Digestive diseases
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The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. ⋯ Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use.
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Adenosine triphosphate (ATP) is essential for the myriad of metabolic processes upon which life is based and is known widely as the universal energy currency unit of intracellular biologic reactions. ATP, adenosine diphosphate, adenosine, as well as other purines and pyrimidines also serve as ubiquitous extracellular mediators which function through the activation of specific receptors (viz. P2 receptors for nucleotides and purinergic P1 receptors for adenosine). ⋯ Increased understanding of mechanisms of extracellular ATP scavenging and specifically conversion to nucleosides by ectonucleotidases of the CD39 family have also led to novel insights into the exquisite balance of nucleotide P2-receptor and adenosinergic P1-receptor signaling in inflammatory and hepatic diseases. Further, CD39 and other ectonucleotidases exhibit genetic polymorphisms in humans which alter levels of expression/function and are associated with predisposition to inflammatory and immune diseases, diabetes and vascular calcification, amongst other problems. Development of therapeutic strategies targeting purinergic signaling and ectonucleotidases offers promise for the management of disordered inflammation and aberrant immune reactivity.
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Hepatocellular carcinoma (HCC) is heterogeneous in histopathology, pathogenesis and biological behavior. There is accumulating evidence that the expression of 'stemness'-related markers such as K19, EpCAM and CD133 in HCC is associated with an aggressive biological behavior and poor clinical outcome compared to conventional HCCs that do not express stemness-related markers. Compared to conventional HCCs, these tumors more frequently demonstrate infiltrative growth patterns, vascular invasion and more intratumoral fibrous stroma, and there is a spectrum of morphological and immunophenotypic features between HCCs with stemness-related marker expression, scirrhous HCCs and combined hepatocellular-cholangiocarcinoma with stem cell features. ⋯ These tumors have also been recognized as a specific subtype in recent molecular classifications, and increasing interest in the molecular pathogenesis of HCCs with stemness-related marker expression will shed light on the development of targeted therapy for these tumors. Therefore, it is important that pathologists identify HCCs expressing stemness-related markers such as K19 during routine pathological evaluation of surgically resected or biopsied HCC tissue, as it will help to identify a high-risk subgroup of HCCs characterized by increased chemoresistance, earlier recurrence after surgical and/or locoregional treatment, increased invasiveness/metastasis and poor overall survival. We will discuss the clinicopathological characteristics of a HCC subtype expressing stemness-related markers and its future perspectives.
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Our therapeutic goals for the treatment of ulcerative colitis and Crohn's disease are evolving. Until the last decade the goals were primarily the treatment of symptoms. ⋯ Over the past decade there has been increasing evidence in favor of more 'objective' measures of biologic disease activity including biomarkers such as C-reactive protein and mucosal healing in Crohn's disease and the histologic resolution of active inflammation in ulcerative colitis. The objective changes have provided expanded therapeutic goals based on longer-term maintenance therapies with the potential to modify the chronic disease behavior and to reduce pharmacoeconomic costs (reductions in hospitalizations, surgeries and neoplasia).
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To discuss a cure for IBD, one should first define the concept 'a cure'. If it is intended as the general restoration of health, this is already possible, as many current therapies do a good job in inducing long periods of remission in Crohn's disease, and colectomy can technically cure ulcerative colitis. If it is more strictly defined as the complete and permanent elimination of the cause, predisposing and permissive factors, reinstatement of normal microbial ecology and restoration of mucosal immune homeostasis, then a cure for IBD is out of reach, at least for now. ⋯ To achieve a cure, one key approach is currently missing: the integration of knowledge from all the pathogenic components. We continue to learn more and more about each component using traditional 'canonical' systems, which allow the accumulation of data without taking into consideration the other components. We are still not studying the 'omes' of IBD, we should be using 'omics' technologies that can generate a more global vision of IBD pathogenesis on which to base novel, multiple pathway-integrated therapies.