tbuckley/cabot-search huggingface dataset:
O5.08 * INTRA-OPERATIVE NEUROPHYSIOLOGICAL MONITORING AND SMALL CRANIOTOMIES: RESULTS IN A CONSECUTIVE SERIES OF 85 PATIENTS WITH BRAIN TUMORS
Authors: G. Carrabba, G. Bertani, F. Cogiamanian, G. Ardolino, A. Di Cristofori, B. Zarino, M. Locatelli, S. Barbieri, M. Caroli, P. Rampini
Journal: Neuro-Oncology (2014)

INTRODUCTION: Intra-operative neurophysiological monitoring and brain mapping techniques represent nowadays the gold standard for surgical resection of brain tumors. Brain mapping usually requires the exposure of a large area of brain cortex in order to identify the different eloquent sites (e.g. primary motor strip, speech arrest sites). Thus, relatively large classic fronto-temporal craniotomies are generally performed. Nevertheless, in recent years the use of small craniotomies targeted on the tumor has gained popularity thanks to Neuronavigation systems and to the low morbidity rates associated with shorter surgical procedures and reduced anesthestic drug administration. Aim of this study was to review our experience which combines extensive neurophysiological monitoring and small craniotomies. Length of surgical time, intra-operative and post-operative complications, length of stay, extent of resection rate and the neurological outcomes were assessed. PATIENTS AND METHODS: Eighty-five consecutive patients (54 Males, 31 Females; Median Age 55 years, range 12-77) underwent surgery with brain mapping and intra-operative neurophysiological monitoring for resection of a brain tumor in eloquent location under asleep-asleep (62 patients) or asleep-awake (23 patients) anesthesia. Pre- and post-operative assessment included in-depth neuropsychological evaluation and MRI. Tumor histologies were the following: 74 gliomas (60 HGG, 14 LGG), 6 metastases and 5 other tumor histologies (2 cavernomas, 2, meningiomas, 1 AVM). The bone flap was tailored to the size of the tumor; no cortex other than that which was strictly necessary for tumor resection was exposed. The intra-operative neurophysiological monitoring included: EEG, SSEP, transcranial MEP and/or cortical MEP, ECoG; direct electrical stimulation (DES) was performed using bipolar and monopolar probes. RESULTS: Median surgical time was 230 minutes (range 90-390). Intra-operative complications included 9 seizures (3 requiring pharmacological treatment, 6 regressing after cold irrigation) and 5 electrical seizure. Post-operative neurosurgical complications were the following: 8 seizures and 4 re-operation for hematoma. Seventy-three patients (86%) could be discharged home while 12 (14%) were transferred to rehabilitation. In only 3 patients (3.5%) a permanent new neurological deficit could be noted at 3-month follow-up. Median post-operative stay was 7 days (range 3-45). CONCLUSIONS: In our experience a small craniotomy supported by extensive neurophysiological monitoring and brain mapping permitted to achieve satisfactory results in terms of complications, hospitalization, and neurological outcomes.
Abstract 1293: Neutrophil gelatinase-associated lipocalin regulates the expression of angiogenic cytokines and VEGF in human breast and ovarian cancer cells
Authors: Jiang Yang, Marsha A. Moses
Journal: Cancer Research (2010)

Abstract Neutrophil gelatinase-associated lipocalin (NGAL; lipocalin 2) is a small extracellular protein (25 kDa) that is a member of the lipocalin protein family. It has been shown to bind ferric siderophores and to play an important role in iron metabolism. Increased NGAL levels have been reported in a variety of epithelial cancers, including breast, ovary, pancreas, colon, esophagus and thyroid cancer. We have recently reported that NGAL promotes breast cancer progression by inducing the epithelial to mesenchymal transition. In the course of these studies, we observed an increase in microvessel density in NGAL-expressing tumors. In the current study, we explored the potential role of NGAL in tumor angiogenesis by studying its effects on the expression of angiogenic factors. We first determined the levels of vascular endothelial growth factor (VEGF) in NGAL-expressing cells derived from the MCF-7 human breast cancer cell line. Using reverse-transcriptase PCR and ELISA, VEGF was found to be induced by NGAL at both the transcript and protein levels. Consistently, HIF-1α, one of the most important transcriptional regulators of VEGF, was observed to be accumulated in the nuclei of NGAL-expressing cells. Silencing of HIF-1α in NGAL-expressing cells significantly reduced VEGF expression. Consistent with this NGAL-induced VEGF production, there was a significant increase in endothelial cell migration towards the conditioned media collected from NGAL-expressing cells. Interestingly, treatment with a VEGF-neutralizing antibody only partially inhibited the migration-inducing activity of the conditioned media, suggesting that NGAL might induce the secretion of other angiogenic factors. To investigate this possibility, a panel of angiogenic factors was compared between the conditioned media collected from NGAL-expressing cells and control MCF-7 cells using antibody arrays. Several angiogenic cytokines, including IL-6, MCP-1 and GM-CSF, were found to be upregulated with NGAL expression. The effects of NGAL on VEGF and angiogenic cytokine production were also studied in SKOV-3 ovarian cancer cells. In this study, NGAL was silenced in SKOV-3 cells using specific siRNAs. The levels of both VEGF and IL-6 were found to be reduced after NGAL silencing, suggesting that NGAL's control of VEGF and cytokine production may be common among cancer cell types. These results suggest a novel mechanism through which NGAL may promote tumor angiogenesis and progression. (This work is supported by NIH R01 CA118764, P01 CA045548 and The Advanced Medical Foundation.) 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 1293.
Rescue of defective ATP8B1 trafficking by CFTR correctors as a therapeutic strategy for familial intrahepatic cholestasis
Authors: Wendy L. van der Woerd, Catharina G.K. Wichers, Anna L. Vestergaard, Jens Peter Andersen, Coen C. Paulusma, Roderick H.J. Houwen, Stan F.J. van de Graaf
Journal: Journal of Hepatology (2016)
Acute Generalized Miliary Tuberculosis in Adults
Authors: Carleton B. Chapman, C. Merrill Whorton
Journal: New England Journal of Medicine (1946)

ACUTE generalized miliary tuberculosis is a condition that results from the sudden and often overwhelming hematogenous dissemination of tubercle bacilli from an established focus to many of the organs of the body. The large number of small, acute tubercles that develop in these organs have been said to resemble millet seeds in size and appearance, whence stems the adjective "miliary." The clinical course is so varied that diagnosis before death is often not achieved. The condition should be rigidly differentiated from the various forms of nonprogressive or slowly progressive, more or less localized forms of disseminated tuberculosis. The hematogenous dissemination . . .
Abstract 3754: Methionine adenosyltransferase IIα regulates histone methyltransferase G9a expression in colorectal cancer stem cells.
Authors: Kai-Chun Li, Shih-Ting Cha, Chia-Yu Chu, Min-Liang Kuo
Journal: Cancer Research (2013)

Abstract Histone modification is critical for regulation of chromatin structure and gene transcription in cells and recent evidences have characterized that histone methylation may contribute to tumorigenesis and cancer malignancies. In general, the methyl donor for methylation is synthesized from S-adenosylmethionine (SAM), in a reaction catalyzed from methionine by methionine adenosyltransferase (MAT). Our previous studies have demonstrated the expression of histone methyltransferase G9a, which is responsible for histone H3 lysine 9 methylation, not only correlates to tumor aggressiveness but also plays a crucial role in regulation of colorectal cancer stem cells (CSCs), which endow high tumorigenecity, drive metastasis and therapy-resistance. We discover that G9a is enriched in CSCs and knockdown of its expression will promote differentiation, inhibit drug-resistance and metastatic ability of CSCs. Here, we further report that MATIIα expression is specifically elevated in the nucleus and interacts with G9a in CSCs. Overexpression of MATIIα in non-CSCs will increase G9a expression, self-renewal ability and stemness marker expression. In contrast, knockdown of MATIIα decreases G9a expression, it reveals that the self-renewal ability will be blocked in CSCs. Furthermore, inhibition of MATIIα expression by its inhibitor, SAM, can also decrease G9a expression and stem-cell like characteristics. Taken together, we first demonstrate that the expression and the function of G9a are both maintained by MATIIα in colorectal CSCs. These findings provide a new insight into understanding of the link between the metabolic enzyme and epigenetic regulator in CSCs, which may be a therapeutic target in the future. Citation Format: Kai-Chun Li, Shih-Ting Cha, Chia-Yu Chu, Min-Liang Kuo. Methionine adenosyltransferase IIα regulates histone methyltransferase G9a expression in colorectal cancer stem 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 3754. doi:10.1158/1538-7445.AM2013-3754
Growth Hormone Therapy in Adults and Children
Authors: Mary Lee Vance, Nelly Mauras
Journal: New England Journal of Medicine (1999)

Growth hormone is produced by the somatotroph cells of the anterior pituitary. Its secretion is stimulated by growth hormone–releasing hormone and inhibited by somatostatin, which are both produced by the hypothalamus. Growth hormone secretion is pulsatile, and the amplitude of the pulses is greatest at night. Twenty-four-hour growth hormone secretion is maximal during puberty and declines gradually thereafter in both women and men. Growth hormone acts by binding to receptors on liver cells and other cells. One growth hormone molecule binds to two receptor molecules on the target cell, initiating a cascade of events that results in the secretion of . . .
[Radiation and Childhood Cancer]: Response
Authors: Richard Wakeford
Journal: Environmental Health Perspectives (1996)

Sellafield or some other reported leukemia dusters, leaves little room for doubt by con- duding that "a causal interpretation of the association between childhood leukemia and paternal preconceptional irradiation reported by Gardner et al. cannot be sustained."Taken as a whole, while contributing to the ongoing discussion on intrauterine and preconceptional exposure risks for childhood cancers, Wakeford's paper in no way invalidates the major condusions from our review of the literature on health hazards from low- dose exposures.
Effectiveness of Electronic Medical Record-Embedded Consultation Support System for Iodinated Radiocontrast Media Hypersensitivity Prevention – an Observational Study in a Tertiary Hospital
Authors: Min-Suk Yang, Min-Hye Kim, Sang-Il Choi, Jae-Hyoung Kim, Woo-Jung Song, Sae-Hoon Kim, Hye-Ryun Kang, Heung-Woo Park, Yoon-Seok Chang, Sang Heon Cho, Kyung-Up Min
Journal: Journal of Allergy and Clinical Immunology (2013)
AB1458-HPR Factors of importance for maintaining work as perceived by men with arthritis
Authors: J. Hjalmarsson Österholm, M. Björk, C. Håkansson
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Employment rates are significantly lower among individuals with arthritis compared to a general population. During the last decade new biological medications have revolutionized the treatment for many individuals with arthritis (1), reducing the disease activity and symptoms in a positive way, but also causing major direct costs since the new medications are very expensive (2). Even though the effect is good some individuals still report disability like pain, fatigue (3) and work disability (4). This indicates that even though biological medicines generate a positive remission of the disease, disability such as work disability can still be present and needs to be evaluated. Previous research about individuals with arthritis and their ability to work has mainly had a quantitative design focusing on what affects work and facilitates the ability to work for women. There is, however, limited research about how men with arthritis perceive their ability to maintain working. <h3>Objectives</h3> The aim of this study was thus to explore how men with arthritis perceive their ability to maintain working. <h3>Methods</h3> Nine employed men with arthritis were purposively sampled. Interviews were performed and were inspired by the central concepts of the Model of Human Occupation. The Empirical Phenomenological Psychological method was modified and used to analyze and interpret collected data. <h3>Results</h3> The findings consist of six themes and fifteen sub-themes. The results showed that men with arthritis perceived a desire to work, adjusted their activity pattern, were aware of their own capabilities, had good work conditions, had environmental support and used effective medication to maintain their ability to work. <h3>Conclusions</h3> This study has provided an understanding of how men with arthritis maintain their ability to work. In conclusion, to treat the symptoms of arthritis, in the more traditional way that for example hand dysfunction and pain are treated, may prevent sick-leave but as found in the present study the ability to work is complex and new strategies to support ability to work need to be developed in the occupational aspects of rheumatology care. <h3>References</h3> Simard JF, Arkema EV, Sundström A, Geborek P, Saxne T, Baecklund E, et al. Ten years with biologics: to whom do data on effectiveness and safety apply? Rheumatology 2011;50:204-13. Curtis JR, Singh JA. Use of biologics in rheumatoid arthritis: current and emerging paradigms of care. Clin Ther 2011;33:679-707. Linden C, Bjorklund A. Living with rheumatoid arthritis and experiencing everyday life with TNF-alpha blockers. Scand J Occup Ther 2010;17:326-34. Neovius M, Simard JF, Klareskog L, Askling J. Sick leave and disability pension before and after initiation of antirheumatic therapies in clinical practice. Ann Rheum Dis 2011;70:1407-14. <h3>Disclosure of Interest</h3> None Declared
Abstract 2494: Identification of mithramycin analogues with increased potency and more selective inhibition of EWS-FLI1 for the treatment of Ewing sarcoma
Authors: Meti Gebregiorgis, Girma Woldemichael, Min He, Min H. Kang, Luz E. Núñez, Francisco Morís, Malcolm A. Smith, Lee J. Helman, Patrick J. Grohar
Journal: Cancer Research (2012)

Abstract Background: Ewing Sarcoma Family Tumors (ESFT) is characterized by a chromosomal translocation, most commonly, between chromosomes 11 and 22, resulting in the fusion of the EWS and FLI1 genes. The fusion protein EWS-FLI1 is known to function as a constitutively activated transcription factor responsible for the oncogenic phenotype of ESFT. The identification of potent and specific inhibitors of EWS-FLI1 offers the hope of improved outcomes for ESFT patients. We have recently identified mithramycin, an antineoplastic antibiotic produced by Streptomyces plicatus, as a potent inhibitor of EWS-FLI1. In this report, we have investigated a series of mithramycin structural analogs in an effort to find compounds with better pharmacological properties. Methods: We evaluated the relative effects of the mithramycin analogs on ESFT viability using MTS, XTT and IncuCyte® real time cell confluence assays. The compounds were screened against a panel of pediatric cell lines within the Pediatric Preclinical Testing Program (PPTP) to evaluate selectivity. Western blot analysis and luciferase assays were used to determine the effects on EWS-FLI1 downstream target expression. Results: The mithramycin analogs 6 and 16 exhibit better potency and improved selectivity relative to mithramycin for both cell viability and downstream target inhibition. Furthermore, compound 6 is known to have a higher 200mg/kg maximum tolerated dose (MTD) relative to the 5 mg/kg MTD of mithramycin in xenograft models. Conclusions: In comparison to the drug mithramycin, we have shown that some of its structural analogs display better pharmacological properties such as increased potency and more specificity for ESFT cells. These results indicate that studies of analogs of DNA binding drugs are an important aspect of transcription factor drug development. We are working to further characterize the mechanism of these analogs and evaluate them in an in vivo model. The ultimate goal would be to translate these compounds to the clinic and improve therapeutic outcomes in patients with ESFT. 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 2494. doi:1538-7445.AM2012-2494
Case 36-2014
Authors: Kristian R. Olson, Suzanne K. Freitag, Jason M. Johnson, John A. Branda
Journal: New England Journal of Medicine (2014)

An 18-year-old woman was admitted to the hospital because of fever, pharyngitis, facial swelling, and diplopia. Imaging studies showed an abscess in the right parotid gland. Despite antibacterial therapy, her condition worsened. Diagnostic procedures were performed.
AB0950 Concordance between Joint Symptoms and Ultrasonography Findings in Patients with Rheumatoid Arthritis
Authors: A. Hirata, T. Ogura, N. Hayashi, N. Yamashita, K. Mizushina, S. Nakahashi, S. Takenaka, M. Imamura, R. Kujime, H. Kameda
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Recently ultrasonography (US) has been prevalent as a valid and objective modality of joint examination. As a result, accumulating findings of the association between joint US observations and physical examination of the joints or a composite measure of disease activity of rheumatoid arthritis (RA) have been available. Although usefulness of patient-reported outcome such as RAPID-3 has been reported, the association between patient-reported joint symptoms and US findings at each joint level has been rarely investigated. Therefore, we have examined the concordance between joint symptoms and US findings. <h3>Methods</h3> Twenty-eight patients with RA (86% female, the mean age 66 years) were asked for the self-evaluation of joint symptoms including pain and considerable stiffness in (proximal) interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow, shoulder, knee and ankle joints. Those joints were evaluated by physical examination for the presence of tenderness and/or swelling, and also by US for the presence of synovitis was defined as gray-scale (GS) imaging score ≥1 or a synovial power Doppler (PD) signal score ≥2. <h3>Results</h3> The overall concordance rate between joint symptoms and US synovitis was low (κ coefficient =0.37; 95%CI 0.29-0.44), and it tended to be improved by joint examination by board-certified rheumatologists (κ =0.45; 95%CI 0.38-0.52). And the κ value between joint symptoms and US synovitis was 0.39 (95%CI 0.30-0.47) in small (PIP, MCP and wrist) joints, while it was 0.27 (95%CI 0.12-0.43) in large (shoulder, elbow, knee and ankle) joints. In addition, both joint symptom and US synovitis showed a trend toward better concordance with joint swelling than tenderness in small (κ =0.56 and 0.48 versus 0.50 and 0.33, respectively) and large joints (κ =0.36 and 0.44 versus 0.29 and 0.34, respectively). <h3>Conclusions</h3> The concordance between patient-reported joint symptoms and US synovitis was poor, suggesting the importance of joint examinations by rheumatologists and by US, if available, including asymptomatic joints. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4892
Neuropathology of heavy metal intoxication.
Authors: M R Krigman
Journal: Environmental Health Perspectives (1978)

The basis for utilizing altered morphology, i.e., pathology, in defining diseases of the nervous system is presented. The importance of recognizing the dynamics of pathologic processes is emphasized, particularly in understanding the pathogenesis of neural diseases. Demonstrative examples of the neuropathology of human heavy metal toxicity are presented. The limitations of descriptive pathology are considered, and the potentials of quantitative (morphometric) analysis for studying pathologic processes are introduced.
815 CHARACTERISTICS OF T CELL SUBSETS AND PROGRAMMED DEATH 1 EXPRESSION ON T CELLS IN HBV-RELATED HEPATOCELLULAR CARCINOMA (HCC)
Authors: C. Wu, Y.Y. Hao, J. Xia, R. Huang, Y.F. Wu, J. Zhang, Y.D. Qiu
Journal: Journal of Hepatology (2012)
Abstract SY30-03: Monitoring tumor evolution by clonal tracking in ctDNA.
Authors: Carlos Caldas
Journal: Cancer Research (2013)

Abstract Clonal evolution and the resulting tumor heterogeneity presents challenges for molecular diagnostics, tumor burden monitoring and studying mechanisms of drug resistance. In breast cancer circulating mutant cell free DNA (ctDNA) can be used as a ‘liquid biopsy’ to tackle all of these challenges. I will present our data that provides proof of principle for the use of ctDNA to track clonal evolution/clonal selection in both metastatic breast cancer and localized breast cancer treated with neo-adjuvant therapy. Citation Format: Carlos Caldas. Monitoring tumor evolution by clonal tracking in ctDNA. [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 SY30-03. doi:10.1158/1538-7445.AM2013-SY30-03
Abstract SY28-02: Tumor targeting with antimitotic monoclonal antibody drug conjugates.
Authors: Peter Senter
Journal: Cancer Research (2013)

Abstract Monoclonal antibodies (mAbs) have played a major role in cancer medicine, with active drugs such as trastuzumab, cetuximab, bevacizumab and rituximab in a wide range of therapeutic applications. The mechanism of activity of these agents involves cell signaling, effector functions through interactions with Fcγ receptor positive cells, and complement fixation. The activity of mAbs can be enhanced through the generation of antibody drug conjugates (ADCs) that are capable of delivering cytotoxic agents with some degree of selectivity to tumor cells. Early work in this field involved the use of clinically approved anticancer drugs that generally were low in potency. Consequently, the resulting ADCs had suboptimal activities. Because of this, significant attention was directed towards the identification of appropriate drugs for targeted delivery, the most successful being antimitotic drugs such as monomethyl auristatin E (MMAE), and maytansinoids. These drugs inhibit tubulin polymerization and arrest cell growth in a cell-cycle dependent manner. Successful delivery of these agents requires drug, linker, and conjugation optimization, in addition to judicious selection of an antigen target on tumor cell surfaces. Brentuximab vedotin, a conjugate comprised of the anti-CD30 mAb cAC10 conjugated with MMAE through a highly stable peptide linker, is an example of how addressing these considerations can lead to ADCs with pronounced clinical efficacy. In August 2011, brentuximab vedotin received accelerated approval by the US Food and Drug Administration for use in relapsed or refractory Hodgkin lymphoma and relapsed or refractory systemic anaplastic large cell lymphoma, two diseases with significant unmet medical needs. An overview of how this targeted antimitotic drug was developed and how we are extending the technology will be provided. Citation Format: Peter Senter. Tumor targeting with antimitotic monoclonal antibody drug conjugates. [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 SY28-02. doi:10.1158/1538-7445.AM2013-SY28-02