In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway.

The disulfide isomerase ERp57, originally found in the endoplasmic reticulum, is located in multiple cellular compartments, participates in diverse cell functions and interacts with a huge network of binding partners. It was recently suggested as an attractive new target for cancer therapy due to its critical role in tumor cell proliferation. Since a major bottleneck in cancer treatment is the occurrence of hypoxic areas in solid tumors, the role of ERp57 in cell growth was tested under oxygen depletion in the colorectal cancer cell line HCT116.

Overcoming hypoxia-induced resistance of pancreatic and lung tumor cells by disrupting the PERK-NRF2-HIF-axis.

Hypoxia-induced resistance of tumor cells to therapeutic treatment is an unresolved limitation due to poor vascular accessibility and protective cell adaptations provided by a network, including PERK, NRF2, and HIF signaling. All three pathways have been shown to influence each other, but a detailed picture remains elusive. To explore this crosstalk in the context of tumor therapy, we generated human cancer cell lines of pancreatic and lung origin carrying an inducible shRNA against NRF2 and PERK.

Tumor cells rely on the thiol oxidoreductase PDI for PERK signaling in order to survive ER stress.

Upon ER stress cells activate the unfolded protein response through PERK, IRE1 and ATF6. Remarkable effort has been made to delineate the downstream signaling of these three ER stress sensors after activation, but upstream regulation at the ER luminal site still remains mostly undefined. Here we report that the thiol oxidoreductase PDI is mandatory for activation of the PERK pathway in HEK293T as well as in human pancreatic, lung and colon cancer cells.

Does improved postgraduate capacity shift the balance of power for nurse specialists in a low-income country: A mixed methods study.

Aim: To explore nurse specialists' experiences of change and influence on practice two years after graduating with a postgraduate degree.

Background: In the absence of further study opportunities for nurses in their own country, a master's degree was introduced to train the first group of nurse specialists in Mozambique.

Design: Within a hybrid evaluation framework an exploratory, sequential mixed methods design was followed.

Autophagy induced by ionizing radiation promotes cell death over survival in human colorectal cancer cells.

Autophagy is commonly described as a cell survival mechanism and has been implicated in chemo- and radioresistance of cancer cells. Whether ionizing radiation induced autophagy triggers tumor cell survival or cell death still remains unclear. In this study the autophagy related proteins Beclin1 and ATG7 were tested as potential targets to sensitize colorectal carcinoma cells to ionizing radiation under normoxic, hypoxic and starvation conditions.

PDI is an essential redox-sensitive activator of PERK during the unfolded protein response (UPR).

Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) that results in transient suppression of protein translation to allow recovery but leads to cell death when stress cannot be resolved. Central to initiation of the UPR is the activation of the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that the thiol oxidoreductase ERp57 and protein disulfide isomerase-A1 (PDI), which belong to the same family of luminal ER oxidoreductases, have strikingly opposing roles in the regulation of PERK function.

Impulse oscillometry is sensitive to bronchoconstriction after eucapnic voluntary hyperventilation or exercise.

Airway responses were compared following 6-minute eucapnic voluntary hyperventilation and 6-minute exercise challenges by examining resting and post-challenge impulse oscillometry and spirometry variables. Twenty-two physically active individuals with probable exercise-induced bronchoconstriction took part in this study. Impulse oscillometry and spirometry were performed at baseline and for 20 minutes post-challenge at 5-minute intervals.

Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise.

Study Objective: The efficacy of using impulse oscillometry (IOS) as an indirect measure of airflow obstruction compared to spirometry after exercise challenges in the evaluation of exercise-induced bronchoconstriction (EIB) has not been fully appreciated. The objective was to compare airway responses following room temperature and cold temperature exercise challenges, and to compare whether IOS variables relate to spirometry variables.

Design: Spirometry and IOS were performed at baseline and for 20 min after challenge at 5-min intervals.

Effects of cysteine donor supplementation on exercise-induced bronchoconstriction.

Purpose: Reactive oxygen/nitrogen species (ROS/RNS) in resident airway cells may be important in bronchoconstriction following exercise. Glutathione (GSH) is a major lung antioxidant and could influence pathological outcomes in individuals with exercise-induced bronchoconstriction (EIB). This study examined the effects of supplementation with undenatured whey protein (UWP) in subjects exhibiting airway narrowing following eucapnic voluntary hyperventilation (EVH), a surrogate challenge for diagnosis of EIB.

Lung function measured by impulse oscillometry and spirometry following eucapnic voluntary hyperventilation.

Background: The efficacy of impulse oscillometry (IOS) to measure airway calibre change is not fully established.

Objectives: To evaluate lung function change after eucapnic voluntary hyperventilation (EVH), and to compare IOS indices with spirometric maximal expiratory flow measurements.

Methods: Twenty subjects (10 airway hyperresponsive [AHR+] and 10 normal [AHR--]) underwent IOS and spirometry before and for 15 min after 6 min EVH (inhaling 5% CO2, 21% O2, balance N2) at a target ventilation of 30 times the baseline value of the forced expiratory volume in 1 s (FEV1) at 20 degrees C.

Cold air inhalation does not affect the severity of EIB after exercise or eucapnic voluntary hyperventilation.

Introduction: Exercise-induced bronchoconstriction (EIB) is thought to result from osmotic and thermal events of air conditioning during exercise at high ventilation rates. The purpose of this study was to evaluate lung function after exercise and eucapnic voluntary hyperventilation (EVH) while breathing both room-temperature and cold-temperature dry bottled air.

Methods: Twenty-two subjects were identified as EIB probable by a fall of >or=7% in forced expiratory volume in the first second of exhalation (FEV1) using a 6-min room-temperature EVH challenge (RTEVH; 22.

Bronchoconstriction provoked by exercise in a high-particulate-matter environment is attenuated by montelukast.

Airborne ultrafine and fine particulate matter (PM1 from fossil-fueled internal combustion engines may cause abnormal airway narrowing. Because of high PM1 exposure from ice resurfacing machines, the ice-rink athlete is especially vulnerable to PM1 toxicity. The purpose of this study was to evaluate protection by a single dose of montelukast in college ice hockey players following PM1 exposure exercise.

Montelukast has no ergogenic effect on cycle ergometry in cold temperature.

Purpose: To examine the effects of a single 10-mg dose of ML on physical performance in EIB- and EIB+ athletes.

Methods: Twenty-four male college ice hockey players performed two 6-min maximal work accumulation bouts on an electronically braked cycle ergometer in subfreezing conditions (-2.5 +/- 0.

Baseline lung function, exercise-induced bronchoconstriction, and asthma-like symptoms in elite women ice hockey players.

Purpose: Exercise-induced bronchoconstriction (EIB) is high among ice rink athletes and may be related to exercise ventilation of rink air pollutants. Impaired postchallenge expiratory flows are common for this population; however, baseline lung function and symptoms have not been fully evaluated.

Methods: We examined resting lung function and asthma-like symptoms in relation to airway hyperresponsiveness in National Team female ice hockey players (N = 43).