Клинический случай эффективного лечения пневмонии, вызванной полирезистентными штаммами, с использованием ингаляционного колистиметата натрия

Patients with nosocomial infections stay in the hospital 2–3 times longer than patients without signs of infection.It results in 3–4-fold increase of costs and 5–7-fold elevated risk of death. The choice of rational regimes of antimicrobial therapy in such cases is very difficult.The objective: to demonstrate the efficacy of a combination of prolonged intravenous infusion of meropenem and inhaled sodium colistimethate in the treatment of the patient with the pulmonary infection caused by Kl. pneumoniae and Ac. baumanii, which were resistant to a wide range of antibiotics.Пациенты с внутрибольничными инфекциями находятся в стационаре в 2‒3 раза дольше, чем пациенты без признаков инфекции. Это является причиной повышения стоимости лечения в 3‒4 раза, а риска летального исхода – в 5‒7 раз. Подбор рациональных схем антимикробной терапии в таких случаях весьма затруднен.Цель демонстрации: показать эффективность комбинации пролонгированной внутривенной инфузии меропенема и ингаляционного введения колистиметата натрия при лечении пациента с легочной инфекцией, вызванной Kl. pneumoniae и Ac. baumanii, резистентных к широкому спектру антибиотиков

Far-red fluorescent murine glioma model for accurate assessment of brain tumor progression

Simple Summary The creation of stable fluorescent glioma cell lines opens prospects for the detailed characterization of the molecular mechanisms of glioma origin and pathogenesis, and the development of breakthrough therapeutic approaches to achieve maximum glioma destruction and minimize the risk of future metastases. Herein, we generated and characterized a novel fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein, TurboFP635 (Katushka). Using the orthotopic mouse glioma model and epi-fluorescence imaging, we demonstrate the detection of fluorescent glioma GL261-kat cells in mice, and observe an increase in the fluorescence signal during glioma progression, which is accompanied by a gradual development of neurological deficit and behavioral alterations in mice. We show that GL261-kat cells can be a useful tool for studying glioma biology, because they can accurately and non-invasively monitor the characteristics of glioma growth in brain tissue in orthotopic mouse models. Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma initialization and pathogenesis, as well as for the development of new anti-cancer strategies. Herein, a new fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein (TurboFP635; Katushka) was generated and characterized, and then validated in a mouse orthotopic glioma model. By using epi-fluorescence imaging, we detect the fluorescent glioma GL261-kat cells in mice starting from day 14 after the inoculation of glioma cells, and the fluorescence signal intensity increases as the glioma progresses. Tumor growth is confirmed by magnetic resonance imaging and histology. A gradual development of neurological deficit and behavioral alterations in mice is observed during glioma progression. In conclusion, our results demonstrate the significance and feasibility of using the novel glioma GL261-kat cell line as a model of glioma biology, which can be used to study the initialization of glioma and monitor its growth by lifetime non-invasive tracking of glioma cells, with the prospect of monitoring the response to anti-cancer therapy

Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine

Background: Anti-cancer therapy is more successful when it can also induce an immunogenic form of cancer cell death (ICD). Therefore, when developing new treatment strategies, it is extremely important to choose methods that induce ICD and thereby activate anti-Tumor immune response leading to the most effective destruction of tumor cells. The aim of this work was to analyze whether the clinically widely used photosensitizers, photosens (PS) and photodithazine (PD), can induce ICD when used in photodynamic therapy (PDT). Methods: Cell death in murine glioma GL261 or fibrosarcoma MCA205 cells was induced by PS-or PD-PDT and cell death was analyzed by MTT or flow cytometry. Intracellular distribution of PS and PD was studied by using the laser scanning microscope. Calreticulin exposure and HMGB1 and ATP release were detected by flow cytometry, ELISA and luminescence assay, respectively. Immunogenicity in vitro was analyzed by co-culturing of dying cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and maturation (CD11c+CD86+, CD11c+CD40+) of BMDCs and production of IL-6 in the supernatant were measured. In vivo immunogenicity was analyzed in mouse tumor prophylactic vaccination model. Results: We determined the optimal concentrations of the photosensitizers and found that at a light dose of 20 J/cm2 (\u3bbex 615-635 nm) both PS and PD efficiently induced cell death in glioma GL261 and fibrosarcoma MCA205 cells. We demonstrate that PS localized predominantly in the lysosomes and that the cell death induced by PS-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) and by ferrostatin-1 and DFO (ferroptosis inhibitors), but not by the necroptosis inhibitor necrostatin-1 s. By contrast, PD accumulated in the endoplasmic reticulum and Golgi apparatus, and the cell death induced by PD-PDT was inhibited only by z-VAD-fmk. Dying cancer cells induced by PS-PDT or PD-PDT emit calreticulin, HMGB1 and ATP and they were efficiently engulfed by BMDCs, which then matured, became activated and produced IL-6. Using dying cancer cells induced by PS-PDT or PD-PDT, we demonstrate the efficient vaccination potential of ICD in vivo. Conclusions: Altogether, these results identify PS and PD as novel ICD inducers that could be effectively combined with PDT in cancer therapy