therapeutic target for its clinical management.

Trastuzumab modified silica nanoparticles loaded with doxorubicin for targeted and synergic therapy of breast cancer.

Untargeted delivery as well as low efficacy are two main obstacles for effective breast cancer therapy. Here in this study, we surface modified silica nanoparticles (SLN) with Trastuzumab (Tra) to construct a tumor-targeting carrier (Tra-SLN) for specific drug delivery to human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. In addition, Tra-SLN could also loaded with broad-spectrum anticancer drug doxorubicin (DOX) to finally construct a drug delivery system (DDS) capable of co-delivering Tra and DOX (Tra-SLN/DOX). Our results demonstrated that the as-prepared Tra-SLN/DOX was nanoscale particles with spheroid appearance which showed preferable stability in physiological environments. In addition, the Tra-SLN/DOX could specifically target to HER2 overexpressed MCF-7 cells. Both in vitro and in vivo experiments revealed that the Tra-SLN/DOX exerted enhanced anticancer efficacy when compared with Tra or DOX alone. It was suggested that Tra-SLN/DOX might be a promising platform for enhanced therapy of breast cancer.

Positive Effect of Higher Adult Body Mass Index on Overall Survival of Digestive System Cancers Except Pancreatic Cancer: A Systematic Review and Meta-Analysis.

High body mass index (BMI) has been inconsistently associated with overall survival (OS) of digestive system cancers (DSCs). This meta-analysis was conducted to investigate whether high BMI was associated with DSCs prognosis. 34 studies were accepted, with a total of 23,946 DSC cases. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for OS in BMI categories from individual studies were extracted and pooled by random-effect model. The overall HR of DSCs except pancreatic cancer for OS of adult overweight cases was 0.76 (95% CI = 0.67-0.85). DSC individuals except pancreatic cancer with adult obesity were at decreased risk for OS (HR = 0.85, 95% CI = 0.72-0.98). Among DSC patients except pancreatic cancer, the overall HR for the highest versus the lowest BMI category was 0.82 (95% CI = 0.71-0.92). Additionally, comparing the highest and lowest BMI categories, the combined HR of pancreatic cancer was 1.22 (95% CI = 1.01-1.43). Our meta-analysis suggested an increased OS among adult overweight and obese DSC survivors except pancreatic cancer. Overweight and obesity in adulthood may be important prognostic factors that indicate an increased survival from DSC patients except pancreatic cancer.

MicroRNA-30b targets CBX3 and regulates cell proliferation, apoptosis, and migration in esophageal squamous cell carcinoma via the JAK2/STAT3 signaling pathway.

The present study aimed to investigate whether miR-30b plays a pivotal role in the progression of esophageal squamous cell carcinoma (ESCC) as well as to elucidate its possible regulatory mechanism. The expression levels of miR-30b in the ESCC tissues and cells were determined. The TE-1 cells were transfected with the miR-30b mimic, the mimic control, the miR-30b inhibitor, the inhibitor control, the pCDNA3.1-Chromobox 3 (pCDNA3.1-CBX3) and/or the blank vector, while the TE-2 cells were transfected with the miR-30b mimic and/or the mimic control. Cell proliferation, cell apoptosis, and cell migration of the different transfected groups were evaluated. The luciferase reporter assay was performed to detect the relationship between miR-30b, and CBX3. Furthermore, the relationship between miR-30b, CBX3, and the JAK2/STAT3 signaling pathway was explored. Significant downregulation of miR-30b was observed in the ESCC tissues and cells, while CBX3 was upregulated in the ESCC tissues and cells. The inhibition of miR-30b promoted cell proliferation, inhibited cell apoptosis, and enhanced cell migration in ESCC, which was similar to the effects of CBX3 overexpression. In fact, CBX3 was confirmed to be a direct target of miR-30b. The overexpression of miR-30b decreased the expression levels of p-JAK2/JAK2 and p-STAT3/JAK3 significantly, which was obviously reversed after the simultaneous overexpression of CBX3. Our results revealed that the downregulation of miR-30b may increase cell proliferation, inhibit cell apoptosis, and promote cell migration in ESCC by targeting CBX3 and activating the JAK2/STAT3 signaling pathway. Thus, miR-30b may serve as a useful marker for predicting the progression of ESCC.