The gastrointestinal microbiota in colorectal cancer cell migration and invasion

Colorectal carcinoma is the third most common cancer in developed countries and the second leading cause of cancer-related mortality. Interest in the influence of the intestinal microbiota on CRC emerged rapidly in the past few years, and the close presence of microbiota to the tumour mass creates a unique microenvironment in CRC. The gastrointestinal microbiota secrete factors that can contribute to CRC metastasis by influencing, for example, epithelial-to-mesenchymal transition. Although the role of EMT in metastasis is well-studied, mechanisms by which gastrointestinal microbiota contribute to the progression of CRC remain poorly understood. In this review, we will explore bacterial factors that contribute to the migration and invasion of colorectal carcinoma and the mechanisms involved. Bacteria involved in the induction of metastasis in primary CRC include Fusobacterium nucleatum, Enterococcus faecalis, enterotoxigenic Bacteroides fragilis, Escherichia coli and Salmonella enterica. Examples of prominent bacterial factors secreted by these bacteria include Fusobacterium adhesin A and Bacteroides fragilis Toxin. Most of these factors induce EMT-like properties in carcinoma cells and, as such, contribute to disease progression by affecting cell-cell adhesion, breakdown of the extracellular matrix and reorganisation of the cytoskeleton. It is of utmost importance to elucidate how bacterial factors promote CRC recurrence and metastasis to increase patient survival. So far, mainly animal models have been used to demonstrate this interplay between the host and microbiota. More human-based models are needed to study the mechanisms that promote migration and invasion and mimic the progression and recurrence of CRC

Managing intoxications with nicotine-containing e-liquids

INTRODUCTION: Nicotine is an addictive and poisonous agent. The recent development of e-cigarettes has caused a new demand for highly concentrated nicotine-containing solutions. These concentrated nicotine solutions have also increased the risk of nicotine overdoses. AREAS COVERED: Essential factors for nicotine exposure are the concentration of the nicotine-containing e-liquid solution and its pharmacokinetics. Liquid nicotine refills contain nicotine in varying concentrations, which vary widely between and within products. The pharmacokinetics of nicotine are dependent on the route of administration, renal/hepatic clearance and urinary pH. The dose is another essential determinant of nicotine exposure. There is a considerable discrepancy between the generally accepted lethal dose and symptoms reported in case studies. Ingested doses correlate poorly to clinical symptoms. Symptoms of liquid nicotine toxicity vary from mild to severe between patients and are the result of overstimulation of nicotinic acetylcholine receptors, which may lead to fatal respiratory failure and cardiovascular collapse. EXPERT OPINION: The literature on nicotine-containing e-liquid intoxications originating from vaping device refills are mainly case reports. Based on these case reports, we propose a treatment plan which is primarily symptomatic. Research should focus on providing insight on its toxicity, based on oral and transdermal pharmacokinetics and on toxicodynamics

A review of the pharmacodynamic effect of chemo-herbal drug combinations therapy for cancer treatment

There is mounting evidence that cancer patients co-administer herbal drugs with chemotherapy, however, information on the pharmacodynamic (PD) effects of such combination therapy is scarce. Natural products including crude extracts, herbal formulas, and bioactive compounds from plants hold great potential to prevent and treat cancers. More importantly, some herbal drugs can reduce the incidence of chemotherapy-induced toxicity including oral mucositis, gastrointestinal toxicity, hepatotoxicity etc. This review focuses on the effectiveness of some herbal products as adjuvant therapy and describes the possible mechanisms of chemo-herbal drug PD interactions in enhancing the efficacy/ or reducing the side effects of chemotherapy. We also highlighted recent advances in preclinical in vitro and in vivo studies to establish the effectiveness of herbal medicine to enhance efficacy or counteract chemotherapy-induced side effects. In addition, we draw particular attention to the synergistic effects of chemo-herbal drug combination therapy to prevent and treat cancers using evidence from clinical trials. We concluded that herbal drugs hold great potential as adjuvant therapy for the prevention and treatment of chemotherapy-induced side effects. It is important to also highlight that the clinical evidence on chemo-herbal drug combination therapy is limited. There is an urgent need for an in-depth PD evaluation including the safety pharmacology of chemo-herbal drug combination therapy as well as reliable evidence from multicentre clinical trials to establish the beneficial or negative effects of chemo-herbal drug combination therapy in the ongoing fight against cancer