11 research outputs found
Small Interfering RNA Targeted to IGF-IR Delays Tumor Growth and Induces Proinflammatory Cytokines in a Mouse Breast Cancer Model
Insulin-like growth factor I (IGF-I) and its type I receptor (IGF-IR) play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2′-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD). Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2′-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines
Rosacea
Rosacea is an inflammatory, chronic-recurring dermatitis of the face. It is common in adult females with I\u2013II phototype. It is characterized clinically by the presence of one or more of the following features: flushing, erythema, telangiectasia, papules, pustules, and nodules. Ocular involvement can also occur. Etiopathogenetic role of Demodex folliculorum and Helicobacter pylori has not been confirmed. The National Rosacea Society Expert Committee divided the disease into four clinical varieties (rosacea characterized by flushing and erythema, with or without telangiectasia, papulopustular rosacea, phymatous rosacea, and ocular rosacea). According to Cochrane, topical metronidazole and azelaic acid as well as oral tetracyclines and metronidazole are effective in the treatment of rosacea. Literature data about the use of peelings are very poor. In some patients, salicylic acid, azelaic acid, and mandelic acid were used
Production of ethanol from lignocellulosic materials using thermophilic bacteria: Critical evaluation of potential and review
Perception in attention deficit hyperactivity disorder
A large body of research demonstrated that individuals with attention deficit hyperactivity disorder (ADHD) suffer from various neuropsychological deficits. In contrast, less is known and only divergent evidence exists on perceptual functions of individuals with ADHD. This is problematic as neuropsychological and perceptual functions are closely interrelated and are often difficult to disentangle in behavioral assessments. This study presents the conduct and results of a systematic literature review on perceptual functions in children and adults with ADHD. This review considers studies using psychophysical methods (objective measurements) and self- and informant reports (subjective measurements). Results indicate that individuals with ADHD have altered perceptual functions in various domains as compared to typically developing individuals. Increased perceptual functions in individuals with ADHD were found with regard to olfactory detection thresholds, whereas reduced perceptual functions were evident for aspects of visual and speech perception. Moreover, individuals with ADHD were found to experience discomfort to sensory stimuli at a lower level than typically developing individuals. Alterations of perceptual functions in individuals with ADHD were shown to be moderated by various factors, such as pharmacological treatment, cognitive functions, and symptom severity. We conclude by giving implications for daily life functioning and clinical practice