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Cancer is a worldwide burden resulting in millions of deaths each year. In particular, gastrointestinal tumors are life-threatening malignancies and one of the leading reasons for death in developed countries. Phytochemicals can be found in grains, vegetables, fruits and several foods. Many phytochemicals, such as curcumin, genistein, luteolin, vitexin-2-O-xyloside, avenanthramides, quercetin, epigallocatechin-3-gallate (EGCG), resveratrol, sulforaphane, piperine and thymoquinone have been used in combination with different chemotherapeutic agents for their synergistic anticancer effects against various forms of cancer. In this review, we describe the antitumor properties and biological effects of combinations of phytochemicals and anticancer drugs against gastrointestinal tumors: colon cancer, gastric cancer, liver cancer, pancreatic cancer. We focus on the molecular pathways, oncoproteins and tumor suppressors modulated by the combination of phytochemicals with antitumor drugs and on the biomarkers of the hallmarks of cancer influenced by these therapeutic strategies in cancer cell lines, xenograft models and clinical trials. The increased knowledge of biomarkers and molecular pathways regulated by the combination of phytochemicals and conventional anticancer drugs in both in vitro and in vivo models will remarkably improve the efficacy of these therapeutic strategies against gastrointestinal tumors in future innovative clinical applications. [ABSTRACT FROM AUTHOR]

Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their effects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomitant onset of toxic effects, especially on the heart. Notably, it has been clearly demonstrated that, besides their direct action on transcription (genomic effects), THs also have non-genomic effects, mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by their endogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has been attracting increasing interest because some of its metabolic effects are similar to those induced by T3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it has been hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2 might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, while concomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides. Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomic effects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2, also in relation to its possible clinical use as a drug. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) represent chronic idiopathic disorders, including Crohn's disease (CD) and ulcerative colitis (UC), in which one of the trigger factors is represented by aberrant immune interactions between the intestinal epithelium and the intestinal microbiota. The involvement of heat shock proteins (HSPs) as etiological and pathogenetic factors is becoming of increasing interest. HSPs were found to be differentially expressed in the intestinal tissues and sera of patients with CD and UC. It has been shown that HSPs can play a dual role in the disease, depending on the stage of progression. They can support the inflammatory and fibrosis process, but they can also act as protective factors during disease progression or before the onset of one of the worst complications of IBD, colorectal cancer. Furthermore, HSPs are able to mediate the interaction between the intestinal microbiota and intestinal epithelial cells. In this work, we discuss the involvement of HSPs in IBD considering their genetic, epigenetic, immune and molecular roles, referring to the most recent works present in the literature. With our review, we want to shed light on the importance of further exploring the role of HSPs, or even better, the role of the molecular chaperone system (CS), in IBD: various molecules of the CS including HSPs may have diagnostic, prognostic and therapeutic potential, promoting the creation of new drugs that could overcome the side-effects of the therapies currently used.