27 research outputs found
Endobronchial Lipomas: Rare Benign Lung Tumors, Two Case Reports
Abstract:Endobronchial lipoma is a rare benign lung tumor. Here we present two cases. One case is the first report of the association of and endobronchial lipoma with a hilar lipoma. We discuss the epidemiology, difficulties in establishing the diagnosis, and the management of this rare condition
Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors
Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)
yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR
mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs.
Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise
from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal\u2013epithelial
transition factor (MET) amplification, epithelial\u2013mesenchymal transformation, phenotypic change from
NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic
strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of
multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being
investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib
and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance
(T790M) mutations, are currently under clinical development. Other therapeutic strategies include
inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies
against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor
regulation.
Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the
importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed
crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes
in NSCLC
Role of tachykinins in asthma
The sensory neuropeptides substance P (SP) and neurokinin A (NKA) are localized to sensory airway nerves, from which they can be released by a variety of stimuli, including allergen, ozone, or inflammatory mediators. Sensory nerves containing these peptides are relatively scarce in human airways, but it is becoming increasingly evident that inflammatory cells such as eosinophils, macrophages, lymphocytes, and dendritic cells can produce the tachykinins SP and NKA. Moreover, immune stimuli can boost the production and secretion of SP and NKA. SP and NKA have potent effects on bronchomotor tone, airway secretions, and bronchial circulation (vasodilation and microvascular leakage) and on inflammatory and immune cells. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and angiotensin-converting enzyme. The airway effects of the tachykinins are largely mediated by tachykinin NK1 and NK2 receptors. Tachykinins contract smooth muscle mainly by interaction with NK2 receptors, while the vascular and proinflammatory effects are mediated by the NK1 receptor. In view of their potent effects on the airways, tachykinins have been put forward as possible mediators of asthma, and tachykinin receptor antagonists are a potential new class of antiasthmatic medication