tbuckley/cabot-search huggingface dataset:
Granulocyte Colony-Stimulating Factor: Effective in Ameliorating Fluorouracil Based Myelosuppression?
Authors: K. Christman, L. Saltz, G. Schwartz, C. Friedrich, D. Kelsen
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Granulocyte Colony-Stimulating Factor: Effective in Ameliorating Fluorouracil Based Myelosuppression? Get access Kathy Christman, Kathy Christman Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard Saltz, Leonard Saltz Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, NY Correspondence to : Leonard Saltz, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary Schwartz, Gary Schwartz Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Carl Friedrich, Carl Friedrich Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar David Kelsen David Kelsen Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 10, 19 May 1993, Pages 826–827, https://doi.org/10.1093/jnci/85.10.826 Published: 19 May 1993 Article history Received: 02 March 1992 Accepted: 03 March 1993 Published: 19 May 1993
Christopher Grainger Livingston Raper
Authors: R. Austen
Journal: BMJ (2014)

Christopher Grainger Livingston Raper, who died suddenly in Sunningwell, Oxfordshire, was born in Shaftesbury, where the night before his birth he had been indirectly underneath the stairs of the lodgings where his mother was sheltering from the Luftwaffe during an air raid warning. His father, Alan, was a doctor in the Royal Army Medical Corps at a nearby army hospital, where he tended to, among others, German pilots who had been shot down. That night, a bomb fell and exploded close to, but mercifully not on, the hospital. A year later, Christopher Raper’s father was drafted for overseas duty, and, leaving the Clyde in convoy for Singapore, was fortunately diverted to East Africa on the fall of Singapore to the Japanese. Christopher was not to see his father again for four years.

After the war, in 1947, Alan Raper …
Abstract 1879: The exomes of the NCI60 and their implications for cancer pharmacogenomics
Authors: Ogan D. Abaan, Sean R. Davis, Sven Bilke, Eric C. Polley, Robert L. Walker, Marbin Pineda, Yuelin J. Zhu, William Reinhold, Susan L. Holbeck, Richard M. Simon, James H. Doroshow, Yves Pommier, Paul S. Meltzer
Journal: Cancer Research (2012)

Abstract Acquired and constitutional genetic variations in cancers have a substantial influence on response to therapy. The NCI60 panel of cell lines provides a unique opportunity to investigate this problem. These 60 human tumor cell lines represent 9 cancer types, and are richly characterized as the result of many previous studies which have collected various biochemical and genomics data [1]. In addition, there exists a comprehensive dataset of sensitivity and resistance profiles of over 100,000 compounds with potential antineoplastic activity. However, characterization of coding region DNA sequence variants has been lacking. In this study, we sequenced the whole exomes of the NCI60 cell lines and identified single nucleotide variants and short insertions/deletions. Variants found by sequencing were in excellent agreement with variants previously identified by SNP analysis or targeted capillary sequencing. Even though most cell lines displayed similar mutation counts, cell lines with microsatellite instability displayed a hypermutator phenotype. In addition, observation from ti/tv ratio and nature of base changes revealed preservation of possible carcinogen specific DNA mutation signatures. Deleterious variants were identified at higher frequency in known cancer genes while TP53 mutations where the most frequent event among the NCI60. Finally, notable instances of correlation between gene/pathway mutations with sensitivity to certain drug/compounds was identified. For example, sensitivity to vemurafenib was highly correlated with BRAF mutation. This comprehensive dataset enhances the value of cell lines widely used as disease models in many laboratories by adding depth to the existing genomic data. Our analysis identifies a large number of genomic variants correlated with drug responsiveness, including a number of genes known to be targeted by specific agents as well as numerous candidates for future investigation. 1. Shankavaram, U.T., et al., CellMiner: a relational database and query tool for the NCI-60 cancer cell lines. BMC Genomics, 2009. 10: p. 277. 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 1879. doi:1538-7445.AM2012-1879
Preventive Medicine in Obstetrics
Authors: Dugald Baird
Journal: New England Journal of Medicine (1952)

JOHN CLARENCE CUTTER, as has previously been mentioned, was born in 1851 and graduated at Harvard Medical School in 1877, after which he went to Japan as professor of physiology and comparative anatomy in the College of Agriculture in Saffara. Possibly the experience gained in the nine years he held this post strengthened his great belief in the part that preventive medicine might play in influencing the destiny of man. In his will he allocated half of the net income of his estate to the founding of an annual course of lectures on preventive medicine. I am proud to be, . . .
Warfarin in Heart Failure
Authors: John W. Eikelboom, Stuart J. Connolly
Journal: New England Journal of Medicine (2012)

Despite major advances in the management of heart failure with angiotensin-converting–enzyme inhibitors, beta-blockers, and resynchronization therapy, there are more than 1 million hospitalizations for heart failure in the United States each year, and mortality remains high.1 As compared with the general population, patients with heart failure have an increased risk of stroke and of systemic thromboembolic events, which are believed to arise from within the heart as a result of left ventricular stasis, endocardial dysfunction, and a systemic hypercoagulable state.2 Heart failure is a risk factor for atrial fibrillation, which, even if asymptomatic, further increases the risk of stroke.3 Consequently, . . .
Abstract 2160: Regulation of DHX33 during oncogenic stress and its crucial role in Ras-initiated tumor formation
Authors: Yandong Zhang, Jason D. Weber
Journal: Cancer Research (2012)

Abstract Previously we found that DHX33 is pivotal for RNA polymerase I transcription, changes in DHX33 levels have a dramatic impact on RNA polymerase I activity. In this report, we explore the regulation of DHX33 protein levels by ARF/p53 pathway and Ras signaling. In wild type primary fibroblasts, Ras V12 infection induced a transient increase in DHX33 protein level as well as rRNA transcriptional rate which was eventually overcome by suppression from ARF/p53 pathway. ARF/p53 dependent reduction of DHX33 occurred at the translational level, while Ras activation induced DHX33 levels both at the level of transcription and translation. The induction of DHX33 by Ras activation is sensitive to inhibitors of PI3K, mTOR as well as MAPK. Induction of DHX33 by Ras V12 is pivotal for enhanced rDNA transcription, enhanced protein translation, and thus, the oncogenecity of Ras V12, as DHX33 knockdown abolished the increase in rRNA transcription and protein translation, and completely inhibited the tumorigenecity of Ras V12 both in semisolid agar and xenografts. Our results implicate that DHX33 level could be an important factor to adjust rDNA transcriptional rate in response to ARF induction and Ras activation. Most importantly, we identified DHX33 as a novel downstream target of Ras signaling to regulate rRNA transcription and pointed toward its pivotal role in Ras-initiated tumor formation and therapeutic value to treat Ras mutated cancer patients. 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 2160. doi:1538-7445.AM2012-2160
SAT0487 Ultrasound Image and Synovial Pathology of the Joints in the Patients with Rheumatoid Arthritis. Comparison between the Large Joints and the Small Joints.
Authors: A. Abe, H. Ishikawa, A. Murasawa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the treatment of rheumatoid arthritis (RA), early diagnosis and tight control increased their importance in the era of biological therapy. Ultrasonography (US) of the various joints enables an evaluation of synovits and bone erosion in real time. It is proved to be useful to detect synovitis in the early stage of the disease. <h3>Objectives</h3> The objectives of this study were to investigate whether the image of ultrasonography (US) at the operated joint reflects synovial pathology or clinical indicators, and to compare the results in the large joints (LJs) with those in the small joints (SJs). <h3>Methods</h3> Orthopaedic surgery was performed on 170 joints in 149 patients with RA. There were 48 LJs including 2 shoulders, 24 elbows and 22 knees, and 122 SJs including 59 wrists, 39 fingers, 7 ankles and 17 toes. Preoperatively, US was performed and grade of Power Doppler (PD) signal was evaluated. PD signal consists 4 grades from grade 0 to 3. Grade 0 is no signal, grade 1 is just dot signal, grade 2 is the signal agglutinated but the signal positive area is below a half of whole hypertrophic synovium, grade 3 is the signal agglutinated but the signal positive area is over a half of whole hypertrophic synovium. Rooney score of synovial pathology, Larsen grade at the operated joint, disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (4), matrix metalloproteinase (MMP)-3, C-reactive protein (CRP) were investigated. At the operation, synovial tissue was collected from the part, in which PD signal was highest. Rooney score represents the histological features in the synovium of RA. It includes 6 features i.e. synoviocytes hyperplasia, fibrosis, proliferating blood vessels, perivascular infiltrates of lymphocytes, focal aggregates of lymphocytes, diffuse infiltrates of lymphocytes. Each item was scored on a scale of 1 to10 depending on its severity. <h3>Results</h3> In LJs, 33 joints were in grade 0 or 1 in PD signal (group L), and 15 were in grade 2 or 3 (group H). In SJs, 69 joints were in group L and 53 were in group H. Totally, DAS28-ESR(4), CRP, MMP-3 and Rooney score in group H were significantly higher than those in group L. In comparison between group L and group H, difference in DAS28-ESR(4), MMP-3 and CRP in LJs was more than that in SJs. Whereas, difference in Rooney score in LJs was less than that in SJs. <h3>Conclusions</h3> PD signal in the image of US reflects synovial pathology and clinical indicators. It reflects systemic inflammation well in LJs and regional distinctive feature of synovitis in SJs., <h3>References</h3> Walther M, Harms H, Krenn V, et al. Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis. Arthrits Rheum 2001;44:331-8. <h3>Disclosure of Interest</h3> None Declared
FRI0221 Tocilizumab increases regulatory t cells and nk cells cytotoxicity in rheumatoid arthritis patients
Authors: C. I. Daien, S. Gailhac, T. Mura, B. Combe, M. Hahne, J. Morel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Inhibition of IL-6 receptor with tocilizumab (TCZ) is an effective strategy for treating rheumatoid arthritis (RA) patients. However, the effect of TCZ on lymphocytes remains poorly studied. Regulatory T cells (Tregs) and NK cytotoxicity are known to be impaired in RA. <h3>Objectives</h3> The objective of the present study was to analyze the effect of TCZ on B, T, NK and NKT cells and to find predictive factors of response. <h3>Methods</h3> To be included, patients should meet ACR/EULAR criteria, require the introduction of TCZ, have corticosteroid doses below 10 mg per day, stable for more than a week and should not have received rituximab in the previous year. Extra-cellular staining with antibodies directed against CD19, CD24, CD27, CD38, IgD, CD3, CD4, CD8, CD25, CD127, CD56, CD16, g9d2 and intra-cellular staining of Granzyme B and Perforine A were performed after ficoll at baseline, 3 and 6 months. IL-10 was measured in sera by ELISA. <h3>Results</h3> Twenty-three patients requiring a treatment with TCZ as well as 31 healthy controls were included. Patients with RA had significantly lower percentage of Tregs as defined by CD4+CD25HiCD127lo (3.8 [2.7-4.9] vs 4.8 [3.5-6.0]% of CD4+ lymphocytes; respectively, p=0.007). After 3 months of TCZ, Tregs significantly increased (+1.27±1.00% of CD4+ cells; p&lt;0.001), meeting normal values. Tregs and IL-10 were correlated at baseline (r=0.52; p=0.01) and variations of Tregs were correlated with variations of IL-10 after 3 months of TCZ (r=0.69; p&lt;0.01). No change in percentage of B, NK and NKT cells subsets was observed. Patients in EULAR remission at 3 months had higher percentage of CD3-CD56+ NK cells at baseline (10.4±7.1 vs 3.6±3.1% of lymphocytes; p=0.01), especially CD56BriCD16- NK cells (0.88±0.68 vs 0.28±0.28% of CD3- cells; p=0.04) than patients with a DAS28 at 3 months above 2.6. NK cells were more frequently positive for perforine A and tended to be more frequently positive for granzyme B after TCZ treatment (+6.8 ±2.9% of CD3-CD56+ cells; p=0.02 and +7.1 ±3.8% of CD3-CD56+ cells; p=0.06, respectively). <h3>Conclusions</h3> TCZ increased the number of phenotypic Tregs. Significant correlation between variation of IL-10 and variations of Tregs suggest than these Tregs are probably functional, at least in terms of IL-10 production. TCZ also seem to restore NK cells cytotoxicity, known to be impaired in RA. Values of NK cells at baseline could help to predict remission after 3 months of treatment. <h3>Acknowledgements</h3> To the French Society of Rheumatology and Roche-Chugaï (France) for their financial support <b>Disclosure of Interest</b>: None Declared
Abstract 2152: p38α MAPK regulates signal transduction between estrogen receptor (ER) and its antagonist by switching ER signaling from the classical to the non-classical pathway
Authors: Guan Chen, Huiying Zhi, Songwang Hou, Phillip Wang, Jian Huang, Zainab Basir, Christopher R. Chitambar, Xiaomei Qi
Journal: Cancer Research (2012)

Abstract Estrogen receptor ≤ (ER) plays a decisive role in breast cancer growth through regulating gene expression via the classical {ERE (estrogen-response element) binding} and the non-classical (AP-1 recruitment by interacting with c-Jun) pathways and serves as the only target for hormone therapy. However, anti-estrogen acts on several cascades beside ER and the implications of these “off-target” effects on hormone sensitivity remain unexplored. Here we report that p38α MAPK is selectively activated by treatment of breast cancer cells with the antiestrogen tamoxifen (TAM) and activated p38α in turn switches ER signaling from the classical to the non-classical pathway leading to increased hormone sensitivity. This occurs primarily through p38α phosphorylating ER/S118 leading to its S118-dependent proteasome-degradation through the E3 ligase E6AP resulting in decreased ERE activity. Unexpectedly, Ser-118 is also required for ER to form a complex with p38α, for p38α to stimulate AP-1, to inhibit ERE, and to sensitize breast cancer cells to TAM-induced growth inhibition and ER/S118 phosphorylation alone is both necessary and sufficient for ER binding to the AP-1 DNA. These results indicate that Ser-118 phosphorylation serves as a central switch for p38α to regulate the ER signaling distribution, which may be targeted to increase breast cancer hormone sensitivity. 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 2152. doi:1538-7445.AM2012-2152
TROPOELASTIN-BOUND PLASMA-ACTIVATED STENTS STRIKINGLY REDUCE THROMBOGENICITY WHILE SIMULTANEOUSLY INHIBITING NEOINTIMAL HYPERPLASIA
Authors: Steven Wise, Miguel Santos, Praveesuda Michael, Anna Waterhouse, Juichien Hung, Anthony Weiss, Marcela Bilek, Martin Ng
Journal: Journal of the American College of Cardiology (2016)
Augmentation of Sodium and Potassium Excretion, Glomerular Filtration Rate and Renal Plasma Flow by Levodopa
Authors: G. Duncan Finlay, Thomas L. Whitsett, Elynore A. Cucinell, Leon I. Goldberg
Journal: New England Journal of Medicine (1971)

Abstract After oral administration of levodopa in single doses of 1 to 2 g, glomerular filtration rate, renal plasma flow and sodium and potassium excretion significantly increased (p less than 0.05) in seven patients with Parkinson's disease. Similar effects were observed in patients initially treated with levodopa and in those receiving the drug for more than three months. Increased sodium and potassium excretion also occurred after administration of levodopa in three patients with congestive heart failure and in one with essential hypertension. The natriuretic effect of levodopa persisted for more than 150 minutes. These results suggest that the natriuretic effects of levodopa might be of value in the treatment of congestive heart failure. Natriuresis could also contribute to the orthostatic hypotension that commonly occurs in the levodopa-treated patient.
Abstract 3702: 2-Hydroxyflavanone inhibits renal cancer growth by inhibiting tumor cell proliferation and angiogenesis
Authors: Lokesh Dalasanur Nagaprashantha, Rit Vatsyayan, Jyotsana Singhal, Poorna Lelsani, Yogesh Awasthi, Sanjay Awasthi, Sharad S. Singhal
Journal: Cancer Research (2011)

Abstract Renal cell carcinoma (RCC) is one of the top ten cancers prevalent in USA. Loss-of-function mutation in the VHL is an established risk factor for RCC contributing to 75% of total reported cases of RCC. Loss of VHL leads to highly vascularized phenotype of renal tumors. Intake of oranges has been proven to reduce the risk of RCC in multi-center international clinical trials. Hence, we studied effects of 2HF, an active anti-cancer compound of oranges, in VHL- mutant RCC. Our in vitro investigations revealed that 2HF selectively inhibits VHL-mutant RCC by inhibiting EGFR signaling which is increased due to VHL mutations in RCC. Our results also revealed for the first time, that 2HF inhibits GSTπ activity. 2HF inhibited cyclin B1 and CDK4, and induced G2/M phase arrest in VHL-mutant RCC. Importantly, 2HF inhibited the angiogenesis in VHL-mutant RCC by decreasing VEGF expression. Our in vivo studies in mice xenografts confirmed our in vitro results as evident by decreased levels of proliferation marker, Ki67 and angiogenic marker CD31, in 2HF treated (0.01%, w/w) mice xenografts of VHL-mutant RCC. 2HF also increased the expression of E-cadherin in VHL-mutant RCC which would be of significance in restoring the normal epithelial phenotype. Collectively, our in vitro and in vivo results revealed the potent anti-proliferative and anti-angiogenic effects of 2HF in VHL-mutant RCC, sparing normal cells, which could have significant implications not only in the specific management of VHL-mutant RCC but also in treating other VHL syndromes with highly vascularized phenotype. (Supported in part by NIH grant CA 77495 (SA), CA 155350, Cancer Research Foundation of North Texas, and Institute for Cancer Research &amp; the Joe &amp; Jessie Crump Fund for Medical Education (SSS)) 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 3702. doi:10.1158/1538-7445.AM2011-3702
Phylogenetic reorganization of the basal ganglia: A necessary, but not the only, bridge over a primate Rubicon of acoustic communication
Authors: Hermann Ackermann, Steffen R. Hage, Wolfram Ziegler
Journal: Behavioral and Brain Sciences (2014)

Abstract In this response to commentaries, we revisit the two main arguments of our target article. Based on data drawn from a variety of research areas – vocal behavior in nonhuman primates, speech physiology and pathology, neurobiology of basal ganglia functions, motor skill learning, paleoanthropological concepts – the target article, first, suggests a two-stage model of the evolution of the crucial motor prerequisites of spoken language within the hominin lineage: (1) monosynaptic refinement of the projections of motor cortex to brainstem nuclei steering laryngeal muscles, and (2) subsequent “vocal-laryngeal elaboration” of cortico-basal ganglia circuits, driven by human-specific FOXP2 mutations. Second, as concerns the ontogenetic development of verbal communication, age-dependent interactions between the basal ganglia and their cortical targets are assumed to contribute to the time course of the acquisition of articulate speech. Whereas such a phylogenetic reorganization of cortico-striatal circuits must be considered a necessary prerequisite for ontogenetic speech acquisition, the 30 commentaries – addressing the whole range of data sources referred to – point at several further aspects of acoustic communication which have to be added to or integrated with the presented model. For example, the relationships between vocal tract movement sequencing – the focus of the target article – and rhythmical structures of movement organization, the connections between speech motor control and the central-auditory and central-visual systems, the impact of social factors upon the development of vocal behavior (in nonhuman primates and in our species), and the interactions of ontogenetic speech acquisition – based upon FOXP2 -driven structural changes at the level of the basal ganglia – with preceding subvocal stages of acoustic communication as well as higher-order (cognitive) dimensions of phonological development. Most importantly, thus, several promising future research directions unfold from these contributions – accessible to clinical studies and functional imaging in our species as well as experimental investigations in nonhuman primates.