tbuckley/cabot-search huggingface dataset:
P4-07-20: Apoptosis in Circulating Tumor Cells (CTCs) of Early and Metastatic Breast Cancer Patients.
Authors: G Kallergi, G Konstantinidis, M Papadaki, S Agelaki, D Mavroudis, C Stournaras, V Georgoulias
Journal: Cancer Research (2011)

Abstract Background: Metastasis has been associated with the presence of circulating (CTCs) and disseminated (DTCs) tumor cells in peripheral blood and bone marrow of breast cancer patients, respectively. Recent studies have confirmed that the detection of CTCs and DTCs represents a strong and independent prognostic factor for decreased disease-free and overall survival. However, it is not clear so far whether all CTCs are capable to generate metastasis or some of them are destined to die. The aim of the present study was to analyze the presence of apoptotic CTCs in patients with early and metastatic breast cancer. Patients and methods: Double staining immunofluorescent (IF) expreriments were performed in peripheral blood mononuclear cells (PBMC) cytospins of patients with early (n=23) and metastatic breast cancer (n=29), prior to the initiation of adjuvant and first-line chemotherapy, respectively. Pancytokeratin A45-B/B3 antibody (as a marker of CK-positive cells) was coupled with either M30 (marker of apoptotic cells) or Ki67 (marker of proliferating cells) antibodies. Apoptotic CTCs were also evaluated using a polycaspase detection kit. Results: Significantly lower proportions of apoptotic CTCs were detected in metastatic compared to early breast cancer patients using the polycaspase kit (3% vs 49%, p=0.0001). These results were confirmed with M30 staining (32% vs 67%, in metastatic and early disease, respectively, p=0.023). The median percentage of apoptotic CTCs per patient was also lower in advanced compared to early disease patients (0% vs 100% with the polycaspase kit and 15% vs 70% with M30 staining). Ki67 positive CTCs were identified in 56% of early and metastatic patients, while the ratio of Ki67-positive/Total CTCs was 15% and 36% respectively. Conclusions: Apoptotic CTCs are more commonly observed in early compared to metastatic breast cancer, whereas, Ki-67 positive CTCs are more frequently encountered in metastatic disease. The differential incidence of apoptotic and proliferative CTCs in early and metastatic disease is probably related to disease progression. The evaluation of these markers in CTCs from patients with breast cancer may provide useful prognostic information and could be used to monitor the effectiveness of therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-20.
Abstract 759: Regulation of androgenic signaling by yes-associated protein, YAP, in prostate cancer cells.
Authors: Ahmet Alptekin, Gamze Kuser Abali, Qiang Wang, Bekir Cinar
Journal: Cancer Research (2013)

Abstract Androgenic signaling plays a central role in prostate tumor development, progression, and metastasis. The molecular circuitry contributing to these pathological events is still a mystery. Previously, we reported that the hippo-like protein kinase Mst1/2 antagonized androgen receptor (AR) and prostate tumor cell growth (Cinar et al., Cancer Res., 2011). Here, we studied the role of yes-associated protein (YAP) oncogene, a prominent nuclear effector of the Mst/Hippo tumor suppressor network, in regulating AR and in prostate tumor cell growth in vitro. As revealed by co-immunoprecipitation (IP) and western blot experiments, we first showed that endogenous YAP formed protein complexes with endogenous AR. The complex formation between the two proteins mainly occurred in cell nuclei was further enhanced by androgen stimulation. Our luciferase-promoter reporter analysis demonstrated that enforced YAP expression increased the androgen-mediated and AR-responsive promoter reporter gene activation, and the carboxyl-terminal site of YAP, which consists of PDZ and coiled-coiled protein-protein interaction domains, appeared to be responsible for AR transactivation. Chromatin-IP and PCR analysis of the bound and uncross-linked genomic DNA revealed that YAP interacted with the DNA regions where AR also binds, and androgen enhanced the interaction between YAP and chromatin DNA. We also provided evidence that, compared to vector control, enforced YAP expression promoted androgen-dependent and independent cell growth, and silencing YAP by RNAi reduced the growth of castration-resistant prostate tumor cells in vitro. Our findings indicate that YAP is a physiologic binding partner and positive regulator of androgenic signaling, and suggest that the Hippo-YAP pathway plays a critical role in human prostate tumor progression. Citation Format: Ahmet Alptekin, Gamze Kuser Abali, Qiang Wang, Bekir Cinar. Regulation of androgenic signaling by yes-associated protein, YAP, in prostate cancer cells. [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 759. doi:10.1158/1538-7445.AM2013-759
AB1201 Study of Music Therapy Using Musical Instruments for Patients with Rheumatoid Arthritis
Authors: Y. Miura, T. Maeda, K. Fukuda, I. Yamazaki, M. Kurosaka
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Music Therapy is the clinical and evidence-based use of music interventions to accomplish individualized goals within a therapeutic relationship by a credentialed professional who has completed an approved music therapy program. Music therapy interventions can be designed to alleviate pain, manage stress, and promote physical rehabilitation in addition to express feelings, enhance memories, improve communication, and promote wellness. Recently music therapy is much further innovated in rehabilitation for such as dementia and parkinsonism, however, few reports have been made for arthritis including rheumatoid arthritis (RA). <h3>Objectives</h3> Since 2010, we have held music therapy activity annually in monthly patient education classes for patients with RA. In this study we surveyed the effects of music therapy for patients with RA. <h3>Methods</h3> Music therapy activity was conducted by a credentialed music therapist, a volunteer pianist, hospital staffs, and healthcare students. Six Japanese songs were sung with a piano accompaniment. Three of 6 were sung and simultaneously played with chime bars (a sort of hand bells) following colored notes by the participants. General health condition, pain, and state anxiety were surveyed by self-rating questionnaire including 10cm visual analog scale (VAS), face pain rating scale, and State Trait Anxiety Index (STAI). Results were statistically analyzed with Wilcoxon signed-rank test or Student9s t-test. <h3>Results</h3> Thirty patients with RA (28 females and 2 males) were participated the survey. Twenty were in 60s, 10 in 50s and 10 in 70s. Modified health assessment questionnaire (mHAQ) of the attendee was 0.55±0.62 (0-2.6). VAS was significantly improved from 2.8±2.9 to 2.4±2.7 (p&lt;0.05), face scale was significantly improved from 6.1±5.1 to 4.2±4.2 (p&lt;0.01), and state anxiety of STAI was also significantly improved from 39.0±10.9 to 32.0±10.5 (p&lt;0.01) by music therapy. A patient could not play the instrument by physical disability and another patient had some joint pain by playing. However, almost all the participants were in favor of playing chime bars. <h3>Conclusions</h3> Music therapy using musical instruments improves pains and physical and psychological conditions of patients with RA. <h3>Disclosure of Interest</h3> None declared
Growth Hormone for the Elderly?
Authors: Mary Lee Vance
Journal: New England Journal of Medicine (1990)

IN addition to promoting linear growth in prepubertal children, growth hormone is often described as having anabolic, lipolytic, and diabetogenic properties. These descriptions are based on the results of diverse short-term studies of humans, animals, and isolated tissues, many of which involved the use of large doses of growth hormone. Until the production of growth hormone by recombinant-DNA methods began, the small supply of pituitary-derived human growth hormone limited its use to the treatment of children with growth hormone deficiency. The wide availability of synthetic human growth hormone has made possible long-term studies of other potentially beneficial uses of growth . . .
Characterization of acute myeloid leukemia with MLL rearrangements – no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts
Authors: H-F Tien, C-H Hsiao, J-L Tang, W Tsay, C-H Hu, Y-Y Kuo, C-H Wang, Y-C Chen, M-C Shen, D-T Lin, K-H Lin, K-S Lin
Journal: Leukemia (2000)
DISCRIMINATORY POWER OF INTENSIVE CARE UNIT SCORING SYSTEMS FOR OUTCOME PREDICTION IN PATIENTS UNDERGOING EXTRACORPOREAL MEMBRANE OXYGENATION FOLLOWING CARDIOVASCULAR SURGERY
Authors: Lore Schrutka, Georg Goliasch, Christian Roth, Binder Christina, Gottfried Heinz, Irene Lang, Gerald Maurer, Herbert Koinig, Barbara Steinlechner, Alexander Niessner, Klaus Distelmaier
Journal: Journal of the American College of Cardiology (2016)
AB0360 Results of total hip prosthesis in patients with rheumatoid arthritis according to the received therapy
Authors: S. Lapshina, I. Akhtyamov, L. Myasoutova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Total hip prosthesis is an effective method of relieving pain and improving function the hip in patients with rheumatoid arthritis (RA). Topical drug therapy remains the question of RA therapy in perioperative period. <h3>Objectives</h3> To review the results of total hip prosthesis according to baseline disease activity and received therapy. <h3>Methods</h3> Total hip prosthesis was used on 36 RA patients (32 women, 4 men) with a mean age of 49,5 ± 15,82 years. Disease duration at the time of surgery was 12,45 ± 5,53 years. High disease activity by DAS28 was observed in 10 patients (27.8%), moderate - in 19 (52.8%), low - in 7 (19.4%) patients, the mean DAS28 4,5 ± 1,7. At the time of surgery (before and after), 24 (66.7%) of the patients continued to take basic anti-rheumatic drugs (DMARDs) - (methotrexate 7.5-15 mg per week -15, leflunomide - 7, sulfasalazine - 2). 6 (16.6%) patients received biological therapy: infliximab - 2, adalimumab -1, rituximab - 3, which were canceled before the operation in accordance with the terms specified in the national guidelines. 19 (52.8%) patients received steroids, of which, in combination with DMARDs - 7 (19.4%). Before the surgery, in the postoperative period and after 6 months joint pain on a visual analogue scale (VAS), the activity of the disease - DAS28, functional capacity index HAQ have been evaluated <h3>Results</h3> For 6 months after surgery VAS decreased by 2.5 times to 31,7 ± .19,4 mm (p &lt;0.05), disease activity decreased (high - 4 (11.1%), moderate 17 (47.2%), low -15 (41,7%)), D DAS28 = 1,1 ± .0,7, HAQ index decreased from 1,63 ± 0,91 to 1,04 ± 0, 78 (p &lt;0.05). VAS in patients receiving steroids alone (n = 12) was - 24,9 ± .18,6 mm, steroids + DMARD (n = 7) - 29,1 ± 19,7 mm, only DMARDs (n = 11) 34,8 ± 18,9 mm, biological therapy + DMARD (n = 6) 37,4 ± 20,8 mm. Activity decreasing - D DAS28 – did not depend from treatment. Functional capacity in patients in the group (n = 17), receiving DMARDs with or without biological therapy (D HAQ = -0,69 ± 0,34) compared to patients receiving steroids without basic therapy (n = 12) - D HAQ = -0,48 ± 0,31 was significantly better improved (p &lt;0.05). Deep vein thrombosis complication was observed in one patient treated with steroids, the development of soft-tissue infection of the operated joint, required the use of antibiotics in one patient treated with steroids at the time of surgery. <h3>Conclusions</h3> Total hip prosthesis is an effective way to improve functional capacity, to relieve pain and to reduce the activity of RA. Functional ability after surgery is higher in patients using DMARDs continuously and receiving biological therapy compared to patients receiving steroids. <h3>Disclosure of Interest</h3> None Declared
A5.11 Vaccination against TNF and side effects in<i>listeria</i>infection model
Authors: N Belmellat, L Faunonnier, B Ryffel, MC Boissier, E Assier
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Anti-TNF therapy has been a successful treatment strategy for rheumatoid arthritis disease, but is associated with reduced resistance to infection. Recently, active anti-TNF immunotherapy has shown its promising efficiency in a pilot phase IIA clinical trial. In mice, TNF is essential to control <i>Listeria monocytogenes</i>. We aimed at better defining the infectious risk/benefit ratio of TNF-a neutralisation of active immunotherapy strategy. For this purpose, we developed a vaccine (mTNF-K) targeting murine TNF-a by coupling the cytokine to the carrier protein keyhole limpet hemocyanin (KLH). We reported mTNF-K attenuated collagen-induced arthritis (CIA) to same extent as etanercept. <h3>Objectives</h3> Here we evaluated the safety of TNF-a blockade induced by the vaccine in <i>Listeria</i> infection model. <h3>Materials and methods</h3> 4 groups of 10 C57Bl/6 mice were used and compared with a murine TNF KO group (same background). Wild type mice were treated either by mTNF-K, etanercept, KLH or PBS. Vaccines were emulsified in CFA (day 0) or IFA (days 13, 27 and 40) before injections. All groups were infected at day 44 by 10<sup>4</sup> cfu of <i>Listeria monocytogenes</i> (LO28 strain). Mice groups were divided in two arms: one was euthanized 4 days post-infection, and the bacterial burden was evaluated in the spleen and the liver; survival of the lasting mice was evaluated until day 11. Blood sampling was conducted at day 34 and 47 in order to evaluate anti-TNF-a antibody production. <h3>Results</h3> A sustained anti-TNF-a antibody production was obtained in mTNF-K vaccinated mice. At day 4 post-infection, mTNF-K and non-targeted-TNF-a treatments groups (KLH, PBS) presented lower bacterial burden in liver and spleen than TNF KO and etanercept groups. At day 11, all mice of PBS and mTNF-K groups survived to infection. Large lesions in livers were observed only within TNF KO and etanercept groups. <h3>Conclusions</h3> Active immunotherapy with mTNF-K vaccine seems to preserve adequate host immunity against <i>Listeria </i>infection in this model.
Steatorrhea Following the Use of Antibiotics
Authors: Reuben R. Merliss, Arthur Hoffman
Journal: New England Journal of Medicine (1951)

IN THE last two years several new antibiotics have become available. Three of these, — aureomycin, chloramphenicol and terramycin, — affect a wide range of bacteria and, since they are effective orally and are reputed to be without serious toxicity, have been widely used. It is generally known, however, that they may produce black tongue, vaginitis, pruritus and and proctitis. More recently Woods and his co-workers1 contributed greatly by pointing out the occurrence of prolonged diarrhea and pulmonary disease following the use of antibiotics. They attributed this to an overgrowth of monilia secondary to destruction of competing bacteria, causing an . . .
Abstract 4794: An undesired effect of chemotherapy: gemcitabine promotes pancreatic cancer cell invasiveness through upregulation of CXCR4.
Authors: Sumit Arora, Arun Bhardwaj, Seema Singh, Sanjeev K. Srivastava, Steven McClellan, William E. Grizzle, Laurie B. Owen, Ajay P. Singh
Journal: Cancer Research (2013)

Abstract Pancreatic cancer (PC) remains a therapeutic challenge with a rising incidence and unabated mortality. Gemcitabine (GEM), the current standard of care drug, is largely ineffective due to chemoresistance, thus underscoring the need for a refined understanding of the molecular mechanisms that drive drug-resistant nature of this malignancy. Recently, we have shown that CXCL12/CXCR4 signaling axis is involved in conferring chemoresistance to PC cells. Here, we explored the effect of GEM on this resistance mechanism and its functional consequences. Our data demonstrated that GEM upregulated CXCR4 expression in two PC cell lines (MiaPaCa and Colo357) in a dose- and time- dependent manner. GEM-induced CXCR4 expression was dependent on generation of reactive oxygen species (ROS) as it was abrogated upon pre-treatment of PC cells with radical scavenger N-acetyl-L-cysteine (NAC). CXCR4 upregulation by GEM correlated with time-dependent accumulation of p65/NF-κB and HIF-1α in the nucleus. An enhanced binding of p65/NF-κB and HIF-1α to the CXCR4 promoter was observed in chromatin immunoprecipitation assay in GEM-treated PC cells, while their silencing by RNA interference suppressed GEM-induced CXCR4 expression. ROS induction upon GEM treatment preceded the nuclear accumulation of p65/NF-κB and HIF-1α and suppression of ROS diminished these effects. Effect of ROS on p65/NF-κB and HIF-1α was mediated through activation of ERK1/2 and Akt and their pharmacological inhibition also suppressed GEM-induced CXCR4 upregulation. Lastly, our data demonstrated that GEM-treated PC cells were more motile and exhibited significantly greater invasiveness against a CXCL12 gradient. Altogether, these findings reinforces the role of CXCL12/CXCR4 signaling in GEM resistance and point toward an undesired effect of chemotherapy that is potentiation of invasion and spread of resistant tumor cells. Citation Format: Sumit Arora, Arun Bhardwaj, Seema Singh, Sanjeev K. Srivastava, Steven McClellan, William E. Grizzle, Laurie B. Owen, Ajay P. Singh. An undesired effect of chemotherapy: gemcitabine promotes pancreatic cancer cell invasiveness through upregulation of CXCR4. [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 4794. doi:10.1158/1538-7445.AM2013-4794
Abstract 1303: Key roles for Gab1, phosphatidylinositol-3-kinase, COX-2, prostaglandin E2 and TGF-alpha in linoleic acid-induced upregulation of lung and breast cancer cell growth.
Authors: Keith D. Kikawa, Clarissa R. Martins, Eric D. Johnson, Kristen Beck, Michael Mouradian, Ronald S. Pardini
Journal: Cancer Research (2013)

Abstract The omega-6 polyunsaturated fatty acid, linoleic acid (LA), is prevalent in Western diets and is known to enhance the tumorigenesis of mammary cancer models; with previous work demonstrating an upregulation of phosphatidylinositol-3-kinase (PI3K) signaling may play a key role. In this study, a mechanism for LA's upregulation of cancer cell growth is defined. High levels of LA in animal diets or cell culture medium initiates a series of events beginning with increased cyclooxygenase (COX) activity, which leads to increased prostaglandin E2 (PGE2) production, that subsequently increases matrix metalloproteinase (MMP) levels and transforming growth factor alpha (TGF-α). TGF-α is a classic growth factor for the epidermal growth factor receptor 1 (EGFR), which plays a role in a large number of cancers. The Grb2-associated binding protein 1 (Gab1) is a scaffolding protein that can complex with EGFR to activate PI3K signaling. Recent studies in our laboratory reveal LA supplementation of the breast cancer cell line BT-474 and the lung adenocarcinoma cell line A549 greatly increases the association between Gab1 and EGFR, while at the same time dramatically decreasing Gab1 protein levels. These changes are concomitant with increases in activated Akt (pAkt), a downstream signaling component in the PI3K signaling pathway. Moreover, inhibitors of EGFR, PI3K and Gab1-specific siRNAs are capable of reversing LA-induced upregulation of pAkt, as well as observed increases in cell proliferation for these models. These data establish Gab1 as major target in LA-induced enhancement of tumorigenesis. Citation Format: Keith D. Kikawa, Clarissa R. Martins, Eric D. Johnson, Kristen Beck, Michael Mouradian, Ronald S. Pardini. Key roles for Gab1, phosphatidylinositol-3-kinase, COX-2, prostaglandin E2 and TGF-alpha in linoleic acid-induced upregulation of lung and breast cancer cell growth. [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 1303. doi:10.1158/1538-7445.AM2013-1303
AMPULECTOMIA ENDOSCÓPICA: EFICACIA Y SEGURIDAD EN EL TRATAMIENTO DE NEOPLASIA AMPULAR PRECOZ
Authors: A Herreros De Tejada Echanojauregui, M Hernandez, JL Calleja Panero, JC Fernandez-Rial, A Colas, M Jimenez, E Muñiz, L Abreu Garcia
Journal: Endoscopy (2013)

Introducción: Las neoplasias ampulares (NA) suponen casi un 2% de todas las neoplasias del tracto digestivo. La ampulectomía endoscópica (AE) es una modalidad terapéutica aceptable de formas precoces. Objetivo: Conocer la eficacia y seguridad de la AE en un registro prospectivo en centro de tercer nivel. Material y Métodos: Análisis prospectivo de AE con intención curativa llevados a cabo en nuestro centro tras sospecha de NA intraepitelial (adenoma-adenocarcinoma intramucoso) mediante estudio endoscópico con biopsias, ecoendoscopia y TAC abdominopélvico. La AE se realizó mediante inyección submucosa de la lesión con salino/glicerol 10% y posterior resección en bloque o piecemeal con asa de polipectomía, seguida de colocación de prótesis plásticas biliar (8,5F) y/o pancreática (5Fr). Se realizó seguimiento mínimo de 12 meses, con control endoscópico cada 3 meses. Resultados: En un periodo de 18 meses (Diciembre 2010-Junio-2012) fueron identificados 4 pacientes con NA (diagnóstico pre-AE: adenoma (2) y adenoma con DAG (2)). El éxito técnico inicial fue del 100%. En 2 casos se colocaron de forma combinada prótesis biliar y pancreática y en los 2 restantes solo prótesis biliar. Se registraron complicaciones en 2 pacientes: pancreatitis aguda y perforación duodenal con ingreso prolongado (1 caso); hemorragia digestiva diferida con buen control endoscópico (1 caso). El diagnóstico histológico final fue: adenocarcinoma intramucoso (T1a) en 3 casos y adenoma túbulovelloso en 1 caso. Durante el seguimiento 1 paciente presentó adenoma residual con resolución completa tras realizar mucosectomía en 2 ocasiones. No hubo evidencia de lesión residual ni fallecimiento tras un seguimiento medio de 23 meses (rango 13 – 31). Conclusiones: La AE combinada con colocación de prótesis bilio-pancreática es una técnica eficaz a medio plazo en el tratamiento de NA, aunque no exenta de complicaciones potencialmente graves. Permite una mejor evaluación histológica que la biopsia simple, que con frecuencia se asocia a infra-estadiaje.
Are medical students confident about preventive counselling for non-communicable diseases? A cross-sectional survey of medical students in China, USA, and Australia
Authors: Enying Gong, Yan Yu, Yuxuan Yang, Zhifang Li, Bo Zhou, Yi Zhao, Shen Yuan, Ruijuan Zhang, Matthew Sebranek, Lennert Veerman, Mu Li, Shu Chen, Wenjie Ma, Liping Huang, KaWing Cho, Stephen Leeder, Lijing L. Yan
Journal: The Lancet Global Health (2016)

Background Achieving the WHO goal of a 25% reduction in premature mortality from non-communicable diseases (NCDs) by 2025 requires effective action by health-care providers. Medical students, as future health-care providers and the main human resource to achieve such targets, should prepare themselves to implement preventive strategies. This study aims to investigate whether medical students from China, the USA, and Australia had equipped themselves to providing counselling on NCD prevention and lifestyle modification.