tbuckley/cabot-search huggingface dataset:
Abstract 1558: Paracrine signaling through Mycn enhances tumor-vascular microenvironment in neuroblastoma
Authors: Yvan H. Chanthery, W. Clay Gustafson, William A. Weiss
Journal: Cancer Research (2011)

Abstract Neuroblastoma, a tumor of peripheral neural crest origin, numbers among the most common childhood cancers. Both amplification of the proto-oncogene MYCN and increased vascular density mark high-risk disease. Since angiogenesis is regulated by phosphatidylinositol-3’ kinase (PI3K), we tested a clinical PI3K inhibitor, NVP-BEZ235, in MYCN-dependent neuroblastoma. NVP-BEZ235 decreased angiogenesis in a primary human neuroblastoma (MYCN-amplified orthotopic xenograft), and improved survival in a transgenic mouse model for MYCN-driven neuroblastoma. Using both gain and loss of function approaches, we demonstrate that the anti-angiogenic efficacy of NVP-BEZ235 was critically dependent on Mycn, in vitro and in-vivo. Thus, clinical PI3K/mTOR inhibitors drive degradation of Mycn in tumor cells, with secondary paracrine blockade of tumor-vascular microenvironment. These observations argue that NVP-BEZ235 should be tested in children with high-risk, MYCN amplified neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1558. doi:10.1158/1538-7445.AM2011-1558
Abstract 2164: High fat diet-induced intraprostatic inflammation involves association between Stat-3 and NF-kappaB: Role in pathogenesis of prostate cancer
Authors: Eswar Shankar, Eugene V. Vykhovanets, Olena V. Vykhovanets, Natarajan Bhaskaran, Sanjeev Shukla, Sanjay Gupta
Journal: Cancer Research (2011)

Abstract Western style high-fat diet (HFD) is a risk factor for obesity, diabetes, and cancer. In our previous studies we have demonstrated that HFD increases oxidative stress and inflammation in the prostate of NF-kappaB-luciferase transgenic reporter mice (Vykhovanets et al., Prostate 2010). However, the molecular mechanism(s) underlying HFD-induced inflammation in the prostate largely remains unknown. Signal transducer and activator of transcription (Stat-3) and nuclear factor-kappa B are the important signaling pathways that are activated during inflammation. The pro-inflammatory cytokines induced are the transcriptional targets of Stat-3 and NF-kappaB and are known to be involved in their activation. We examined the role of HFD in increasing the nuclear activation of Stat-3 and NF-kappaB and the mechanism(s) involved leading to inflammation of the prostrate. Male 16 week old C57BL/6J mice were either fed with regular diet (RD) or HFD for 4 and 8 weeks. The animals were sacrificed at the end of each time period. HFD intake caused significant increase in the plasma levels of IL-6 and IL-17, after 4 weeks of feeding that further increased after 8 weeks, compared to mice fed with RD. These cytokines have been reported to induce Stat-3. HFD intake also caused marked increase in the levels of IL-1beta and TNFalpha which are known activators of NF-kappaB. A significant increase in the levels of PKCepsilon was observed after 4 weeks of HFD feeding in these mice. Elevated levels of PDK1 and p-Akt (Ser473) were observed in the prostate tissues of HFD group. Increase in the levels of kinases corroborated with the nuclear translocation of Stat-3 and NF-kappaB/p65/RelA with significantly increased expression of Tyr705, Ser727 Stat-3 and Ser536 p65/RelA in the prostrate of HFD mice. An association between Ser727 Stat-3 and Ser 536 p65/RelA was observed in the nucleus of prostate tissue of HFD group. Furthermore, increased DNA binding of p65/RelA and Stat-3 as well as their association was observed in HFD group. Taken together, HFD increases inflammation in the prostate through activation of Stat-3 and NF-kappaB and their association may play a key role in the pathogenesis of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2164. doi:10.1158/1538-7445.AM2011-2164
Abstract 5407: The upregulation of BTLA and PD-1 defines a novel subset of dysfunctional tumor antigen-specific CD8+ T cells
Authors: Julien Fourcade, Zhaojun Sun, Ornella Pagliano, Philippe Guillaume, Immanuel F. Luescher, Cindy Sander, John M. Kirkwood, Daniel Olive, Vijay Kuchroo, Hassane M. Zarour
Journal: Cancer Research (2012)

Abstract Cytotoxic T cells present at the periphery or at tumor sites recognize tumor epitopes presented by melanoma cells but fail to induce tumor rejection in melanoma patients. Inhibitory receptors including PD-1 and Tim-3 expressed by spontaneous CD8+ T cells directed against the cancer-germline antigen NY-ESO-1 play a role in promoting tumor-induced T cell dysfunction. In the present study, we show that BTLA is upregulated on spontaneous NY-ESO-1-specific CD8+ T cells and that BTLA+PD-1+Tim-3− CD8+ T cells represent the largest subset of NY-ESO-1-specific CD8+ T cells in melanoma patients. BTLA+PD-1+Tim-3− CD8+ T cells are partially dysfunctional, producing less IFN-γ than BTLA−PD-1+Tim-3− and BTLA−PD-1−Tim-3− but more IFN-γ, TNF and IL-2 than highly dysfunctional BTLA+PD-1+Tim-3+ NY-ESO-1-specific CD8+ T cells. Unlike PD-1, BTLA expression by NY-ESO-1-specific CD8+ T cells does not increase with higher T cell dysfunction or upon cognate antigen stimulation, suggesting that BTLA upregulation occurs independently of functional exhaustion driven by high antigen load. Finally, BTLA pathway blockade adds to PD-1 and Tim-3 blockades, enhancing NY-ESO-1-specific CD8+ T cell expansion, proliferation and cytokine production. Collectively, our findings support the targeting of BTLA, PD-1 and Tim-3 pathways to reverse tumor-induced T cell dysfunction in patients with advanced melanoma. This work was supported by the National Institutes of Health/National Cancer Institute grants R01CA90360 and R01CA157467 (to H.M. Zarour), an award from the Melanoma Skin Spore grant NCI P50CA121973 (to H.M. Zarour) and a grant from the Cancer Research Institute (to H.M. Zarour). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5407. doi:1538-7445.AM2012-5407
NOVEL INSIGHTS INTO THE PHYSIOLOGY OF CARDIAC-CORONARY INTERACTION: A FIRST-IN-HUMAN STUDY UTILISING INVASIVE REAL-TIME SIMULTANEOUS MEASURES OF CORONARY AND LEFT VENTRICULAR HEMODYNAMICS
Authors: Tiffany Patterson, Simone Rivolo, Brian Clapp, Divaka Perera, Michael Marber, Jack Lee, Simon Redwood
Journal: Journal of the American College of Cardiology (2016)
AB0611 Hypovitaminosis d and osteopenia/osteoporosis in a haemophilia population
Authors: D. Melchiorre, S. Linari, G. Montorzi, D. Bartolozzi, M. Borderi, M. Benelli, M. Morfini, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent reports show a correlation between haemophilia and bone mineral density reduction. HIV, HCV and their treatments are independently associated to an increased risk of osteoporosis. A pivotal role in bone mineralization is played by Vitamin D. <h3>Objectives</h3> This study compares Vitamin D level, bone metabolism markers and bone mineral density (BMD) in haemophiliacs with or without co-infections. <h3>Methods</h3> 78 adult patients with severe or moderate haemophilia A or B and HIV and/or HCV infection were studied. BMD was measured by dual energy X-ray absorptiometry (DeXA) at femoral area (F) and lumbar spine (L) and was correlated to laboratory values and haemophilic arthropathy assessed using the World Federation of Haemophilia orthopaedic joint scale (WFH score) and the radiological Pettersson score. <h3>Results</h3> DeXA showed a homogeneous F-BMD reduction of a part from the belonging group, while L-BMD was significantly lower in pts with HIV and HCV infection (p&lt;0.05). The WFH score was higher in pts with HIV and HCV infection (p&lt;0.002) and in pts with HCV infection (p&lt;0.006). The radiological score was higher in pts with HCV infection than in the other pts (p&lt;0.001). Overall 25-hydroxyvitamin D was reduced in 87% of patients, in particular in 100% of pts with HIV and HCV, 73% of pts with HCV infection and 88% of un-infected subjects. Bone-specific alkaline phosphatase (b-ALP) and telopeptide were increased in all pts (p&lt;0.001 and p&lt;0.01). <h3>Conclusions</h3> The worse clinical and radiological scores in patients with infections are most likely related to the amount of patients with more severe coagulopathy in those groups. A high prevalence of hypovitaminosis D has been found in haemophiliacs, a part from the belonging group. The homogeneous F-BMD reduction could be explained by the pivotal role of arthropathy; the lower L-BMD in co-infected and the increase of b-ALP and telopeptide in co-infected and mono-infected groups suggest the faster bone metabolism in case of infections. <h3>Disclosure of Interest</h3> None Declared
P67 Laryngeal Narrowing In Chronic Obstructive Pulmonary Disease (copd): A Mechanism For Generating Intrinsic Peep?
Authors: M. Baz, G. Haji, A. Menzies-Gow, R. Tanner, N. Hopkinson, M. Polkey, J. Hull
Journal: Thorax (2014)

<h3>Introduction and rationale</h3> Patients with COPD often exhibit pursed lip breathing during exercise, a strategy to help overcome a rise in intrinsic PEEP secondary to dynamic hyperinflation. A similar role for laryngeal closure to optimise respiratory mechanics during exertion is postulated. <h3>Objectives</h3> Assessment of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. <h3>Methods</h3> and Measurements: We studied 30 age and sex matched subjects (n = 11 healthy, n = 8 mild to moderate COPD, n = 11 severe COPD). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing was calculated at the glottic and supra-glottic aperture at rest and peak exercise. <h3>Results</h3> Expiratory laryngeal narrowing was pronounced in patients with COPD at rest and peak exercise and related to FEV<sub> 1 </sub>(r=-0.53, p &lt; 0.05 and r=-0.70, p &lt; 0.001 respectively). Glottic narrowing at peak exercise correlated with inspiratory duty cycle time (Ti/Ttot) (Figure), this was not seen at rest (r=-0.79, P &lt; 0.0001 and r=-0.07, p = 0.77 respectively). Laryngeal closure at peak exercise inversely correlated with peak oxygen uptake (r=-0.68, p &lt; 0.01). <h3>Conclusion</h3> Dynamic laryngeal closure during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity.
Observed Cognitive Performance and Deviation From Familial Cognitive Aptitude at Age 16 Years and Ages 18 to 20 Years and Risk for Schizophrenia and Bipolar Illness in a Swedish National Sample
Authors: Kenneth S. Kendler, Henrik Ohlsson, Briana Mezuk, Jan O. Sundquist, Kristina Sundquist
Journal: JAMA Psychiatry (2016)

Proposal of an innovative approach to clarify the mechanism through which poor cognitive performance in adolescence impacts risk for schizophrenia (SZ).To determine whether the developmental processes that predispose to SZ are better reflected by the observed cognitive performance in adolescence or the deviation of that performance from the individual's familial cognitive aptitude (FCA).A prospective cohort design. Risk for SZ and bipolar illness (BPI) are predicted by school achievement (SA) at age 16 years and IQ at ages 18 to 20 years and the deviation of that performance from an individual's FCA. Familial cognitive aptitude is calculated from the SA, IQ, and educational attainment in biological relatives.Diagnoses of SZ or BPI in the Swedish Hospital Discharge Register and the Swedish Outpatient Register.Participants were 996 886 individuals with recorded SA and 106 187 individuals with recorded IQ born in Sweden between January 1, 1972, and December 31, 1990, with sufficient numbers of biological relatives to calculate their FCA. The first cohort is 48.7% female, and the second is all male. Risk for SZ was strongly predicted by the deviation of SA from the FCA (hazard ratio [HR], 0.56; 95% CI, 0.49-0.63) but not with the observed SA (HR, 1.01; 95% CI, 0.91-1.13). Similar results were obtained for IQ (HR, 0.53; 95% CI, 0.37-0.77 for the deviation from the FCA and HR, 1.07; 95% CI, 0.78-1.46 for the observed IQ). After matching SZ and control probands on cognitive performance, the siblings of the SZ probands had SA and IQs that did not differ from population means and were significantly higher in cognitive performance than for the siblings of control probands. Correlations in SA and IQs between the pre-SZ probands and their siblings were significantly lower than those observed between the matched control probands and their siblings. Risk for BPI was more weakly predicted by deviations from the FCA. No differences were found in the SA and IQs of siblings of BPI vs matched control probands.The neurodevelopmental processes that predispose to SZ are not well reflected by cognitive performance per se but rather are much better indexed by the deviation in cognitive ability from that expected from an individual's FCA. The lowered cognitive performance in the pre-SZ probands appears to arise from qualitative developmental impairments rather than an unlucky combination of the genetic and environmental risk factors widely distributed within their family.
Abstract P4-16-05: Benefit from Postoperative Radiotherapy for N1 Breast Cancer
Authors: Y-CS Tsai, H-CS Cheng, B-L Yu, C-F Horng, C-M Chen, J-MJ Jian, N-M Chu, M-H Tsou, M-C Liu, AT Huang
Journal: Cancer Research (2012)

Abstract Purpose: To evaluate the outcomes for patients with Stage II breast cancer and one to three positive lymph nodes after mastectomy who were treated with observation or adjuvant radiotherapy to the chest wall (CW) and regional lymphatics; and to identify a group of patients who benefit from postmastectomy radiotherapy (PMRT). Methods and Materials: The subjects were 716 patients diagnosed between 1990 and 2007 with Stage II breast cancer (one to three positive lymph nodes) treated with mastectomy at the Koo Foundation Sun Yat-Sen Cancer Center. 283 patients had undergone PMRT to the CW and regional lymphatics according to in-house treatment guideline or physician decision. Since 2003, we recommend PMRT for patients who had 2 or more risk factors; age less than 40 y/o, T2 disease, GrII/GrIII, prominent lymphovascular invasion (LVI), presence of extracapsular spreading (ECS), and negative Estrogen Receptor (ER(−)). Survival was analyzed by the Kaplan—Meier method. The survival free of isolated locoregional disease(LRR), metastasis free survival(MFS), disease free survival(DFS), and overall survival(OS) were analyzed according to the delivery of radiotherapy or not. Results: The median follow-up was 80 months. LRR, MFS, DFS and OS were significantly improved by PMRT. The 5- and 10-year LRR rate without PMRT was 89.9% and 81.6%, respectively and, with PMRT was 97.7% and 97.0% respectively (p &amp;lt;0.0001). The 5- and 10-year MFS rate without PMRT was 84.4% and 76.5%, respectively, and, with PMRT, was 90.8% and 87.2% respectively (p = 0.0153). The 5- and 10-year DFS rate without PMRT was 80.8% and 69.8%, respectively, and, with PMRT, was 89.6% and 86.1% respectively (p = 0.001). The 5- and 10-year OS rate without PMRT was 89.1% and 77.3%, respectively, and, with PMRT, was 94.6% and 86.2% respectively (p = 0.0039). 239 patients had less than 2 risk factors, their LRR, MFS and DFS did not benefit from PMRT. Conclusion: Our data suggest that adjuvant PMRT improve LRR, MFS, DFS and OS for stage II breast cancer with one to three positive lymph nodes who had 2 or more risk factors (Age less than 40 y/o, T2, GrII/GrIII, LVI, ECS, ER(−)). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-05.
Abstract 3717: Evaluation and comparison of breast cancer risk prediction models for Hispanic and non-Hispanic white women in the Women's Health Initiative
Authors: Matthew P. Banegas, Mitchell H. Gail, Andrea LaCroix, Beti Thompson, M. Elena Martinez, Jean Wactawski-Wende, Esther M. John, F. Allan Hubbell, Shagufta Yasmeen, Hormuzd A. Katki
Journal: Cancer Research (2011)

Abstract Introduction: The National Cancer Institute (NCI) Breast Cancer Risk Assessment Tool (BCRAT) has not been previously validated for use in Hispanic women. We evaluated and compared BCRAT risk projections for Hispanic and non-Hispanic White (NHW) participants in the Women's Health Initiative (WHI). Methods: We used data on 6,248 Hispanic and 127,426 NHW post-menopausal WHI participants aged 50 years and older. Absolute risks of developing invasive breast cancer over the WHI main and extension studies were calculated using the BCRAT and an updated BCRAT using 1993-2007 SEER breast cancer incidence rates. We assessed model calibration by the ratio of observed to expected number of breast cancers (O/E ratio) and discriminatory accuracy with the concordance statistic (c-statistic). Results: In the WHI main study, the BCRAT underestimated the number of breast cancers in Hispanics (O/E ratio=1.18, 95% CI = 0.99, 1.40) and NHWs (O/E ratio=1.18, 95% CI = 1.14, 1.21). The updated BCRAT was well calibrated for Hispanics (O/E ratio=1.08, 95% CI = 0.91, 1.28) and NHWs (O/E ratio=0.98, 95% CI = 0.96, 1.01). The c-statistic was 0.629 (95% CI = 0.582, 0.676) for Hispanics and 0.575 (95%CI = 0.566, 0.583] for NHWs. In the WHI extension study, where women reported being screened less frequently, BCRAT overestimated risk in both Hispanics and NHWs. Conclusion: Underestimation of breast cancer risk by the BCRAT in Hispanic and NHW women was corrected by using updated SEER breast cancer incidence rates. Recalibrating the BCRAT with current SEER incidence rates and racial/ethnic specific relative risk estimates may improve the predictive accuracy for Hispanic women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3717. doi:10.1158/1538-7445.AM2011-3717
SP0100 Myopathy in systemic sclerosis
Authors: U. Walker
Journal: Annals of the Rheumatic Diseases (2013)

Patients with systemic sclerosis (SSc) frequently report muscle weakness. The reported prevalence of muscle involvement in SSc varies largely. There is no consensus whether or not an inflammatory myopathy in SSc should be merely considered as an organ complication of SSc, or as SSc-myositis overlap. Muscle weakness due to direct involvement of skeletal muscles in the disease process needs to be differentiated from myopathy secondary to disuse (fatigue, articular disease, cardiopulmonary involvement), kachectic atrophy, or from medications (statins, antimalarials etc.). Elevated muscle enzymes in patients' serum may be only moderately elevated, or be completely within normal limits. Myopathy may be demonstrated by electromyography, skeletal muscle biopsy or magnetic resonance imaging. Blood oxygenation dependent (BOLD) MRI has demonstrated impaired skeletal muscle microcirculation. <h3>Disclosure of Interest</h3> None Declared
Abstract 2207: Functional interrogation of the colorectal cancer genome identifies numerous suppressors of anchorage-independent growth
Authors: Ugur Eskiocak, Sang B. Kim, Peter Ly, Andres I. Roig, Sebastian Biglione, Kakajan Komurov, Crystal Cornelius, Woodring E. Wright, Michael A. White, Jerry W. Shay
Journal: Cancer Research (2011)

Abstract INTRODUCTION: High throughput cancer genome sequencing efforts are leading to the identification of frequently mutated genes in cancer. Unfortunately, the extreme diversity of lesions being detected presents a challenge to segment causal from coincidental mutations and to elucidate how causal lesions disrupt regulatory networks to drive cancer processes. AIMS AND METHODS: Given that a common early perturbation in solid tumor initiation is bypass of matrix-dependent proliferation restraints, we used immortalized human colonic epithelial cells (HCECs) to identify suppressors of anchorage-independent growth by conducting a soft-agar based shRNA screen within frequently mutated colorectal cancer (CRC) genes. RESULTS AND CONCLUSIONS: Remarkably, depletion of 65 of the 151 frequently CRC-mutated genes tested collaborated with K-RASV12 or TP53 knockdown to promote anchorage-independent proliferation of HCECs. These candidates fall under a variety of different signaling pathways, but in particular JNK signaling was found to be a master suppressor of anchorage-independent growth in normal HCECs. We have identified additional members of an extensive gene network specifying matrix-dependent proliferation, by constructing an interaction map of these confirmed progression suppressors with the ∼700 rare CRC-mutated genes and experimentally verifying soft-agar growth enhancement in response to depletion of these genes. Collectively, this study reveals a profound diversity of fragile nodes within a fundamental tumor suppressor network, perturbation of which leads to enhanced cell-autonomous proliferative fitness. These studies establish the importance of functionally annotating cancer genomes using biologically relevant assays. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2207. doi:10.1158/1538-7445.AM2011-2207
Case 1-2008
Authors: Marc A. de Moya, Andrew T. Reisner, Glenn M. LaMuraglia, Sanjeeva P. Kalva
Journal: New England Journal of Medicine (2008)

A 45-year-old man was transferred to the emergency department because of the sudden onset of abdominal pain, followed by hypotension. Except for a history of alcohol abuse and probable hepatic cirrhosis, he had been well until the morning of admission, when he experienced sharp abdominal pain while lifting a heavy object. He went to a local health center, where hypotension was noted, and was transferred to this hospital. Diagnostic and therapeutic procedures were performed.