bluuebunny/crossref_metadata_2025_split huggingface dataset:
Faecal haemoglobin concentration is related to severity of colorectal neoplasia
Authors: Digby Jayne , Fraser Callum G , Carey Francis A , McDonald Paula J , Strachan Judith A , Diament Robert H , Balsitis Margaret , Steele Robert J C 
Published: February 2013

AimsGuaiac faecal occult blood tests are being replaced by faecal immunochemical tests (FIT). We investigated whether faecal haemoglobin concentration (f-Hb) was related to stage in progression of colorectal neoplasia, studying cancer and adenoma characteristics in an evaluation of quantitative FIT as a first-line screening test.MethodsWe invited 66 225 individuals aged 50–74 years to provide one sample of faeces. f-Hb was measured on samples from 38 720 responders. Colonoscopy findings and pathology data were collected on the 943 with f-Hb≥400 ng Hb/ml (80 µg Hb/g faeces).ResultsOf the 814 participants with outcome data (median age: 63 years, range 50–75, 56.4% male), 39 had cancer, 190 high-risk adenoma (HRA, defined as ≥3 or any ≥10 mm) and 119 low-risk adenoma (LRA). 74.4% of those with cancer had f-Hb>1000 ng Hb/ml compared with 58.4% with HRA, and 44.1% with no pathology. Median f-Hb concentration was higher in those with cancer than those with no (p<0.002) or non-neoplastic (p<0.002) pathology, and those with LRA (p=0.0001). Polyp cancers had lower concentrations than more advanced stage cancers (p<0.04). Higher f-Hb was also found in those with HRA than with LRA (p<0.006), large (>10 mm) compared with small adenoma (p<0.0001), and also an adenoma displaying high-grade dysplasia compared with low-grade dysplasia (p<0.009).Conclusionsf-Hb is related to severity of colorectal neoplastic disease. This has ramifications for the selection of the appropriate cut-off concentration adopted for bowel screening programmes.
Transarterial treatment with Onyx of Cognard type IV anterior cranial fossa dural arteriovenous fistulas
Authors: Li Chuanhui , Wu Zhongxue , Yang Xinjian , Li Youxiang , Jiang Chuhan , He Hongwei 
Published: February 2013

Background and purposeCognard type IV anterior cranial fossa dural arteriovenous fistulas (DAVFs) are rare lesions with a high risk of intracranial hemorrhage. We present our experience with the use of Onyx via the arterial route in these aggressive lesions.Materials and methodsBetween October 2009 and October 2011, six consecutive patients diagnosed with Cognard type IV anterior cranial fossa DAVFs were treated transarterially with Onyx in our department. All patients were male; mean age was 55 years (range 38–68). Four patients presented with intracranial hemorrhage as the initial manifestation; one patient presented with seizures at the time of diagnosis and experienced intracranial hemorrhage during the antiepileptic therapy; and the other patient was asymptomatic.ResultsIn five patients, complete obliteration was achieved with transarterial Onyx injection in a single treatment session; in the remaining patient, subtotal occlusion was achieved and gamma knife treatment was followed. The average time of injection was 19 min (range 5–28) for every pedicle catheterized and the average amount of Onyx was 3.2 ml (range 0.4–6.3) for each lesion. All patients recovered uneventfully after embolization. No mortality or permanent morbidity was observed in this series. Follow-up digital subtraction or MR angiography confirmed durable obliteration of the fistulas in five cured cases. No patients suffered intracranial hemorrhage during the follow-up period.ConclusionsIn this small series, our experience with the use of Onyx for arterial embolization of Cognard type IV DAVFs is encouraging, with durable complete cure in most lesions without severe complications.
Distinct trends of pulsatility found at the necks of ruptured and unruptured aneurysms
Authors: Patti Jordan , Viñuela Fernando , Chien Aichi 
Published: February 2013

BackgroundAneurysm hemodynamics has been shown to be an important factor in aneurysm growth and rupture. Although pulsatility is essential for blood flow and vascular wall function, studies of pulsatile flow properties in brain aneurysm disease are limited.ObjectiveTo investigate differences in pulsatility within a group of ruptured and unruptured aneurysms by implementing patient-specific pulsatile flow simulation.Methods41 of 311 internal carotid artery aneurysms were selected from an aneurysm database (29 unruptured and 12 ruptured) and used for patient-specific hemodynamic simulations of pulsatile flow. Flow pulsatility changes in ruptured and unruptured groups were analyzed by comparing different components of blood flow. Pulsatility index (PI) was used to quantify the pulsatility of blood flow in each group at the aneurysm neck, body, dome, and parent artery.ResultsWithin the parent artery, PI did not significantly differ between ruptured and unruptured groups (0.58). Within unruptured aneurysms, values of PI similar to that of the parent artery were found (0.61). Trends of significantly higher PI (1.99) were found within ruptured aneurysms (p<0.001). These differences were localized at the aneurysm neck, where PI in ruptured (1.93) and unruptured (0.59) aneurysms was significantly different (p<0.001).ConclusionsA trend towards a lower PI, similar to that in the parent artery, was found in unruptured aneurysms, while ruptured aneurysms followed a trend of higher pulsatility. The difference was significant at the aneurysm neck, indicating that pulsatility and this location may be important aspects of aneurysm rupture and a useful predictor of the risk of aneurysm rupture.
CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer
Authors: Du Lei , Rao Guanhua , Wang Hongyi , Li Baowei , Tian Weili , Cui Jiantao , He Leya , Laffin Brian , Tian Xiuyun , Hao Chunyi , Liu Hongmin , Sun Xin , Zhu Yushan , Tang Dean G. , Mehrpour Maryam , Lu Youyong , Chen Quan 
Published: February 2013

AbstractCancer stem cells are implicated in tumor progression, metastasis, and recurrence, although the exact mechanisms remain poorly understood. Here, we show that the expression of cellular prion protein (PrPc, PRNP) is positively correlated with an increased risk of metastasis in colorectal cancer. PrPc defines a subpopulation of CD44-positive cancer stem cells that contributes to metastatic capacity. PrPc+CD44+ colorectal cancer stem cells displayed high liver metastatic capability, unlike PrPc−CD44+ stem cells, that was inhibited by RNAi-mediated attenuation of PrPc. Notably, administration of PrPc monoclonal antibodies significantly inhibited tumorigenicity and metastasis of colorectal cancer stem cells in mouse models of orthotopic metastasis. PrPc promoted epithelial to mesenchymal transition (EMT) via the ERK2 (MAPK1) pathway, thereby conferring high metastatic capacity. Our findings reveal the function of PrPc in regulating EMT in cancer stem cells, and they identify PrPc as candidate therapeutic target in metastatic colorectal cancer. Cancer Res; 73(8); 2682–94. ©2013 AACR.
CSF1R Signaling Blockade Stanches Tumor-Infiltrating Myeloid Cells and Improves the Efficacy of Radiotherapy in Prostate Cancer
Authors: Xu Jingying , Escamilla Jemima , Mok Stephen , David John , Priceman Saul , West Brian , Bollag Gideon , McBride William , Wu Lily 
Published: February 2013

Abstract
Radiotherapy is used to treat many types of cancer, but many treated patients relapse with local tumor recurrence. Tumor-infiltrating myeloid cells (TIM), including CD11b (ITGAM)+F4/80 (EMR1)+ tumor-associated macrophages (TAM), and CD11b+Gr-1 (LY6G)+ myeloid-derived suppressor cells (MDSC), respond to cancer-related stresses and play critical roles in promoting tumor angiogenesis, tissue remodeling, and immunosuppression. In this report, we used a prostate cancer model to investigate the effects of irradiation on TAMs and MDSCs in tumor-bearing animals. Unexpectedly, when primary tumor sites were irradiated, we observed a systemic increase of MDSCs in spleen, lung, lymph nodes, and peripheral blood. Cytokine analysis showed that the macrophage colony-stimulating factor CSF1 increased by two-fold in irradiated tumors. Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy. Mechanistic investigations revealed the recruitment of the DNA damage-induced kinase ABL1 into cell nuclei where it bound the CSF1 gene promoter and enhanced CSF1 gene transcription. When added to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than irradiation alone. Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs that can limit the efficacy of radiotherapy. Furthermore, they suggest that CSF1 inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes. Cancer Res; 73(9); 2782–94. ©2013 AACR.
Chemotherapy Acts as an Adjuvant to Convert the Tumor Microenvironment into a Highly Permissive State for Vaccination-Induced Antitumor Immunity
Authors: Kang Tae Heung , Mao Chih-Ping , Lee Sung Yong , Chen Alexander , Lee Ji-Hyun , Kim Tae Woo , Alvarez Ronald D. , Roden Richard B.S. , Pardoll Drew , Hung Chien-Fu , Wu T.-C. 
Published: February 2013

Abstract
Multiple classes of pharmacologic agents have the potential to induce the expression and release of proinflammatory factors from dying tumor cells. As a result, these cells can in theory elicit an immune response through various defined mechanisms to permanently eradicate disseminated cancer. However, the impact of chemotherapy on the tumor-specific immune response in the context of the tumor microenvironment is largely unknown. Within the tumor microenvironment, the immune response promoted by chemotherapy is antagonized by an immune-suppressive milieu, and the balance of these opposing forces dictates the clinical course of disease. Here, we report that high antigen exposure within the tumor microenvironment following chemotherapy is sufficient to skew this balance in favor of a productive immune response. In elevating antigen exposure, chemotherapy can achieve long-term control of tumor progression without the need of an additional adjuvant. We found that chemotherapy initiated this phenomenon in the tumor microenvironment through an accumulation of dendritic cells, which stimulated CD8+ T cells and the type I IFN pathway. From this conceptual base, we developed a simple approach to cancer therapy combining chemotherapy and vaccination that may be widely applicable. Cancer Res; 73(8); 2493–504. ©2013 AACR.
Acrylamide Hemoglobin Adduct Levels and Ovarian Cancer Risk: A Nested Case–Control Study
Authors: Xie Jing , Terry Kathryn L. , Poole Elizabeth M. , Wilson Kathryn M. , Rosner Bernard A. , Willett Walter C. , Vesper Hubert W. , Tworoger Shelley S. 
Published: February 2013

Abstract
Background: Acrylamide is a probable human carcinogen formed during cooking of starchy foods. Two large prospective cohort studies of dietary acrylamide intake and ovarian cancer risk observed a positive association, although two other studies reported no association.
Methods: We measured acrylamide exposure using red blood cell acrylamide and glycidamide hemoglobin adducts among women in two large prospective cohorts: the Nurses' Health Study and Nurses' Health Study II. Between blood collection and 2010, we identified 263 incident cases of epithelial ovarian cancer, matching two controls per case. We used logistic regression models to examine the association between acrylamide exposure and ovarian cancer risk, adjusting for matching factors, family history of ovarian cancer, tubal ligation, oral contraceptive use, body mass index, parity, alcohol intake, smoking, physical activity, and caffeine intake.
Results: The multivariate-adjusted relative risk (RR) of ovarian cancer comparing the highest versus lowest tertile of total acrylamide adducts was 0.79 (95% CI, 0.50–1.24, P trend = 0.08). The comparable RR of ovarian cancer among non-smokers at blood draw was 0.85 (95% CI, 0.57–1.27, P trend = 0.14). The association did not differ by tumor histology (serous invasive versus not), P for heterogeneity = 0.86. Individual adduct types (acrylamide or glycidamide) were not associated with risk.
Conclusions: We observed no evidence that acrylamide exposure as measured by adducts to hemoglobin is associated with an increased risk of ovarian cancer.
Impact: Our finding indicates that acrylamide intake may not increase risk of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 22(4); 653–60. ©2013 AACR.
Modulation of p53 C-Terminal Acetylation by mdm2, p14ARF, and Cytoplasmic SirT2
Authors: van Leeuwen Ingeborg M.M. , Higgins Maureen , Campbell Johanna , McCarthy Anna R. , Sachweh Marijke C.C. , Navarro Ana Marín , Laín Sonia 
Published: February 2013

Abstract
Acetylation of C-terminal lysine residues in the p53 tumor suppressor is associated with increased stability and transcription factor activity. The function, protein level, and acetylation of p53 are downregulated by mdm2, which in its turn is inhibited by the p14ARF tumor suppressor. Here, we show that p14ARF increases the level of p53 acetylated at lysine 382 in a nuclear chromatin-rich fraction. Unexpectedly, this accumulation of p53AcK382 is dramatically enhanced in the presence of ectopic mdm2. In light of these observations, we propose that p14ARF increases the binding of p53–mdm2 complexes to chromatin, thereby limiting the access of protein deacetylases to p53. Supporting this notion, we show that p53AcK382 can be deacetylated in the cytoplasm and that sirtuin SirT2 catalyzes this reaction. These results help understand why inhibition of both SirT1 and SirT2 is needed to achieve effective activation of p53 by small-molecule sirtuin inhibitors. Mol Cancer Ther; 12(4); 471–80. ©2013 AACR.
Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives
Authors: Dieci Maria Vittoria , Arnedos Monica , Andre Fabrice , Soria Jean Charles 
Published: February 2013

AbstractThe fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifications, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, class-specific toxicity profiles and correctly designing clinical trials to address these different issues.Significance: FGF/FGFR pathway deregulations are increasingly recognized across different human cancers. Understanding the mechanisms at the basis of these alterations and their multiple roles in cancer promotion and drug resistance is a fundamental step for further implementation of targeted therapies and research strategies. Cancer Discov; 3(3); 264–79. ©2012 AACR.
A Blood-Based Gene Expression Test for Obstructive Coronary Artery Disease Tested in Symptomatic Nondiabetic Patients Referred for Myocardial Perfusion Imaging The COMPASS Study
Authors: Thomas Gregory S. , Voros Szilard , McPherson John A. , Lansky Alexandra J. , Winn Mary E. , Bateman Timothy M. , Elashoff Michael R. , Lieu Hsiao D. , Johnson Andrea M. , Daniels Susan E. , Ladapo Joseph A. , Phelps Charles E. , Douglas Pamela S. , Rosenberg Steven 
Published: February 2013

Background—
Obstructive coronary artery disease diagnosis in symptomatic patients often involves noninvasive testing before invasive coronary angiography. A blood-based gene expression score (GES) was previously validated in nondiabetic patients referred for invasive coronary angiography but not in symptomatic patients referred for myocardial perfusion imaging (MPI).

Methods and Results—

This prospective, multicenter study obtained peripheral blood samples for GES before MPI in 537 consecutive patients. Patients with abnormal MPI usually underwent invasive coronary angiography; all others had research coronary computed tomographic angiography, with core laboratories defining coronary anatomy. A total of 431 patients completed GES, coronary imaging (invasive coronary angiography or computed tomographic angiography), and MPI. Mean age was 56±10 years (48% women). The prespecified primary end point was GES receiver-operating characteristics analysis to discriminate ≥50% stenosis (15% prevalence by core laboratory analysis). Area under the receiver-operating characteristics curve for GES was 0.79 (95% confidence interval, 0.73–0.84;
P
<0.001), with sensitivity, specificity, and negative predictive value of 89%, 52%, and 96%, respectively, at a prespecified threshold of ≤15 with 46% of patients below this score. The GES outperformed clinical factors by receiver-operating characteristics and reclassification analysis and showed significant correlation with maximum percent stenosis. Six-month follow-up on 97% of patients showed that 27 of 28 patients with adverse cardiovascular events or revascularization had GES >15. Site and core-laboratory MPI had areas under the curve of 0.59 and 0.63, respectively, significantly less than GES.

Conclusions—
GES has high sensitivity and negative predictive value for obstructive coronary artery disease. In this population clinically referred for MPI, the GES outperformed clinical factors and MPI.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01117506.
Yield and Diagnostic Value of Stress Myocardial Perfusion Imaging in Patients Without Known Coronary Artery Disease Presenting With Syncope
Authors: AlJaroudi Wael A. , Alraies M. Chadi , Wazni Oussama , Cerqueira Manuel D. , Jaber Wael A. 
Published: February 2013

Background—
American College of Cardiology/American Heart Association appropriate use criteria recommend performing stress myocardial perfusion imaging (MPI) for intermediate- to high-risk patients presenting with syncope but not for low-risk patients. However, there are limited data to support these recommendations. We investigated the yield of stress MPI for the evaluation of syncope in patients at risk but without known coronary artery disease.

Methods and Results—
Using the Cleveland Clinic Institutional Review Board–approved MPI database, we identified consecutive patients without known coronary artery disease who underwent stress MPI between 2006 and 2012 for diagnostic workup of syncope. Patients were stratified into low-, intermediate-, and high-risk groups using the Framingham risk score. For patients with abnormal MPI, left heart catheterization were reviewed if performed. There were 700 patients (mean age, 62±15 years; 55% female) who had undergone stress MPI for syncope; 659 patients (94%) had normal perfusion. Of the 41 patients with abnormal MPI, 18 had left heart catheterization (9 were false-positive); there were 23 remaining patients with abnormal MPI (16 having moderate to severe perfusion defect size) but who did not have a left-side angiogram and could have undiagnosed significant coronary artery disease. The diagnostic yield of stress MPI was similarly low among all cardiovascular risk categories.

Conclusions—
Stress MPI for evaluation of syncope in patients without known coronary artery disease has a low-diagnostic yield among all risk categories; thus, reaffirmation and revision of the appropriateness criteria should be considered.
Relationship of Delayed Enhancement by Magnetic Resonance to Myocardial Perfusion by Positron Emission Tomography in Hypertrophic Cardiomyopathy
Authors: Bravo Paco E. , Zimmerman Stefan L. , Luo Hong-Chang , Pozios Iraklis , Rajaram Mahadevan , Pinheiro Aurélio , Steenbergen Charles , Kamel Ihab R. , Wahl Richard L. , Bluemke David A. , Bengel Frank M. , Abraham M. Roselle , Abraham Theodore P. 
Published: February 2013

Background—
Presence of delayed enhancement (DE) on cardiac magnetic resonance (CMR) is associated with worse clinical outcomes in hypertrophic cardiomyopathy. We investigated the relationship between DE on CMR and myocardial ischemia in hypertrophic cardiomyopathy.

Methods and Results—

Hypertrophic cardiomyopathy patients (n=47) underwent CMR for assessment of DE and vasodilator stress ammonia positron emission tomography to quantify myocardial blood flow and coronary flow reserve. The summed difference score for regional myocardial perfusion was also assessed. Patients in the DE group (n=35) had greater left ventricular wall thickness (2.09±0.44 versus 1.78±0.34 cm;
P
=0.03). Stress myocardial blood flow (2.25±0.46 versus 1.78±0.43 mL/min per gram;
P
=0.01) and coronary flow reserve (2.78±0.32 versus 2.01±0.52;
P
<0.001) were significantly lower in DE-positive patients. Summed difference score (7.3±6.6 versus 0.9±1.4;
P
<0.0001) was significantly higher in patients with DE. A coronary flow reserve <2.00 was seen in 18 patients (51%) with DE but in none of the DE-negative patients (
P
<0.0001). CMR and positron emission tomography showed visually concordant DE and regional myocardial perfusion abnormalities in 31 patients and absence of DE and perfusion defects in 9 patients. Four DE-positive patients demonstrated normal regional myocardial perfusion, and 3 DE-negative patients had (apical) regional myocardial perfusion abnormalities.

Conclusions—
We found a close relationship between DE by CMR and microvascular function in most of the patients studied. However, a small proportion of patients had DE in the absence of perfusion abnormalities, suggesting that microvascular dysfunction and ischemia are not the sole causes of DE in hypertrophic cardiomyopathy patients.