Abstract:
BACKGROUND:Pancreatic ductal adenocarcinoma (PDA) is a devastating disease that killed nearly 38,000 people in the United States this past year. OBJECTIVE:Treatment of PDA typically includes surgery and/or chemotherapy with gemcitabine. No reliable biomarker exists for prognosis or response to chemotherapy. Two previously proposed prognostic markers, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), are regulated by Hu protein antigen R (HuR), an mRNA binding protein that we have previously demonstrated to be a promising predictive marker of gemcitabine response. This study was designed to evaluate the clinical utility of HuR, COX-2, and VEGF as potential prognostic and predictive biomarkers for PDA. METHODS:A tissue microarray of 53 PDA specimens from patients who underwent potentially curative pancreatic resection was analyzed. HuR, COX-2, and VEGF status were correlated with clinicopathologic and survival data. We also performed ribonucleoprotein immunoprecipitation assays using an HuR antibody to assess VEGF and COX-2 mRNA binding to HuR in pancreatic cancer cells. RESULTS:Roughly 50% (27/53) of patients had high cytoplasmic HuR expression. These patients had worse pathologic features as assessed by T staging (P = 0.005). Only cytoplasmic HuR status correlated with tumor T staging, whereas VEGF (P = 1.0) and COX-2 (P = 0.39) expression did not correlate with T staging. Additionally, HuR status was an unprecedented positive predictive marker for overall survival in patients treated with gemcitabine, pushing median survival over 45 months in the high cytoplasmic HuR expressing patient population compared with less than 23 months in the low cytoplasmic HuR expressing patient group (P = 0.033 for log-rank test and P = 0.04 in a Cox regression model) for the low versus high cytoplasmic HuR expressing group. We also validated that mRNA transcripts for both VEGF and the gemcitabine metabolizing enzyme, deoxycytidine kinase, are specifically bound by HuR in pancreatic cancer cells. CONCLUSIONS:HuR is a useful prognostic biomarker for PDA patients as indicated by its association with higher tumor T stage. Additionally, HuR status is a robust predictor of outcome for patients with resected PDA in the setting of adjuvant gemcitabine therapy. Finally, HuR binds to VEGF mRNA implying that HuR, in part, regulates VEGF expression in PDA. This study supports the notion that HuR status should be used by clinicians for the individualized treatment of PDA in the future.
journal_name
Ann Surgjournal_title
Annals of surgeryauthors
Richards NG,Rittenhouse DW,Freydin B,Cozzitorto JA,Grenda D,Rui H,Gonye G,Kennedy EP,Yeo CJ,Brody JR,Witkiewicz AKdoi
10.1097/SLA.0b013e3181f1fd44subject
Has Abstractpub_date
2010-09-01 00:00:00pages
499-505; discussion 505-6issue
3eissn
0003-4932issn
1528-1140pii
00000658-201009000-00010journal_volume
252pub_type
杂志文章abstract::This study examines the influence of total parenteral nutrition (TPN) compared with 5% dextrose (D5) infusion on skeletal muscle and adipose tissue lipoprotein lipase (LPL) activity in nutritionally depleted, injured and infected patients. The plasma concentrations of glucose, free fatty acid (FFA), triglyceride and i...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-198112000-00003
更新日期:1981-12-01 00:00:00
abstract::A previously described balloon tipped dilatation catheter has been used during revascularization surgery to dilate lesions which potentially could limit the runoff of the saphenous bypass grafts. A total of 34 lesions were dilated in 25 patients. Restudy of 12 patients (15 lesions) demonstrated positive results and no...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-198002000-00017
更新日期:1980-02-01 00:00:00
abstract:OBJECTIVE:To estimate long-term mortality following major burn injury compared with matched controls. SUMMARY BACKGROUND DATA:The effect of sustaining a major burn injury on long-term life expectancy is poorly understood. METHODS:Using health administrative data, all adults who survived to discharge after major burn ...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0000000000002722
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND AND AIMS:The lower esophageal sphincter (LES) in patients with gastroesophageal reflux disease often has a low resting pressure and a short abdominal length. The mechanism by which this occurs is unknown. We hypothesize that gastric distension causes progressive effacement of the abdominal portion of the LES...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0b013e3181e3e411
更新日期:2010-07-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to assess how thermal ablation of colorectal liver metastases affects the outgrowth of micrometastases in the transition zone (TZ) between ablated tissue and the unaffected reference zone (RZ) in 2 different murine models. BACKGROUND:Thermal destruction therapies of nonresectable co...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0b013e3181a38ef5
更新日期:2009-05-01 00:00:00
abstract::Fibrin deposition in response to bacterial peritonitis appears to predispose to residual infection in the peritoneal cavity. Our previous studies have demonstrated that intraperitoneal fibrinolysis using human recombinant tissue plasminogen activator (t-PA) prevented abscess formation in a rat intra-abdominal sepsis m...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-199002000-00003
更新日期:1990-02-01 00:00:00
abstract::A technique for repairing benign hilar hepatic duct strictures using transhepatic intubation with a large bore silastic stent is described. This procedure has been used in 10 patients. In 9 instances the stricture involved the common hepatic duct, and in one patient the right and left hepatic ducts. Nine of the strict...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-197605000-00005
更新日期:1976-05-01 00:00:00
abstract::An experimental model was developed in dogs to correlate radioisotope scan findings of iatrogenic, in vivo, splenic injury with the natural history of the injury as determined by the clinical course and both gross and microscopic observations. It was found that small subcapsular injuries do not appear as discrete foca...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-197804000-00011
更新日期:1978-04-01 00:00:00
abstract:OBJECTIVES:Recent data from Iraq supporting early aggressive use of fresh frozen plasma (FFP) in a 1:1 ratio to packed red blood cells (PRBCs) has led many civilian trauma centers to adopt this resource intensive strategy. METHODS:Prospective data were collected on 806 consecutive trauma patients admitted to the inten...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0b013e31818990ed
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:The objective of our study was to determine if differences in outcomes at treating facilities can help explain these age-based racial disparities in survival after trauma. BACKGROUND:It has been previously demonstrated that racial disparities in survival after trauma are dependent on age. For patients younge...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0000000000000809
更新日期:2015-07-01 00:00:00
abstract::: Since their discovery, neutrophil extracellular traps (NETs) have been implicated in a broad array of functions, both beneficial and detrimental to the host. Indeed, NETs have roles in infection, sepsis, wound healing, thrombotic disease, and cancer propagation, all of which are directly implicated in the care of su...
journal_title:Annals of surgery
pub_type: 杂志文章,评审
doi:10.1097/SLA.0000000000003586
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:To evaluate the long-term outcome of patients with esophageal cancer after resection of the extraesophageal component of the neoplastic process en bloc with the esophageal tube. SUMMARY BACKGROUND DATA:Opinions are conflicting about the addition of extended resection of locoregional lymph nodes and soft tiss...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-200107000-00005
更新日期:2001-07-01 00:00:00
abstract::Intestinal ischemia-reperfusion is a common clinical event associated with both clinical and experimental distant organ injury. In particular, the pulmonary microvasculature appears to be susceptible to injury resulting from systemic inflammatory mediator activation. This study was designed to evaluate the hypothesis ...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-199301000-00009
更新日期:1993-01-01 00:00:00
abstract::Records of 32 patients with 34 villous and tubulovillous adenomas of the duodenum, treated at the Cleveland Clinic over the past 21 years, were reviewed. Twenty-two patients (69%) had complete resection of the adenoma; the incidence of malignancy was 47%. Five patients underwent a Whipple procedure; 4 patients had seg...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-198803000-00002
更新日期:1988-03-01 00:00:00
abstract:OBJECTIVE:To study risk factors for early and late death after heart transplantation in the current era. SUMMARY BACKGROUND DATA:The current cardiac transplant population differs from earlier periods in that an increasing number of sicker patients, such as those with ventricular assist device (LVAD) support, prior car...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-200009000-00002
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVES:Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND:The union internationale contre le ...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0000000000000968
更新日期:2014-11-01 00:00:00
abstract::Descriptions of the fasciae of the lower half of the face and of the adjacent cervical fasciae have long been puzzling and descriptively much too complex. For this reason, medical students, young medical and dental practitioners, and at times even senior surgeons frequently do not understand the anatomy of the cervico...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-198612000-00015
更新日期:1986-12-01 00:00:00
abstract:OBJECTIVE:The authors assessed the impact of gastrinoma resection on the subsequent development of hepatic metastases in Zollinger-Ellison syndrome. SUMMARY BACKGROUND DATA:The symptoms of acid hypersecretion can be controlled medically in Zollinger-Ellison syndrome with high-dose pharmacologic therapy. The current ro...
journal_title:Annals of surgery
pub_type: 临床试验,杂志文章
doi:10.1097/00000658-199409000-00008
更新日期:1994-09-01 00:00:00
abstract::Over the past 27 years cavernous hemangioma of the liver has been diagnosed in 12 nonoperated patients and in 16 patients who had resection of the lesion at Strong Memorial Hospital. In almost all patients the diagnosis was suggested by an imaging procedure. In the 12 nonoperated patients the average size of the tumor...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-198705000-00003
更新日期:1987-05-01 00:00:00
abstract:OBJECTIVE:To establish criteria for venous reconstruction of middle hepatic vein (MHV) tributaries of the right liver graft in adult-to-adult living donor liver transplantation (LDLT). SUMMARY BACKGROUND DATA:In adult LDLT using the right hemiliver, the MHV is usually separated from the graft, which results in potenti...
journal_title:Annals of surgery
pub_type: 临床试验,杂志文章
doi:10.1097/00000658-200208000-00013
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVE:To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA:Conflictin...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-199808000-00014
更新日期:1998-08-01 00:00:00
abstract:AIM OF STUDY:The objective of this study was to determine the pattern of recurrence after one or more episodes of adhesive small bowel obstruction (ASBO) during a follow-up period of up to 40 years. Furthermore, we wanted to analyze possible factors with an influence on the recurrence rate and to study the magnitude of...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/01.sla.0000132988.50122.de
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVE:The management and outcome of 138 abdominal shotgun wounds were examined over a 5-year period. SUMMARY BACKGROUND DATA:It has been proposed that exploratory laparotomy may be unnecessary and even overused in a subset of patients with abdominal shotgun wounds. METHODS:Data on shotgun wound patients from Octo...
journal_title:Annals of surgery
pub_type: 临床试验,杂志文章
doi:10.1097/00000658-199503000-00009
更新日期:1995-03-01 00:00:00
abstract:INTRODUCTION:Initial excitement for Natural Orifice Transluminal Endoscopic Surgery (NOTES) has been partly tempered by the reality that a NOTES procedure without laparoscopic or needleoscopic-assistance has not been performed by most groups. After safely performing laparoscopically-assisted transvaginal cholecystectom...
journal_title:Annals of surgery
pub_type: 临床试验,杂志文章
doi:10.1097/SLA.0b013e3181a802e2
更新日期:2009-06-01 00:00:00
abstract:OBJECTIVE:To review the current concepts in the mediastinal staging of nonsmall cell lung cancer (NSCLC), evaluating traditional and modern staging modalities. SUMMARY BACKGROUND DATA:Staging of NSCLC includes the assessment of mediastinal lymph nodes. Traditionally, computed tomography (CT) and mediastinoscopy are us...
journal_title:Annals of surgery
pub_type: 杂志文章,评审
doi:10.1097/01.SLA.0000081086.37779.1a
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVE AND BACKGROUND:Watch-and-wait approach in rectal cancer relies on the identification of a clinical complete response (CR) after neoadjuvant (chemo)radiotherapy. This is mainly performed by rectal examination, magnetic resonance imaging, and endoscopy. Endoscopy has been less well studied, and the objective of...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/SLA.0000000000003718
更新日期:2019-12-09 00:00:00
abstract:BACKGROUND:The optimal transfusion threshold after surgery in children is unknown. We analyzed the general surgery subgroup of the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study to determine the impact of a restrictive versus a liberal transfusion strategy on new or progressive multiple orga...
journal_title:Annals of surgery
pub_type: 杂志文章,随机对照试验
doi:10.1097/SLA.0b013e3181c5dc2e
更新日期:2010-03-01 00:00:00
abstract::The development of effective, non-toxic (local and systemic) methods for the rapid chemical (enzymatic and non-enzymatic) debridement of third degree burns would dramatically reduce the morbidity and mortality of severely burned patients. Sepsis is still the major cause of death of patients with extensive deep burns. ...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-197410000-00032
更新日期:1974-10-01 00:00:00
abstract:OBJECTIVE:To review the literature on current management of hepatocellular carcinoma (HCC). BACKGROUND:Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. There have been substantial advances in the surgical and medical treatment of HCC within...
journal_title:Annals of surgery
pub_type: 杂志文章,评审
doi:10.1097/SLA.0b013e31820d944f
更新日期:2011-03-01 00:00:00
abstract::The role of surgery in the treatment of gastrinoma is unclear. The purpose of this study was to determine prospectively the surgical cure rate using a controlled clinical trial. Eleven patients who fit the entry criteria underwent abdominal exploration and attempted tumor resection for cure. A historical control group...
journal_title:Annals of surgery
pub_type: 杂志文章
doi:10.1097/00000658-199001000-00002
更新日期:1990-01-01 00:00:00