Role of ER Stress Response in Photodynamic Therapy: ROS Generated in Different Subcellular Compartments Trigger Diverse Cell Death Pathways

We have analyzed the molecular mechanisms of photoinduced cell death using porphyrins with similar structure differing only in the position of the ethylene glycol (EG) chain on the phenyl ring. Meta- and para-positioned EG chains targeted porphyrins to different subcellular compartments. After photoactivation, both types of derivatives induced death of tumor cells via reactive oxygen species (ROS). Para derivatives pTPP(EG)4 and pTPPF(EG)4 primarily accumulated in lysosomes activated the p38 MAP kinase cascade, which in turn induced the mitochondrial apoptotic pathway. In contrast, meta porphyrin derivative mTPP(EG)4 localized in the endoplasmic reticulum (ER) induced dramatic changes in Ca2+ homeostasis manifested by Ca2+ rise in the cytoplasm, activation of calpains and stress caspase-12 or caspase-4. ER stress developed into unfolded protein response. Immediately after irradiation the PERK pathway was activated through phosphorylation of PERK, eIF2α and induction of transcription factors ATF4 and CHOP, which regulate stress response genes. PERK knockdown and PERK deficiency protected cells against mTPP(EG)4-mediated apoptosis, confirming the causative role of the PERK pathway

КЛИНИЧЕСКИЙ ОПЫТ ПРИМЕНЕНИЯ ВНУТРИПРОСВЕТНОЙ БРАХИТЕРАПИИ НА АППАРАТЕ «MULTISOURCE» У БОЛЬНЫХ РАКОМ ЛЕГКИХ И ТРАХЕИ

Treatment of primary and recurrent cancer of the trachea and main bronchi is a complex clinical problem. The article presents own experience of contact intraluminal radiation therapy in patients of this group. Efficacy and toxicity of this treatment was evaluated.Лечение первичного и рецидивного рака трахеи и главных бронхов является сложной клинической задачей. В статье представлен собственный опыт применения внутрипросветной контактной лучевой терапии улиц данной группы. Дана оценка эффективности и токсичности данного вида лечения