Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs.

Hormesis induced by low-dose ionizing radiation (LDIR) is often mirrored by its stimulation of cell proliferation. The mitogen-activated protein kina

Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. The aim of our study was to observe the efficiency and safety of the combined treatment of radiofrequency ablation (RFA) with cellular immunotherapy (CIT) for HCC patients. In our study, 62 patients with HCC who were treated with radical RFA were divided into two groups: RFA alone (32 patients) and RFA/CIT (30 patients). Autologous mononuclear cells were collected from the peripheral blood and separated by apheresis, and then induced into natural killer (NK) cells, γδT cells and cytokine‐induced killer (CIK) cells. These cells were identified by flow cytometry with their specific antibodies and then were infused intravenously to RFA/CIT patients for three or six courses. The tumor recurrent status of these patients was evaluated with computed tomography or magnetic resonance imaging every 3 months after RFA. Progression‐free survival (PFS), liver function, viral load and adverse effects were examined. The results implied that PFS was higher in RFA/CIT group than that in RFA group. In RFA/CIT group, six courses had better survival prognosis than three courses. Viral load of hepatitis C was decreased in two of three patients without antiviral therapy in RFA/CIT group, but was increased in RFA group. No significant adverse reaction was found in the patients with CIT. In summary, these preliminary results suggest that combination of sequential CIT with RFA for HCC patients was efficient and safe, and may be helpful in the prevention of the recurrence for the patients with HCC after RFA.

Malnutrition is a problem affecting tumor patients greatly. This study aims to investigate whether demographic characteristics are related to the malnutrition of cancer patients. Twenty-three thousand nine hundred and four (23,904) patients with 16 common malignant tumors were enrolled in the study. Patient Generated Subjective Global Assessment (PG-SGA) was used as a screening tool to assess the nutritional risk of patients and analysis of variance was used to compare PG-SGA scores of patients. Correlations between PG-SGA scores and demographic characteristics were evaluated by correlation analysis. We observed that 57.88% tumor patients had some degree of malnutrition (score ≥4) and only 20.61% were well-nourished (score 0–1). Screening scores were higher among older patients for most of the tumors. PG-SGA scores showed the significant difference between females and males in some tumors. In addition, the PG-SGA scores of some tumors were significantly different in various types of medical insurances, education levels, occupations, regions, and nationalities. Correlation analysis indicated the existence of associations between PG-SGA scores and demographic characteristics. Understanding the distribution of nutritional risk of tumor patients and the correlations between the PG-SGA scores and demographic characteristics could help identify subgroups who may benefit from targeted interventions to improve the effect of clinical treatment and the quality of life for oncology patients.

Low-dose bortezomib increases the expression of NKG2D and DNAM-1 ligands and enhances induced NK and γδ T cell-mediated lysis in multiple myeloma Low-dose bortezomib increases the expression of NKG2D and DNAM-1 ligands and enhances induced NK and γδ T cell-mediated lysis in multiple myeloma

The CRISPR-associated Cas9 system can modulate disease-causing alleles both in vivo and ex vivo, raising the possibility of therapeutic genome editing. In addition to gene targeting, epigenetic modulation by the catalytically inactive dCas9 may also be a potential form of cancer therapy. Granulin (GRN), a potent pluripotent mitogen and growth factor that promotes cancer progression by maintaining self-renewal of hepatic stem cancer cells, is upregulated in hepatoma tissues and is associated with decreased tumor survival in patients with hepatoma. We synthesized a group of dCas9 epi-suppressors to target GRN by tethering the C terminus of dCas9 with three epigenetic suppressor genes: DNMT3a (DNA methyltransferase), EZH2 (histone 3 lysine 27 methyltransferase), and KRAB (the Krüppel-associated box transcriptional repression domain). In conjunction with guide RNAs (gRNAs), the dCas9 epi-suppressors caused significant decreases in GRN mRNA abundance in Hep3B hepatoma cells. These dCas9 epi-suppressors initiated de novo CpG DNA methylation in the GRN promoter, and they produced histone codes that favor gene suppression, including decreased H3K4 methylation, increased H3K9 methylation, and enhanced HP1a binding. Epigenetic knockdown of GRN led to the inhibition of cell proliferation, decreased tumor sphere formation, and reduced cell invasion. These changes were achieved at least partially through the MMP/TIMP pathway. This study thus demonstrates the potential utility of using dCas9 epi-suppressors in the development of epigenetic targeting against tumors.