tbuckley/cabot-search huggingface dataset:
Amelioration by Ingestion of Phenylalanine of Toxic Effects of Chloramphenicol on Bone Marrow
Authors: D. Ingall, J. D. Sherman, F. Cockburn, R. Klein
Journal: New England Journal of Medicine (1965)

THE major toxic effect of chloramphenicol is the production of bone-marrow arrest and aplastic anemia. Early in the development of chloramphenicol toxicity, vacuoles appear in the erythroid and myeloid precursors of the bone marrow.1 2 3 4 The relation of these early, reversible lesions to later, more serious bone-marrow depression is unknown. Similar cytoplasmic vacuoles in the erythrogones have been reported in erythremic myelosis (Di Guglielmo's syndrome) and acute alcoholism, and in normal infants as well as those with phenylketonuria receiving a phenylalanine-deficient diet.5 6 7 8 The lesions in the infants receiving such diets were reversed by the addition of phenylalanine. Therefore, an attempt was . . .
Abstract 3058: miRNA networks mediate the tumor suppressive function of FOXO proteins.
Authors: Monica Nadler, Robin Zabolian, Kenneth Ndebele, thierry bertomeu, Octavian Bucur, Bodvael Pennarun, Roya Khosravi-Far
Journal: Cancer Research (2013)

Abstract FOXO transcription factors, as regulators of a variety of cellular functions, including promotion of apoptotic cell death, are negatively regulated by various oncogenic signaling cascades and have emerged as bona fide tumor suppressors. Indeed, studies by others and us have shown that the suppression of FOXO function is critical in promoting evasion of apoptosis and is a significant occurrence in several hematological malignancies. Consequently, FOXO proteins signify an important therapeutic target in hematopoietic malignancies as well as other types of cancer, where repression of FOXO plays a key role in malignancy. Since transcription factors are not yet easily “druggable," it is vital to identify mediators of FOXO function that can be readily targeted. It is now apparent that aberrant miRNA expression plays a major role in cell and tissue-specific manner in the pathogenesis of various types of cancers including hematological malignancies. Both miRNA loss of function and miRNA overexpression have been shown to target key cellular proteins and contribute to cancer pathogenesis. Conversely, miRNA genes themselves have been shown to be direct targets of transcription factors that are known as important tumor suppressors or oncogenic proteins. Through a systematic screening approach, we have identified members of three miRNA clusters that are dependent on FOXO transcription factors for expression. We have observed that the level of these miRNAs is dependent on BCR-ABL status of hematopoeitc cells and they their levels are changed in specimens from Leukemia patients. Our studies indicates a mechanism of action for FOXO tumor suppressors whereby members of two miRNA families are direct transcriptional targets of FOXO3. Moreover, these miRNAs target and reduce the expression of two key oncogenic factors, the serine/threonine kinase mTOR, and proto-onocogene c-myc, to keep cell growth at bay and prevent tumorigenesis. Our investigations have unraveled the miRNA arm of the FOXO tumor suppression network. Citation Format: Monica Nadler, Robin Zabolian, Kenneth Ndebele, thierry bertomeu, Octavian Bucur, Bodvael Pennarun, Roya Khosravi-Far. miRNA networks mediate the tumor suppressive function of FOXO proteins. [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 3058. doi:10.1158/1538-7445.AM2013-3058 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Physician-Assisted Suicide — Polling Results
Authors: James A. Colbert, Joann Schulte, Jonathan N. Adler
Journal: New England Journal of Medicine (2013)

Recently, we gave readers the opportunity to share their opinions on physician-assisted suicide in Clinical Decisions, an interactive feature in which experts discuss a controversial topic and readers vote and post comments. We presented the case of a 72-year-old man in Oregon who was receiving palliative care for metastatic pancreatic cancer and was contemplating physician-assisted suicide.1 State laws in Oregon2 and Washington3 permit physicians to assist patients with such requests through the use of life-terminating drugs.Experts provided opposing viewpoints . . .
Abstract 5139: Therapeutic targets for neuroblastoma by genome scale siRNA screens
Authors: Heather Howie, Masafumi Toyoshima, James E. Annis, Lauren Richard, Julie R. Park, Carla Grandori
Journal: Cancer Research (2012)

Abstract ∼ 30 % of Neuroblastoma harbor amplifications of the MYCN oncogene, which is the strongest molecular marker of poor prognosis. However, a subset of high-risk neuroblastoma does not carry alterations of the MYCN gene and the molecular pathways underlying their aggressive behavior remains to be elucidated. We have utilized a functional genomics approach with both genetically defined cell systems, as well as molecularly defined neuroblastoma cell lines, to identify critical survival pathways that distinguish MYCN-amplified versus non-amplified neuroblastoma. The results of high throughput siRNA screens targeting the druggable genome will be presented and discussed in light of public microarray data and validation experiments carried out in our laboratory. These findings revealed that different chromatin-remodeling genes, DNA-repair and developmental pathways differentiate MYCN amplified neuroblastoma versus non-amplified, thus highlighting specific new therapeutic targets associated with MYCN status as well as other molecular markers. In addition to pinpointing novel therapeutic targets for high-risk neuroblastoma, our study also functional defines signaling pathways activated in high-risk neruoblastoma and could be utilized to guide rational therapeutic choices. 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 5139. doi:1538-7445.AM2012-5139
Abstract LB-239: Genetic approaches for next generation of breast cancer tailored therapies
Authors: Jose Silva, Ruth Rodriguez
Journal: Cancer Research (2011)

Abstract Cancer therapy has radically changed during the last decade. Novel therapies based on the specific molecular changes that drive tumorigenesis in every patient are emerging as low toxicity and more efficient alternatives to classical treatments. However, even these ideal tailored therapies fail to provide a long-term cure and can only delay the progression of the disease. An alternative promising approach is the use of genetic synthetic lethal interactions. These occur when two genetic alterations that are individually innocuous appear in the same cell causing growth inhibition. This concept can be exploited to identify genes that, when inhibited, exclusively reduce the viability of tumor cells that carry a preexisting genetic lesion. Although synthetic lethality has always been proposed as an attractive anticancer approach with proven success, identification of these genetic interactions has remained elusive mainly because of the lack of proper genetic tools. However, RNA interference (RNAi) technology has emerged as a very powerful approach to attenuate the expression of any chosen gene. Thus, we envision using RNAi to identify genes that, when attenuated, exclusively reduce the viability of tumor cells carrying specific genetic lesions without affecting normal ones. During the last years, we have pioneered the development of RNAi based genetic tools for studies in mammalian cells. Thus, we have generated a highly efficient RNAi library that allows us to block any gene of interest in the human genome. Additionally, we have developed a microarray-based analytical platform that, when combined with our RNAi library, greatly facilitates genome-wide RNAi studies. This technology represents a unique opportunity to identify synthetic lethal effects with major cancer alterations. In this project we have started to apply our state-of-the-art technology to uncover synthetic lethal interaction with the major breast cancer genes (ErbB2, c-Myc, Cyclin-D1 and RB). These functional studies have already revealed that Stat-3 is synthetic lethal with activation of ErbB2. Thus, attenuating the activation levels of Stat-3 using small molecules inhibitors or RNAi silencing differentially reduced the viability of cells transformed with an ErbB2 oncogene. Mechanistically, we have linked this effect to the activation of an autocrine loop in which ErbB2 transformed cells secrete interleukin-6 (IL6) and upregulate its bona fide receptor IL6R. This activates the canonical JAK/STAT3 pathway increasing their tolerance to oncogene-induced stress. 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 LB-239. doi:10.1158/1538-7445.AM2011-LB-239
ACUTE KIDNEY INJURY DEFINITION AND IN-HOSPITAL MORTALITY IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Nicola Cosentino, Giancarlo Marenzi, Gabriele Crimi, Marco Moltrasio, Mara Rubino, Stefano Buratti, Valentina Milazzo, Alberto Somaschini, Rita Camporotondo, Stefano Cornara, Gaetano De Ferrari, Antonio Bartorelli
Journal: Journal of the American College of Cardiology (2016)
Abstract 3828: RDEA119 synergy the anti-tumor effect of sorafenib in renal cell carcinoma cells
Authors: Mi Joung Kim, Jung Jin Hwang, Jene Choi, Sang-wook Lee, Choung-Soo Kim
Journal: Cancer Research (2011)

Abstract The MEK signaling pathway is over-expressed in more than 30 percentages of cancers, leading to cell growth and proliferation. Renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is a particularly vascularized solid tumor where the Raf/MEK/ERK pathway is activated; suggesting that inhibition of this pathway may have therapeutic targets. Sorafenib as a multi-kinase inhibitor against Raf, VEGFR-2, PDGFR, c-kit, and FLT3 approved by the FDA for treatment of advanced renal cell and hepatocellular carcinomas. Since it was reported recently that combination treatment with sorafenib and MEKI exerted synergistic effect on cell proliferation in HCC, we studied the anti-proliferative effect of RDEA119 as a single agent or in combination with sorafenib for the treatment of RCC and HCC. We examined cell death effect on cell viability in 8 kinds of RCC cells and 6 kinds HCC cells. Treatment with RDEA119 inhibited proliferation of TK-10, UO31, A497 (RCC) and HepG2 (HCC) cells. In the case of combination treatment, pre-treatment with RDEA119 potentiated anti-proliferative effect of sorafenib in A498 cells (ccRCC and VHL-/-). This combination showed synergism in combination index and isobolograms analyzed by CalcuSyn software. Furthermore, the combination treatment activated caspases-3, -9 and -8, which resulted in intrinsic and extrinsic apoptosis. To figure out cell death mechanism activated by this combination, we analyzed the phosphorylation of phospho-ERK (p-ERK) and p-AKT in A498 cells. Single treatment with RDEA119 decreased p-ERK effectively, but increased p-AKT. On the other hand, sorafenib alone decreased p-AKT, but increased p-ERK. However, combination treatment with RDEA119 and sorafenib inhibited phosphorylation of MEK and AKT completely. The combination treatment decreased the level of p-GSK3β and anti-apoptotic protein, MCL-1 which are related to survival. Our study indicates that MEK inhibitor (MEKI) alone suppressed cell proliferation and the combination of MEKI with sorafenib increased apoptosis synergistically by decreasing activation of AKT pathway as well as ERK pathway in A498 cells. These results suggest that it may be a new therapeutic modality for treatment of ccRCC. 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 3828. doi:10.1158/1538-7445.AM2011-3828
INFLUENCE OF LESION LOCATION ON THE DIAGNOSTIC ACCURACY OF ADENOSINE-FREE CORONARY PRESSURE WIRE MEASUREMENTS: THE CONTRAST (CAN CONTRAST INJECTION BETTER APPROXIMATE FFR COMPARED TO PURE RESTING PHYSIOLOGY?) SUBSTUDY
Authors: Yuhei Kobayashi, Nils Johnson, Colin Berry, Bernard De Bruyne, K. Lance Gould, Allen Jeremias, Keith Oldroyd, Nico Pijls, William Fearon
Journal: Journal of the American College of Cardiology (2016)
OP0273 Does Spinal MRI Add Incremental Diagnostic Value to MRI of the Sacroiliac Joints Alone in Non-Radiographic Axial Spondyloarthritis?
Authors: U. Weber, V. Zubler, Z. Zhao, R. G. Lambert, S. M. Chan, S. J. Pedersen, M. Ostergaard, W. P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The definition of a positive MRI as major criterion in the Assessment of SpondyloArthritis classification criteria for axial spondyloarthritis (SpA) is based on MRI of the sacroiliac joints (SIJ) alone. It is not known whether additional MRI of the spine may enhance diagnostic certainty over and above SIJ MRI alone. <h3>Objectives</h3> To assess the incremental diagnostic value of spinal MRI evaluated both separately from and combined with SIJ MRI in non-radiographic SpA (nr-axSpA) compared to SIJ MRI alone. <h3>Methods</h3> The study sample comprised 2 independent cohorts A/B of 130 consecutive patients with back pain ≤50 years newly referred to 2 university clinics, and 20 healthy controls (HC), in whom both SIJ and spinal MRI were available. Patients were classified according to clinical examination and pelvic radiography as having nr-axSpA (n=50), ankylosing spondylitis (AS; n=33), or mechanical back pain (MBP; n=47). SIJ and spinal MRI were assessed by 3 blinded readers according to standardized modules. Readers recorded presence/absence of SpA and their level of confidence in this conclusion by global evaluation of the MRI scans (T1SE and STIR sequences) on a 0-10 scale (0 = definitely not SpA; 10 = definite SpA). SIJ alone and spinal MRI alone were read independently 6 months apart, with another interval of 1-12 months to the combined assessment of both SIJ and spinal MRI. We analysed differences between SIJ alone versus spinal MRI alone, and SIJ alone versus combined read of SIJ and spinal MRI. This was done descriptively by the percentage (number) of subjects according to the mean of 3 readers for SIJ MRI and spinal MRI separately, and for combined MRI. <h3>Results</h3> For cohorts A/B, 15.8%/28.0% of nr-axSpA patients considered having a negative SIJ MRI were re-classified as being positive for SpA by global evaluation of combined SIJ and spinal scans. However, 28.6%/11.1% of MBP controls and 18.3% of healthy volunteers, who showed a negative SIJ MRI, were falsely re-classified as having SpA by combined SIJ and spinal MRI. Low confidence (5-7) in a diagnosis of SpA by global evaluation of SIJ MRI increased to high confidence (8-10) by combined MRI in 3.5% and 8.6% of nr-axSpA patients in the 2 cohorts. Percentage of subjects (mean of 3 readers) <h3>Conclusions</h3> Combined spinal and SIJ MRI added little incremental value compared to SIJ MRI alone for diagnosing nr-axSpA patients and enhancing confidence in this diagnosis. <h3>Disclosure of Interest</h3> None Declared
PMO-084 The evolution of a virtual peg assessment team: activity and complications
Authors: S C Donnelly, R Sweis, V Sayer, L Bensaid, B Hayee
Journal: Gut (2012)

<h3>Introduction</h3> Patients referred for percutaneous Endoscopic Gastrostomy (PEG) insertion often have multiple co-morbidities which do not improve with PEG feeding and lead to significant post-procedure complications. Pre-assessment of patients for PEG insertion improves morbidity and mortality, but is often time-consuming and labour-intensive. An electronic patient record (EPR) could facilitate assessment of patients and multi-disciplinary communication, while a detailed referral form could speed up the information gathering and assessment process. Starting in February 2011 in our Trust, patients referred for PEG were formally pre-assessed at the bedside by a Consultant Gastroenterologist and Nurse Endoscopist. In June 2011 a new electronic referral form was introduced. As a result of the improvements from February to May, a “virtual” assessment team including a Senior Dietician, Speech and Language Therapist, Elderly Care and Palliative Care physician was convened. The referral form was sent by secure email to the team and a virtual discussion took place with formal MDT meeting held when deemed prudent by consensus. Bedside assessment could then be restricted an assessment of fitness for the endoscopic procedure. Data were collected prospectively throughout the year and compared to practice in the preceding 12 months. <h3>Methods</h3> Retrospective casenote analysis was conducted using the EPR and Endoscopy databases (Endosoft<sup>®</sup>) to include all PEG insertions performed. Prospective data collection were possible for all cases undergoing formal and virtual assessment. <h3>Results</h3> In 2010, 96 PEG insertions were performed (median 6 per month), compared to 49 within the “formal” and “virtual” team periods (median 2 per month, p&lt;0.005). Patients did not differ significantly by age or gender. 30d mortality was 9/96 (9.4%) in 2010 and 2/49 in 2011 (4.1%; p=0.33). Rates of infection, aspiration pneumonia, buried bumper syndrome and other complications fell significantly (p&lt;0.001). The number of referrals not leading to insertion fell significantly between the formal and virtual assessment periods (p&lt;0.01) with no PEGs inserted in June and July. In addition, the time from referral to insertion increased significantly across these periods (p&lt;0.01). In the later part of 2011 an increase in referrals and appropriate insertions was observed—without a concomitant rise in complications. <h3>Conclusion</h3> Introduction of a “virtual” team for PEG assessment reduced the number of procedures required (freeing time for other endoscopic procedures), and post-insertion complications. There was a non-significant trend for improved 30-day mortality. A “minimal input” approach to PEG assessment based on a detailed referral form is therefore feasible, safe and associated with significantly reduced rates of post-procedure morbidity. <h3>Competing interests</h3> None declared.
Mandatory rural practice proposed in India
Authors: G. Mudur
Journal: BMJ (1995)

India's health advisory body has proposed mandatory rural service for medical graduates and wants a greater role for traditional medicine. The proposals from the Central Council of Health and Family Welfare are intended to boost the delivery of health care across the country.

The council has also spelt out guidelines for setting up new hospitals to be funded jointly by the government and the private sector.

The council wants the rules governing medical education to be changed so that future medical graduates receive only a provisional degree until they have completed a three year rural tenure. The council has also asked the Indian Medical Council to consider making rural …
Alcohol Consumption and the Risk of Breast Cancer in Women&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C La Vecchia, A Decarli, S Franceschi, S Pampallona, G Tognoni
Journal: JNCI Journal of the National Cancer Institute (1985)

The relationship between breast cancer and alcoholic beverage consumption was investigated in a case-control study of 437 women with breast cancer and 437 age-matched controls admitted to the hospital for acute conditions apparently unrelated to alcohol consumption. Compared to the relative risks (RR) for women who had never drunk alcohol, the RR for those reporting 1–3 and more than 3 alcoholic drinks per day were 1.24 and 1.93, respectively. A similar positive trend in risk with increasing daily consumption was evident for wine alone, and the point estimates were above unity for beer and spirits. Allowance for all identified potential confounding factors (including the major risk factors for breast cancer and a few selected dietary items) did not appreciably change any of the alcohol-related estimates. The RR, however, were higher at younger ages and did not rise with increasing duration of use. Nonetheless, the findings of the present study and their similarity with those of another case-control study conducted in northeastern Italy indicate that the association between alcoholic beverage consumption and breast cancer in this population is probably real, though not necessarily causal.
RENTABILIDAD DE LAS BIOPSIAS DUODENALES PARA EL DIAGNÓSTICO DE LA ENFERMEDAD CELIÁCA
Authors: MI Higuera, P García, A Castellano, MG Ganoza, C Golmayo, D De Frutos, A Santos, M Gil, L Espinosa, A Barbero, E Poves
Journal: Endoscopy (2014)

Introducción: La enfermedad celiaca (EC) es una enteropatía de base inmunológica por intolerancia permanente al gluten, en individuos genéticamente predispuestos; con una prevalencia entre 0.33% y 1%.
Abstract 3648: S100A9 play a role in MDSC expansion and migration but not in their activation
Authors: Thomas Condamine, Pingyan Cheng, Je-In Youn, Myrna L. Ortiz, Thomas Vogl, Johannes Roth, Dmitry I. Gabrilovich
Journal: Cancer Research (2011)

Abstract S100A9 is a pro-inflammatory molecule, secreted by myeloid cells, which has been reported to recruit leukocytes to the sites of inflammation or tumors. Up-regulation of S100A9 expression in myeloid progenitor cells was implicated in inhibition of DC differentiation and promotion of expansion of myeloid-derived suppressor cells (MDSC). These cells have been well described as a major component used by the tumor to be protected from the immune system. In order to determine if extracellular and intracellular S100A9 has similar effects on myeloid cell differentiation and function, we evaluated the effect of recombinant S100A9. Our results demonstrated that in contrast to overexpression of S100A9 in hematopoietic progenitor cell (HPC), the treatment of HPC with recombinant S100A9 did not affect their differentiation to mature macrophages, or dendritic cells. The same treatment does not affect the suppressive activity of MDSC purified from naïve or tumor-bearing mice either. However, recombinant S100A9 had strong chemotactic effect on MDSC. Interestingly, its effect on immature myeloid cells isolated from naïve tumor-free mice was substantially lower. Recently, it has been suggested that MDSC need two different signals: one – required for their expansion and inhibited differentiation of mature myeloid cells and the other one – for activation. Our data suggest that S100A9 may mediate first signals but not the second one. Intracellular up-regulation of S100A9 promotes expansion of MDSC and contributes to block of their differentiation, whereas extracellular S100A9 via cell receptors induce MDSC migration. A better understanding of how MDSC migrate into the tumor and how S100A9 is involved in this process could lead to the generation of new treatment aiming to block the migration of MDSC inside the tumor. 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 3648. doi:10.1158/1538-7445.AM2011-3648