7-Azaindole-fused heterocycles with antitumor activity

A multipronged approach to unveil the emerging role of Hsp60 in chronic obstructive pulmonary disease

Inflammation is a major component of chronic obstructive pulmonary disease (COPD) and its cause and mechanisms are still incompletely understood. For example, the role of heat shock proteins (Hsps), many of which are molecular chaperones, has not been explored in detail in COPD, despite the fact that these molecules are known to participate in inflammation in other diseases. It has been shown that extracellular Hsps can signal certain types of T cells, macrophages, dendritic cells, and neutrophils and, thereby, elicit inflammation and immunity. However, these phenomena have not been investigated in COPD despite: a) the increasing awareness of Hsp participation in inflammation and immunity; …

Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD.

Background In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. Objectives To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Methods Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NA…

3-CHLOROETHYL-PYRROLO[2,1-D][1,2,3,5]TETRAZINES: SYNTHESIS AND ANTITUMOR ACTIVITY

PYRROLO[3,2-H]QUINAZOLINE AS PHOTOCHEMOTHERAPEUTIC AGENTS

Th17-related cytokine expression is increased in the bronchial mucosa of stable COPD patients

Background: There is an increased number of activated Tl lymphocytes in the bronchial mucosa of stable COPD patients but are absent studies on Th17 cells and their effector cytokines.Objectives: To investigate the expression of retinoic orphan receptor(ROR)C2, interleukin(IL)-17A,IL-17F,IL-21,IL-22 and IL-23 in bronchial biopsies from patients with stable COPD of different severity(stage 2 to 4)compared with age-matched control subject(smokers with normal lung function and lifelong non-smokers).Methods: The expression of RORC2,IL-17A,IL-17F,IL-21,IL-22 and IL-23 was measured in the bronchial mucosa using immunohistochemistry and/or real time quantitative polymerase chain reaction. Results: …

Condensed azaindole with antitumor activity

PYRROLO[3,4-H]QUINAZOLINES WITH ANTITUMOR ACTIVITY

Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD

Bruno Balbi,1 Claudia Sangiorgi,1 Isabella Gnemmi,1 Ilaria Ferrarotti,2 Davide Vallese,1 Elena Paracchini,1 Lorena Delle Donne,1 Luciano Corda,3 Paolo Baderna,4 Angelo Corsico,2 Mauro Carone,1 Paola Brun,5 Francesco Cappello,6,7 Fabio LM Ricciardolo,8 Paolo Ruggeri,9 Sharon Mumby,10 Ian M Adcock,10 Gaetano Caramori,9 Antonino Di Stefano11Istituti Clinici Scientifici Maugeri, IRCCS, Division of Pneumology and Laboratory of Cytoimmunopathology of the Heart and Lung, Veruno, Italy; 2Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy; 3Medicina Respiratoria, Seconda Medicina Interna, Spedali Civili, Brescia, Italy; 4Division of Pneumology, Aosta Hospital, Aos…

New topoisomerase I inhibitors with condensed-azaindole structure