S erotonin (5HT), a well-known neurotransmitter and vasoactive substance, also regulates a wide range of physiological actions in the gastrointestinal tract. 1 5HT is a potent mitogen for many different cell types, 2 including hepatocytes, 3 and it is crucial for liver regeneration. 4 On a cellular level 5HT acts predominately
Microtubule-dependent effects are partly regulated by factors that coordinate polymer dynamics such as the microtubule-destabilizing protein stathmin (oncoprotein 18). In cancer cells, increased microtubule turnover affects cell morphology and cellular processes that rely on microtubule dynamics such as mitosis and migration. However, the molecular mechanisms deregulating modifiers of microtubule activity in human hepatocarcinogenesis are poorly understood. Based on profiling data of human hepatocellular carcinoma (HCC), we identified far upstream element binding proteins ( M icrotubules are cytoplasmic components of the cytoskeleton that play a critical role in the maintenance of cell morphology, division, intracellular transport, and motility. Microtubule polymers consist of ␣-and -tubulin heterodimers and are characterized by continuous transition between phases of shrinkage (depolymerization/catastrophe) and elongation (polymerization/rescue). This dynamic instability is regulated by several factors, including microtubule-associated proteins and microtubule destabilizers such as stathmin. 1 The cytosolic phosphoprotein stathmin (oncoprotein 18) is expressed in most proliferating cells, and its concentration increases during the S-phase of the cell cycle. In this context, stathmin facilitates microtubule shortening by tubulin sequestration and active promotion of microtubule catastrophe, depending on the sequential phosphorylation status of four serine residues. 2 When cells enter mitosis, stathmin is inactivated by phosphorylation, allowing the formation of the mitotic spindle; subsequent reactivation of stathmin by dephosphorylation is necessary for the exit from mitosis. 1
Hepatocellular carcinomas (HCCs) and bile duct carcinomas (BDCs) have a poor prognosis. Therefore, surveillance strategies including sensitive and specific serum markers for early detection are needed. Recently, Golgi Phosphoprotein 2 (GOLPH2) has been proposed as a serum marker for HCC, but GOLPH2 expression data in liver tissues was not available. Using tissue microarrays and immunohistochemistry, we semiquantitatively analyzed GOLPH2 protein expression in patients with HCC (n ؍ 170), benign liver tumors (n ؍ 22), BDC (n ؍ 114) and normal liver tissue (n ؍ 105). A newly designed sandwich enzyme-linked immunoassay (ELISA) was used to analyze GOLPH2 levels in the sera of patients with HCC (n ؍ 62), hepatitis C virus (HCV) (n ؍ 29), BDC (n ؍ 10), and healthy control persons (n ؍ 12). By immunohistochemistry 121/170 (71%) of HCC showed strong GOLPH2 expression, which was significantly associated with a higher tumor grade (P ؍ 0.01). A total of 97/114 (85%) BDCs showed a strong GOLPH2 expression which proved to be an independent prognostic factor for overall survival (P < 0.05). Serum levels of GOLPH2 measured by ELISA were significantly elevated in patients with HCC with underlying HCV infection (median 18 mg/L, P < 0.05) and patients with BDC (median ؍ 14.5 mg/L, P < 0.01) in comparison to healthy controls (median 4 mg/L). Conclusion: GOLPH2 protein is highly expressed in tissues of HCC and BDC. GOLPH2 protein levels are detectable and quantifiable in sera by ELISA. In patients with hepatitis C, serial ELISA measurements in the course of the disease appear to be a promising complementary serum marker in the surveillance of HCC. GOLPH2 should be further evaluated as a serum tumor marker in BDC on a larger scale.
Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases.
Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.
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