Combination of flavone acetic acid (FAA) with adriamycin,cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells

Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.     

Relationships between leisure-time physical activity, obesity and disability in elderly men

BACKGROUND AND AIMS: Relationships have already been shown between leisure-time physical activity, obesity and body composition in young adults. However, this association needs to be confirmed in the elderly. The aim of this study was to investigate the relationship between leisure-time physical activity, obesity, preservation of muscle mass and disability in elderly men. METHODS: Cross-sectional analysis of a sample of 85 community-dwelling men, 68 to 79 years of age. Body mass index (BMI) was used to quantify obesity. Body composition was evaluated using Dual Energy X-ray Absorptiometry. Disability was measured using a modified version of the Activities of Daily Living scale. Leisure-time physical activity was evaluated by a validated self-administered questionnaire. RESULTS: A negative relation between obesity and weekly walking was observed. Walking less than 30 minutes per day was associated with a 2.7 greater probability of being obese (95% CI 1.1-6.7). High-intensity exercise, such as brisk walking or gardening, was inversely correlated with body fat (R = -0.296, p < 0.01) and directly correlated with appendicular skeletal mass (R = 0.238, p < 0.05). The prevalence of disability was the highest (58%) among overweight elderly subjects at the lowest tertile of exercise. Multiple logistic regression selected BMI as a positive predictor and high-intensity exercise as a negative predictor of disability. CONCLUSIONS: Our study shows that, in elderly men, leisure-time physical activity is inversely associated with body fat, BMI, and reported disability, but positively associated with appendicular fat-free mass. The highest prevalence of reported disability was observed in sedentary subjects with BMI higher than 25 kg/m2.     

Pediatric scaphoid fracture: diagnostic performance of various radiographic views

Emergency Radiology - The purpose of this study was to systematically investigate the performance of different radiographic views in the identification of scaphoid fractures in children. This...     

EMILIN2 down‐modulates the Wnt signalling pathway and suppresses breast cancer cell growth and migration

EMILIN2 is an extracellular matrix (ECM) protein that exerts contradictory effects within the tumour microenvironment: it induces apoptosis in a number of tumour cells, but it also enhances tumour neo‐angiogenesis. In this study, we describe a new mechanism by which EMILIN2 attenuates tumour cell viability. Based on sequence homology with the cysteine‐rich domain (CRD) of the Frizzled receptors, we hypothesized that EMILIN2 could affect Wnt signalling activation and demonstrate direct interaction with the Wnt1 ligand. This physical binding leads to decreased LRP6 phosphorylation and to the down‐modulation of β‐catenin, TAZ and their target genes. As a consequence, EMILIN2 negatively affects the viability, migration and tumourigenic potential of MDA‐MB‐231 breast cancer cells in a number of two‐ and three‐dimensional in vitro assays. EMILIN2 does not modulate Wnt signalling downstream of the Wnt–Frizzled interaction, since it does not affect the activation of the pathway following treatment with the GSK3 inhibitors LiCl and CHIR99021. The interaction with Wnt1 and the subsequent biological effects require the presence of the EMI domain, as there is no effect with a deletion mutant lacking this domain. Moreover, in vivo experiments show that the ectopic expression of EMILIN2, as well as treatment with the recombinant protein, significantly reduce tumour growth and dissemination of cancer cells in nude mice. Accordingly, the tumour samples are characterized by a significant down‐regulation of the Wnt signalling pathway. Altogether, these findings provide further evidence of the complex regulations governed by EMILIN2 in the tumour microenvironment, and they identify a key extracellular regulator of the Wnt signalling pathway. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Effect of a Glyphosate-Based Herbicide on Gene Expressions of the Cytokines Interleukin-1β and Interleukin-10 and of Heme Oxygenase-1 in European Sea Bass,Dicentrarchus labrax L.

Glyphosate-based herbicides are the most frequently used herbicides in the world. We evaluated the effect of Roundup 360 SL on the expression of interleukin-1β (il-1β), interleukin-10 (il-10) and heme-oxygenase-1 (ho-1) in the gills, intestines and spleen of young European sea bass (Dicentrachus labrax L.), aged 8 mo. A group of fish was exposed to 647 mg/L of Roundup for 96 h. This treatment did not alter gene expression levels of il-1β and il-10 cytokine in the intestines, but significantly lowered both levels in the gills (p = 0.02 and p = 0.04 respectively). Expression levels of ho-1 were increased significantly in the three organs of fish from the treated group (the gills p = 0.04, the intestines p = 0.004 and the spleen p < 0.001). These changes may in turn negatively impact the immune system of European sea bass exposed to Roundup.     

Arteroportal fistulas between the accessory right hepatic, gastroduodenal and superior mesenteric arteries and portal vein: a difficult technical problem to overcome in liver transplantation

BACKGROUND: Fistulous communications between the accessory right hepatic (ARHA), gastroduodenal (GD), and superior mesenteric (SMA) arteries and the portal vein (PV) may represent a contraindication for liver transplantation (LT). MATERIAL: A patient with HCV-related liver cirrhosis and progressive liver decompensation underwent preoperative LT work-up. Doppler ultrasound (DU), Angiography and MRI revealed arteroportal fistulas (APF) and diversion of mesenteric-splenoportal flow through spontaneous splenorenal shunts (SSRS) in the systemic circulation. The patient was transplanted and the ARHA and GDA were distally sectioned; the HA was anastomosed to the donor HA; the superior mesenteric vein (SMV) was detached from the splenopancreatic venous bed by sectioning and ligating the Henle trunk, by ligating an posterior-inferior pancreatic vein and, finally, by positioning an iliac vein interposition graft between the SMV and the donor PV. The postanastomotic SMV trunk and recipient PV were ligated below and above the pancreatic head, respectively. RESULTS: Reperfusion and late liver function were good. DU and MRI studies showed an effective portal flow and the maintenance of a normal splenopancreatic vein outflow through the SSRS. DISCUSSION: APF represent a serious clinical problem, particularly in patients who need LT. The persistence of arterial flow into the PV is dangerous for the long-term liver function. A particular surgical strategy, strictly tailored to the hemodynamic conditions, has to be planned. CONCLUSIONS: Extrahepatic multiple APF would no longer to represent a contraindication to LT, although this claim needs to be confirmed in the light of further experience and a longer-term follow-up.     

Long-term outcome after coronary artery bypass grafting in patients with severe left ventricular dysfunction

BACKGROUND: The aim of this study was to define the potential for long-term survival with severe left ventricular dysfunction after coronary bypass and to quantify any improvement in overall functional status. METHODS: Left ventricular dysfunction was confirmed preoperatively and the long-term survival and functional outcome after bypass was determined by follow-up studies obtained during the span of a decade. RESULTS: From 1/1990 to 12/1999, 86 patients with severe left ventricular dysfunction (mean ejection fraction, 0.18 +/- 0.03; range, 0.10 to 0.20) underwent coronary artery bypass grafting. There were 10 perioperative deaths (11% mortality). The mean survival was 55 months (standard deviation +/- 34 months; range, 2 to 141 months) with an actual 5-year survival rate of 59% (actuarial 5-year 65%, 10-year 33%). Echocardiography obtained between 1 and 6 months, 6 months and 1 year, 1 and 2 years, 2 and 4 years, 4 and 6 years, and 6 and 11 years showed the ejection fraction improved to 0.29 +/- 0.08 (p < 0.001), 0.31 +/- 0.14 (p < 0.002), 0.35 +/- 0.08 (p < 0.001), 0.27 +/- 0.10 (p = 0.002), 0.36 +/- 0.14 (p = 0.004), and 0.30 +/- 0.11 (p = 0.004), respectively. At 1 to 6 months, 6 months to 1 year, and 1 to 2 years, the diastolic left ventricular dimension was unchanged, but the systolic left ventricular dimension decreased significantly from 5.02 +/- 0.77 cm to 4.26 +/- 0.91 cm (p = 0.046), 3.98 +/- 1.43 cm (p = 0.08), and 4.10 +/- 1.14 cm (p = 0.07). The preoperative New York Heart Association classification for all patients improved from 2.8 +/- 0.8 to 1.6 +/- 0.7 (p < 0.001) after a mean of 53 months (standard deviation +/- 34 months). CONCLUSIONS: Patients with severe left ventricular dysfunction can derive long-term benefit from coronary bypass through improved left ventricular contractility as documented by a significantly decreased systolic left ventricular dimension and increased ejection fraction. Successful bypass is associated with a 59% actual 5-year survival rate and significantly improved New York Heart Association functional class.