Aberrant expressions of annexin A10 short isoform, osteopontin and alpha-fetoprotein at chromosome 4q cooperatively contribute to progression and poor prognosis of hepatocellular carcinoma

Chromosome 4q exhibits high frequency of allelic loss in hepatocellular carcinoma (HCC). This study aimed to elucidate the interaction of the frequent aberrant mRNA expression of alpha-fetoprotein (AFP), osteopontin (OPN) and a novel short isoform of annexin A10 (ANXA10S) at 4q in the tumor progression among 294 patients who received surgical resection of unifocal primary HCC. AFP overexpression, OPN overexpression and ANXA10S down-regulation correlated with high-grade and high-stage tumors, early tumor recurrence (all P<0.0001), and lower 10-year survival (all P=0.000001). The AFP overexpression correlated with OPN overexpression (P=0.0026) and ANXA10S down-regulation (P=0.00001), while OPN overexpression correlated with ANXA10S down-regulation (P=0.00001). Pair-wise combinations revealed interactive effects between these genetic variants for tumor grade, tumor stage and early recurrence (all P<0.0001). HCCs with more genetic aberrations had more frequent high tumor grade, portal vein invasion (stage IIIB-IV) and early recurrence (all P<0.0001). The 10-year survival rate for HCCs with all three genetic alterations was the lowest (7%), followed by those with two (22%) or one event (29%), and the highest for those without these changes (43%), P=0.000001. The prognostic stratification using these molecular factors was similar to that of histopathological staging. These three genetic alterations also helped to identify different subgroups of patients of stage II HCC but with different prognosis (P=0.015). In conclusion, the aberrant expressions of AFP, OPN and ANXA10S cooperatively contribute to tumor progression and poor prognosis, and are useful for molecular staging of HCC and the subclassification of stage II HCC without vascular invasion.     

Putranjivain A from Euphorbia jolkini inhibits proliferation of human breast adenocarcinoma MCF-7 cells via blocking cell cycle progression and inducing apoptosis

Putranjivain A, isolated from the whole plant of Euphorbia jolkini Bioss (Euphorbiaceae), was investigated for its antiproliferative activity in human breast adenocarcinoma MCF-7 cells. The results showed that putranjivain A inhibited the proliferation of MCF-7 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. Enzyme-linked immunosorbent assay showed that putranjivain A increased the expression of p21/WAF1 concomitantly as MCF-7 cell underwent G0/G1 arrest. An enhancement in Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by putranjivain A. Our study reports here for the first time that the induction of p21/WAF1 and the activity of Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of putranjivain A in MCF-7 cells.     

Concomitant Bentall operation plus aortic arch replacement surgery

BackgroundThe Bentall operation is recommended for thoracic aortic dissection or aneurysm involving the aortic root. However, if the lesion extends to the aortic arch, concomitant Bentall operation plus aortic arch replacement (CoBAAR) surgery is required. CoBAAR is challenging because of its complex cardiopulmonary procedure, prolonged cardiopulmonary bypass time, and demanding operative techniques. Therefore, surgical mortality and morbidity rates for CoBAAR are very high. However, the Bentall operation performed as a single procedure may lead to reoperation if the residual aneurysm progresses. Therefore, CoBAAR as a one-stage surgery can lower the need for reoperation and possible further complications.MethodsNine patients received CoBAAR during January 2005 to May 2010. Six patients were diagnosed with Sanford type A aortic dissection and three with nondissecting ascending aortic and arch aneurysm. Four patients received a Bentall operation plus hemiarch replacement. The others received a Bentall operation plus total arch replacement along with elephant trunk because of extensive lesions.ResultsThe in-hospital mortality was 11.1% (1 patient with total arch replacement). Morbidity included stroke (2 patients), spinal cord injury (1 patient), mechanical ventilation for more than 72 hours (5 patients), and temporary renal dialysis (3 patients). Eight patients survived.ConclusionCoBAAR is a demanding operative technique requiring complex cardiopulmonary bypass. However, surgeons can perform this procedure on extensive ascending aortic dissection or aneurysm patients, achieving satisfactory results.     

Community-onset Clostridium difficile infection at a tertiary medical center in southern Taiwan, 2007–2015

Background

Clostridium difficile infection (CDI) is well-known as the major cause of infectious diarrhea in hospitalized patients. Community-onset CDI (CO-CDI) is an emerging threat. However, clinical information of CO-CDI in Taiwan remains scarce.

Renal Function-Dependent Associations of Statins with Outcomes of Ischemic Stroke

Aim: Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function.Methods: We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke.Results: Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3–5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m². Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60–89 mL/min/1.73 m². Statin therapy in patients with an eGFR of 60–89 mL/min/1.73 m² may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57).Conclusions: In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.     

Snail regulates Nanog status during the epithelial–mesenchymal transition via the Smad1/Akt/GSK3β signaling pathway in non-small-cell lung cancer

The epithelial–mesenchymal transition (EMT), a crucial step in cancer metastasis, is important in transformed cancer cells with stem cell-like properties. In this study, we established a Snail-overexpressing cell model for non-small-cell lung cancer (NSCLC) and investigated its underlying mechanism. We also identified the downstream molecular signaling pathway that contributes to the role of Snail in regulating Nanog expression. Our data shows that high levels of Snail expression correlate with metastasis and high levels of Nanog expression in NSCLC. NSCLC cells expressing Snail are characterized by active EMT characteristics and exhibit an increased ability to migrate, chemoresistance, sphere formation, and stem cell-like properties. We also investigated the signals required for Snail-mediated Nanog expression. Our data demonstrate that {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, SB431542, LDN193189, and Noggin pretreatment inhibit Snail-induced Nanog expression during EMT. This study shows a significant correlation between Snail expression and phosphorylation of Smad1, Akt, and GSK3β. In addition, pretreatment with SB431542, LDN193189, or Noggin prevented Snail-induced Smad1 and Akt hyperactivation and reactivated GSK3β. Moreover, {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 pretreatment prevented Akt hyperactivation and reactivated GSK3β without altering Smad1 activation. These findings provide a novel mechanistic insight into the important role of Snail in NSCLC during EMT and indicate potentially useful therapeutic targets for NSCLC.