tbuckley/cabot-search huggingface dataset:
Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI)
Authors: Johanna Kurko, Maaria Tringham, Laura Tanner, Kirsti Näntö-Salonen, Mari Vähä-Mäkilä, Heli Nygren, Päivi Pöhö, Niina Lietzen, Ismo Mattila, Anu Olkku, Tuulia Hyötyläinen, Matej Orešič, Olli Simell, Harri Niinikoski, Juha Mykkänen
Journal: Metabolism (2016)
Ten years' experience with LSA2-L2 therapy for childhood advanced lymphoblastic lymphoma.
Authors: J A Katz, E Hvizdala, J Shuster, J M Falletta, M Schwenn, S B Murphy
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.10.2054 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8410135 Ten years' experience with LSA2-L2 therapy for childhood advanced lymphoblastic lymphoma. J A KatzxJ A KatzSearch for articles by this author , E HvizdalaxE HvizdalaSearch for articles by this author , J ShusterxJ ShusterSearch for articles by this author , J M FallettaxJ M FallettaSearch for articles by this author , M SchwennxM SchwennSearch for articles by this author , S B MurphyxS B MurphySearch for articles by this author https://doi.org/10.1200/JCO.1993.11.10.2054 PDF "Ten years' experience with LSA2-L2 therapy for childhood advanced lymphoblastic lymphoma.." Journal of Clinical Oncology, 11(10), pp. 2054–2055© 1993 by American Society of Clinical Oncology
Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis
Authors: Valeriya Malysheva, Marco Antonio Mendoza-Parra, Mohamed-Ashick M. Saleem, Hinrich Gronemeyer
Journal: Genome Medicine (2016)

Alterations in genetic and epigenetic landscapes are known to contribute to the development of different types of cancer. However, the mechanistic links between transcription factors and the epigenome which coordinate the deregulation of gene networks during cell transformation are largely unknown.We used an isogenic model of stepwise tumorigenic transformation of human primary cells to monitor the progressive deregulation of gene networks upon immortalization and oncogene-induced transformation. We applied a systems biology approach by combining transcriptome and epigenome data for each step during transformation and integrated transcription factor-target gene associations in order to reconstruct the gene regulatory networks that are at the basis of the transformation process.We identified 142 transcription factors and 24 chromatin remodelers/modifiers (CRMs) which are preferentially associated with specific co-expression pathways that originate from deregulated gene programming during tumorigenesis. These transcription factors are involved in the regulation of divers processes, including cell differentiation, the immune response, and the establishment/modification of the epigenome. Unexpectedly, the analysis of chromatin state dynamics revealed patterns that distinguish groups of genes which are not only co-regulated but also functionally related. Decortication of transcription factor targets enabled us to define potential key regulators of cell transformation which are engaged in RNA metabolism and chromatin remodeling.We reconstructed gene regulatory networks that reveal the alterations occurring during human cellular tumorigenesis. Using these networks we predicted and validated several transcription factors as key players for the establishment of tumorigenic traits of transformed cells. Our study suggests a direct implication of CRMs in oncogene-induced tumorigenesis and identifies new CRMs involved in this process. This is the first comprehensive view of the gene regulatory network that is altered during the process of stepwise human cellular tumorigenesis in a virtually isogenic system.
Abstract IA09: Nucleosome barriers to transcription
Authors: Steven Henikoff, Christopher M. Weber, Sheila S. Teves, Srinivas Ramachandran
Journal: Cancer Research (2016)

Abstract Nucleosomes are barriers to transcription in vitro, but is this the case in vivo? To address this question, we have introduced a simple and general method to comprehensively map the positions of elongating and arrested RNA polymerase II (RNAPII) at nucleotide resolution. We find that the nucleosomes are barriers to RNAPII elongation at essentially all genes, with the +1 nucleosome downstream of the transcriptional start site the strongest barrier. Depletion of the histone variant H2A.Z from a nucleosome strengthens the barrier to RNAPII, which suggests that H2A.Z has evolved to reduce nucleosome barrier strength. One potential mechanism for overcoming the nucleosome barrier to transcription is the DNA torsional stress created by RNA polymerase transit, which can unwrap and destabilize nucleosomes. We find that inhibiting topoisomerases results in both increased torsion measured at high resolution and increased turnover of nucleosomes, confirming this mechanism in vivo. We have also applied H4S47C-anchored cleavage mapping to identify non-canonical nucleosomes, leading to the characterization of chromatin remodeling intermediates at a subset of +1 nucleosome positions. Citation Format: Steven Henikoff, Christopher M. Weber, Sheila S. Teves, Srinivas Ramachandran. Nucleosome barriers to transcription. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr IA09.
Medicine and books: Our NHS: A celebration of 50 years
Authors: James E Sabin
Journal: BMJ (1998)

Ed Gordon Macpherson 

BMJ Books, £25, pp 227 

ISBN 0 7279 1279 8 

As an interested and largely admiring observer of the NHS, I have been perplexed by two aspects of its history. First, why are there so many audits, commissions, committees, green papers, inquiries, plans, reorganisations, reports, and white papers? Second, why is this national treasure enveloped in what Enoch Powell described in the 1960s as a “continual, deafening chorus of complaint which rises day and night from every part”? Our NHS: A celebration of 50 years, an engrossing collection of 30 highly personal writings, suggests a surprising answer. 

The authors are equally informed, involved, and persuasive, but their messages are entirely inconsistent with each other. For Somerled Fergusson the NHS “ceased to exist” with the creation of the internal market in 1991. In contrast, Brian Edwards finds the shift “from administration to management” highly productive and long overdue. Rudolf Klein reassures us that “the ideals that shaped the NHS in 1948 ... remain the benchmarks for testing any proposals for reform,” but for Melanie Phillips the dream of 1948 “has been lost.” 

For me a powerful single story emerges from the discordant individual narratives. The core principles of the NHS—a healthcare system paid for by collective funds, available to all, guided by need, and largely free of charge—have survived for 50 years. The central importance of general practice has, if anything, grown. Public health and social services may not be optimally integrated with medical care, but they have never been far outside the NHS tent. 

For 50 years, however, the NHS has had to balance the dualities of cost v quality, needs v wants, individual v population, and more. No system can “solve” these tensions. No society can get health care “right.” The best that can be hoped for is an imperfect compromise, inevitably disappointing in varying degrees to all of the stakeholders. 

The United Kingdom and the NHS have handled the essentially impossible situation of healthcare policy as well or better than any other society or system in the 20th century. I believe the key has been the famous British capacity for “muddling through.” The 30 contributors and all those they represent are like members of an extended farming family, constantly complaining about the limitations of the family homestead, blaming each other for mistakes, but endlessly tinkering to improve the arrangements, and ultimately tied to each other in a common enterprise. 

This remarkable ability to allow vigorous expression of conflict, while both containing it and adapting through the innumerable commissions and reports, is the homoeostatic genius of the NHS. If forced to wager, I would bet that it will still be going—multiply reorganised, continually and appropriately complained about at home but respected from abroad—when the next “celebration” is published in 2048.
Abstract B1-27: Optimal combined anticancer therapy that can overcome cell-type specific drug resistance of breast cancer
Authors: Minsoo Choi, Kwang-Hyun Cho
Journal: Cancer Research (2015)

Abstract Breast cancer is a complex disease associated with various genomic alterations that influence the dynamical change of signaling network. The inherent heterogeneous characteristics of breast cancer cells often result in variable anti-cancer drug resistance. Despite the recent progress of targeted cancer therapy, the underlying mechanism of such variable drug resistance still remains unclear and needs to be investigated. To tackle this problem with respect to a breast cancer signaling network, we have reconstructed differential breast cancer singling networks by integrating various genomic data of breast tumors and analyzed their state transition dynamics through perturbation simulations that mimick various anti-cancer drug treatments. We then categorized heterogeneous breast cancer cell types into three groups: sensitive, moderate, or resistant to drugs. For each group, we identified a distinct core-signaling mechanism underlying the drug resistance on the basis of attractor landscape analysis. Finally, we have identified an optimal drug combination that can maximize cell death regardless of heterogeneous breast cancer cell types. Our study shows that the attractor landscape analysis of a breast cancer signaling network can unravel the hidden mechanism underlying individual variation in drug responses and provide a new therapeutic strategy that can overcome variable drug resistance. Acknowledgements: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea Government, the Ministry of Science, ICT &amp; Future Planning (2014R1A2A1A10052404, 2013M3A9A7046303, and 2010-0017662). Citation Format: Minsoo Choi, Kwang-Hyun Cho. Optimal combined anticancer therapy that can overcome cell-type specific drug resistance of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-27.
Synergistic targeting tenascin C and neuropilin-1 for specific penetration of nanoparticles for anti-glioblastoma treatment
Authors: Ting Kang, Qianqian Zhu, Di Jiang, Xingye Feng, Jingxian Feng, Tianze Jiang, Jianhui Yao, Yixian Jing, Qingxiang Song, Xinguo Jiang, Xiaoling Gao, Jun Chen
Journal: Biomaterials (2016)
385 Intrahepatic and peripheric T cell responses in genotype 1B hepatitis C virus infected patients with persistently normal and elevated aminotransferase levels
Authors: F. Akyuz, N. Polat, S. Kaymakoglu, K. Demir, N. Aksoy, S. Badur, Y. ÇCakaloglu, A. Okten
Journal: Journal of Hepatology (2004)
Novel Evidence That Crosstalk Between Three Evolutionarily Ancient Proteolytic Enzyme Cascades (coagulation, fibrinolysis, and complement) Plays An Important Role In Mobilization Of Hematopoietic Stem/Progenitor Cells (HSPCs)
Authors: Sylwia Borkowska, Malwina Suszynska, Katarzyna Mierzejewska, Marta Budkowska, Daria Salata, Barbara Dolegowska, Janina Ratajczak, Magdalena Kucia, Mariusz Z Ratajczak
Journal: Blood (2013)
Abstract P3-03-05: Establishment and evaluation of ER+ breast cancer models using an optimized methodology for exogenous hormone delivery
Authors: MJ Wick, T Vaught, J Meade, L Gamez, M Farley, AW Tolcher, D Rasco, A Patnaik, RL Drengler, A Rosenthal, KP Papadopoulos
Journal: Cancer Research (2016)

Abstract Preclinical in vivo models of estrogen receptor positive (ER+) breast cancer rely on exogenous supplementation of hormones for growth. This requirement leads to animal toxicity and mortality over time, limiting development and drug testing in these types of models. Efficacy of test agents, particularly endocrine therapies, may also be altered in these models due to excessive hormone exposure, highlighting the need to improve methods for the establishment and testing of ER+ breast models. We have developed an alternative method of hormone supplementation in ER+ breast cancer models and optimized this method for testing of endocrine therapies. Using two cell-based breast models, we demonstrated improved breast tumor take and time to tumor volume endpoint while reducing animal toxicity and mortality associated with standard hormone supplementation. Subsequent studies identified the lowest effective dose (LED) of supplement for hormone dependent model growth with a preclinically relevant time to tumor volume endpoint. Activity of endocrine therapies including tamoxifen, letrozole, fulvestrant and exemestane were compared at the standard and LED hormone concentrations. In these studies tamoxifen treatment resulted in tumor regressions which was not appreciably improved using the LED dose of supplement. However letrozole activity was improved in the LED study suggesting hormone supplementation can impact activity of some agents. Using this process we also generated a panel of ER+ patient-derived xenograft (PDX) models, including two novel hormone therapy responsive models from chemo-naïve or hormone therapy pretreated patients, designated ST986 and ST2177, respectively. This improved method of hormone supplementation diminishes the adverse effects of standard hormone supplementation and provides utility for development of anticancer therapies in ER+ breast models. Citation Format: Wick MJ, Vaught T, Meade J, Gamez L, Farley M, Tolcher AW, Rasco D, Patnaik A, Drengler RL, Rosenthal A, Papadopoulos KP. Establishment and evaluation of ER+ breast cancer models using an optimized methodology for exogenous hormone delivery. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-03-05.
Book: Pain: The Science and Culture of Why We Hurt
Authors: Paul Keeley
Journal: BMJ (2004)

A colleague in my specialty once wrote a great aphorism: “The human body is not at all like a machine: it is more like a weather system, inherently unstable and unpredictable.” Pain is one of those parts of human experience where the interaction of body, mind, and—if you believe in such things—spirit or soul do not have clear boundaries. Pain can be a simple somatic experience, but such a pure experience is rare, and the norm is that the experience is somatopsychic. Hence there are insights into pain and its concomitant suffering from outside the clinical and laboratory sciences.​sciences.




Figure 1



Marni Jackson

Bloomsbury, £7.99, pp 384 ISBN 0 7475 6558 9

Rating: ★




Marni Jackson has attempted a bold project: to try to encapsulate both the science and culture of what happens when we experience pain. In a relatively short book, and given that she has put her own experiences at the centre of the work, it is little surprise that she falls some considerable way short of her goal. Another difficulty is that in trying to relate such a broad subject in terms of her own experience she necessarily misses incorporating the broad range of experience outside her own. The result is a rather eclectic mix of subjects. In trying to be illustrative with the examples and objective with the evidence she attempts to square a particularly unsquarable circle. The philosopher Ludwig Wittgenstein had much to say about pain, but the one dictum of his that she might usefully employ would be, “Whereof one cannot speak, thereof one must be silent.” She is given to rather aimless speculation—an occupational hazard, I guess, in a journalist.

The strength of the book is that it does impart the subjective nature of pain—pain is what the patient says it is. The text, however, is vexatious. The author has the irritating habit of referring to the likes of neurophysiologist Ronald Melzack as “Ron” throughout the book, in much the same way that used car salesmen use your first name in an overly familiar way.

Marni Jackson is to be commended for trying to make the experience of pain intelligible to a broad readership in terms that are not mechanistic or reductionist and that incorporate a holistic approach. There is a huge need for a book that looks in a circumspect and balanced way at the cultural, psychological, and scientific aspects of pain management and that frames it in a humane, patient centred way. Unfortunately, this is not that book.
Abstract P1-10-26: Frozen glove could be a new hope for prevention of chemotherapy induced peripheral neuropathy
Authors: T Nakayama, H Yasojima, T Morimoto, K Yoshidome, M Mizutani, T Takashima, N Matsunami, A Enami, M Kagawa, T Nomura, E Shiba, T Nishi, S Kamigaki, Y Kozuma, T Yoshinami, N Masuda
Journal: Cancer Research (2016)

Abstract Introduction Chemotherapy induced peripheral neuropathy (CIPN) is a major problem for patients who receive chemotherapy, and it sometimes deteriorate patients' QOL. Many CIPN prevention trials have been conducted, but no one succeeded to date. Objectives To investigate if frozen glove (FG) prevents peripheral neuropathy induced by nanoparticle albumin-bound paclitaxel (nab-PTX). Methods We conducted CIPN prevention study using FG, as part of multi-institutional phase II study which analyze efficacy and safety of nab-PTX (260mg/m2 q3w) followed by FEC (500/100/500 mg/m2, q3w) in pre-operative setting (KBCSG-TR 1213 trial). Each patient wore an FGs for a total of 60 minutes (15mins before and after nab-PTX treatment) on both hands. CIPN were assessed during treatment period with nab-PTX by the Patient Neurotoxicity Questionnaire (PNQ) and the FACT/GOG (Gynecologic Oncology Group) Neurotoxicity (Ntx) subscale. Patients were asked to access PNQ and FACT/GOG Ntx on a daily basis and recorded in the CIPN diary. Results Sixty two patients were registered for KBCSG-TR 1213 trial. And forty two pts (68%) who turned in the diary were analyzed. Median age and median body mass index (BMI) was 48 years old and 21.6 kg/m2, respectively. We analyzed following 6 categories, 1) symptoms of hands and arms, 2) symptoms of foots, 3) symptoms of general, 4) symptoms of ears 5) muscle weakness of hands and arms and 6) muscle weakness of foots. Median time to each event was 1) 25.5 days, 2) 5days, 3) 3days, 4) not available, 5) 46.5days, 6)4 days. By using FG, time to event of hands and arms was much longer compared with that of foots. Conclusions CIPN could be prevented or lessened by FG. Randomized phase II CIPN prevention study has been just launched. Citation Format: Nakayama T, Yasojima H, Morimoto T, Yoshidome K, Mizutani M, Takashima T, Matsunami N, Enami A, Kagawa M, Nomura T, Shiba E, Nishi T, Kamigaki S, Kozuma Y, Yoshinami T, Masuda N. Frozen glove could be a new hope for prevention of chemotherapy induced peripheral neuropathy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-26.
Access to Medications for Cardiovascular Diseases in Low- and Middle-Income Countries
Authors: Veronika J. Wirtz, Warren A. Kaplan, Gene F. Kwan, Richard O. Laing
Journal: Circulation (2016)

Cardiovascular diseases (CVD) represent the highest burden of disease globally. Medicines are a critical intervention used to prevent and treat CVD. This review describes access to medication for CVD from a health system perspective and strategies that have been used to promote access, including providing medicines at lower cost, improving medication supply, ensuring medicine quality, promoting appropriate use, and managing intellectual property issues. Using key evidence in published and gray literature and systematic reviews, we summarize advances in access to cardiovascular medicines using the 5 health system dimensions of access: availability, affordability, accessibility, acceptability, and quality of medicines. There are multiple barriers to access of CVD medicines, particularly in low- and middle-income countries. Low availability of CVD medicines has been reported in public and private healthcare facilities. When patients lack insurance and pay out of pocket to purchase medicines, medicines can be unaffordable. Accessibility and acceptability are low for medicines used in secondary prevention; increasing use is positively related to country income. Fixed-dose combinations have shown a positive effect on adherence and intermediate outcome measures such as blood pressure and cholesterol. We have a new opportunity to improve access to CVD medicines by using strategies such as efficient procurement of low-cost, quality-assured generic medicines, development of fixed-dose combination medicines, and promotion of adherence through insurance schemes that waive copayment for long-term medications. Monitoring progress at all levels, institutional, regional, national, and international, is vital to identifying gaps in access and implementing adequate policies.
Immunological Studies with Nucleoproteins from Tissue-Culture Cells. I. Nucleoproteins from Human Leukemic Bone-Marrow (MCN) Cells
Authors: John S. Colter, Vittorio Defendi, Roslyn E. Wallace, Harris H. Bird
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article Immunological Studies with Nucleoproteins from Tissue-Culture Cells. I. Nucleoproteins from Human Leukemic Bone-Marrow (MCN) Cells Get access John S. Colter, John S. Colter Search for other works by this author on: Oxford Academic PubMed Google Scholar Vittorio Defendi, Vittorio Defendi Search for other works by this author on: Oxford Academic PubMed Google Scholar Roslyn E. Wallace, Roslyn E. Wallace Search for other works by this author on: Oxford Academic PubMed Google Scholar Harris H. Bird Harris H. Bird Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 6, June 1958, Pages 1141–1155, https://doi.org/10.1093/jnci/20.6.1141 Published: 01 June 1958 Article history Received: 03 December 1957 Published: 01 June 1958