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Xin Yi Wong Andrew Qi Jun Lim Qianyu Shen John Whay Kuang Chia Min Hoe Chew Wah Siew Tan 《Current medical research and opinion》2020,36(10):1677-1686
Abstract
Objective
Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies. 相似文献3.
Tien‐Yao Tsai Iat‐Lon Leong Ka‐Shun Cheng Lian‐Ru Shiao Tzu‐Hui Su Kar‐Lok Wong Paul Chan Yuk‐Man Leung 《Fundamental & clinical pharmacology》2019,33(1):52-62
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation. 相似文献
4.
Fur-Hsing Wen Jen-Shi Chen Wen-Chi Chou Wen-Cheng Chang Wen Chi Shen Chia-Hsun Hsieh Siew Tzuh Tang 《Journal of pain and symptom management》2019,57(1):64-72
Context
Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.Objectives/Methods
We used multivariate hierarchical linear modeling to simultaneously evaluate associations between five distinct patterns of conjoint symptom distress and functional impairment (symptom-functional states) and subjective caregiving burden, QOL, and depressive symptoms in a convenience sample of 215 family caregiver–patient dyads. Data were collected every 2 to 4 weeks over patients' last 6 months.Results
Caregivers of patients in the worst symptom-functional states (States 3–5) reported worse subjective caregiving burden and depressive symptoms than those in the best two states, but the three outcomes did not differ between caregivers of patients in State 3 and States 4–5. Caregivers of patients in State 5 endured worse subjective caregiving burden and QOL than those in State 4. Caregivers of patients in State 4 suffered worse subjective caregiving burden and depressive symptoms but comparable QOL to those in State 2.Conclusion
Patients' five distinct, conjoint symptom-functional states were significantly and differentially associated with their caregivers' worse subjective caregiving burden, QOL, and depressive symptoms while caring for patients over their last 6 months. 相似文献5.
Varsha Patki Joe Virbasius William S. Lane Ban-Hock Toh Howard S. Shpetner Silvia Corvera 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(14):7326-7330
Phosphatidylinositol 3-kinases (PI 3-kinases) have been implicated in membrane trafficking in the secretory and endocytic pathways of yeast and mammalian cells, but the molecular mechanisms by which these lipid kinases operate are not known. Here we identify a protein of 170 kDa that is rapidly released from cell membranes in response to wortmannin, a potent inhibitor of mammalian PI 3-kinases. The amino acid sequence of peptides from p170 reveal its identity to early endosomal antigen (EEA) 1, an endosomal antigen with homology to several yeast proteins genetically implicated in membrane trafficking. Immunofluorescence analysis of 3T3-L1 adipocytes with antisera against p170/EEA1 reveal a punctate peripheral pattern that becomes diffuse in response to wortmannin. In vitro, p170/EEA1 binds specifically to liposomes containing PIns(3)P, suggesting that the effect of wortmannin on cells is due to inhibition of PIns(3)P production. Thus, p170/EEA1 may define a family of proteins that mediate the regulatory effects of 3′-phosphoinositides on membrane trafficking in yeast and mammalian cells. 相似文献
6.
Satomi-Kobayashi Seimi Kawashima Seinosuke Sakoda Tsuyoshi Ueyama Tomomi Hirase Tetsuaki Kawai Miki Toh Ryuji Iwai Kenji Yokoyama Mitsuhiro 《Circulation journal》2004,68(3):247-253
BACKGROUND: Glycogen synthase kinase-3 beta (GSK-3beta) is involved in many cellular processes, such as metabolism, apoptosis, differentiation and proliferation. Insulin-like growth factor-1 (IGF-1), which is well known to have a hypertrophic effect on cardiomyocytes, inactivates (phosphorylates) GSK-3beta in some cell types. The role of GSK-3beta in cardiomyocytes as a negative regulator of cardiac hypertrophy has been recently reported and the present study investigated the role of GSK-3beta in the cardiac hypertrophy of cultivated neonatal rat cardiomyocytes induced by IGF-1. METHODS AND RESULTS: First, the IGF-1 induced signal transduction leading to GSK-3beta in neonatal rat cardiomyocytes was examined. The phosphatidylinositol (PI) 3-kinase/Akt/GSK-3 beta signaling induced by IGF-1 was investigated using inhibitors of PI 3-kinase and Ad AktAA, a dominant negative form of Akt. Furthermore, using Ad MEK DN, a dominant negative form of MEK, it was found that MEK negatively regulates Akt phosphorylation upon IGF-1 stimulation. Next, it was examined whether GSK-3beta acts as a negative regulator in the cardiac hypertrophy induced by IGF-1. Sustained stimulation by IGF-1 caused cardiac hypertrophy in protein synthesis and cellular morphology, and overexpression of unphosphorylatable GSK-3beta (Ad GSK-3beta S9A) repressed these hypertrophic effects of IGF-1. CONCLUSIONS: GSK-3beta may play an important role as a negative regulator of cardiac hypertrophy induced by IGF-1. 相似文献
7.
A W Gelb P Floyd P Lok S J Peerless M Farrell 《Canadian Anaesthetists' Society journal》1986,33(2):173-177
Barbiturate coma is still recommended for brain protection during periods of temporary focal ischaemia such as during carotid endarterectomy. We tested the hypothesis that a single dose of barbiturate given before a period of protracted severe focal ischaemia would protect against focal cerebral infarction. Sixteen cats had the proximal left middle cerebral artery (MCA) occluded. Eight cats received halothane alone titrated to keep their pulse and blood pressure within the normal range. Eight cats received, in addition to halothane, a bolus of thiopentone sufficient to produce an isoelectric EEG immediately prior to MCA occlusion. Six hours after the occlusions the animals were sacrificed and the brains scored histologically to assess both size and severity of ischaemia. There was no statistically significant difference in the size or severity of the infarcts between the groups. We conclude from this study that the extent of the histological injury was not reduced by a single prophylactic bolus of thiopentone given before prolonged focal cerebral ischaemia. 相似文献
8.
Siew Han Chay A Bakr M Rabie 《American journal of orthodontics and dentofacial orthopedics》2002,122(1):95-102
In this case report, orthodontic intervention was used to move the gingival margin of a maxillary canine incisally by almost 9 mm to mimic a lateral incisor. Increasing the thickness of the labial plate of bone of the canine and subsequently increasing the thickness of the attached gingiva before extrusion prevented gingival recession at a later stage. In many situations, orthodontic treatment can achieve results that could not be attained by restorations and other means of cosmetic dentistry, especially when dealing with gingival margins and gingival height. A step-by-step approach to achieving these treatment objectives is described. 相似文献
9.
A S Lok 《Digestive diseases (Basel, Switzerland)》1992,10(1):46-52
Maternal-infant transmission of hepatitis B virus (HBV) infection is estimated to account for 40-50% of HBV carriers in Chinese populations, but is uncommon among other ethnic groups. The high frequency of maternal-infant transmission among Chinese populations is related to the high prevalence of carrier mothers with replicative HBV infection. The natural course of perinatally acquired HBV infection consists of three phases: an initial phase of immune tolerance followed by a phase of immune clearance and then a non-replicative phase. The initial phase of immune tolerance which may last for several decades contributes to the poor response to interferon therapy. The high prevalence of carrier mothers with replicative infection mandates a combination of passive and active prophylaxis for the newborns. 相似文献
10.
Brendan M McGuire Herbert L Bonkovsky Robert L Carithers Raymond T Chung Leonard I Goldstein John R Lake Anna S Lok Carol J Potter Elizabeth Rand Michael D Voigt Pamela R Davis Joseph R Bloomer 《Liver transplantation》2005,11(12):1590-1596
In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival. 相似文献