There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence.
Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A “liquid biopsy” is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs, and proteins, from peripheral blood or other body fluids and their genomic or proteomic assessment. The liquid biopsy is a minimally invasive and repeatable technique that could play a significant role in screening and diagnosis, and predict relapse and metastasis, as well as monitoring minimal residual disease and chemotherapy resistance in colorectal cancer patients. However, there are still some practical issues that need to be addressed before liquid biopsy can be widely used in clinical practice. Potential challenges may include low amounts of circulating tumor cells and circulating tumor DNA in samples, lack of pre-analytical and analytical consensus, clinical validation, and regulatory endorsement. The aim of this review was to summarize the current knowledge of the role of liquid biopsy in the management of colorectal cancer.
Patients with thyroid cancers refractory to radioiodine (RAI) treatment show a limited response to various therapeutic options and a low survival rate. The recent use of multikinase inhibitors has also met limited success. An alternative approach relies on drugs that induce cell differentiation, as the ensuing increased expression of the cotransporter for sodium and iodine (NIS) may partially restore sensitivity to radioiodine. The inhibition of the ERK1/2 pathway has shown some efficacy in this context. Aggressive thyroid tumors overexpress the isoform-A of the insulin receptor (IR-A) and its ligand IGF-2; this IGF-2/IR-A loop is associated with de-differentiation and stem-like phenotype, resembling RAI-refractory tumors. Importantly, IR-A has been shown to be positively modulated by the non-integrin collagen receptor DDR1 in human breast cancer. Using undifferentiated human thyroid cancer cells, we now evaluated the effects of DDR1 on IGF-2/IR-A loop and on markers of cell differentiation and stemness. DDR1 silencing or downregulation caused significant reduction of IR-A and IGF-2 expression, and concomitant increased levels of differentiation markers (NIS, Tg, TSH, TPO). Conversely, markers of epithelial-to-mesenchymal transition (Vimentin, Snail-2, Zeb1, Zeb2 and N-Cadherin) and stemness (OCT-4, SOX-2, ABCG2 and Nanog) decreased. These effects were collagen independent. In contrast, overexpression of either DDR1 or its kinase-inactive variant K618A DDR1-induced changes suggestive of less differentiated and stem-like phenotype. Collagen stimulation was uneffective. In conclusion, in poorly differentiated thyroid cancer, DDR1 silencing or downregulation blocks the IGF-2/IR-A autocrine loop and induces cellular differentiation. These results may open novel therapeutic approaches for thyroid cancer.
In the past two decades, hepatic surgery has achieved important technical breakthroughs resulting in a drastic reduction of the onset of complications and in an improved post-resective survival. Pre-operative nutritional status is one of the key points for the success of a liver resection. Modern surgical achievement such as the development of living-related liver donation, and the possibility to perform more laparoscopic liver resection gave us the opportunity to extend post-operative protocol focused on early intestinal feeding to tumor patients. The aims of this review were to report the current status of the knowledge regarding nutritional aspects in liver resection patients.
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