Immunotherapy of malignant tumor is a verified and crucial anti-tumor strategy to help patients with cancer for prolonging prognostic survival. It is a novel anticancer tactics that activates the immune system to discern and damage cancer cells, thereby prevent them from proliferating. However, immunotherapy still faces many challenges in view of clinical efficacy and safety issues. Various nanomaterials, especially gold nanoparticles (AuNPs), have been developed not only for anticancer treatment but also for delivering antitumor drugs or combining other treatment strategies. Recently, some studies have focused on AuNPs for enhancing cancer immunotherapy. In this review, we summarized how AuNPs applicated as immune agents, drug carriers or combinations with other immunotherapies for anticancer treatment. AuNPs can not only act as immune regulators but also deliver immune drugs for cancer. Therefore, AuNPs are candidates for enhancing the efficiency and safety of cancer immunotherapy.

In this study, BRL 3A cells were treated with different Cd concentrations (0, 10, 20, and 40 μmol/L) for 12 h and preincubated with or without N-acetyl-L-cysteine (NAC) (2 mmol/L) for 30 min, and cells were treated with Cd (0 and 20 μmol/L), pretreated with p38 inhibitor (SB203580), JNK (c-Jun NH2-terminal kinases) inhibitor (SP600125), and extracellular signal-regulated kinase (ERK) inhibitor (U0126) for 30 min, and then treated with 20 μmol/L Cd for 12 h. Cd decreased cell viability, SOD, and GSH-Px activity in a concentration-dependent manner. Increased MDA level, ROS generation, nuclear condensation, shrinkage, and fragmentation in cell morphology were inhibited by NAC. Cd-induced apoptosis was attenuated by pretreatment with SB203580, SP600125, and U0126. The results of western blot showed that NAC preincubation affected Cd-activated MAPK pathways, p38 and ERK phosphorylation. Cd treatment elevated the mRNA levels of Bax and decreased the mRNA levels of Bcl-2, respectively. The same effect was found in their protein expression levels. These results suggest that oxidative stress and MAPK pathways participate in Cd-induced apoptosis and that the balance between pro- and antiapoptotic genes (Bax and Bcl-2) is important in Cd-induced apoptosis.

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Elf5 expression is inversely correlated with EMT. Elf5 inhibits TGF-β-driven EMT via repressing SMAD3 phosphorylation in prostate cancer cells. In addition, Elf5 can be used as a biomarker of metastasis-free survival in patients with TGF-β-positive prostate cancer.

Oesophageal cancer is the sixth leading cause of cancer-related death and the eighth most common cancer around the world. An estimated 572 034 new oesophageal cancer cases and 508 585 deaths occurred in 2018 worldwide. [1] There are different types of treatments for oesophageal cancer therapy, such as surgery, radiation therapy, chemotherapy chemoradiation, laser, and electric coagulation. [2] Although oesophageal cancer can be treated by a variety of different ways of treatment, it is still rare for patients to be cured and the patient's quality of life is very poor because of cachexia and dysphagia. [3] The prognosis for oesophageal cancer is dismal in China; the relative survival rates are about 20%. [4] As >50% of patients with oesophageal cancer present at an incurable stage and prolonged progression-free survival is possible only in a few, so palliation rather than cure is the treatment goal for the majority of patients. [5] Therefore, it is valuable and urgently needed to design and develop a new treatment with higher efficacy and better quality of life for patients with oesophageal cancer.Palliative care is the placement of a stent at the site of an oesophageal lesion, commonly used to relieve dysphagia and improve the patient's quality of life. [6] Stenting can quickly and effectively relieve dysphagia, but long-term recurrent dysphagia can lead to future complications. Local administration of drug-eluting stents (DESs) for the treatment of oesophageal neoplasm has attracted plenty of scholars' interests. [7] Compared to intravenous administration, the drug concentration is higher and side effects are much lower. The advantages of immediate relief of oesophageal dysphagia and the long-term benefits of continued and prolonged in situ drug treatment make DESs promising. However, the first clinical trial of paclitaxel-eluting nonvascular DES performed at Guy's Hospital in London showed no clinical effectiveness. [8] This lack of success may be caused by the drop-dipping method for loading paclitaxel, which failed to be released in the long term. [9] As one of the widely-used carriers for controlled release, electrospinning fibers have shown many outstanding properties, such as a large surface area and superior flexible and tensile performance. [10] Drug-eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen-producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO 2 with the endogenous H 2 O 2 within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional ...

Malignant bone tumor osteosarcoma (OS) displays high metastasis incidence and poor prognosis. Its stem cell properties could serve to explain tumor recurrence and resistance to conventional treatments. In this study, we identified UEV1A as a novel suppressor of OS. Elevated UEV1A diminishes stem cell properties of OS cells and drives them to terminal differentiation. Importantly, UEV1A-overexpressed OS cells delay proliferation and are more sensitive to chemotherapeutic agents than control cells. Uev1A appears to be involved in the BMP signaling pathway in which it collaborates with a ubiquitin E3 ligase Smurf1 to promote Smad1 degradation in a Ubc13-independent manner. Indeed, Smad1 is identified as a dominant downstream effector of Uev1A, which unravels the mechanism underlying Uev1A-orchestrated tumor suppression in OS. The above findings identify UEV1A as a potential OS tumor suppression gene, and shed lights to future OS diagnosis and treatment.

Background Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. Results The particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. Conclusions This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

Previous studies have reported that the Ras homolog family member A (RhoA)/myocardin-related transcription factor A (MRTF-A) nuclear translocation axis positively regulates fibrogenesis induced by mechanical forces in various organ systems. The aim of the present study was to determine whether this signaling pathway was involved in the pathogenesis of nucleus pulposus (NP) fibrosis induced by mechanical overload during the progression of intervertebral disc degeneration (IVDD) and to confirm the alleviating effect of an MRTF-A inhibitor in the treatment of IVdd. NP cells (NPcs) were cultured on substrates of different stiffness (2.9 and 41.7 KPa), which mimicked normal and overloaded microenvironments, and were treated with an inhibitor of MRTF-A nuclear import, ccG-1423. In addition, bipedal rats were established by clipping the forelimbs of rats at 1 month and gradually elevating the feeding trough, and in order to establish a long-term overload-induced model of IVdd, and their intervertebral discs were injected with ccG-1423 in situ. cell viability was determined by cell counting Kit-8 assay, and protein expression was determined by western blotting, immunofluorescence and immunohistochemical staining. The results demonstrated that the viability of NPcs was not affected by the application of force or the inhibitor. In NPcs cultured on stiff matrices, MRTF-A was mostly localized in the nucleus, and the expression levels of fibrotic proteins, including type I collagen, connective tissue growth factor and α-smooth muscle cell actin, were upregulated compared with those in NPcs cultured on soft matrices. The levels of these proteins were reduced by ccG-1423 treatment. In rats, 6 months of upright posture activated MRTF-A nuclear-cytoplasmic trafficking and fibrogenesis in the NP and induced IVdd; these effects were alleviated by ccG-1423 treatment. In conclusion, the results of the present study demonstrated that the RhoA/MRTF-A translocation pathway may promote mechanical overload-induced fibrogenic activity in NP tissue and partially elucidated the molecular mechanisms underlying the occurrence of IVdd.