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| 1 | Calcium signaling and T-type calcium channels in cancer cell cycling显示文摘Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells, free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear; however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers. | James T Taylor Xiang-Bin Zeng Jonathan E Pottle Kevin Lee Alun R Wang Stephenie G Yi lennifer A S Scruggs Suresh S Sikka Ming Li | 2008 | World Journal of Gastroenterology2008，14，32： | 12 |
| 2 | Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart显示文摘出生后的心通过 hypertrophic 生长适应应力和超载,可能病理学或有益的一个过程(生理的肥大) 。生理的肥大改进心脏的性能在健康并且 diseased 个人,然而,宣传这有利改编的机制仍然保持糟糕定义。我们识别 cytokine cardiotrophin (CT1 ) 1 作为能够包括导致的导出 cardiomyocyte 的 angiogenic 信号的心肌层,和刺激的短暂、可逆的肥大概括心的生理的生长的特色的一个因素增加了由脉管形成。CT1 的能力从 caspase 激活的调停 CK2 的制止发源导致生理的肥大,阻止到无限制的病理学的生长的转变。外长的 CT1 蛋白质交货稀释了病理并且在正确的心失败的一个严格的模型恢复了可收缩的功能,建议为这难处理的心脏病的一种新奇处理选择。 | Mohammad Abdul-Ghani Colin Suen Baohua Jiang Yupu Deng Jonathan J Weldrick Charis Putinski Steve Brunette Pasan Femando Tom T Lee Peter Flynn Frans H H Leenen Patrick G Burgon Duncan J Stewar Lynn A Megeney | 2017 | Cell Research2017，27，10： | 8 |
| 3 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 4 | Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial显示文摘 | Matthew T Seymour Sarah R Brown Gary Middleton Timothy Maughan Susan Richman Stephen Gwyther Catherine Lowe Jennifer F Seligmann Jonathan Wadsley Nick Maisey Ian Chau Mark Hill Lesley Dawson Stephen Falk Ann O’Callaghan Kim Benstead Philip Chambers Alfred | 2013 | Lancet Oncology2013，，8： | 6 |
| 5 | Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed. | Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee | 2014 | World Journal of Clinical Oncology2014，5，2： | 5 |
| 6 | Chronic overexpression of PNPLA3^sup I148M^ in mouse liver causes hepatic steatosis显示文摘 | Li John Zhong Huang Yongcheng Karaman Ruchan Ivanova Pavlina T Brown H Alex Roddy Thomas Castro-Perez Jose Cohen Jonathan C Hobbs Helen H | 2012 | EN2012，，11： | 3 |
| 7 | Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘 | Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari | 2013 | Gut2013，，11： | 2 |
| 8 | Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘 | Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari | 2013 | Gut2013，，11： | 2 |
| 9 | Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers显示文摘BACKGROUND Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers(BTC).There is no established second-line therapy,and retrospective reviews report median progression-free survival(PFS)less than 3 mo on second-line therapy.5-Fluorouracil plus irinotecan(FOLFIRI)is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum,though there is a paucity of data regarding its efficacy in this population.AIM To assess the efficacy of FOLFIRI in patients with biliary tract cancers.METHODS We retrospectively identified patients with advanced BTC who were treated with FOLFIRI at MD Anderson,University of Michigan and Mayo Clinic in Jacksonville.Data were collected on patient demographics,BTC subtype,response per RECIST v1.1,progression and survival.RESULTS Ninety-eight patients were included of which 74(75%)had metastatic and 24(25%)had locally advanced disease at the time of treatment with FOLFIRI.The median age was 60(range,22-86)years.The number of patients with extrahepatic cholangiocarcinoma,gall bladder cancer and intrahepatic cholangiocarcinoma were 10,17 and 71,respectively.FOLFIRI was used as 1st,2nd,3rd or 4th–Nth lines in 8,50,36 and 4 patients,respectively.Median duration on FOLFIRI in the entire cohort was 2.2(range,0.5-8.4)mo.The median PFS and overall survival were 2.4(95%confidence interval(CI):1.7-3.1)and 6.6(95%CI:4.7-8.4)mo,respectively.Median PFS for patients treated with FOLFIRI in 1st,2nd,3rd or 4th–Nth lines were 3.1,2.5,2.3 and 1.5 mo,respectively.Eighteen patients received concurrent bevacizumab(n=13)or EGFR-targeted therapy(n=5)with FOLFIRI,with a median PFS of 2.7 mo(95%CI:1.7-5.1).CONCLUSION In this largest multi-institution retrospective review of 98 patients with BTC treated with FOLFIRI,efficacy appears to be modest with outcomes similar to other cytotoxic chemotherapy regimens. | Jonathan D Mizrahi Valerie Gunchick Kabir Mody Lianchun Xiao Phanikeerthi Surapaneni Rachna T Shroff Vaibhav Sahai | 2020 | World Journal of Gastrointestinal Oncology2020，12，1： | 2 |
| 10 | Strategies to tackle the challenges of external beam radiotherapy for liver tumors显示文摘Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies. | Michael I Lock Jonathan Klein Hans T Chung Joseph M Herman Edward Y Kim William Small Nina A Mayr Simon S Lo | 2017 | World Journal of Hepatology2017，9，14： | 2 |
| 11 | Structure and evolution of an obliquely sheared continental margin: Rio Muni, West Mrica显示文摘 | Jonathan P T | 2003 | Tectonophysics2003，374，： | 1 |
| 12 | Defying gravity显示文摘 | Jonathan H C Stephen F T | 1998 | Civil Engineering1998，68，2： | 1 |
| 13 | Intensive chemotherapy and radicaf resections for primary nonse minomatous mediastinaf germ ceff tumors显示文摘 | Garret L W Grant D T Jonathan C N | 2000 | Ann Thorac Surg2000，69，： | 1 |
| 14 | 南沙群岛永暑礁晚全新世软体动物记录与古环境变化显示文摘对南沙群岛永暑礁南永3井软体动物的丰度、营养结构、化学元素和堆积速率的定量分析表明,晚全新世永暑礁潟湖经历了数次相对开放与封闭、与外海交流时强时弱以及盐度多次显著变化的过程。与氧同位素和北半球晚全新世快速气候事件的进一步对比表明,晚全新世快速变化的气候事件也波及到南海,由此造成的潟湖水动力环境、古盐度和沉积速率的变化深刻地影响着软体动物的发育。基于软体动物的替代指标和氧同位素变化的综合分析,初步划分了晚全新世永暑礁潟湖7个变化阶段。 | 冯伟民 Jonathan A T 蓝琇 陈木宏 | 2005 | 热带海洋学报2005，24，4： | 1 |
| 15 | Quality of life, functional outcome and cost of early glottis cancer 显示文摘 | Jonathan C Jonas T | 2003 | Lar2003，113，： | 1 |
| 16 | Gas Cleaning at High Temperatures Using Rigid Ceramic Filters显示文摘 | Jonathan S Guanchuan T Vusumuzi S | 2003 | Advanced Powder Technol2003，14，6： | 1 |
| 17 | Fast and robust spatially constrained Gaussian mixture model for image segmentation显示文摘 | NGUYEN T M JONATHAN W Q M | 2013 | IEEE Trans on Circuits and Systems for Video Technology2013，23，4： | 1 |
| 18 | Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells显示文摘 | James G Krueger Jonathan T | 1995 | J Exp Med1995，182，： | 1 |
| 19 | Gravity-driven structures and rift basin evolution: Rio Muni Basin, offshore equatorial, West Africa显示文摘 | Jonathan P T | 1995 | AAPG Bulletin1995，79，8： | 1 |
| 20 | Changes in lung composition and regional perfusion and tissue distribution in patients With ARDS 显示文摘 | Jonathan D Andrew T David M | 2011 | Respirology2011，15，8： | 1 |
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