IR induces overexpression and activity of the MET oncogene through the ATM-NF-κB signaling pathway; MET, in turn, promotes cell invasion and protects cells from apoptosis, thus supporting radioresistance. Drugs targeting MET increase tumor cell radiosensitivity and prevent radiation-induced invasiveness.
The close relationship between activation of blood coagulation and cancer is an old enigma. In 1865, migrans trombophlebitis ('a condition of the blood that predisposes it to spontaneous coagulation') was described as a forewarning of occult malignancy (Trousseau's sign). This pioneering observation emphasized the existence of haemostasis disorders associated with cancer onset; this phenomenon has since been extensively reported in clinical and epidemiological studies, but has so far resisted a mechanistic explanation. Here we report a mouse model of sporadic tumorigenesis based on genetic manipulation of somatic cells. Targeting the activated, human MET oncogene to adult liver caused slowly progressing hepatocarcinogenesis. This was preceded and accompanied by a syndrome manifesting first with blood hypercoagulation (venous thromboses), and then evolving towards fatal internal haemorrhages. The pathogenesis of this syndrome is driven by the transcriptional response to the oncogene, including prominent upregulation of plasminogen activator inhibitor type 1 (PAI-1) and cyclooxygenase-2 (COX-2) genes. In vivo analysis showed that both proteins support the thrombohaemorrhagic phenotype, thus providing direct genetic evidence for the long-sought-after link between oncogene activation and haemostasis.
Acute diarrhea is one of the most common reasons why pet owners seek veterinary care for their canine companions. In many cases, signs resolve spontaneously or with symptomatic therapy without a specific cause being discovered. However, life-threatening cases can occur. The etiology is complex, including infectious diseases (endoparasites, virus, bacteria, protozoa, fungal agents) by both zoonotic and non-zoonotic pathogens, dietary indiscretion, endocrine diseases, and stress (e.g., travel or environmental changes). In the last years, the role played by oxidative stress in the pathogenesis of acute and chronic enteropathies, independently from the initial noxa, has been highlighted by many researches in both humans and animals. As a result, a series of dietary antioxidant compounds have been studied for their potential use in the treatment of intestinal inflammation. This review summarizes the traditional therapeutic and nutritional options to manage canine acute diarrhea, highlighting the need to explore the role of oxidative stress and potential antioxidant supplementation, especially polyphenols, during acute diarrheic episodes.
Dexamethasone is a potent synthetic corticosteroid widely employed as a therapeutic agent in cattle. Besides this legal use, corticosteroids are also administered at low dosages as growth-promoters either alone or in combination with other steroids or with beta-agonists. For this reason, appropriate control plans are established to survey corticosteroid misuse, using liver or urine as biological matrices. Since few data are available about the kinetics of dexamethasone excretion in meat cattle, an experimental study was designed to assess the drug residue levels in urines following either a therapeutic (60 microg of dexamethasone sodium phosphate/kg b.w., for three consecutive days) or a growth-promoting schedule (0.7 or 1.4 mg of dexamethasone sodium phosphate per capita/day for 60 days). The urinary elimination of dexamethasone, which was predominantly excreted in the unmodified form, was determined by high-performance liquid chromatography/tandem mass spectrometry at different time intervals, i.e. during the treatments and after appropriate withdrawal times. Our findings confirm the high and rapid rate of dexamethasone urinary excretion irrespective of the nature of the treatment, and provide useful reference values that can be conveniently employed for forensic purposes.
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