Research Spotlight

Shimura, T., S. Toden, N. L. Komarova, C. Boland, D. Wodarz and A. Goel (2020). “A comprehensive in vivo and mathematic modeling-based kinetic characterization for aspirin-induced chemoprevention in colorectal cancer.” Carcinogenesis Jan 6. [Epub ahead of print].

Full text of this article.

Accumulating evidence suggests that aspirin has anti-tumorigenic properties in colorectal cancer (CRC). Herein, we undertook a comprehensive and systematic series of in vivo animal experiments followed by 3D-mathematical modeling to determine the kinetics of aspirin’s anti-cancer effects on CRC growth. In this study, CRC xenografts were generated using four CRC cell lines with and without PIK3CA mutations and microsatellite instability, and the animals were administered with various aspirin doses (0, 15, 50, and 100 mg/kg) for 2 weeks. Cell proliferation, apoptosis and protein expression were evaluated, followed by 3D-mathematical modeling analysis to estimate cellular division and death rates and their impact on aspirin-mediated changes on tumor growth. We observed that aspirin resulted in a dose-dependent decrease in the cell division rate, and a concomitant increase in the cell death rates in xenografts from all cell lines. Aspirin significantly inhibited cell proliferation as measured by Ki67 staining (P < 0.05-0.01). The negative effect of aspirin on the rate of tumor cell proliferation was more significant in xenograft tumors derived from PIK3CA mutant versus wild-type cells. A computational model of 3D-tumor growth suggests that the growth inhibitory effect of aspirin on the tumor growth kinetics is due to a reduction of tumor colony formation, and that this effect is sufficiently strong to be an important contributor to the reduction of CRC incidence in aspirin-treated patients. In conclusion, we provide a detailed kinetics of aspirin-mediated inhibition of tumor cell proliferation, which support the epidemiological data for the observed protective effect of aspirin in CRC patients.

Schlomer, B. J. and C. L. Secrest (2020). “Bilateral Ureteropelvic Junction Disruptions in a 17-Year-Old with Bilateral Ureteral Duplications: Impact of Unrecognized Duplications and Unique Management of Nephrocutaneous Fistula.” Urology Jan 17. [Epub ahead of print].

Full text of this article.

A case of bilateral ureteropelvic junction (UPJ) disruptions in a patient with bilateral duplication anomalies is presented. A UPJ disruption with a duplication anomaly has not been reported let alone bilateral duplication anomalies. The unrecognized duplication anomalies led to isolated and obstructed upper pole segments that were managed by bilateral heminephrectomies. A nephrocutaneous fistula developed after one of the heminephrectomies that was successfully managed using a method of percutaneous fulguration and fibrin sealant. In UPJ disruption cases, the possibility of a duplicated collecting system should be considered as an unrecognized duplication may complicate management and prolong recovery.

Petrescu, A. D., S. Grant, E. Williams, G. Frampton, N. Parks, H. Blaney, M. Davies, R. John, E. H. Reinhart, M. McMillin and S. DeMorrow (2020). “Coordinated Targeting of Galanin Receptors on Cholangiocytes and Hepatic Stellate Cells Ameliorates Liver Fibrosis in Multidrug Resistance Protein 2 Knockout Mice.” Am J Pathol Jan 14. [Epub ahead of print].

Full text of this article.

Galanin (Gal) is a peptide with a role in neuroendocrine regulation of the liver. In this study, we assessed the role of Gal and its receptors, Gal receptor 1 (GalR1) and Gal receptor 2 (GalR2), in cholangiocyte proliferation and liver fibrosis in multidrug resistance protein 2 knockout (Mdr2KO) mice as a model of chronic hepatic cholestasis. The distribution of Gal, GalR1, and GalR2 in specific liver cell types was assessed by laser-capture microdissection and confocal microscopy. Galanin immunoreactivity was detected in cholangiocytes, hepatic stellate cells (HSCs), and hepatocytes. Cholangiocytes expressed GalR1, whereas HSCs and hepatocytes expressed GalR2. Strategies were used to either stimulate or block GalR1 and GalR2 in FVB/N (wild-type) and Mdr2KO mice and measure biliary hyperplasia and hepatic fibrosis by quantitative PCR and immunostaining of specific markers. Galanin treatment increased cholangiocyte proliferation and fibrogenesis in both FVB/N and Mdr2KO mice. Suppression of GalR1, GalR2, or both receptors in Mdr2KO mice resulted in reduced bile duct mass and hepatic fibrosis. In vitro knockdown of GalR1 in cholangiocytes reduced alpha-smooth muscle actin expression in LX-2 cells treated with cholangiocyte-conditioned media. A GalR2 antagonist inhibited HSC activation when Gal was administered directly to LX-2 cells, but not via cholangiocyte-conditioned media. These data demonstrate that Gal contributes not only to cholangiocyte proliferation but also to liver fibrogenesis via the coordinate activation of GalR1 in cholangiocytes and GalR2 in HSCs.

Kirsch, R., K. Matthews and V. Williams (2020). “Using Global Criteria to Detect Malnutrition: Application in Disease States.” Nutr Clin Pract 35(1): 85-97.

Full text of this article.

The accurate diagnosis and subsequent treatment of malnutrition is an essential component of nutrition care because of the known negative impacts of malnutrition on patient outcomes. The detection of malnutrition is influenced by disease-specific characteristics, practice settings, and the availability of resources. This article explores how malnutrition diagnosis through the application of the Global Leadership Initiative on Malnutrition global consensus on malnutrition diagnostic criteria is impacted by the unique characteristics of the heart failure, oncology, and trauma populations.

Heshmati, J., F. Golab, M. Morvaridzadeh, E. Potter, M. Akbari-Fakhrabadi, F. Farsi, S. Tanbakooei and F. Shidfar (2020). “The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor gamma coactivator 1alpha gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial.” Diabetes Metab Syndr Jan 8;14(2):77-82. [Epub ahead of print].

Full text of this article.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical ingredient found in turmeric and has antioxidant pharmacologic actions that may benefit patients with polycystic ovarian syndrome (PCOS). The aim in this trial was to evaluate the efficacy of curcumin supplementation on oxidative stress enzymes, sirtuin-1 (SIRT1) and Peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC1alpha) gene expression in PCOS patients. METHODS: Seventy-two patients with PCOS were recruited for this randomized, double-blinded, clinical trial. Thirty-six patients received curcumin, 1500 mg (three times per day), and 36 patients received placebo for 3 months. Gene expression of SIRT1, PGC1alpha and serum activity of glutathione peroxidase (Gpx) and superoxide dismutase (SOD) enzymes were evaluated at the beginning of trial and at 3-month follow-up. RESULTS: Sixty-seven patients with PCOS completed the trial. Curcumin supplementation significantly increased gene expression of PGC1alpha (p = 0.011) and activity of the Gpx enzyme (p = 0.045). Curcumin also non-significantly increased gene expression of SIRT1 and activity of the SOD enzyme. CONCLUSIONS: Curcumin seems to be an efficient reducer of oxidative stress related complications in patients with PCOS. Further studies on curcumin should strengthen our findings.