Advanced nanotechnology: An arsenal to enhance immunotherapy in fighting cancer.

Cancer remains a major disease process with considerable healthcare and socioeconomic impact worldwide. Unfortunately, standard treatments using chemotherapy often do not effectively control cancer progression or prevent relapse. Over the past decades, the development of targeted therapies has substantially improved outcomes. Recently, immunotherapy has emerged as a new alternative for more effective cancer treatment and may even bring hope of a cure. Cancer immunotherapy functions by reinforcing a patient's immune defense system to fight the disease. Clinically, promising immunotherapy approaches have, however, been limited by unpredictable response and strong adverse effects. A drug delivery system (DDS) that effectively targets tumor and reduces drug exposure to normal tissue would mitigate these limitations. In this regard, nanotechnology has been intensively studied as a DDS for targeting tumors with various oncologic drugs. Several have resulted in improved treatment and outcome. Research has shown that nanoparticle drug delivery technologies can also be applied to immunotherapy. In this review, the current state of nanotechnology will be discussed. Because most cancer immunotherapies approved in recent years are protein drugs, this article will focus on a micellar nanocomplex (MNC) technology, a DDS platform especially suited for targeted delivery of these therapeutics to solid tumors.

Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis.

DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway.

Drugs for plant chromosome and chromatin research.

Eukaryotic genomes are organized into chromosomes. Genetic information regularly becomes damaged and requires repair in order to ensure genome stability. Furthermore, expression of individual genetic elements on the chromosome(s) is controlled by several factors, including chromatin. Understanding the functions of chromatin may provide efficient tools for regulating gene expression. There has been great progress in understanding genome control using genetic mutations, but the use of mutants is sometimes not possible or may require additional interference with DNA or chromatin structure using specific treatments in order to obtain phenotypes. Therefore, chemical genetics has become an integral part of plant genome research. Here, we summarize information on the most commonly used drugs for chromatin and DNA damage repair studies, with the aim of simplifying the choice of drug and the estimation of possible side effects for current and future research.

Effect of potassium deficiency on antioxidant status and cadmium toxicity in rice seedlings.

BACKGROUND: Cadmium (Cd) is one of the most toxic heavy metals and inhibits physiological processes of plants. Potassium (K) is an essential macronutrient in plants. K deficiency and Cd stress represent two different abiotic stress conditions that occur in the field simultaneously. In this study, effects of K deficiency on antioxidant status and Cd toxicity in rice seedlings were investigated. RESULTS: K deficiency significantly decreased K concentration in shoots and roots. However, fresh weight and dry weight of rice seedlings were not affected by K deficiency. The activities of antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, glutathione reductase, and catalase) in K-deficient leaves were higher than respective control leaves. However, K deficiency had no effect on the content of antioxidants (ascorbate and glutathione). Cd toxicity was judged by the decrease in biomass production, chlorosis, and induction of oxidative stress. Based on these criteria, we demonstrated that K deficiency protected rice seedling from Cd stress. Moreover, chlorophyll concentration was higher in K-deficient shoots and roots than their respective control shoots and roots. CONCLUSIONS: Our results indicated that K deficiency protects rice seedlings from Cd toxicity. This protective effect of K deficiency is mainly due to enhanced antioxidant enzyme activities but not inhibition of Cd uptake.

Deep neck infection in children.

OBJECTIVES: Deep neck infection is a potentially life-threatening disease and rarely seen in children. Because of the obscure complaints and symptoms, the diagnosis of deep neck infection may be delayed, which may result in inappropriate treatment. This retrospective study was aimed at analyzing the occurrence of complications, diagnostic methods and proper managements of deep neck infection in children. METHODS: A retrospective study was performed on 30 children with deep neck infection treated from October 1999 through October 2003. The etiology, clinical symptoms, laboratory examination, radiological examination, bacteriology, and treatments were retrospectively analyzed. RESULTS: The most common predisposing factors were tonsillitis and upper respiratory tract infection. The most common symptoms were fever (93.3%) and painful swelling of the neck (70.0%). Both peritonsillar (24.3%) and parapharyngeal space infections (24.3%) were the most common, followed by submandibular space infections (18.9%). The most common pathogens isolated were Staphylococcus aureus (27.3%) and viridans streptococci (22.7%). The mean duration of hospitalization was 7.9 days, with a range from 2 to 18 days. Complications occurred in 2 patients, including recurrence and pulmonary edema. CONCLUSIONS: Deep neck infection should be suspected in a child who presents with fever and painful swelling of the neck. Staphylococcus aureus and viridans streptococci were the most common pathogens. Computed tomography scan should be performed in time and infections in peritonsillar and ,parapharyngeal spaces were the most common.