tbuckley/cabot-search huggingface dataset:
835 GLOBAL ANALYSIS OF LIVER MIRNAS EXPRESSION IN CHRONIC HEPATITIS C LEADING TO A SIGNATURE TO PREDICT RESPONSE TO TREATMENT
Authors: E. Estrabaud, I. Bieche, F. Carrat, S. De Muynck, M. Lapalus, O. Lada, M. Martinot-Peignoux, D. Valla, P. Bedossa, P. Marcellin, M. Vidaud, T. Asselah
Journal: Journal of Hepatology (2012)
Abstract 1748: Metformin overcomes cisplatin-resistance in triple negative breast cancer
Authors: Ying Ka Ingar Lau, Jacquelyn M. Shaw, Julie L. Campbell, Matthew A. Maurer
Journal: Cancer Research (2011)

Abstract Background: Triple negative breast cancers (TNBC) account for approximately 15% of breast cancer but 30% of deaths. The majority of TNBC are basal breast cancers that have higher rate of relapses as compared with other breast cancer subtypes, indicating there exists a sub-population of tumor cells that are highly resistant to chemotherapies. Platinum-based agents and PARP inhibitors have shown efficacy in basal breast cancers with BRCA1/2 mutation background. In this study, we expand the analysis to basal breast cancer lines without BRCA1/2 mutations. Results and Methods: We treated a panel of basal breast cancer lines (HCC70, MDA-MB-468, BT549, HCC1143) with cisplatin and observed that 6 µM of cisplatin were able to kill &amp;gt;99% of a confluent plate of these cell lines. The cisplatin-resistant population, however, behaved very differently in these lines. Cisplatin-resistant MDA-MB-468 cells had similar phenotype as cisplatin-sensitive cells and they repopulated the whole plate in a short time. Cisplatin-resistant cells in the other 3 TNBC lines had a different phenotype than the cisplatin-sensitive cells and remained quiescent for 2-3 weeks before proliferating in a vertical fashion. The vertical string of cells eventually detached from the plate and kept expanding as clusters of cells in suspension. Screening through various drugs, we observed that 2 mM of metformin as a combined treatment with cisplatin was able to irradicate these cisplatin-resistant cells in both MDA-MB-468 and BT549 cell lines. Additionally, we demonstrated that using aminoimidazole carboxamide ribonucleotide (AICAR), an AMP kinase (AMPK) activator, and Rapamycin, an mTORC1 inhibitor had the same effect as metformin indicating the AMPK-mTOR axis might be important for the survival of cisplatin-resistant cells. Conclusions: TNBC without BRCA1/2 mutation are sensitive to cisplatin treatment but possess a sub-population of resistant cells. We demonstrated that cisplatin-resistant cells in TNBC lines behaved differently after cisplatin treatment and that combined treatment of metformin and cisplatin may be able to overcome this resistance. Future experiments include comparing this combination with the combined treatment of cisplatin and PARP inhibitor, which might have effect in cisplatin-sensitive cells but not in cisplatin-resistant cells. 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 1748. doi:10.1158/1538-7445.AM2011-1748
Comparison of Physiologic Ejection Fraction Responses to Differing Stimuli: Implications for Clinical Testing
Authors: C. Noel Bairey, Ling de Yang, Daniel S. Berman, Lynne Roy, Kathy Suyenaga, Ponce Tapnio, Alan Rozanski
Journal: Clinical Nuclear Medicine (1988)

Noel Bairey, C.; de Yang, Ling; Berman, Daniel S.; Roy, Lynne; Suyenaga, Kathy; Tapnio, Ponce; Rozanski, Alan Author Information
Late Reactions to Metallic Foreign Bodies
Authors: Thomas W. Botsford, D. Richard Freni
Journal: New England Journal of Medicine (1948)

FEW military or civilian surgeons have allowed a wound to heal around a metallic foreign body without wondering what the eventual outcome would be. Will the foreign body migrate, act as a focus of infection or cause pain, or will it become encapsulated and cause no symptoms? Today, many veterans have foreign bodies imbedded in various regions of the body, and in the months since the cessation of hostilities, we have had the opportunity of studying and treating a few late reactions caused by such bodies. This communication presents observations on a group of 40 patients who have been treated . . .
Idiopathic Varicose Veins of the Upper Extremity
Authors: Donald M. Clark, Richard Warren
Journal: New England Journal of Medicine (1954)

THE term "varicose veins" customarily suggests, immediately, and almost exclusively, abnormal dilatations and tortuosities of the saphenous veins of the lower extremity. If one then stops to reflect where else in the body they may occur, the veins of the left pampiniform plexus, the esophagus and the inferior hemorrhoidal plexus are recognized as obvious, if less common, sites.Varicosities of the veins of the upper extremity are rare and are usually provoked only by such considerable increases in venous pressure as are the result of arteriovenous fistulas of long standing or of obstruction by tumor or thrombosis to the great . . .
Abstract 4332: Proprotein convertases as target for therapy of pediatric sarcomas
Authors: Michele Bernasconi, Valentina D'Alessandro, Beat C. Bornhauser, Felix Niggli, Beat W. Schaefer
Journal: Cancer Research (2012)

Abstract One of the biggest challenges of treating children with cancer is achieving complete remission, while ensuring that they will be able to lead normal, productive life in adulthood. To improve therapies for embryonal pediatric tumors such as rhabdomyosarcoma (RMS) the most common soft tissue sarcoma in children, we have selected by in vivo phage display for peptides that bind to RMS with high specificity. We have shown that coupling of Doxorubicin to RMS-P3, a RMS targeting peptide, considerably increases its therapeutic impact in a mouse model for RMS. We have identified proprotein convertases (PC), a family of ten serine proteases which convert inactive proprotein into their active form, as targets RMS binding peptides. Now we aimed at elucidating the contribution to RMS growth in vivo of the two proprotein convertases, furin and PC7, which are highly expressed in RMS tumors. To this end, we have generated a panel of RMS cell lines overexpressing furin, overexpressing a specific intrinsic PC inhibitor called α1-PDX, as well as cell lines were expression of furin or PC7 has been stably blocked by shRNA. These cells have been tested for their growth, migration and invasion potential in vitro as well as for their growth in vivo as subcutaneous xenografts. Histological analysis of tumor sections, in particular of microvessel density and angiogenesis has been performed to reveal if PC activity correlates with RMS progression. Our results confirm a strong correlation between PCs activity and RMS growth in vivo and suggest furin and PC7 as viable targets for therapeutic intervention and warrant further studies in the development of novel therapeutic approaches based both on specific inhibition of PCs protease activity and on targeted drug delivery by PCs targeting peptides. 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 4332. doi:1538-7445.AM2012-4332
AB0739 Giant cell arteritis (GCA): Are we following current european guidelines?
Authors: A. Tan, T. Chee, M. Lambert, N. Amft
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> GCA is the most common primary systemic vasculitis associated with siginificant morbidity. Guidance on management have been issued by the British Society for Rheumatology (BSR) and European League Against Rheumatism (EULAR). <h3>Objectives</h3> We as a rheumatology department wished to identify if our current practice in diagnosing and managing GCA was adequate. A retrospective study looking at rheumatology patients with GCA who had temporal artery biopsy (TAB) between November 2006-November 2010 was performed. BSR and EULAR recommendations were used as standards <h3>Methods</h3> 131 patients across all specialties had TAB for GCA. We analysed only patients who were seen and managed exclusively within the rheumatology department. <h3>Results</h3> 46 rheumatology patients (31 females, 15 males) with a diagnosis of GCA had TAB. Mean age at diagnosis was 68 years. Mean time between commencement of symptoms and TAB performed was 62.26 days, between commencement of steroids and TAB performed was 28.88 days; and between first Rheumatology appointment and TAB performed was 17.88 days. 9 and 13 patients were not started on bisphophonates and gastroprotection respectively when steroids were commenced. 33 patients were not started on aspirin when diagnosed. 44 patients received adequate steroid dose tapering advice but did not receive a leaflet on temporal arteritis and steroid therapy, and a steroid card on commencement of steroid therapy. <h3>Conclusions</h3> Key areas for improvement include earlier recognition of symptoms by patients and primary care, shorter duration between commencement of steroids and TAB being performed, improvement in time between first rheumatology appointment to TAB; and increased use of aspirin, bisphosphonates and gastroprotection. <h3>References</h3> Dasgupta B et al. BSR and BHPR Guidelines for the management of giant cell arteritis. Rheumatology 2010;49(8):1594-1597. Mukhtyar C et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2009;68:318-323. <h3>Disclosure of Interest</h3> None Declared
P147 Current smokers face increased risk of Acute Lung Injury post oesophagectomy compared to former smokers- implications for therapy and trial design?: Abstract P147 Table 1.
Authors: RCA Dancer, D Parekh, CS Calfee, DF McAuley, GD Perkins, DR Thickett
Journal: Thorax (2013)

<h3>Introduction</h3> Patients undergoing oesophagectomy have ~25% risk of developing post-operative Acute Lung Injury (ALI). A recent meta-analysis showed that smoking cessation prior to an operation reduces the risk of respiratory complications [1]. We hypothesised that current smokers would have an increased risk of ALI post-oesophagectomy compared with former smokers. <h3>Methods</h3> We analysed data from 14 current smokers and 37 former smokers recruited to the translational sub-study of the BALTI prevention trial. Extravascular Lung Water Index (EVLWI) and Pulmonary Vascular Permeability Index (PVPI) were measured using PICCO. Plasma and Bronchoalveolar lavage fluid (BALF) cytokine levels were measured by ELISA. <h3>Results</h3> Current smokers were significantly younger and had a lower BMI than former smokers. Current smokers were more likely to develop post-operative ALI which required ventilation but there was no difference in the rate of respiratory infection. PVPI was significantly higher immediately post op and on day 1 post op and EVLWI was significantly higher on day 1 post op in current smokers (see table). Plasma levels of FAS ligand were significantly lower in current smokers pre-op, post-op and on day 1 post-op. Pre-op plasma levels of sICAM1 were significantly higher in current smokers but there was no difference in post-op levels. Plasma levels of IL-17 were lower pre-op, post-op and on day 1, although only the post-op difference reached significance. In BAL, levels of VEGF were significantly lower and levels of IL1ra and TNFR1 were significantly higher in current smokers (see table). <h3>Conclusion</h3> Current smokers have a higher risk of Acute Lung Injury following oesophagectomy than former smokers. This finding is supported by higher post-operative levels of extravascular lung water and pulmonary vascular permeability and differences in both plasma and BAL cytokines in current smokers. Our data highlights the importance of encouraging patients to stop smoking prior to major surgery as well as the need to control for smoking history in trials aiming to ameliorate lung injury in this patient group. <h3>References</h3> Wong, J. <i>et al</i>. Short-term preoperative smoking cessation and postoperative complications: a systematic review and meta-analysis. <i>Can J Anaesth</i>, 2012. 59(3): 268–79
394 IN VIVO ORAL DOSING OF THE TLR7 AGONIST GS-9620 INDUCES AN ANTI-VIRAL GENE EXPRESSION SIGNATURE IN MURINE LIVER CONCURRENT WITH UNDETECTABLE SERUM LEVELS OF IFN-a
Authors: S. Pflanz, A. Fosdick, T. Cihlar, M. Subramanian
Journal: Journal of Hepatology (2013)
HEART FAILURE WITH INTERMEDIATE LEFT VENTRICULAR EJECTION FRACTION
Authors: Hye Bin Gwag, Ga Yeon Lee, Minsun Kim, Jiseok Kang, Jin-Oh Choi, Eun-Seok Jeon, Dong-Ju Choi, Jae-Joong Kim, Kyung-Kook Hwang, Shung Chull Chae, Sang Hong Back, Byung-Su Yoo, Myeong-Chan Cho, Byung-Hee Oh, Seok-Min Kang, Hyun-Young Park, Young Keun Ahn
Journal: Journal of the American College of Cardiology (2016)
Risk Factors of Breast Cancer in Relation to Classical Histopathology.
Authors: H. Olsson, C. Ellberg
Journal: Cancer Research (2009)

Abstract Background: Classical histopathological groups of breast cancer have recently been less studied in relation to etiological factors than the new more molecular oriented taxonomy such as luminal A,B, Her2-neu and basal type of breast cancer. In the present investigation we have related histopathology to breast cancer risk factors to shed light on the possibility that the classical taxonomy may have a biological meaning presently not fully recognized.Material and methods:In 1677 consecutive breast cancer patients the following risk factors were related to histopathology; parity, HRT use, breast cancer screening, vertical inheritance of breast cancer (possibly dominant), horizontal inheritance of breast cancer (possibly recessive), and germline mutation carrier status (BRCA1, BRCA2, CDKN2A, p53). Patients with mixed tumor types were excluded. All analyses were age adjusted and factors were simultaneously adjusted for.Results: A germline mutation was present in 1.5% of the cases. A relationship between medullary tumors and BRCA1 mutations was seen. Germline mutation carriers were in further analysis excluded. Among remaining cases a vertical family history was present in 23% and a horizontal one in 5% of the cases. A horizontal family history was significantly associated with tubular tumor type (OR=3.9, 1.4-10.4) and age, and non-significantly associated with tumor progesterone receptor content (OR=1.7, 0.8-4.0), and lobular tumor type (OR=1.4, 0.6-3.2). A vertical family history was significantly related to tumor multifocality (OR=2.3, 1.5-3.5), tumor bilaterality (OR=2.1, 1.4-3.0) and screening detection (OR=1.5, 1.1-2.1), while age and a tubuloductal tumor type (OR=0.5, 0.3-0.9) were significantly negatively related. Patients with ductal and mucinous tumors had significantly fewer children (OR=0.9, 0.8-0.99) and (OR=0.6, 0.4-0.8) respectively, while patients with comedocancer had significantly more children (OR=1.2, 1.1-1.4) .HRT use increased non significantly the risk for lobular breast cancer, while significantly being related to mixed lobular cases.Conclusion.These results demonstrate that classical histopathological groups are related to breast cancer risk factors and indeed may have a biological relationship to etiological factors.Especially factors related to parity, HRT use and family history seem to relate to different histopathological groups. Molecular signatures as well as classical histopathology should be used in future risk factor studies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6065.
Abstract 2459: Discovery of small molecule TAK1 inhibitors with antiproliferative activity in cell lines derived from hematological malignancies.
Authors: Dorin Toader, Jamal C. Saeh, Nin Guan, Francoise Powell, Raymond Chen, Corinne Reimer, Kate Byth
Journal: Cancer Research (2013)

Abstract Transforming growth factor β-activated kinase 1 (TAK1), a member of the MAPKKK family, is a key mediator of proinflammatory and stress signaling. It was shown previously that inhibition of TAK1 via the use of siRNA or small-molecule kinase inhibitors can inactivate NF-κB, down-regulate p38, and activate the intrinsic caspase pathway, resulting in profound induction of apoptosis. Herein we report the discovery of 5-fluoro-4-(imidazo[1,2-b]pyridazin-3-yl)-N-phenylpyrimidin-2-amines as TAK1 ATP competitive small molecule inhibitors. These compounds inhibit the kinase activity of TAK1 in vitro with low nanomolar potency. Evidence is presented that supports a mechanism of action consistent with inhibition of TAK1 kinase activity within the NF-κB pathway. Optimization of potency and selectivity for this series from hit to lead will be discussed, including the structure-based design and crystallographic determination of the binding mode. The outcome of efforts aimed at improving the in vivo pharmacokinetics of compounds is described. Results of kinase selectivity profiling for both an in vitro probe compound - AZ TAK1 - and an in vivo probe compound will be presented. Furthermore, we report low nanomolar antiproliferative activities in cell lines derived from Haematological Malignancies for these compounds. This cellular activity profile is suggesting that TAK1 inhibition presents therapeutic potential in Haematological Cancers. Citation Format: Dorin Toader, Jamal C. Saeh, Nin Guan, Francoise Powell, Raymond Chen, Corinne Reimer, Kate Byth. Discovery of small molecule TAK1 inhibitors with antiproliferative activity in cell lines derived from hematological malignancies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2459. doi:10.1158/1538-7445.AM2013-2459
Atrial Fibrillation in Heart Failure
Authors: Bruce A. Koplan, William G. Stevenson
Journal: Circulation (2016)

H eart failure (HF) promotes atrial fibrillation (AF) by con- tributing to electric and structural changes.The development of AF in patients with preexisting congestive HF is associated with increased adverse events, including HF progression and mortality. 1,2However, large, randomized trials have failed to demonstrate that maintenance of sinus rhythm with antiarrhythmic drug therapy improves mortality. 3Some would argue that the development of AF is a marker of deterioration and that therapy will have little benefit.However, many would agree that sinus rhythm is a good thing.AF patients who have sinus rhythm restored have better functional capacity than those who remain in sinus rhythm. 4However, the electrophysiological changes that accompany HF are likely to reduce the chances of long-term maintenance of sinus rhythm.There is also concern that adverse effects of antiarrhythmic drugs, often amiodarone, in this population offset the benefit of sinus rhythm.Achieving sinus rhythm with catheter ablation offers the potential to maintain sinus rhythm without offsetting adverse drug effects.
Undocumented Injustice? Medical Repatriation and the Ends of Health Care
Authors: Michael J. Young, Lisa Soleymani Lehmann
Journal: New England Journal of Medicine (2014)

The authors review the history and motivations behind medical repatriation, the transfer of undocumented patients in need of subacute care to their country of origin. They argue that involuntary medical repatriation violates the ethical duties of health care providers.
Intérêt de la coloscopie au décours d'une bactériémie à germe d'origine digestive (BGOD)
Authors: AL Pelletier, S Diamantis, E Farfour, PL Woerther, T Vallot, C Rioux
Journal: Endoscopy (2011)

Introduction: La coloscopie permet de chercher une porte d'entrée à une BGOD quand aucune origine ne paraît évidente. Sa pertinence n'a pas été évaluée en dehors des infections à Streptococcus bovis.
Abstract P1-05-19: Modeling Cancer Recurrence and the Therapeutic Effect of Adjuvant Systemic Therapy
Authors: S Ganesan, G Bhanot, M Boemo, JH Lee
Journal: Cancer Research (2012)

Abstract Despite complete surgical removal of early stage cancers, recurrence can occur at distant locations in time spans ranging from months to decades. This is due to the presence of disseminated cancer cells that can ultimately transition into active growth leading to recurrence. Systemic adjuvant therapy can decrease the incidence of distant relapse and lead to improved survival in some cancers. In this study, data on natural recurrence patterns of different breast cancer subtypes is used to build a probabilistic model of distant recurrence. The central hypothesis of this model is that after initial local therapy, a fraction of patients will have the presence of one or more disseminated dormant metastatic foci (DMF). The transition of DMF into actively growing metastatic foci (AMF) is described using a stochastic model. DMF of individual breast cancer subclasses each have a distinct probability per unit time of entering active growth. Fitting of this model to clinical trial data of early stage breast cancers treated with surgery alone demonstrates that DMF present in estrogen receptor negative (ER−) cancers and Luminal B cancer have greater probabilities of transition to active growth per unit time than Luminal A breast cancers. Clinical trial data were then used to determine the effect of adjuvant therapy on the dynamics of tumor recurrence. The data strongly support a model in which adjuvant chemotherapy works by eliminating only a fraction of DMF that have transitioned into AMF during the time of chemotherapy treatment. Thus short duration adjuvant chemotherapy would have greater efficacy in ER−, HER+ and Luminal B breast cancers, which have fast dynamics of recurrence, and little effect in Luminal A breast cancers with far slower dynamics of recurrence. Similarly, analysis of adjuvant hormonal therapy trial data, demonstrate that hormonal therapy also affects only DMF that transition into active growth during the period of hormonal therapy. This model can explain why extended duration therapy of up to 5 years is more effective than shorter duration of adjuvant hormonal therapy. Interestingly some adjuvant treatments, such as trastuzumab for HER2+ breast cancers, affect recurrence rates in a way that suggest that these interventions directly kill DMF. This model of tumor recurrence has several clinical implications that could inform future clinical trial design. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-19.