tbuckley/cabot-search huggingface dataset:
Abstract P4-02-04: Impact of CYP2D6 Genotype and Side-Effects on Adherence Rates to Tamoxifen in Premenopausal Breast Cancer Patients
Authors: M Hubalek, A Oberguggenberger, V Meraner, B Beer, J Giesinger, H Oberacher, B Sperner-Unterweger, C. Marth
Journal: Cancer Research (2010)

Abstract Background: Only few studies have investigated the issue of breast cancer patients’ adherence to tamoxifen therapy and factors influencing adherence behavior. Especially in the context of different CYP2D6 genotypes adherence to tamoxifen has not been extensively studied yet. Variations in the CYP2D6 genotype, as well as patients taking inhibitors of CYP2D6 (e.g. antidepressants) contribute to different side effects and adherence rates to adjuvant tamoxifen. Materials and Methods: 106 premenopausal breast cancer patients who met inclusion criteria were consecutively included in the study at the outpatient unit of the Department of Gynecology, Innsbruck Medical University. Within their routine after care appointment patients completed a comprehensive PRO assessment including the FACT-B/ES, the HADS and a self-report questionnaire on adherence behavior (SMAQ). The multi-method approach comprised the Simplified Medication Adherence Questionnaire, a semi-structured interview, physicians’ ratings and blood levels for tamoxifen metabolites. Additionally, the CYP2D6 genotype was determined in all patients participating in this part of the study. Results: 19% patients were poor metabolizer (PM), 51% intermediate metabolizer (IM), 29% extensive metabolizer (EM) and 7% ultra-rapid metabolizer (UM). Significant group differences with regard to tamoxifen and endoxifen serum concentrations were found between the metabolization groups (p=0.044). UMs had the lowest tamoxifen and highest endoxifen concentrations. Only 3.2% of the patients analyzed had no measurable tamoxifen concentrations in their serum. All non-compilant patients were from the extensive metabolizer group. However, during follow-up 25% (2/6) of patients with UM genotype, 13% (4/30) with EM genotype, 1% (1/50) with IM genotype and 0% (0/19) with the PM genotype discontinued their tamoxifen therapy due to therapy related side effects. In addition anti-depressants were more frequently prescribed in the extensive metabolizer group leading to lower levels of the active metabolite endoxifen. Conclusion: A trend towards higher hot flashes was observed in the EM and UM group. We did not find significant differences in QOL between CYP2D6 metabolizing groups. Trend level significance was found for global QOL (on a descriptive level) physical well-being and emotional well-being. Non-adherence to tamoxifen therapy is more frequent in patients with CYP2D6 EM and UM genotype. These preliminary data may explain part of the current controversy over CYP2D6 genotype predicting response to tamoxifen and suggest that patients most likely to benefit from tamoxifen are paradoxically most likely to stop their tamoxifen therapy prematurely. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-02-04.
SP0157 Guidelines for the management of primary systemic vasculitis application to practice
Authors: J. Mooney
Journal: Annals of the Rheumatic Diseases (2013)

The ANCA –associated vasculitides (AAV's), Granulomatosis with polyangiitis (Wegener's) (GPA), Churg -Strauss syndrome (CSS) and microscopic polyangiitis (MPA) are a group of rare, potentially life-threatening conditions which if untreated can be fatal. They are characterized by systemic illness, multi-system disease, with inflammation of blood vessel walls (vasculitis), which can lead to aneurysm formation, haemorrhage and infarction (Watts &amp; Scott 2003). Many organs can be affected such as the kidney, heart, lung, upper and lower airways and the nervous system. They share a number of clinical features and are therefore treated using similar treatment protocols. <h3>Management of AAV</h3> The aim of treatment is to induce remission, preserve organ function, and reduce mortality and toxicity of medication. Treatment should commence as early as possible to avoid irreversible organ damage. Treatment is mainly split into three phases 1) induction of remission 2) maintenance and 3) long term follow up. Guidelines have been published for the management of AAV (Lapraik et al 2007, Mukhtyar et al 2009) and there is general consensus that cyclophosphamide and steroids are the first choice for induction of remission. Once remission is achieved azathioprine continues to have the safest profile (Ntatsaki et al 2011).These patients require regular and careful follow up to assess organ function and damage, early detection of disease relapse and detection of drug toxicity and side effects of medication. The role of the nurse will be discussed in the management of these patients. <h3>References</h3> Lapraik C, Watts R, Bacon P, et al. (2007) B SR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology; 4: 1615 -16 Mukhtyar C, Guillevin L, Cid MC, et al. (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis; 68: 310 -17 Ntatsaki E, Mooney J, Watts R.A (2011) ANCA vasculitis—time for a change in treatment, paradigm? Not yetRheumatology, 50(6):1019-1024 Watts RA. Scott DGI (2003)Overview of the inflammatory vasculitides. Rheumatology 3Ed. Eds Hochberg MC, Silman A, Smolen JS, Weinblatt ME, Weissman MH; 1583-91 <h3>Disclosure of Interest</h3> None Declared
Abstract 1502: Increased expression of KLK7 and KLK10 in papillary thyroid cancer
Authors: Melanie MacEwan, Vikas Mehta, E. Ashley Darr, Suqing Xie, Theodore S. Nowicki, Codrin Iacob, Nina Suslina, Ismael Reyes, Stimson Schantz, Edward Shin, Raj Tiwari, Jan Geliebter
Journal: Cancer Research (2011)

Abstract The American Cancer Society estimates that there will be approximately 44,670 new cases of thyroid cancer and 1,690 deaths due to the disease in the United States in 2010. Approximately 80% of these cancers are papillary thyroid carcinoma (PTC), representing the most common endocrine malignancy. Kallikreins are serine proteases that have many physiological functions, including the remodeling of extracellular matrix (ECM). As PTC has the ability to degrade and remodel the ECM to facilitate penetration through the thyroid capsule and invasion of extra-thyroidal tissues, we investigated the expression of kallikrein 7 (KLK7) and kallikrein 10 (KLK10) in PTC. RNA expression of KLK7 and KLK10 in PTC was measured using real-time RT-PCR (normalized to GAPDH) (n = 26) and found to be significantly upregulated, with a mean fold change of 28.8 and 27.8 (P&amp;lt;0.05), in the tumor samples, relative to matched, normal tissue. Immunohistochemical analysis for KLK7 and KLK10 on patient samples (n = 16) revealed significantly increased immunohistochemical scoring/expression, with a mean increase of 3.0 and 2.7 (scale of 1-4; p&amp;lt; 0.001), respectively, in cancerous tissues, compared to adjacent, normal tissue on the same section. The data revealed a significant correlation between the expression of KLK7 and KLK10 on the both RNA level (Spearman r = 0.63, P&amp;lt;0.01), and on the protein level (Spearman r = 0.687, p&amp;lt;0.01). This coordinate expression suggests that the two kallikreins may share similar regulatory sequences. These data indicate that KLK7 and KLK10 may be useful biomarkers for the diagnosis of PTC in thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1502. doi:10.1158/1538-7445.AM2011-1502
Abstract 5071: Defining the role of canonical MAPK signaling in glioma initiation and maintenance
Authors: Kristin J. Lastwika, James P. Robinson, Mathew W. VanBrocklin, Sebastian Brandner, Sheri L. Homen
Journal: Cancer Research (2010)

Abstract Mutations in receptor tyrosine kinase (RTK) growth factor receptors e.g., EGFR, PDGFR, MET and ERBB2 which result in constitutive downstream signaling of the canonical mitogen activated protein kinase (MAPK) (e.g., RAS/RAF/MEK/ERK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways, are found in almost all World Health Organization (WHO) grade II, III, and IV astrocytomas. KRAS, BRAF and CRAF mutations occur in approximately 6%, 72% and 2% of low grade gliomas (WHO Grade I), respectively. A recent study also found a 5-fold increase in RAF serine/threonine kinase activity in a significant series of grade III and IV gliomas, coupled with a 12-fold increase in BRAF and a 2-fold increase in CRAF protein levels. By using an established glioma mouse model, it has been demonstrated that KRas, CRAF or BRAF expression in nestin expressing neural progenitor cells, combined with either Akt activation or Ink4a/Arf loss, leads to the development of high grade gliomas. Together, these data clearly demonstrate the importance of MAPK signaling in glioma development. However, KRAS, BRAF and CRAF are all differently regulated. To further validate a role for canonical MAPK signaling in glioma formation, we have evaluated the effect of constitutive MEK1 activity in glioma formation in vitro and in vivo. While expression of activated MEK1 alone is not sufficient for tumorigenesis, the combination of activated MEK1 and Akt, or MEK1 with Ink4a/Arf loss leads to glioma formation. To assess the efficacy of targeting MAPK signaling in gliomas, we treated a large panel human GBM cell lines with the MEK inhibitor PD0325901 alone and in combination with the PI3K/mTOR inhibitor BEZ235. Cell lines with the highest levels of ERK activation were the most sensitive to MEK inhibition while those with the highest levels of AKT activation were protected from apoptosis following MAPK inhibition. Treatment with BEZ235, in combination with PD0325901, caused significantly higher levels of apoptosis in the glioma cell lines. Importantly, neither treatment induced apoptosis in normal human astrocytes. Our studies demonstrate that activation and signaling through the MAPK pathway following Ink4a/Arf loss or Akt activation can give rise to high grade gliomas; moreover MAPK inhibition, when combined with PI3K/mTOR inhibition may prove to be an effective treatment for gliomas. 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 5071.
ESTENOSIS EN EL BYPASS GASTRICO LAPAROSCÓPICO. EXPERIENCIA EN 600 PACIENTES
Authors: J Espinel, JL De la Cruz, R Diez, AB Domínguez, J Canga, E Pinedo
Journal: Endoscopy (2010)

Objetivos: Evaluar la seguridad y eficacia de la dilatación con balón hidrostático (CRE) sin control radioscópico, en pacientes con obesidad mórbida tratados mediante bypass laparoscópico.
LOW LEVELS OF GROWTH DIFFERENTIATION FACTOR 11 AND HIGH LEVELS OF ITS INHIBITOR FOLLISTATIN-LIKE 3 ARE ASSOCIATED WITH ADVERSE CARDIOVASCULAR OUTCOMES IN HUMANS
Authors: Bettina Heidecker, Kristoff Olson, Alexis Beatty, Ruth Dubin, Shintaro Kato, Richard Lawn, Ashwin Murthy, Mathilda Regan, David Sterling, Mary Whooley, Peter Ganz
Journal: Journal of the American College of Cardiology (2015)
Effect of Intravenous Urea in Invert Sugar on Heme Catabolism in Sickle-Cell Anemia
Authors: Thomas A. Bensinger, M. Jeffrey Maisels, Laviza Mahmood, Paul R. McCurdy, Marcel E. Conrad
Journal: New England Journal of Medicine (1971)

Parenteral administration of urea in invert sugar, said to be effective in managing sickle-cell crises, may act in part by a hemolytic mechanism. Hence, we studied endogenous carbon monoxide production, an index of heme degradation, in five patients with sickle-cell anemia before and after the intravenous infusion of 80 to 90 g of urea in invert sugar solution. A significant increase in carbon monoxide production followed the infusion of urea. This result suggests that the treatment caused an increase in heme turnover.
Improved Detection of Disseminated Pheochromocytoma Using Post Therapy I-131 MIBG Scanning
Authors: LOUISE CAMPBELL, BILL MOURATIDIS, PAUL SULLIVAN
Journal: Clinical Nuclear Medicine (1996)

A 50-year-old man had metastatic pheochromocytoma to the left frontal bone. The primary adrenal tumor was removed 12 years previously. Bone scanning and diagnostic I-131 and I-123 MIBG imaging showed metastatic lesions in the right femur and midthoracic spine. However, post-therapy I-131 MIBG scanning showed extensive and widespread metastatic disease. Post-therapeutic I-131 MIBG whole-body scanning was necessary to more fully assess the extent of metastatic pheochromocytoma.
Abstract 1524: Overcoming temozolomide resistance in MGMT positive glioblastoma by targeting ALDH1
Authors: Andrea Schäfer, Julian Teufel, Ingrid Höpner, Florian Ringel, Markus Bettstetter, Jürgen Schlegel
Journal: Cancer Research (2011)

Abstract Despite aggressive therapy, including radical surgical resection, radiation, and chemotherapy, the prognosis for patients with glioblastoma (GBM) remains poor and relapse occurs regularly. Implementation of the chemotherapy drug temozolomide (TMZ), as a standard in adjuvant GBM therapy, significantly increased the overall survival of patients with an epigenetic silenced MGMT promoter (MGMT-). To date, no comparable therapeutic approach for GBM patients with MGMT expression (MGMT+) is applied. Tumor re-growth in MGMT+ and MGMT- GBM corroborates the tumor stem cell (TSC) paradigm, postulating that a therapy-resistant subpopulation of cells harbors the ability to keep the tumor alive and growing. Recently, we presented aldehyde dehydrogenase 1 (ALDH1) as a marker for glioblastoma cells with stem cell capacity. In this study, we demonstrate that ALDH1 overexpression in established and primary MGMT+ GBM cell lines correlates with resistance to TMZ, while concomitant inhibition of ALDH1 by 4-diethylaminobenzaldehyde (DEAB) or tetraethylthiuramdisulfide (DSF) re-sensibilized the cells significantly. Application of TMZ in combination with DEAB strikingly attenuated the stem cell capacity of both MGMT + and MGMT – cells. For further verification of the specific impact of ALDH1 on therapy resistance, shRNA constructs were applied. Moreover, immunohistochemical analysis of ALDH1 expression in specimens of glioblastoma patients revealed a significant correlation between expression of this enzyme and a poor clinical prognosis. All these findings demonstrate that ALDH1 is a marker for brain tumor stem cells, a strong predictor of clinical outcome and a potential target for an improved therapy of MGMT positive GBM. 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 1524. doi:10.1158/1538-7445.AM2011-1524
OP0002 Pathomechanism of Bone Destruction in Chronic Gouty Arthritis
Authors: S.-J. Kee, Y.-N. Cho, H.-M. Jin, M.-J. Kim, J.-E. Kim, H.-J. Jung, Y.-W. Park
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gout is an inflammatory arthritis caused by the deposition of monosodium urate monohydrate (MSU) crystals within joints during chronic hyperuricemia. Chronic tophaceous gout may lead to bone destruction by osteoclastogenesis. However, the cellular mechanisms by which of cytokines are involved in osteoclastogenesis in response to MSU crystals remain to be clarified. <h3>Objectives</h3> The aims of this study is to analyze the cellular expressions of pro-resorptive cytokines in gouty tophus tissues, to determine the capacity of MSU crystals to induce these cytokines, and to understand the mechanisms of bone destruction in chronic gout. <h3>Methods</h3> Fourteen fixed, paraffin-embedded, uninfected tophus samples were analyzed immunohistochemically. Peripheral blood mononuclear cells (PBMCs) were cultured <i>in vitro</i> with MSU crystals, and gene expression was assessed by reverse transcription-polymerase chain reaction. <i>In vitro</i> osteoclastogenesis was performed using PBMCs and synovial fluid mononuclear cells (SFMCs). <h3>Results</h3> CD4+ T cells, CD8+ T cells, CD20+ B cells, and mast cells infiltrated tophus tissues. Tartrate-resistant acid phosphatase (TRAP)+ osteoclasts were present around tophi and in osteolytic lesions. Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha were produced from infiltrated mononuclear cells, whereas receptor activator of nuclear factor κB ligand (RANKL) was strongly expressed in T cells. However, osteoprotegerin (OPG) was not or weakly expressed in tophus tissues. MSU crystals induced the expressions of IL-1, IL-6, TNF-alpha and RANKL in PBMCs, but inhibited OPG expression. In addition, the pro-resorptive cytokines were highly expressed in SFMCs of gouty arthritis patients. Furthermore, <i>in vitro</i> osteoclastogenesis was enhanced in SFMC cultures, but inhibited in T cell-depleted SFMC cultures. <h3>Conclusions</h3> Our study demonstrates that RANKL-expressing T cells and TRAP+ osteoclasts are present within gouty tophus tissues, and that infiltrating cells express pro-resorptive cytokines. Furthermore, our data show that MSU crystals have the potential to induce pro-resorptive cytokines, and T cells are involved in osteoclastogenesis in chronic gout. <h3>Disclosure of Interest</h3> None Declared
Unilateral Hyperlucent Lung in a Child Caused by a Foreign Body Identified With V/Q Scintigraphy
Authors: Hans Balink, James Collins, Astrid G.W. Korsten-Meijer, Bart L. Rottier
Journal: Clinical Nuclear Medicine (2012)

A 5-year-old girl presented with episodes of coughing, inspiratory stridor, and occasionally squeaking breath sounds. There was no history of a foreign body aspiration. Initially, she was diagnosed with allergic asthma. However, signs and symptoms continued despite a trial of inhaled corticosteroids. A chest radiograph showed a hyperlucent right lung, mainly in the upper lobe, with decreased vascular markings compatible with Swyer-James-MacLeod syndrome, or foreign body aspiration. V/Q imaging showed markedly diminished right lung ventilation and perfusion, especially in the upper lobe, with a hot spot in the area of the right bronchus. At bronchoscopy, a pistachio nutshell was removed from the right main bronchus.
Columbia/HCA and the Resurgence of the For-Profit Hospital Business
Authors: Robert Kuttner
Journal: New England Journal of Medicine (1996)

Hospitals, surprisingly, have emerged as a prime growth industry attractive to entrepreneurs. Seemingly, a legacy of overbuilding combined with competitive cost-cutting pressures should reduce the earnings of nonprofit and for-profit hospitals alike, making them unattractive investment candidates. Yet in the 1990s, for-profit hospital chains on a buying binge have outpaced the stock market. Conversions of nonprofit to investor-owned hospitals have accelerated, reaching a level of 58 in 1995, up from 34 in 1994.1 This two-part article addresses the medical, ethical, and public-policy issues posed by the resurgence of for-profit chains and their acquisition of nonprofit community hospitals. The prime case . . .
A Subcutaneous Reservoir for Intrathecal Therapy of Fungal Meningitis
Authors: Richard D. Diamond, John E. Bennett
Journal: New England Journal of Medicine (1973)

Subcutaneous cerebrospinal-fluid reservoirs were inserted into 15 patients with cryptococcal meningitis, four with coccidioidal meningitis, and two with chronic meningitis of undetermined cause. Complications associated with 17 reservoirs in 12 patients necessitated reservoir removal or prevented later use for intrathecal therapy. Nine of these complications were related to reservoir insertion, and eight to problems related to later usage. Insertion may have been a contributing cause of death in three patients and of neurologic deterioration in another four. In nine patients there were 10 cerebrospinal-fluid bacterial infections apparently related to reservoir usage or insertion. Reservoirs were cleared of bacterial infection and continued to be functional in four of the five patients who completed a course of treatment with antibiotics alone. Successful anti-fungal therapy was clearly attributable to intraventricular therapy in three patients with cryptococcosis and three with coccidioidomycosis. Advantages of this mode of therapy should be carefully weighed against potential risks in patients with cryptococcosis, in whom the value of intrathecal therapy is not uniformly accepted.
Abstract LB-473: The HDAC inhibitor entinostat targets erbB2/erbB3 receptors via functional cooperation of miR-125a, miR-125b, and miR-205 in breast cancer cells
Authors: Shuiliang Wang, Jingcao Huang, Choon-Kee Lee, Bolin Liu
Journal: Cancer Research (2012)

Abstract Breast cancer is highly heterogeneous and has been classified into five distinct subtypes, among which erbB2-overexpressing (erbB2+) and basal breast cancers have the least favorable prognosis and express erbB receptors that are excellent targets for anti-cancer therapies. We previously reported that the class I HDAC inhibitor, entinostat (also known as MS-275, SNDX-275, Syndax Pharmaceuticals, Inc., Waltham, MA) selectively inhibited proliferation and induced apoptosis in erbB2+ breast cancer cells. Entinostat preferably targeted erbB2 and erbB3 receptors rather than the epidermal growth factor receptor (EGFR). Here, we study the molecular mechanism through which entinostat downregulates erbB2/erbB3 and promotes the breast cancer cells undergoing apoptosis. We showed that entinostat dramatically reduced the protein levels of erbB2/erbB3, whereas it had no significant effect on their mRNA expression in MDA-MB-453 and BT474 breast cancer cells. In addition, entinostat specifically decreased the endogenous, but not the exogenous erbB2/erbB3, suggesting that it did not promote erbB2/erbB3 protein degradation. Therefore, we hypothesizes that entinostat reduces erbB2/erbB3 receptors through transcription-independent mechanism; it may inhibit erbB2/erbB3 protein translation via induction of specific miRNA. Quantitative real-time (qRT) PCR revealed that entinostat significantly upregulated the expression of three erbB2/erbB3-targeting miRNAs, miR-125a, miR-125b, and miR-205 in erbB2+ breast cancer cells. Specific miRNA inhibitors were used to determine whether these miRNAs played a causal role in entinostat-induced downregulation of erbB2/erbB3 and apoptosis. While inhibition of any one of the three miRNAs failed to block entinostat action, simultaneous inhibition of any two of them significantly abrogated entinostat-induced erbB2/erbB3 reduction and apoptosis. Collectively, these data demonstrate that entinostat targets erbB2/erbB3 receptors via functional cooperation of miR-125a, miR-125b, and miR-205. Our findings suggest that miRNA-mediated epigenetic regulation may represent a novel strategy targeting erbB2/erbB3 to treat the aggressive erbB2+ breast cancer. The combinations of entinostat and erbB2-targeted therapy may be more efficacious for breast cancer patients whose tumors overexpress erbB2. This hypothesis will be directly tested by a recently initiated clinical study determining the activity of entinostat in combination with lapatinib in breast cancer patients that are erbB2+ and progressed on trastuzumab. 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 LB-473. doi:1538-7445.AM2012-LB-473
Looking at the Whole Picture
Authors: Carol Donagh, John Bruzzi, Briain MacNeill, Mark DaCosta, Jeffrey S. Berman, Anthony W. O'Regan
Journal: New England Journal of Medicine (2011)

A 50-year-old woman presented with rapidly progressive shortness of breath. Five months earlier, she had received a diagnosis of invasive breast carcinoma and had undergone mastectomy. Her fifth cycle of chemotherapy was completed 10 days before presentation.