Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment.

Aim: The central CO chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO chemosensitivity; its ablation or inhibition attenuates CO chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders.

Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma.

Background: The attenuated, genetically engineered vaccinia virus has been shown to be a promising oncolytic virus for the treatment of patients with solid tumors, through both direct cytotoxic and immune-activating effects. Whereas systemically administered oncolytic viruses can be neutralized by pre-existing antibodies, locoregionally administered viruses can infect tumor cells and generate immune responses. We conducted a phase I clinical trial to investigate the safety, feasibility and immune activating effects of intrapleural administration of oncolytic vaccinia virus (NCT01766739).

Next-generation immunotherapy for solid tumors: combination immunotherapy with crosstalk blockade of TGFβ and PD-1/PD-L1.

Introduction: In solid tumor immunotherapy, less than 20% of patients respond to anti-programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) agents. The role of transforming growth factor β (TGFβ) in diverse immunity is well-established; however, systemic blockade of TGFβ is associated with toxicity. Accumulating evidence suggests the role of crosstalk between TGFβ and PD-1/PD-L1 pathways.

Etonogestrel Administration Reduces the Expression of PHOX2B and Its Target Genes in the Solitary Tract Nucleus.

Heterozygous mutations of the transcription factor are responsible for Congenital Central Hypoventilation Syndrome, a neurological disorder characterized by inadequate respiratory response to hypercapnia and life-threatening hypoventilation during sleep. Although no cure is currently available, it was suggested that a potent progestin drug provides partial recovery of chemoreflex response. Previous in vitro data show a direct molecular link between progestins and PHOX2B expression.

Expiratory activity during sleep in children.

Sleep irregularities and respiratory events (apnea, O desaturation or a combination thereof) are often present in the infant population. While inspiration is the main active process in the act of breathing, expiration is generally thought to occur passively. Although commonly considered as quiet during sleep, expiratory abdominal muscles have been proposed to be recruited to promote ventilation, facilitate gas exchange, and reduce the work of breathing during conditions of increased respiratory drive, exercise, or airway obstruction.

Imaging CAR T-cell kinetics in solid tumors: Translational implications.

Success in solid tumor chimeric antigen receptor (CAR) T-cell therapy requires overcoming several barriers, including lung sequestration, inefficient accumulation within the tumor, and target-antigen heterogeneity. Understanding CAR T-cell kinetics can assist in the interpretation of therapy response and limitations and thereby facilitate developing successful strategies to treat solid tumors. As T-cell therapy response varies across metastatic sites, the assessment of CAR T-cell kinetics by peripheral blood analysis or a single-site tumor biopsy is inadequate for interpretation of therapy response.

Breathing During Sleep in the Postnatal Period of Rats: The Contribution of Active Expiration.

Breathing is most vulnerable to apneas and other disturbances during sleep in both humans and rodents, especially in the newborn period. We recently demonstrated in adult rats that, in contrast to the atonia typical of skeletal muscles during rapid eye movement sleep, the normally passive expiratory muscles become active, and their activity is associated with stabilization of breathing and increased ventilation. In this study, we investigated the relationship between respiration and expiratory muscle recruitment across sleep states during the first 2 weeks of rat postnatal development.