tbuckley/cabot-search huggingface dataset:
Abstract 325: ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridization
Authors: Takaya Ishihara, Hitoshi Tsuda, Akiko Hotta, Ken-ichi Kozaki, Akira Yoshida, Hiroshi Yoshimura, Koichi Ito, Issei Imoto, Johji Inazawa
Journal: Cancer Research (2010)

Abstract Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than a year after diagnosis. To date, however, cytogenetic information on this disease has been very limited. Significant genomic copy-number alterations, such as amplifications and homozygous losses, are useful landmarks for identifying oncogenes and tumor-suppressor genes (TSGs), respectively. We have performed bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (array-CGH), which allows the high resolution, high throughput and quantitative copy-number analysis throughout the genome, in various cancers, and identified many novel cancer-related genes. In ATC, we have reported DUSP26 as a novel growth-promoting gene from an amplified region detected in ATC cell lines by the array-CGH using an in-house low-density cancer-targeting array (Yu Wei et al.,Oncogene 2007). In the course of a program to screen a panel of ATC cell lines for genomic copy-number aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11.22 and belong to the HECT ubiquitin ligase family. The expression of ITCH was increased in four of 14 ATC cell lines (28.6%), including 8305C with a copy-number amplification of this gene, and six of seven primary cases (85.7%). Among the primary thyroid tumors, a considerable number of ITCH high expressers were found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%). Furthermore, knockdown of ITCH by specific small interfering RNA significantly inhibited the growth of ITCH-overexpressing cells, whereas ectopic overexpression of ITCH promoted growth of ATC cell lines with a relatively weak expression. These observations indicate ITCH to be the most likely target for 20q11.22 amplification and to play a crucial role in the progression of thyroid carcinoma. 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 325.
Successful Intermittent Chemoprophylaxis for<i>Pneumocystis carinii</i>Pneumonitis
Authors: Walter T. Hughes, Gaston K. Rivera, Michael J. Schell, Delaine Thornton, Lennie Lott
Journal: New England Journal of Medicine (1987)

We conducted a prospective, randomized clinical trial over a two-year period in patients with acute lymphocytic leukemia to assess the effectiveness of trimethoprim-sulfamethoxazole given on three consecutive days each week as compared with daily in the prevention of Pneumocystis carinii pneumonitis. P. carinii pneumonitis did not develop in any of 92 patients receiving the drug daily (30,602 patient-days) or in any of 74 who received it three consecutive days a week (27,329 patient-days), whereas the incidence of the infection expected without prophylaxis is 21 percent. One patient, excluded from both groups because of an adverse reaction to sulfonamides in the past, acquired P. carinii pneumonitis. Especially noteworthy was a difference in the occurrence of systemic mycoses, with 10 cases in the daily-treatment group and only 1 case in the three-days-a-week group (P = 0.024). No differences were observed in the rates of other infections or adverse effects associated with the drug. We conclude that trimethoprim-sulfamethoxazole is as effective given three days a week as it is given daily in the prevention of P. carinii pneumonitis and that the intermittent schedule has the advantages of less frequent fungal infections and lower cost. Intermittent chemoprophylaxis may be especially beneficial to certain patients who are unable to tolerate the daily doses.
Systems approach to personalized molecular medicine.
Authors: G Mills
Journal: Cancer Research (2009)

Abstract Abstract #MS2-1 The realization of the promise of personalized molecular medicine will require the efficient development and implementation of novel targeted therapeutics. The overall likelihood of response to particular drugs represents the interaction between predictors of sensitivity with predictors of resistance. The phosphatidylinositol 3'kinase (PI3K) pathway is aberrant at multiple levels across a wide variety of tumors making it the most common activating aberration in cancer. This has led to the development and now early clinical testing of drugs targeting multiple components of the pathway. The efficient utilization of these drugs will require the ability to accurately determine mutation and activation status in tumors as well as determining the interaction between the PI3K pathway and other pathways in driving tumor pathophysiology. The PI3K pathway is critically important to cellular function and is thus under exquisite homeostatic control. The feedforward and feedback loops in the pathway determine the response to perturbation of the pathway by mutation or therapeutic intervention. Strikingly inhibition of the pathway at the level of mTOR or AKT results in the activation of potent feedback loops resulting in activation of multiple cell surface tyrosine kinases, PI3K itself and AKT. This may contribute to the observation that mTOR inhibitors appear to make some patient tumors grow more rapidly an unexpected and disappointing consequence. Our preliminary systems biology-based mathematical and experimental models of the PI3K signaling network accurately predict these consequences as well as the biochemical processes involved. Further, the models suggest combinations of targeted therapeutics likely to reverse the negative effects of the mTOR inhibitors converting the outcome from negative to positive in terms of tumor growth. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr MS2-1.
A Large Bladder Calculus and Severe Vesicoureteric Reflux as Seen on Tc-99m MAG3 Renography
Authors: MYLES WEBB, WILLIAM FONG
Journal: Clinical Nuclear Medicine (2002)

From the Department of Nuclear Medicine, Royal Brisbane Hospital, Queensland, Australia Received for publication January 14, 2002. Revision accepted April 17, 2002. Correspondence: Myles Webb, Department of Nuclear Medicine, Royal Brisbane Hospital, Herston Road, Herston, Queensland, Australia 4029. E-mail: [email protected]
Clinical Applications of Research on Angiogenesis
Authors: J Folkman
Journal: New England Journal of Medicine (1995)

Angiogenesis is fundamental to reproduction, development, and repair. All these processes depend on the tightly regulated growth of blood vessels that can “turn on” and “turn off” within a brief period. When blood vessels grow unabated, angiogenesis becomes pathologic and sustains the progression of many neoplastic and non-neoplastic diseases. The realization that tumor growth requires new blood vessels and the identification of chemical factors that mediate angiogenesis have broadened our understanding of pathologic processes and opened new avenues to the diagnosis and treatment of these diseases.Tumor hypervascularity was initially thought to reflect inflammatory vasodilation of preexisting host vessels, a . . .
EUS-Guided Trucut Biopsy adds Significant Information to EUS-Guided FNA in Selected Patients: A Prospective Study
Authors: A Saftoiu, P Vilmann, B Guldhammer Skov, CV Georgescu
Journal: Endoscopy (2006)

Background: EUS-guided Trucut biopsy (EUS-TCB) has recently emerged as a method that tries to overcome the limitations of EUS-guided fine needle aspiration (EUS-FNA) by providing a core-tissue specimen needed to increase the yield and accuracy of diagnosis. Methods: The aim of our study was to evaluate whether EUS-TCB adds any information to EUS-FNA, in selected patients, and to assess the diagnostic yield, overall accuracy and complications of EUS-TCB as compared with EUS-FNA. The study included prospectively 30 patients which un-derwent both procedures. Results: The yield of adequate tissue harvesting was similar for EUS-FNA and EUS-TCB (96.4% versus 89.3%, P=NS), with the same number of passes done. The diagnostic accuracy of EUS-FNA was also similar with that of EUS-TCB for the diagnosis of malignant mediastinal masses (73.7% versus 68.4%, P=NS). However, the accuracy for obtaining a specific diagnosis was significantly lower for EUS-FNA as compared with EUS-TCB (5.3% and 68.4%, P<0.005). EUS-TCB did not appear to help as a rescue procedure in mediastinal tumors, after a false negative result of EUS-FNA. All cases of submucosal tumors were correctly classified by EUS-TCB as GIST or leiomyo-mas, while EUS-FNA raised only a suspicion of mesenchymal tumor. Conclusion: EUS-TCB was certainly useful when immunohistochemistry was needed, for e.g. in submucosal tumors and lymphoma, as well as to confirm and characterize the primary or metastatic origin of mediastinal masses. The information provided by EUS-FNA and EUS-TCB are comple-mentary, especially in selected cases where a complete histological diagnosis has an important im-pact on the clinical management.
Abstract 2908: Promyelocytic leukemia-retinoic acid receptor α forms complexes with Fas and FLIP and impairs Fas-mediated apoptosis
Authors: Rong-Hua Tao, Zuzana Berkova, Jillian Wise, Urszula Daniluk, Felipe Samaniego
Journal: Cancer Research (2010)

Abstract Fas plays a critical role in cell proliferation and in the selective killing of autoreactive lymphocytes and abnormal cells, including infected cells. To explain the common expression of Fas and the resistance to the Fas-induced apoptosis observed in some normal and cancer cells, we have screened cells for potential regulators of the Fas death receptor. By using mass spectroscopy analysis of Fas-associated proteins, we identified peptides derived from promyelocytic leukemia (PML). PML enhances pro-apoptotic signaling, while the promyelocytic leukemia-retinoic acid receptor α (PMLRARα) activates pro-survival pathways. Given these opposing functions, we tested whether PMLRARα, which typically operates in a dominant-negative manner, blocks Fas-mediated apoptosis. Co-immunoprecipitation analysis demonstrated that PMLRARα interacts with Fas in acute promyelocytic leukemia (APL)-derived NB4 cells, U937-PR9 cells and in APL primary cells. The binding of PMLRARα to Fas was mapped to the B-box domain of PMLRARα. Flow cytometry analysis of propidium iodide-stained and Annexin-V-stained cells challenged with Fas ligand (FasL) or agonistic anti-Fas antibody (CH-11) indicated that the presence of PMLRARα was associated with blocked Fas-mediated apoptosis at early and late stages. The knockdown of PMLRARα with shRNA sensitized the NB4 cells to Fas-mediated apoptosis. Expression of PMLRARα in U937-PR9 cells prevented Fas-mediated cleavage of procaspase-8 and also prevented procaspase-8 from binding to the Fas complex upon stimulation with the agonistic anti-Fas antibody (CH-11). Further analysis indicated that PMLRARα bound to FLIPL/S and forms a complex with Fas associated with suppression of Fas signaling. These data suggest that cancer-specific inhibitors of Fas such as PMLRARα block Fas-mediated apoptosis and thus can contribute to cancer development and resistance to therapy. Our results may provide an explanation for the long-known role of PMLRARα and PML in the regulation of Fas signaling, which we have shown to occur by direct regulation. We have identified an attractive potential target to the regulation of apoptosis at the PMLRARα-Fas and PML-Fas interfaces. By neutralizing the effect of death receptor inhibitors such as PMLRARα and other potential inhibitors, we can improve on the success of the many chemotherapeutic treatments that depend on activation of death receptors for effective elimination of cancer cells. 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 2908.
A Widespread Epidemic of Typhoid Fever Traced to a Common Exposure
Authors: William A. Neill, J. D. Martin, E. A. Belden, W. Yates Trotter
Journal: New England Journal of Medicine (1958)

EACH summer members of a religious group assemble from across the nation to participate in the annual conference at their MonArk Springs, Missouri, encampment. In 1956 representatives began to arrive on Friday, July 20, and before the meeting was over on July 29, over 550 participants originating from 15 states extending from Pennsylvania to California had attended for a few hours to the full ten days. Although diarrhea affected over half the attendants, it did not seriously interfere with the camp meeting. When they returned to their resident states, none were aware of their common exposure to typhoid fever at . . .
Comparison of Conventional Anterior Surgery and Laparoscopic Surgery for Inguinal-Hernia Repair
Authors: Mike S.L. Liem, Yolanda van der Graaf, Cees J. van Steensel, Roelof U. Boelhouwer, Geert-Jan Clevers, Willem S. Meijer, Laurents P.S. Stassen, Johannes P. Vente, Wibo F. Weidema, Augustinus J.P. Schrijvers, Theo J.M.V. van Vroonhoven
Journal: New England Journal of Medicine (1997)

Inguinal hernias can be repaired by laparoscopic techniques, which have had better results than open surgery in several small studies.
AB0991 The Role of Metal Artefact Correction Techniques in Patients with Metallic Joint Prostheses
Authors: M.R. Backhouse, R. Hodgson, M.H. Stone, A.C. Redmond, P. O'Connor
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Magnetic Resonance (MR) offers the potential to identify early loosening and assess peri-articular soft tissue structures in patients with metal joint prostheses. Unfortunately, conventional MR is currently incapable of assessing the prosthesis-bone interface in patients with joint replacements because of field inhomogeneity resulting from metal related paramagnetic and ferromagnetic effects. New Slice-Encoding Metal Artefact Correction (SEMAC) techniques have been developed that may allow visualisation of the bone and soft tissues close to metal work. <h3>Objectives</h3> In order to explore the clinical utility of the technique, we conducted a retrospective audit of conventional MR and the newer metal suppression techniques. <h3>Methods</h3> Patients who had previously received hip prostheses and were undergoing clinical review were imaged using both conventional and metal suppression MR techniques using a Siemens Avanto 1.5T MR scanner as part of their routine clinical care. T1 TSE and STIR coronal and T1 and STIR SEMAC sequences were assessed. The femoral and acetebaular components were consensus scored by two experienced musculoskeletal radiologists for diagnostic quality. Each prosthesis zone was scored using a five point scale: (0) definitely non-diagnostic; (1) probably non-diagnostic; (2) possibly diagnostic; (3) probably diagnostic; (4) definitely diagnostic. Abnormalities were assessed on both radiographs and MRI using a four point scale: (0) none; (1) mild; (2) moderate; (3) severe. Effusion and bone-cement interface were assessed by prosthesis zone. These abnormalities were defined as increased signal on STIR sequences with intermediate signal on T1 scans. <h3>Results</h3> Images were reviewed from 19 patients (mean age = 64; SD = 12 years) with a variety of hip prostheses (Charnley = 4, Corail = 7, Furlong = 1, Metal-on-Metal = 7). SEMAC increased the number of diagnostically useful images (defined as ≥2) in all Gruen zones for both STIR and T1 images (Table 1). Importantly, this also translated into to an increased ability to identify abnormalities: Use of SEMAC enabled identification of more abnormalities in all Gruen zones and doubled the number of effusions visible (Table 2). <h3>Conclusions</h3> The use of SEMAC sequences substantially improved image quality and enabled identification of more peri-prosthetic complications in patients with metallic joint prostheses. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1494
Abstract 1634: Metabolomic profiling for early detection of colorectal neoplasia
Authors: David C. Montrose, Levy Kopelovich, Xi Kathy Zhou, Rhonda Yantiss, Kotha Subbaramaiah, Andrew Dannenberg
Journal: Cancer Research (2012)

Abstract Introduction: Colorectal cancer (CRC) is the 3rd leading cause of cancer-related deaths in the world. Colonoscopy is widely used for early detection and removal of colorectal neoplasia to prevent CRC. However, it is both invasive and costly underscoring the need for new strategies to identify subjects for whom colonoscopy is most appropriate. Metabolomics is a high throughput method of detecting small molecules which provides a platform for identifying novel biomarkers of colorectal neoplasia. In this study, we investigated whether metabolic changes could be identified in the feces and plasma in a model of experimental CRC. Methods: Five week old male A/J mice were administered six weekly intraperitoneal injections of either azoxymethane (AOM) (10mg/kg) (n=40) or 0.9% saline (n=35). Following injections, feces, plasma and tumor tissue or normal colonic mucosa were collected and stored at −80oC for metabolomic analysis. Five mice from the AOM injected group were sacrificed at each of three time points (three, five and seven weeks after the last injection) to assess tumor burden. UPLC/MS/MS and GC/MS were used to quantify metabolite levels in feces, plasma and tissue. Results: Histological analysis of tumor burden in the colon showed a progressive increase as a function of time after AOM administration. Metabolomic analysis revealed a large number of significantly changed metabolite levels in both the feces and plasma during colon carcinogenesis. These included amino acids and peptides in feces as well as bile acids in the plasma. A select number of these metabolites were found to progressively change as a function of time in both feces and plasma in relation to increased tumor burden. Significantly, certain metabolites changed in the same direction in feces and tumor tissue, plasma and tumor tissue as well as across all three matrices, suggesting that these may be tumor-derived. For example, samples from AOM injected mice showed increased levels of sarcosine and 2-hydroxyglutarate, metabolites previously implicated in prostate cancer and gliomas/AML, respectively. Conclusions: This study demonstrates the potential utility of metabolomic analyses for the early detection of colorectal neoplasia. Additionally, the finding of increased levels of two onco-metabolites (sarcosine, 2-hydroxyglutarate) in colorectal neoplasia suggests their potential involvement in colon carcinogenesis. Future studies in humans will be required to determine the significance of these findings. 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 1634. doi:1538-7445.AM2012-1634
P14 Does Vitamin D Axis have an effect on the severity of Asthma?
Authors: R. Sathyamurthy, S. Manney, A. Wood, G. Perkins, C. Webster, M. Krishna, A. Mansur
Journal: Thorax (2010)

<h3>Background</h3> Vitamin D (VD) has been suggested to play a role in the development of asthma and frequency of asthma exacerbation1. Vitamin D Binding Protein (VDBP) is thought to influence the development of COPD through its immunomodulatory effect2. This study explores the role of vitamin D axis in relation to asthma severity. <h3>Method</h3> An observational case control study with a healthy group (H) and subgroups of severity of asthma – steroid ‘naïve’ mild asthma (MA), severe asthma (SA), severe asthma dependent on oral corticosteroids (SACS) and ‘type 1 brittle’ asthma (BA1) was conducted. VD, VDBP, spirometry, Fractional exhaled nitric oxide (FeNO) and exacerbations requiring oral corticosteroids/year (E) were recorded in all the patients. The data were analysed by Kruskal Wallis and Spearmans rank correlation test. The study was conducted between July 2009 and April 2010. <h3>Results</h3> Sixty subjects [16M; mean age: 39 years (19–57)] were recruited into this study. The parameters measured are shown in Abstract P14 Table 1. We observed no significant difference in serum VD between the healthy group and any of the asthma subgroups (p=0.52), or indeed between all asthmatics grouped together and healthy controls. Similarly, there was no significant difference in serum VDBP between any of the above groups (p=0.52). VD or VDBP serum levels did not correlate with exacerbations (r<sub>s</sub>=0.08, p=0.28 for VD and r<sub>s</sub>=−0.04, p=0.76 for VDBP), FEV1, or FeNO. <h3>Conclusion</h3> VD and VDBP level in various asthma groups, did not differ significantly from healthy volunteers in this cohort, and did not correlate with lung function, asthma exacerbations, or exhaled nitric oxide. We conclude that vitamin D axis may not play a significant role in asthma severity or exacerbations although a small effect could not be excluded which would require a larger study for confirmation.
Three simultaneous, food-borne, multi-country outbreaks of hepatitis A virus infection reported in EPIS-FWD in 2013: what does it mean for the European Union?
Authors: C M Gossner, E Severi
Journal: Eurosurveillance (2014)

Between March and May 2013, three multi-country outbreaks of hepatitis A virus (HAV) infection were reported through the Epidemic Intelligence Information System for Food- and Water-borne diseases (EPIS-FWD) of the European Centre for Disease Prevention and Control (ECDC). The aim of this work is to put these outbreaks into a European Union (EU) and European Economic Area (EEA) perspective and highlight opportunities for improving detection and investigation of such outbreaks. Although HAV outbreaks are not unusual in the EU/EEA, having three large food-borne multi-country outbreaks declared within three months is an unexpected event, particularly when at least two of these outbreaks are associated with frozen berries. Factors influencing the occurrence of these events include the increased number of susceptible Europeans, the limited coverage of HAV vaccination, the global trade of potentially contaminated products introduced in the EU/EEA, and the 'awareness chain effect' leading to a wave of notifications. Further studies should be conducted to understand the risk posed by frozen berries. Laboratory capacity and surveillance of viral infections in the EU/EEA, as well as HAV vaccination recommendations to travellers to endemic countries should be strengthened. Finally, timely reporting food-borne events through EPIS-FWD, to ensure timely response.
The Threat to Medical-Records Research
Authors: L. Joseph Melton
Journal: New England Journal of Medicine (1997)

The potential for misuse of personal information by insurers and employers has heightened concern about the confidentiality of medical records. Despite the absence of documented abuses related to approved research projects,1 legislation has been passed in Minnesota that restricts access to medical records for research purposes, and similar measures are proposed in some federal legislation. Such restrictions pose an obvious threat to patient-oriented investigations, such as observational outcome studies, that are based on existing medical-records data and require personal identifiers to link initial interventions with ultimate results. Clinicians and patients alike mostly take for granted the availability of this information, . . .