Search

Treatment of cancer with chemotherapeutic drugs is associated with numerous adverse effects as well as the eventual development of resistance to chemotherapy. There is a great need for complementary therapies such as botanicals and nutritional supplements with little or no side effects that prevent resistance to chemotherapy and reduce its adverse effects. Inflammation plays a major role in the development of chemoresistance and the adverse effects of chemotherapy. Phytochemicals have well-established anti-inflammatory effects; thus, they could be used as complementary therapies along with chemotherapy to increase its efficacy and reduce its toxicity. Botanical compounds inhibit the NF-κB signaling pathway, which plays an important role in the generation of inflammation, chemotherapy resistance, and modulation of cell survival and apoptosis. Botanicals have previously been studied extensively for their cancer chemopreventive activities and are generally considered safe for human consumption. The present review focuses on the modulation of inflammation by phytochemicals and their role in increasing the efficacy and reducing the toxicity of cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Among American men, prostate cancer is the most common, non-cutaneous malignancy that accounted for an estimated 241,000 new cases and 34,000 deaths in 2011. Previous studies have suggested that Wnt pathway inhibitory genes are silenced by CpG hypermethylation, and other studies have suggested that genistein can demethylate hypermethylated DNA. Genistein is a soy isoflavone with diverse effects on cellular proliferation, survival, and gene expression that suggest it could be a potential therapeutic agent for prostate cancer. We undertook the present study to investigate the effects of genistein on the epigenome of prostate cancer cells and to discover novel combination approaches of other compounds with genistein that might be of translational utility. Here, we have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial to mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Methods Using whole genome expression profiling and whole genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and combination treatment, where cell death and cell proliferation was determined. Results Contrary to earlier reports, genistein did not have an effect on CpG methylation at 20 μM, but it did affect histone H3K9 acetylation and induced increased expression of histone acetyltransferase 1 (HAT1). In addition, genistein also had differential effects on survival and cooperated with the histone deacteylase inhibitor vorinostat to induce cell death and inhibit proliferation. Conclusion Our results suggest that there are a number of pathways that are affected with genistein and vorinostat treatment such as Wnt, TNF, G2/M DNA damage checkpoint, and androgen signaling pathways. In addition, genistein cooperates with vorinostat to induce cell death in prostate cancer cell lines with a greater effect on early stage prostate cancer.

Aim: Among the hypomyelinating diseases of childhood, Pelizaeus Merzbacher Disease (PMD) is caused by Xlinked proteolipid protein (PLP) gene mutations, whereas patients without mutations of PLP gene -called Pelizaues Merzbacher-like Disease (PMLD)- includes patients with autosomal recessive gap junction protein α12 (GJA12 /GJC2) gene mutations. The aim of this study was to evaluate clinical severity and progression in time between PMD and PMLD patients. Methods: The motor developmental stages of the patients were reviewed; disease severity was classified according to the walking ability they were able to achieve. Progression pattern was determined according to comparison of neurological findings at the time of the study and at follow-up visits. PMD and PMLD patients were compared in terms of disease severity and progression rates as well as patient groups with a unique causative mutation were analyzed individually. Results: There were 9 PMD patients (mean age 15.2±3.1) and 11 PMLD patients (mean age 12.4±1.9). The presence of severe disease was more common in PMD patients when compared to PMLD. In X-linked PMD, missense mutations had the most severe disease and rapid progression, while deletion mutations had mild disease severity and slow progression. Disease severity and progression patterns seemed to be heterogenous in different causative mutations of PMLD. Conclusion: Although PMLD might have milder disease phenotype when compared to PMD, certain causative mutations in different genetic traits may cause different disease severity and progression patterns. [ABSTRACT FROM AUTHOR]

Purpose: In the present study, we aimed to investigate the effects of tomato powder (TP) on glucose and lipid metabolism, as well as oxidative stress and the NF- κ B, mTOR, and Nrf2 pathways during the aging process in healthy rats., Methods and Results: Male Wistar rats were randomly assigned to four groups as follows: (i) Control group 1 ( n =15, 3-week old): rats were fed standard diet for 7 weeks; (ii) TP group 1 ( n =15, 3-week old): rats were fed standard diet supplemented with TP for 7 weeks; (iii) Control group 2 ( n =15, 8-week old): rats were fed standard diet for 69 weeks; and (iv) TP group 2 (8-week old): rats were fed standard diet supplemented with TP for 69 weeks. TP supplementation significantly reduced the hyperglycemia, hypertriglyceridemia, and hypercholesterolemia and improved liver function and kidney function in 77-week old rats compared with the control animals ( P < 0.05). In addition, TP significantly decreased the serum and liver MDA levels ( P < 0.003 and P < 0.001, respectively) while increasing the activities of liver SOD ( P < 0.001), CAT ( P < 0.008), and GPx ( P < 0.01) compared with the control groups in both 10-week-old and 77-week-old rats ( P < 0.05). Age-related increases in phosphorylation of NF- κ Bp65, mTOR, 4E-BP1, and P70S6K were observed in livers of 77-week-old rats compared to those of 10-week-old rats ( P < 0.001). TP supplementation decreased the expression of NF- κ Bp65 and activation of mTOR, 4E-BP1, and P70S6K in livers of 77-week-old rats compared to the control animals. Moreover, TP supplementation significantly elevated Nrf2 expression in livers of both 10-week-old and 77-week-old rats ( P < 0.05)., Conclusion: TP ameliorates age-associated inflammation and oxidative stress through the inhibition of NF- κ Bp65, mTOR pathways, and Nrf2 activation may explain the observed improvement in glucose and lipid metabolism as well as the improved liver and kidney functions.

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti-inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD.

Background: Sox4 is an essential gene, and genetic deletion results in embryonic lethality. In an effort to develop mice with tissue-specific deletion, we bred conditional knockout mice bearing LoxP recombination sites flanking the Sox4 gene, with the LoxP sites located in the Sox4 5'UTR and 3'UTR., Results: The number of mice homozygous for this LoxP-flanked conditional knockout allele was far below the expected number, suggesting embryonic lethality with reduced penetrance. From over 200 animals bred, only 11% were homozygous Sox4(flox/flox) mice, compared to the expected Mendelian ratio of 25% (p<0.001). Moreover, there was a significant reduction in the number of female Sox4(flox/flox) mice (26%) relative to male Sox4(flox/flox) mice (p=0.0371). Reduced Sox4 expression in homozygous embryos was confirmed by in-situ hybridization and Quantitative real-time polymerase chain reaction (QPCR)., Conclusion: LoxP sites in the 5' and 3' UTR of both alleles of Sox4 resulted in reduced, but variable expression of Sox4 message., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)