Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability.

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1.

Role of endoplasmic reticulum stress in renal damage after myocardial infarction.

Myocardial infarction (MI) is associated with renal alterations resulting in poor outcomes in patients with MI. Renal fibrosis is a potent predictor of progression in patients and is often accompanied by inflammation and oxidative stress; however, the mechanisms involved in these alterations are not well established. Endoplasmic reticulum (ER) plays a central role in protein processing and folding. An accumulation of unfolded proteins leads to ER dysfunction, termed ER stress. Since the kidney is the organ with highest protein synthesis fractional rate, we herein investigated the effects of MI on ER stress at renal level, as well as the possible role of ER stress on renal alterations after MI. Patients and MI male Wistar rats showed an increase in the kidney injury marker neutrophil gelatinase-associated lipocalin (NGAL) at circulating level or renal level respectively. Four weeks post-MI rats presented renal fibrosis, oxidative stress and inflammation accompanied by ER stress activation characterized by enhanced immunoglobin binding protein (BiP), protein disulfide-isomerase A6 (PDIA6) and activating transcription factor 6-alpha (ATF6α) protein levels. In renal fibroblasts, palmitic acid (PA; 50-200 µM) and angiotensin II (Ang II; 10-8 to 10-6M) promoted extracellular matrix, superoxide anion production and inflammatory markers up-regulation. The presence of the ER stress inhibitor, 4-phenylbutyric acid (4-PBA; 4 µM), was able to prevent all of these modifications in renal cells. Therefore, the data show that ER stress mediates the deleterious effects of PA and Ang II in renal cells and support the potential role of ER stress on renal alterations associated with MI.

A New Bariatric Procedure: The Stomach Sparing Gastric Sleeve™.

A new restrictive procedure has emerged over the last decade known as the total vertical gastric plication or greater curvature plication (GCP). After our initial experience, the original technique was modified and a new standardized procedure was registered as the Stomach Sparing Gastric Sleeve™ (SSGS). The SSGS reduces the capacity of the stomach by in-folding the greater curvature with containment sutures, creating a sleeve-like stomach. Between March 2012 and August 2015 patients that met the National Institutes of Health (NIH) criteria for gastric banding underwent treatment with the SSGS. The standardized technique requires the use of a customized fenestrated orogastric calibration device. The stomach is then imbricated or in-folded in two layers and containment non-absorbable sutures are placed longitudinally. The two layers of non-absorbable sutures are continuous starting 1 cm below the esophageal gastric (EG) junction and continued distally 3-4 cm from the pylorus spaced evenly at 1 cm intervals and sero-muscular thickness. Symmetry of anteroposterior distribution is also observed leading to the formation of a sleeve-like shaped stomach. Initial and subsequent weight (kg), body mass index (Kg/m²), excess weight loss (%EWL) and complications were recorded. Repeated measures of analysis of variance (ANOVA) were used to assess weight change. The SSGS was performed on the last 624 cases (mean age 43.1±11.6 years). The follow-up time was 3 years, with an %EWL of 56.36±21.83 during the first year and a maintenance of 49.37±30.82 by the third year of follow-up (p=<0.0005). Patients with a BMI of 20-30 Kg/m² had an EWL of 60.46% during the first 6 months after surgery and an EWL of 74.84% in the first year and a maintained EWL after 3 years of 60.45%. The surgical mean time was 45 min. There were no conversions to the open approach. A 0% mortality and 1.12% morbidity were reported. The SSGS has a weight loss comparable to other restrictive procedures, with excellent mid-term excess weight loss in the 20-30 Kg/m² BMI category. This new technique is an improvement over the original technique, as it has been modified specifically to address the complications of the original non-standardized gastric plication. The benefits of this restrictive technique are that it requires no stapling, dividing, or rerouting of the intestines, as well as no need to implant a foreign body device. The disadvantages observed were a steep learning curve and lack of a standardized technique until this publication.