Effect of Combined PD-1 and IL-6 Blockade on K-ras Mutant Lung Cancer

https://openworks.mdanderson.org/sumexp21/1212/thumbnail.jp

Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death in the world by 2020. It is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases, most commonly cigarette smoke. Among smokers with COPD, even following withdrawal of cigarette smoke, inflammation persists and lung function continues to deteriorate. One possible explanation is that bacterial colonization of smoke-damaged airways, most commonly with nontypeable Haemophilus influenzae (NTHi), perpetuates airway injury and inflammation. Furthermore, COPD has also been identified as an independent risk factor for lung cancer irrespective of concomitant cigarette smoke exposure. In this article, we review the role of NTHi in airway inflammation that may lead to COPD progression and lung cancer promotion

Tumor Cell Specific Function of IL-1 Signaling in the Pathogenesis of K-ras Mutant Lung Cancer

Department of Pulmonary Medicinehttps://openworks.mdanderson.org/sumexp22/1113/thumbnail.jp

Enhancement of lung tumorigenesis in a Gprc5a Knockout mouse by chronic extrinsic airway inflammation

<p>Abstract</p> <p>Background</p> <p>Although cigarette smoking is the principal cause of lung carcinogenesis, chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, has been identified as an independent risk factor for lung cancer. Bacterial colonization, particularly with non-typeable <it>Haemophilus influenzae </it>(NTHi), has been implicated as a cause of airway inflammation in COPD besides cigarette smoke. Accordingly, we hypothesized that lung cancer promotion may occur in a chronic inflammatory environment in the absence of concurrent carcinogen exposure.</p> <p>Results</p> <p>Herein, we investigated the effects of bacterial-induced COPD-like inflammation and tobacco carcinogen-enhanced tumorigenesis/inflammation in the retinoic acid inducible G protein coupled receptor knock out mouse model (Gprc5a-/- mouse) characterized by late-onset, low multiplicity tumor formation. Three-month-old Gprc5a-/- mice received 4 intraperitoneal injections of the tobacco-specific carcinogen, NNK, followed by weekly exposure to aerosolized NTHi lysate for 6 months. The numbers of inflammatory cells in the lungs and levels of several inflammatory mediators were increased in Gprc5a-/- mice treated with NTHi alone, and even more so in mice pretreated with NNK followed by NTHi. The incidence of spontaneous lung lesions in the Gprc5a-/- mice was low, but NTHi exposure led to enhanced development of hyperplastic lesions. Gprc5a-/- mice exposed to NNK alone developed multiple lung tumors, while NTHi exposure increased the number of hyperplastic foci 6-fold and the tumor multiplicity 2-fold. This was associated with increased microvessel density and HIF-1α expression.</p> <p>Conclusion</p> <p>We conclude that chronic extrinsic lung inflammation induced by bacteria alone or in combination with NNK enhances lung tumorigenesis in Gprc5a-/- mice.</p

COPD-like Inflammation Induces Neutrophil Invasion and NETosis via the C5a Pathway

https://openworks.mdanderson.org/sumexp22/1127/thumbnail.jp

Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease:Role of Cigarette Smoke Exposure

The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium

Effect of Combined PD-1 and STAT3 Pathway Blockade Treatment on K-ras Mutant Lung Cancer

https://openworks.mdanderson.org/sumexp21/1175/thumbnail.jp

Effect of Cataract Type and Severity on Visual Acuity and Contrast Sensitivity

Purpose: To determine the effect of cataract type and severity in eyes with pure types of age-related lens opacities on visual acuity (VA) and contrast sensitivity in the presence and absence of glare conditions. Methods: Sixty patients with senile cataracts aged 40 years or older with no other ocular pathologies were evaluated for VA and contrast sensitivity with and without glare. Lens opacities were classified according to the Lens Opacities Classification System (LOCS) III. VA was measured using the Snellen chart. Contrast sensitivity was measured with the Vector Vision CSV-1000E chart in the presence and absence of glare by calculating the area under log contrast sensitivity (log CS) function (AULCSF). Results: Cataracts were posterior subcapsular in 26 eyes, cortical in 19 eyes and nuclear in 15 eyes. VA significantly decreased with increasing cataract severity and there was significant loss of contrast sensitivity at all spatial frequencies with increasing cataract severity. AULCSF significantly decreased with increasing cataract severity in the presence and absence of glare conditions. Contrast sensitivity was significantly reduced at high spatial frequency (18 cpd) in cortical cataracts in the presence of glare in day light and at low spatial frequency (3 cpd) in night light. Conclusion: Increased cataract severity is strongly associated with a decrease in both VA and AULCSF. Contrast sensitivity scores may offer additional information over standard VA tests in patients with early age-related cataracts

Elucidating the Mechanistic Role of IL-1R in Late-Stage K-ras Mutant Lung Cancer: Uncovering Therapeutic Potential

https://openworks.mdanderson.org/sumexp23/1088/thumbnail.jp

Comparative Effects of Combustible Cigarette versus Electronic Cigarette Exposures on K-ras Mutant Lung Cancer Promotion

https://openworks.mdanderson.org/sumexp23/1057/thumbnail.jp