MUC1 Contributes to BPDE-Induced Human Bronchial Epithelial Cell Transformation through Facilitating EGFR Activation

Although it is well known that epidermal growth factor receptor (EGFR) is involved in lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals), a glycoprotein component of airway mucus, is overexpressed in lung tumors; however, its role and underlying mechanisms in early stage lung carcinogenesis is still elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are involved in bronchial epithelial cell transformation. Knockdown of MUC1 expression significantly reduced transformation of immortalized human bronchial epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE), the active form of the cigarette smoke (CS) carcinogen benzo(a)pyrene (BaP)s. BPDE exposure robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this pathway significantly increased BPDE-induced cell death and inhibited cell transformation. Suppression of MUC1 expression resulted in EGFR destabilization and inhibition of the BPDE-induced activation of Akt and ERK and increase of cytotoxicity. These results strongly suggest an important role for EGFR in BPDE-induced transformation, and substantiate that MUC1 is involved in lung cancer development, at least partly through mediating carcinogen-induced activation of the EGFR-mediated cell survival pathway that facilitates cell transformation

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Radiobiological studies using gamma and x rays.

There are approximately 500 self-shielded research irradiators used in various facilities throughout the U.S. These facilities use radioactive sources containing either 137Cs or 60Co for a variety of biological investigations. A report from the National Academy of Sciences[1] described the issues with security of particular radiation sources and the desire for their replacement. The participants in this effort prepared two peer-reviewed publications to document the results of radiobiological studies performed using photons from 320-kV x rays and 137Cs on cell cultures and mice. The effectiveness of X rays was shown to vary with cell type

Radiobiological studies using gamma and x rays.

There are approximately 500 self-shielded research irradiators used in various facilities throughout the U.S. These facilities use radioactive sources containing either 137Cs or 60Co for a variety of biological investigations. A report from the National Academy of Sciences[1] described the issues with security of particular radiation sources and the desire for their replacement. The participants in this effort prepared two peer-reviewed publications to document the results of radiobiological studies performed using photons from 320-kV x rays and 137Cs on cell cultures and mice. The effectiveness of X rays was shown to vary with cell type

Chronic BPDE exposure activates Akt and ERK through EGFR in human bronchial epithelial cells.

<p><i>A</i>, Induction of MUC1 expression and EGFR-, Akt- and ERK-activation in HBEC-2 cells by BPDE. Specifically, HBEC-2 cells were treated with the vehicle DMSO or BPDE (0.1 µM) for the indicated weeks. Western blot was the same as in <i>A</i>. β-Actin was detected as a loading control. <i>B</i>, Increased MUC1 expression and EGFR-, Akt- and ERK-activation in transformed HBEC-2 cells by BPDE. HBEC-2 cells were treated with BPDE (0.1 µM) for 12 wk and then seeded in soft agar. Colonies were grown up for 3 wk in transformed cells (TRANS). Wild-type (WT, exposed to sham) HBEC-2 cells were as a negative control. Expression of MUC1 and activation of Akt and ERK were detected by Western blot in both WT and the transfected cells. β-Actin was detected as a loading control.</p

A model of MUC1-mediated EGFR activation and HBEC transformation.

<p>CS carcinogens such as BPDE trigger MUC1 expression in bronchial epithelial cells, facilitating EGFR-mediated cell survival signaling via Akt and ERK activation. Akt and ERK protect cells against DNA damage-mediated apoptosis to promote cell transformation, facilitating lung carcinogenesis.</p

Suppression of EGFR, Akt and ERK activation inhibits BPDE-induced cell transformation.

<p>Graphical and quantitative representation of colony formation in soft agar of BEAS-2B cells exposed to BPDE (0.1 µM) and/or the indicated inhibitors (EGFRin, LY, and U0126) every two days for 1 week. Bars show the averages of colony numbers of 6 randomly selected fields. Data shown are mean ± S.D; ** P<0.01.</p