tbuckley/cabot-search huggingface dataset:
Molecular targeting of HER2 for diagnosis and therapy of breast cancer.
Authors: J Capala, G Kramer-Marek, S Lee, M Hassan, DO Kiesewetter, A Puri, V Chernomordik, A Gandjbakhche, G Griffiths, R Blumenthal
Journal: Cancer Research (2009)

Abstract Abstract #6004 Background: Expression of HER2 receptors in breast cancer is correlated with poor prognosis and may be different in distant metastases as compared to the primary tumor. We are developing methods to assess global expression of HER2 in vivo and to deliver therapeutic agents specifically to HER2-positve cells.&amp;#x2028; Materials and Methods: As the targeting agent we use an Affibody molecule (http://www.affibody.com). These very stable and highly soluble proteins are relatively small (8.3 kDa) and bind to HER2 receptors with high affinity (22 pM). For imaging with PET, SPECT, or optical methods, an appropriate group containing the imaging beacon can be attached by a selective chemical reaction to a unique C-terminal cysteine residue of Affibody. For therapeutic purposes, they can be conjugated to multifunctional nanoparticles containing both imaging and therapeutic agents. We have conjugated affibody molecules with thermo-sensitive liposomes or gold nanoparticles (subsequently activated with neutrons) and characterized their biodistribution using optical imaging and SPECT, respectively. We used PET imaging with 18F-ZHER2-Affibody to monitor the down-regulation of HER2 following four doses (50 mg/kg) of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin, 17-DMAG, an inhibitor of Hsp90 known to decrease HER2 expression. Animals were scanned before and after treatment. Immediately after the last scan, the mice were euthanized and tumors were frozen for ex-vivo analysis of receptor expression. For optical imaging, we used AlexaFluor dyes conjugated with affibody molecules containing an albumin binding domain that extended their circulation time. We have attached nanoparticles (liposomes and gold) to Affibody molecules using the same type of maleimide chemistry.&amp;#x2028; Results: Our results showed that Affibody molecules do not affect the targeted cells and that their binding does not interfere with either the binding or the effectiveness of trastuzumab. 18F-ZHER2-Affibody was eliminated quickly from blood and normal tissues, providing high tumor/blood and tumor/muscle ratios by 1h post injection. The signal obtained from PET and optical imaging correlated well with the number of receptors expressed in the studied tumors as assessed by western blot, ELISA, and IHC. Following 17-DMAG treatment, the level of HER2 expression, estimated by PET imaging, in BT474 and Mcf-7/clone18 tumors decreased 70% and 30%. This change was confirmed by the biodistribution studies, ELISA and western blot.&amp;#x2028; Discussion: This strategy, involving assessment of target presence and distribution in an individual patient followed by optimized, target-specific drug delivery, may significantly improve efficacy of breast cancer treatment while reducing side effects. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6004.
Domain-general mechanisms: What they are, how they evolved, and how they interact with modular, domain-specific mechanisms to enable cohesive human groups
Authors: Kevin MacDonald
Journal: Behavioral and Brain Sciences (2014)

Abstract Domain-general mechanisms are evolutionarily ancient, resulting from the evolution of affective cues signaling the attainment of evolutionary goals. Explicit processing is a particularly important set of domain-general mechanisms for constructing human groups – enabling ideologies specifying future goal states and rationalizing group aims, enabling knowledge of others' reputations essential to cooperation, understanding the rights and obligations of group membership, monitoring group members, and providing appropriate punishments to those who deviate from group aims.
Abstract 259: Functional analysis of the β1 subunit of AMP-activated protein kinase in ovarian cancer
Authors: Cuilan Li, Vincent W. S. Liu, David W. Chan, Hextan Y. S. Ngan
Journal: Cancer Research (2010)

Abstract AMP-activated protein kinase (AMPK) is a heterotrimer composed of a catalytic subunit (α) and two regulatory subunits (β and γ). Each subunit has different isoforms, namely, α1, α2, β1, β2, γ1, γ2 and γ3 encoded by distinct genes, which enable the yielding of 12 possible heterotrimeric complexes. Originally known as a cellular energy-balancing sensor, AMPK was recently found to have strong tumour suppression function. Roles of AMPK have recently been extensively studied in metabolic diseases and human cancers. However, the functional aspects of individual subunits of AMPK are barely investigated. Using quantitative RT-PCR, we found that the AMPK-β1 subunit was over-expressed in ovarian cancer as compared with normal ovary. Over-expression of the AMPK-β1 was further confirmed by immunohistochemical staining (IHC) of the paraffin-embedded ovarian tissues. Clinicopathological data analysis indicates that over-expression of AMPK-β1 correlates with low-grade tumour. Furthermore, from the IHC, the geographical location of the AMPK-β1 in ovarian cancer tissues was also known. In addition to its appearance in the cytoplasm, the AMPK-β1 is also presence in the cell membrane. Since the active form of AMPK (phospho-AMPK) only locates at the cytoplasm, we postulate that AMPK-β1 has addition functions other than just component of the AMPK molecule. To determine the role of AMPK-β1 in ovarian cancer, we have carried out functional analysis of the expression of AMPK-β1 in ovarian cancer. Interestingly, AMPK-β1 was found to inhibit cell growth when forced expressed in ovarian cancer cells. Enforced expression of AMPK-β1 can activate AMPK or down-regulate the level of phospho-AKT in ovarian cancer cells. Additional assays are being studied to further determine the role of AMPK-β1 in ovarian cancer. Understanding the functional role of AMPK-β1 may facilitate the design and development of a new strategy for therapeutic intervention. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 259.
Abstract 1175: The tumor-associated p53 R172H mutation does not display gain-of-function properties in hepatocellular carcinoma
Authors: Leanne G. Ahronian, Brian C. Lewis
Journal: Cancer Research (2012)

Abstract Hepatocellular carcinoma is a highly deadly malignancy, accounting for approximately 600,000 deaths worldwide every year. A common genetic change in HCC, present in 30% of cases, is mutation of the p53 tumor suppressor gene. p53R175H (corresponding to R172H in mice) is a hotspot for mutation that demonstrates “prometastatic” gain-of-function in pancreatic cancer. Since the frequency of p53 mutation increases with tumor grade in HCC, we hypothesized that p53R172H is a gain-of-function mutation in HCC that contributes to an increase in metastasis and a decrease in tumor-free survival. To study the role of p53 mutation in HCC, we used the RCAS-TVA mouse model. Albumin-TVA, p53LSL-R172H/fl, Albumin-cre mice were crossed to Albumin-TVA, p53fl/fl, Albumin-cre mice to generate litters in which half of the progeny are p53fl/fl and half are p53R172H/fl. Injection of these litters with DF1 chicken fibroblasts producing RCAS viruses encoding the mouse polyoma virus middle T antigen (PyMT), resulted in specific infection and expression of PyMT in the liver. We found that p53R172H/fl mice did not have increased tumor incidence, nor did they display increased rates of metastasis, relative to p53fl/fl mice, suggesting that mutant p53 does not display gain-of-function properties during HCC development in vivo. Interestingly, while shRNA-mediated knockdown of p53 in R172H expressing HCC cell lines resulted in decreased cell migration, suggestive of gain-of-function properties, analysis of a panel of HCC cell lines from p53 null and R172H expressing tumors found no differences in anchorage-independent growth and cell migration between the two groups. Thus, although p53R172H expressing HCC cells depend on this mutant for their transformation, p53 mutant cells and tumors do not have enhanced properties relative to p53 null HCC cells and tumors. These data suggest that important pathway(s) impacted by mutant p53 are inhibited by alternate mechanisms in p53 null cells resulting in equivalent phenotypes. Interestingly, cell lines derived from HCCs with conditional p53 deletion exhibit decreased levels of a p63 isoform compared to cells from p53R172H mice. Since p53 mutants have been previously shown to bind and inhibit p63, reduced p63 expression in p53 deficient HCC cells may explain this observation. Elucidation of the role of p63 in regulating HCC migration and metastasis is currently underway. 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 1175. doi:1538-7445.AM2012-1175
AB0361 Changes in number of total hip arthroplasty procedures and patient backgrounds in cases of rheumatoid arthritis
Authors: T. Kawasaki, T. Mimura, N. Okumura, Y. Matsusue
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Hip joints are important for daily like activities, which become limited when destruction occurs. Joint destruction caused by rheumatoid arthritis (RA) can be limited by administration of a biological drug, thus it is considered that the number of surgeries for affected patients will decrease in the future, with some recent reports noting that the number of total hip arthroplasty (THA) procedures for RA patients is decreasing. Bone destruction inhibition by use of methotrexate (MTX) and biological drugs has been suggested. However, few studies have investigated whether hip joint destruction in RA patients was altered by treatment with such new drugs. <h3>Objectives</h3> The purpose of this study was to examine whether the number of RA cases in Japan has shown a decreasing trend. We investigated the records of all patients who underwent THA at our institution during the most recent 12-year period including preoperative X-rays to determine any difference in tendency for hip joint destruction. <h3>Methods</h3> We investigated all patients with RA who underwent a THA procedure at our hospital from January 2000 through December 2011 and noted the number of THA cases each year, age at surgery, duration of RA, and medication administered. In addition, 2 investigators independently evaluated pre-operative X-ray findings using the Larsen classification (1) to determine whether the number of severe cases (Larsen grade 5) of hip joint destruction decreased during the study period. <h3>Results</h3> The total number of primary THA procedures was 561, while RA was diagnosed in 54 patients (9.6%). That latter value showed a decreasing tendency, as 31 of the 54 cases occurred from 2000 to 2005 and 23 from 2006 to 2011, a decrease of approximately 30%. There were few changes in patient background in regard to age at surgery and duration of RA. The rate of steroid use decreased from 80.6% to 65.2%, whereas the rate of MTX rate use increased from 41.9% in the first 6 years of the study to 65.2% in the final 6 years. Furthermore, the rate of biological drug use increased from 0% to 30.4%. Cases classified as Larsen grade 5 by X-ray evaluation decreased to only a single case in the final half from 7 cases in the first half. <h3>Conclusions</h3> The number of patients who underwent THA for RA was decreased and patient backgrounds were also changed. Preoperative X-ray evaluations showed that cases of severe joint destruction in particular were remarkably decreased. <h3>References</h3> Larsen A, et al. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn 1977;18:481-91. <h3>Disclosure of Interest</h3> None Declared
Control of renin release. Effects of d-propranolol and renal denervation on furosemide-induced renin release in the dog.
Authors: J L Osborn, J B Hook, M D Bailie
Journal: Circulation Research (1977)

We determined the effects of </-propranolol and renal denervation on furosemide-induced renin release in the anesthetized dog.rf-Propranolol possesses only membrane-stabilizing properties, whereas the /-isomer produces beta adrenergic blockade.To separate the vascular and macula densa mechanisms of the juxtaglomerular apparatus effectively, nonfiltering kidneys were produced by combining 2.5 hours of renal ischemia with ureteral ligation.In some dogs, renal denervation was accomplished by relocating the nonfiltering kidney into the neck during the 2.5-hour ischemic interval.Administration of d-propranolol in a priming dose of 1 mg/kg, iv, followed by an intravenous infusion of 1 mg/kg per hour decreased renin release in both the filtering and nonfiltering kidney.Subsequent furosemide injection (5 mg/kg, iv) failed to increase renin release in the nonfiltering kidney.Similarly, after the infusion of lidocaine into the renal artery of the nonfiltering kidney (1 mg/kg per hour), furosemide did not alter renin release.In the denervated nonfiltering kidney, furosemide in a dose of 5 mg/kg, iv, increased renin release and decreased renal resistance.Treatment with d-or rf,/-propranolol decreased renin release in five out of six denervated nonfiltering kidneys.Following propranolol, furosemide failed to increase renin release.These results demonstrate that the ability of </,/-propranolol to decrease renin release may be due partially to the membranestabilizing activity of the rf-isomer.Stimulation of renin release by furosemide occurs at both the vascular and macula densa sites which may act independently in the control of renin release.The data demonstrate that, whereas renal sympathetic innervation may modulate renin release under a variety of circumstances, this innervation is not an absolute requirement for renin release at the juxtaglomerular apparatus.
CARDIAC HYPERTROPHY IS EXACERBATED IN AGED MICE LACKING THE OSTEOPROTEGERIN GENE
Authors: Toshihiro Tsuruda, Yilin Hao, Syuji Kurogi, Midori Nakamura, Nobuyuki Udagawa, Etsuo Chosa, Yujiro Asada, Kazuo Kitamura
Journal: Journal of the American College of Cardiology (2016)
VALUE OF CONVENTIONAL AND SPECKLE TRACKING ECHOCARDIOGRAPHY IN THE ASSESSMENT OF BIVENTRICULAR FUNCTION IN SECONDARY MITRAL REGURGITATION AFTER REPAIR WITH THE MITRACLIP SYSTEM
Authors: Antonio Vitarelli, Carlo Gaudio, Enrico Mangieri, Gaetano Tanzilli, Lidia Capotosto
Journal: Journal of the American College of Cardiology (2016)
AB0568 Biologics in Takayasu Arteritis: Preliminary Data from the French Registry
Authors: A. Mekinian, T. Mirault, M. Lambert, J. Sibilia, M. Hie, C. Comarmond, E. Messas, S. Berthier, A. Neel, M. Hamidou, P. Cohen, I. Marie, C. Lavigne, Z. Amoura, L. Guillevin, B. Godeau, O. Fain, P. Cacoub, D. Saadoun
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The aim of this registry is to determine: (1) the real-life use of various biologics in Takayasu arteritis in France; (2) to compare the efficacy of different biologics among them; (3) to evaluate the tolerance; (4) to describe the long term outcome. <h3>Methods</h3> All French practionners from the departments of internal medicine, of vascular medicine and rheumatology will be regularly contacted to declare the patients with TA under biologics. The clinical, biological and radiological data are collected in standardized fill at the baseline, at 6, 12, 24 months and the last visit. All radiological exams will be reviewed by two radiologists blinded to the clinical and biological data. The response to the biologics will be assessed using NIH score, and the outcome will be compared at the least visit to the baseline. The disease activity was determined using the NIH score. <h3>Results</h3> Forty two patients with TA (age 42±15 years, 36 women) were included. At the initiation of biologics, 91% of patients were treated with steroids (prednisone mean amount 27±20 mg/day). Another immunosuppressive agent was associated in 88%: methotrexate (56%), azathioprine (34%) and mycophenolate mofetil (3%). Steroid dependence was noted in 41% of patients. At the time of the biologics initiation the clinical symptoms were upper limb claudication (35%), carotidynia (32%), arterial hypertension (21%), headaches (24%), fever (9%), arthromyalgias (35%), and arterial vascular stroke (12%). Associated disease was noted in 24% of cases: spondyloarthritis (15%), Crohn disease (6%) and sarcoidosis (1%). The various biologics were used in 48 cases for 42 patients. Among them, the biologics was infliximab (52%), etanercept (14%), adalimumab (10%), tocilizumab (31%), anakinra (2%) and rituximab (5%). The biologics duration was 1.8±1.1 year, with the mean follow-up of 3±1.5 years. Two infusion related reactions were noted, one myocardial infarction and 4 severe infections. One patient under tocilizumab experienced adverse effect which was severe neutropenia (&lt;500/mm<sup>3</sup>), but without any infection or antibiotics needs in relation with tocilizumab. The neutropenia needed the decrease of tocilizumab from 8 mg/kg to mg/kg and was then well-tolerated. No death related to biologics treatment was noted. <h3>Conclusions</h3> This is the french registry of TA treated by biologics which aim to describe the real life use of biologics in TA, to compare the different agents and to determine the factors predictives of the treatment response. The registry is ongoing and the efficacy and the tolerance of different biologics will be compared. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5308
Jejunal pyogenic granuloma diagnosed and treated with spiral enteroscopy
Authors: J. Chou, S. Chen, C. Yii, Y. Shih, K. Cheng, H. Chang
Journal: Endoscopy (2012)

A 67-year-old woman presented to our hospital with a 1-year history of melena. She also had history of hepatitis B and C virus-related liver cirrhosis complicated by hepatocellular carcinoma. On examination, her conjunctivae were pale and her nadir hemoglobin was 5.1 g/dL. Esophagogastroduodenoscopy and colonoscopy showed no definite bleeding source, and a diagnosis of obscure gastrointestinal bleeding was made. Capsule endoscopy demonstrated blood oozing in the proximal jejunum ([Fig. 1]) and several angioectasia were identified in the small bowel. We performed spiral endoscopy perorally using an overtube (Discovery Small Bowel overtube; Spirus Medical, Stoughton, Massachusetts, USA) and an enteroscope (Fujinon EN-450T5; Fujinon, Saitama, Japan), which demonstrated a 1.5-cm sub-pedunculated tumor with superficial ulceration in the proximal jejunum, indicative of the bleeding point ([Fig. 2]). We removed the tumor using snare polypectomy; bleeding from the tumor site after polypectomy was successfully stopped with hemoclips ([Fig. 3]). Pathological evaluation of the resected tumor revealed many capillaries of various sizes with acute and chronic inflammatory cell infiltrates, confirming the diagnosis of pyogenic granuloma ([Fig. 4]).
ANP system activity predicts variability of fat mass reduction and insulin sensitivity during weight loss
Authors: Maria Brachs, Susanna Wiegand, Verena Leupelt, Andrea Ernert, Ulrich Kintscher, Reiner Jumpertz von Schwarzenberg, Anne-Marie Decker, Thomas Bobbert, Norbert Hübner, Wei Chen, Heiko Krude, Joachim Spranger, Knut Mai
Journal: Metabolism (2016)
AB0642 Efficacy of anakinra in gouty arthritis in real life population: a report of 36 cases.
Authors: S. Ottaviani, A. Molto, H.-K. Ea, S. Neveu, G. Gill, L. Brunier, E. Palazzo, O. Meyer, P. Richette, T. Bardin, Y. Allanore, F. Lioté, M. Dougados, P. Dieudé
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gout is a common arthritis that occurs particularly in subjects who have frequently associated comorbidities. These comorbid conditions could limit the use of conventional therapies (<i>e.g.</i> colchicine, non-steroidal anti-inflammatory drugs and/or corticosteroids). <h3>Objectives</h3> The aim of the herein study was to evaluate the efficacy and tolerance of anakinra in patients with urate crystal-induced arthritis. <h3>Methods</h3> We performed a multicentric retrospective chart review of patients who received anakinra for gouty arthritis. Demographic information, comorbidities, co-medication, treatment outcomes, adverse event and subsequent flares were recorded. The change of pain (VAS 0-100 mm) and CRP levels were evaluated at baseline and after 3 days of SC injections of anakinra (100 mg). The outcome of anakinra treatment was categorized as: good response (&gt; 50% of improvement of VAS pain and CRP level), partial response (20 to 50% of improvement), or no response. <h3>Results</h3> A total of 36 patients (29 males, mean age: 60.4 ± 13.4 years) who were treated by anakinra for gouty arthritis were included. The mean disease duration was 9.3 ± 9.0 years. All patients had contraindication and/or failure to at least two conventional therapies. The majority (33 [91.7%]) of patients demonstrated a good response to anakinra therapy. IL-1 blockade led to a strong and rapid decrease of VAS pain (72.5 [70.0-80.0] to 20.0 [20.0-30.0] mm, <i>P</i> &lt;0.0001) and CRP level (130.5 [62.3-239.5] to 18.0 [5.0-29.5] mg/l, <i>P</i> &lt;0.0001). After a median follow-up of 7.5 [2.0-12.3] months, a relapse occurred in 12 (33.3%) patients with a median delay to relapse of 22.5 [13.8-97.5] days. Relapse occurred more frequently in patients without prevention of acute flare (<i>P</i>=0.014). None patient under anakinra for long-term use relapsed. Seven infections were noted and no case of neutropenia was observed. <h3>Conclusions</h3> Our results confirm that anakinra is efficient in gouty arthritis, relatively well tolerated and could be a relevant alternative in the management of gouty arthritis, particularly in patients for whom conventional therapies are ineffective or contra-indicated. <h3>Disclosure of Interest</h3> None Declared