tbuckley/cabot-search huggingface dataset:
Abstract 1284: Estrogen receptor alpha transcriptionally regulates p53 in MCF7 human breast cancer cells
Authors: Crystal Berger, Yingjuan Qian, Xinbin Chen
Journal: Cancer Research (2012)

Abstract The p53 tumor suppressor plays a critical role in maintaining genome stability. In response to genotoxic stress, p53 induces target genes for cell cycle arrest, apoptosis, and DNA repair. While p53 is the most commonly mutated gene in all cancers, it is only mutated in 20% of breast cancers. Interestingly, 70% of all breast cancer cases are estrogen receptor (ER) positive and are associated with wild type p53 expression. An ER-positive breast cancer diagnosis generally indicates good patient prognosis and treatment responsiveness with anti-estrogens such as tamoxifen. The relationship between ERα and p53 remains poorly defined. Here, we found that ERα positively regulates p53 expression. Specifically, knockdown of ERα decreases the amount of p53 along with its downstream target p21, a regulator of cell cycle arrest, in MCF7 breast cancer cells. Furthermore, we found that ERα transcriptionally regulates p53 expression via binding to the p53 promoter. Luciferase promoter reporter experiments showed that two estrogen receptor element half sites located at nt −1828 and −1611 from the p53 transcriptional start site responded to addition of ERα with increased reporter activity. Mutation of those two sites resulted in no reporter activity. To determine the biological significance of ERα regulation of p53, we found that knockdown of ERα desensitized cells to growth arrest and cell death upon treatment with DNA damage-inducing drugs in a p53-dependent manner. Conversely, cells overexpressing ERα were sensitized to growth arrest and cell death upon DNA damage-inducing drugs via the p53 pathway. Together, these results provide an insight into the reciprocal regulation of p53 and ERα at the transcript level and how their pathways interact in ER-positive breast cancers under basal and stress conditions. 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 1284. doi:1538-7445.AM2012-1284
FRI0228 Cutaneous vasculitis as a presenting manifestation of neoplasia:
Authors: J. Loricera, V. Calvo-Río, F. Ortiz-Sanjuán, M. González-Lόpez, H. Fernández-Llaca, J. Rueda-Gotor, M. González-Vela, C. Mata-Arnáiz, V. Martínez-Taboada, J. Peña-Sagredo, M. González-Gay, R. Blanco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cutaneous Leukocytoclastic Vasculitis (CLV) may be associated with malignancies, and sometimes it behaves as a paraneoplastic syndrome. This association has been reported in a variable proportion of CLV patients (from 0 to 8%) depending on population selection. <h3>Objectives</h3> Our aim was to assess the frequency and features of CLV associated to neoplasia in a wide and unselected series of CLV. <h3>Methods</h3> Study of CLV associated to neoplasia in a serie of 565 patients diagnosed as having CLV in the Rheumatology and Dermatology Divisions from a University Hospital. <h3>Results</h3> 11 out of 565 patients (1.95%) presenting with CLV were finally diagnosed as having an underlying malignancy (7 hematological/4 solid malignacies). In all of them, skin lesions were the first clinical manifestation. The median to the diagnosis of the malignancy from the onset of CLV was 17 days, (range 8–50). The most frequent skin lesions were palpable purpura (n=10), legs ulcers (n=2) and urticaria (n=1). Other manifestations were constitutional syndrome (n=7) and arthralgias and/or arthritis (n=3). There was no serious visceral vasculitic involvement. Cytopenia was frequently observed in the full blood cell count (n=9), especially in those cases of vasculitis associated to hematological malignancies (immature peripheral blood cells were observed in 4 cases). Immunological testing (ANA, Rheumatoid factor, C3, C4, and ANCA) were negative or within normal range in all cases. Six patients died due to the malignancy and 5 patients recovered following malignancy therapy. <h3>Conclusions</h3> CLV presenting as a paraneoplastic syndrome is a rare condition. The most common underlying malignancy is generally hematological. The prognosis depends on the underlying neoplasia. <h3>Disclosure of Interest</h3> None Declared
AB1147-HPR Investigating Long-Term QOL in Rheumatoid Arthritis Patients with AIMS2 -3-Year Evaluation of Treatment with Biologics-
Authors: M. Kaneko, S. Honjo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> According to the EULAR recommendations on the role of the nurse in the management of chronic inflammatory arthritis, nurses should participate in comprehensive disease management to control disease activity, to reduce symptoms and to improve patient-preferred outcomes [1]. At last year9s EULAR, we reported the successful maintenance of QOL over a period of 2 years in patients who maintained clinical remission or low disease activity long-term through treatment with biologics, as evaluated with the use of AIMS2 (Arthritis Impact Measurement Scales version 2). <h3>Objectives</h3> Nurses at our clinic have been conducting a QOL survey with the use of AIMS2 since 2011 to investigate whether QOL has been maintained over the course of 3 years in patients with rheumatoid arthritis (RA) who reached their treatment goals with biologics. <h3>Methods</h3> The subjects were RA patients who have been maintaining clinical remission or low disease activity through treatment with biologics at our clinic. A survey has been conducted since 2011 in this population, administering the AIMS2 questionnaire between the months of May and August each year. <h3>Results</h3> The AIMS2 questionnaire was administered to 194 patients in 2011, 243 patients in 2012, and 237 patients in 2013. According to the most recent data, the breakdown of the biologics used in treatment was etanercept in 92 cases, infliximab in 43 cases, tocilizumab in 34 cases, adalimumab in 29 cases, abatacept in 23 cases, golimumab in 14 cases, and certolizumab pegol in 2 cases in 2013. When we compared mean values for each item of AIMS2 on a year-by-year basis, we found no major variation in any of the items, confirming that QOL was maintained over the 3-year period (no significant difference for any of the items in the comparison of 2011 vs. 2012 and 2011 vs. 2013). <h3>Conclusions</h3> This study confirmed that QOL was also maintained long-term in patients who maintained clinical remission or low disease activity long-term through treatment with biologics. It is important to maintain the treatment goals set for each patient throughout the entire course of treatment for the disease. By proactively making contact with RA patients by administering QOL questionnaires such as AIMS2, nurses can discover abnormalities early on and sense changes in the efficacy of the treatment, and this ability to take corrective action early on is one factor in maintaining long-term QOL. <h3>References</h3> Yvonne van Eijk-Hustings, et al. Ann Rheum Dis 2012;71:13-19 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2798
Access to Patient-Level Trial Data — A Boon to Drug Developers
Authors: Hans-Georg Eichler, Frank Pétavy, Francesco Pignatti, Guido Rasi
Journal: New England Journal of Medicine (2013)

The European Medicines Agency aims to make patient-level data from clinical trials publicly accessible while protecting privacy; this would improve drug-development efficiency, cost-effectiveness, and comparative-effectiveness analysis and reduce duplication of effort.
Entrapment Neuropathy of the Ilioinguinal Nerve
Authors: Harvey P. Kopell, Walter A. L. Thompson, Allen H. Postel
Journal: New England Journal of Medicine (1962)

AN entrapment neuropathy of the ilioinguinal nerve can cause pain and disability that may present serious diagnostic difficulties. The nerve is analogous to an intercostal nerve since it has both motor and skin sensory functions. The muscular branches innervate the lowest portions of the transversus abdominis and internal oblique muscles and fascia. The peripheral distribution of the nerve is to the skin over the inguinal ligament and the base of the scrotum (or labia). A narrow strip of skin over the iliac crest is innervated by a recurrent branch.The entrapment point of the nerve is medial to the anterosuperior . . .
Abstract 1014: Semaphorin 4D involves in the regulation of cell motility through its receptor Plexin B1 in pancreatic cancer
Authors: Kato Shingo, Kensuke Kubota, Takeshi Shimamura, Noritoshi Kobayashi, Seitaro Watanabe, Yoji Nagashima, Atsushi Nakajima
Journal: Cancer Research (2010)

Abstract Introduction: Semaphorins are a large family of either membrane-bound or secreted proteins that provide axonal guidance in neuronal tissues and regulate cell motility in many types of cells. Recent articles reported that Semaphorin 4D (Sema 4D) enhanced in vitro motility and invasiveness through its receptor Plexin B1 and Met, and increased in vivo metastasis potential in breast cancer. However, these expression and function in pancreatic cancer is not known. Purpose: In the present study, we investigated the clinicopathological significance of Sema 4D and Plexin B1 expression in surgically resected pancreatic ductal adenocarcinoma sections and the regulation of cell motility through the Sema 4D - Plexin B1 signaling pathway. Material &amp; Methods: The mRNA expression level of Sema 4D and Plexin B1 were evaluated by Quantitative Real Time PCR from 12 surgical specimens and 10 normal pancreatic tissues. Expression of Sema 4D and Plexin B1 were also evaluated immunohistochemically from 90 patients. Using pancreatic cancer cell lines, the expression of endogenous Plexin B1 and Met protein was investigated by western blotting. And the phosphorylation of Met protein after stimulating by Sema4D was evaluated. As functional analysis, scratch assay and MTT assay were carried out. Results: The mRNA expression level of Sema 4D and Plexin B1 were significantly high in cancer tissues compared to normal pancreas tissues. Immunostaining showed that Sema 4D strongly expressed in lymphocytes and macrophages, as previously reported. Ninety two percent (83 out of 90 cases) pancreatic cancer samples overexpressed Plexin B1 compared to normal pancreas tissues. Endogenous Plexin B1 and Met protein were detected in eight pancreatic cancer cell lines, with a variety of expression levels. Sema 4D stimulation activated Met protein, and significantly induced cell migration. Discussion: Here we show that Sema 4D involves in the regulation of cell motility through its receptor Plexin B1. And the results of immunostaining suggest that Sema 4D could play a role in the interaction between tumor cells and tumor microenvironment in pancreatic cancer tissues. As many attempts are now ongoing to target the tumor stroma, these findings provide a new insight into molecular targeted therapies for pancreatic cancer. 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 1014.
Autotransplantation of Splenic Tissue After Splenic Injury
Authors: SAMI AJMI, HABIB HASSINE, HABIB ESSABBAH
Journal: Clinical Nuclear Medicine (2003)

From the Department of Nuclear Medicine, Sahloul’s Hospital, Sousse, Tunisia. Received for publication August 22, 2002. Revision accepted November 5, 2002. Reprint requests: Sami Ajmi, Department of Nuclear Medicine, Sahloul’s Hospital, Sousse 4053, Tunisia.
Case 38-2002
Authors: John K. Erban, Zuoquin Tang
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 54-year-old man was admitted to the hospital because of possible metastatic carcinoma with hypercalcemia and renal dysfunction.The patient had been in good health until about six weeks earlier. At that time, he began a reduced-calorie diet with exercise, and after three weeks of that regimen, his body weight had declined from 118.8 kg to 102.7 kg. He believed that his face was thinner than it had been but that his abdomen was enlarging, and he began to have severe, diffuse abdominal pain; lethargy; daily temperatures of up to 38.3°C; and occasional night sweats. Two and . . .
Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons
Authors: Clark T. Sawin, Andrew Geller, Philip A. Wolf, Albert J. Belanger, Errol Baker, Pamela Bacharach, Peter Wilson, Emelia J. Benjamin, Ralph B. D'Agostino
Journal: New England Journal of Medicine (1994)

Low serum thyrotropin concentrations are a sensitive indicator of hyperthyroidism but can also occur in persons who have no clinical manifestations of the disorder. We studied whether low serum thyrotropin concentrations in clinically euthyroid older persons are a risk factor for subsequent atrial fibrillation.
AB1344 Hospital infusion center costs for anti–tumor necrosis factor agents
Authors: J. Schmier, M.A. Cifaldi, J.W. Shaw, M.T. Halpern, N.A. Nickman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tumor necrosis factor (TNF)–inhibiting drugs are provided to patients with rheumatoid arthritis in the form of an intravenous infusion or subcutaneous injection. Although anti-TNF infusions are typically provided in hospital-based centers, the administrators of these centers often have limited understanding of the associated treatment costs. <h3>Objectives</h3> To estimate the total cost of anti-TNF infusion care from a hospital perspective using an activity-based costing approach. <h3>Methods</h3> An activity-based model was developed using several types of infusion center inputs: hourly wages, times to provide care, supply and overhead costs, laboratory test costs, infusion center size, and practice pattern information. The model assumed 8 infusions of infliximab annually. Base case values were derived from a survey of 5 community hospital infusion centers, previously published nurse and pharmacist time estimates, and expert opinion. Costs were derived from standard national sources. An overhead charge of 29.5% was applied to all costs. All costs were measured in or inflated to 2011 US dollars. <h3>Results</h3> The total cost per infusion, including drug and laboratory costs, was estimated to be $3185. Most of this cost was attributable to the acquisition cost of the infused medication. Of the $427 not associated with drug, $93 was associated with recommended laboratory tests. Infusion costs—including labor and supplies associated with preparation, administration, and premedication and treatment of adverse events if necessary—were estimated at $334 per infusion. Of this amount, $121 was attributable to nonlabor categories (eg, capital equipment) and management (eg, inventory and documentation). In contrast, total Medicare reimbursement for a 3-hour infusion would be less than $120. A separate module including indirect costs (ie, lost productivity of patient and/or caregiver, transportation) estimated each infusion visit to be associated with an additional $146 cost to the patient. <h3>Conclusions</h3> Although drug costs contribute most to the cost of anti-TNF infusion care, personnel, supply, and overhead costs can also be substantial. The model developed in this research can be used to quantify the total cost of providing anti-TNF infusion services so that financially responsible treatment strategies can be implemented at a given institution. In a market in which reimbursement and the efficient use of personnel are keenly important, such a tool can help hospital administrators make informed choices about the services to be offered and their financial implications. <h3>Disclosure of Interest</h3> J. Schmier Employee of: Exponent, which received a research grant from Abbott, M. Cifaldi Shareholder of: Abbott, Employee of: Abbott, J. Shaw Shareholder of: Abbott, Employee of: Abbott, M. Halpern Grant/Research support from: Abbott, N. Nickman Consultant for: Exponent, which received a research grant from Abbott
THE DIAGNOSTIC VALUE OF STRESS ECHOCARDIOGRAPHY AND ELECTROCARDIOGRAPHY IN IDENTIFYING OCCULT CORONARY ABNORMALITIES IN PATIENTS WITH ANGINA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Vedant Pargaonkar, Abha Khandelwal, Yuhei Kobayashi, Shigemitsu Tanaka, Maya B. Mathur, Victor Froelicher, Alan Yeung, Jennifer Tremmel
Journal: Journal of the American College of Cardiology (2015)
Response to sunitinib in Chinese KIT-mutated metastatic mucosal melanoma
Authors: Y. Zhu, L. Si, Y. Kong, Z. Chi, X. Yuan, C. Cui, X. Sheng, J. Guo, L. Shen
Journal: Journal of Clinical Oncology (2009)

e20017 Background: To investigate the possible relationship between sunitinib response and KIT mutation as well as KIT expression. Methods: We find that a 75-year male patient with KIT-mutated metastatic mucosal (primary: nasal, metastasis: left adrenal gland, lungs and right eye) melanoma has a very good response to sunitinib 37.5mg/d consecutively. We apply IHC sp assay to detect S100, HMB-45, CD117, VEGFR, PDGFR and EGFR in the melanoma sample of this patient. DNA is also extracted from paraffin-embedded melanoma sample of this patient and PCR is carried out to amplify several exons of C-KIT (exon11,13,17,18),B-RAF(exon11, 15) and N- RAS(exon1, 2). PCR products are sent to be directly sequenced. Clinical response, PFS and OS of the patient are evaluated. Results: Strong expression of S100, HMB45, CD117, VEFGR and PDGFR is detected by IHC in the tissue sample of the patient. Furthermore, direct sequencing after PCR reveals that V559A substitution is detected in exon 11 of KIT, with mutation of T into C at 1776, leading to substitution of Valine by Alanine at 559. No mutation was detected in exon 9, 13, 17, 18 of KIT, B-RAF15, 11 or N-RAS1, 2. The patient received sunitinib 37.5mg/d from July 2008 consecutively and evaluated PR (Recist: tumors shrink 70%) lasting for 5 months with Grade II myelosuppression and stomatitis. Now the patient is still alive and received sunitinib. Conclusions: Our case report suggests that response of melanoma patients to sunitinib might be correlated to KIT mutation and expression, and large-scale clinical trial in patients with KIT mutation and over-expression might be useful to shed light on treatment of melanoma patients with individual targeted therapy. No significant financial relationships to disclose.
FRI0296 Level of confidence in the diagnosis of spondyloarthritis by expert readers in sacroiliac joint MRI: a new gold standard criterion for defining a positive MRI?:
Authors: U. Weber, K. Rufibach, R.G. Lambert, M. Ostergaard, S. Chan, V. Zubler, S.J. Pedersen, W.P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Defining a positive MRI in early axial spondyloarthritis (SpA) requires a gold standard criterion for the diagnosis of SpA and is typically based on clinical findings because structural changes on pelvic radiographs may take more than 10 years to become apparent. However, clinician expert opinion as gold standard has inherent limitations leading to false positive or negative assignments and requires lengthy follow up to ascertain development of radiographic sacroiliitis. Level of confidence in the diagnosis of SpA according to expert global assessment of sacroiliac joint (SIJ) MRI may constitute a candidate gold standard criterion for defining a positive MRI in non-radiographic axial SpA (nr-axSpA). <h3>Objectives</h3> (1) To assess the inter-reader reliability of the level of confidence in the diagnosis of SpA according to expert global assessment of SIJ MRI; (2) To compare this MRI-based criterion with clinician expert opinion. <h3>Methods</h3> The study population comprised 220 consecutive patients with back pain ≤50 years old newly referred to 2 university clinics, and 79 healthy controls. Patients were classified by clinical examination and pelvic radiography as having nr-axSpA (n=74), ankylosing spondylitis (n=60), or mechanical back pain (n=86). SIJ MRI were assessed in random order by 4 blinded expert readers according to a standardized module. Readers recorded their level of confidence in the diagnosis of SpA by global evaluation of the MRI scan on a 0-10 scale (0 = definitely not SpA; 10 = definite SpA). Assignment of a definitive diagnosis of SpA was pre-specified as the majority (at least 3 of 4) of readers recording definite SpA with a confidence level of 8-10. Absence of SpA required all 4 expert readers to record non-SpA (≤4 on 0-10 scale). We calculated the inter-reader agreement for a diagnosis of SpA or non-SpA according to these confidence level cut-offs on global SIJ MRI assessments, and we compared this MRI-based criterion with clinician diagnosis, both by percentage agreement and kappa statistics. <h3>Results</h3> The mean percentage agreement among 6 reader pairs for a diagnosis of SpA/non-SpA according to global SIJ MRI was 92.0% and the mean kappa 0.83. Kappa for agreement regarding level of confidence in the diagnosis of SpA by all 4 readers was excellent (0.83; CI 0.78-0.88). <h3>Conclusions</h3> Level of confidence in the diagnosis of SpA according to expert global assessment of SIJ MRI by expert readers may constitute a candidate gold standard criterion for defining a positive MRI in nr-axSpA. This alternative to clinician expert classification deserves further validation in other inception cohorts of early SpA patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 5629: Prolyl isomerase Pin1 negatively regulates CDK10 stability to induce tamoxifen resistance in breast cancer.
Authors: Prem Kharam, Hong Seok Choi
Journal: Cancer Research (2013)

Abstract Endocrine therapies that inhibit estrogen receptor (ER)-α signaling are the most common and effective treatment for ER-α-positive breast cancer. However, the use of these agents is limited by the frequent development of resistance. The aim of this study was to elucidate the mechanisms by which downregulation of CDK10 expression confers resistance to tamoxifen in breast cancer. Here, we show that peptidyl-prolyl isomerase Pin1 downregulates CDK10 protein as a result of its interaction with and ubiquitination of CDK10, thereby affecting CDK10-dependent Raf-1 phosphorylation (S338). Pin1-/- mouse embryonic fibroblasts (MEFs) show higher CDK10 expression than Pin1+/+ MEFs, whereas CDK10 protein was downregulated in the rescued Pin1-/- MEFs after reexpression of Pin1. Pin1 silencing in SKBR-3 and MCF7 cells increased the CDK10 expression. In human tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 cells, immunohistochemical staining and immunoblotting analysis shows an inverse correlation between the expression of CDK10 and the degree of tamoxifen resistance. There was also a positive correlation between the high level of P-Raf-1 (Ser338) and Pin1 in human tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 (TAMR-MCF7) cells. Importantly, 4-OH tamoxifen (4-OHT), when used in combination with overexpressed CDK10 or Raf-1 inhibitor, increased cleaved PARP and DNA fragmentation to inhibit cologenic growth of MCF7 cells and tamoxifen-resistant MCF7 cells, respectively. On the basis of these findings, we suggest that the Pin1-mediated CDK10 ubiquitination is a major regulator of tamoxifen-resistant breast cancer cell growth and survival. Citation Format: Prem Kharam, Hong Seok Choi. Prolyl isomerase Pin1 negatively regulates CDK10 stability to induce tamoxifen resistance in breast cancer. [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 5629. doi:10.1158/1538-7445.AM2013-5629 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.