tbuckley/cabot-search huggingface dataset:
The US Cancer Moonshot initiative
Authors: C Marjorie Aelion, Collins O Airhihenbuwa, Sonia Alemagno, Robert W Amler, Donna K Arnett, Andrew Balas, Stefano Bertozzi, Craig H Blakely, Eric Boerwinkle, Paul Brandt-Rauf, Pierre M Buekens, G Thomas Chandler, Rowland W Chang, Jane E Clark, Paul D Cleary, James W Curran, Susan J Curry, Ana V Diez Roux, Robert Dittus, Edward F Ellerbeck, Ayman El-Mohandes, Michael P Eriksen, Paul C Erwin, Gregory Evans, John R Finnegan, Linda P Fried, Howard Frumkin, Sandro Galea, David C Goff, Lynn R Goldman, Tomas R Guilarte, Ralph Rivera-Gutiérrez, Paul K Halverson, Gregory A Hand, Cynthia M Harris, Cheryl G Healton, Nils Hennig, Jody Heymann, David Hunter, Wenke Hwang, Resa M Jones, Michael J Klag, Lisa M Klesges, Tim Lahey, Edward F Lawlor, Jay Maddock, William J Martin, Anthony J Mazzaschi, Max Michael, Shan D Mohammed, Philip C Nasca, David Nash, Oladele A Ogunseitan, Ronald A Perez, Michael Perri, Donna J Petersen, Darleen V Peterson, Martin Philbert, Jennifer Pinto-Martin, James M Raczynski, Gary E Raskob, Barbara K Rimer, Louise Ann Rohrbach, Laura L Rudkin, Laura Siminoff, José Szapocznik, Dennis Thombs, Mohammad R. Torabi, Robert M Weiler, Terrie Fox Wetle, Phillip L Williams, Randy Wykoff, Jun Ying
Journal: The Lancet Oncology (2016)
Use of Bisphosphonates in Hypercalcemia Associated With Childhood Cancer
Authors: M. Tezer Kutluk
Journal: Journal of Clinical Oncology (1999)

Article Tools Correspondence Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.6.1960 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561239 Use of Bisphosphonates in Hypercalcemia Associated With Childhood Cancer M. Tezer KutlukxM. Tezer KutlukSearch for articles by this author Show More Hacettepe University Oncology Hospital, Ankara, Turkey https://doi.org/10.1200/JCO.1999.17.6.1960 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Abstract POSTER-BIOL-1328: Endothelin-1/endothelin a receptor-mediated biased signaling is a new player in modulating human ovarian cancer cell tumorigenesis
Authors: Jian-peng Teoh, Kyoung-mi Park, Yongchao Wang, Qiuping Hu, Sangmi Kim, Guangyu Wu, Shuang Huang, Nita Maihle, Il-man Kim
Journal: Clinical Cancer Research (2015)

Abstract The endothelin-1 (ET-1)/endothelin A receptor (ETAR, a G protein-coupled receptor) axis confers pleiotropic effects on both tumor cells and the tumor microenvironment, modulating chemo-resistance and other tumor-associated processes by activating Gαq- and β-arrestin-mediated pathways. While the precise mechanisms by which these effects occur remain to be elucidated, interference with ETAR signaling has emerged as a promising antitumor strategy in many cancers including ovarian cancer (OC). However, current clinical approaches using ETAR antagonists in the absence of a detailed knowledge of downstream signaling have resulted in multiple adverse side effects and limited therapeutic efficacy. To maximize the safety and efficacy of ETAR-targeted OC therapy, we investigated the role of other G protein subunits such as Gαs in the ETAR-mediated ovarian oncogenic signaling. In HEY (human metastatic OC) cells where the ET-1/ETAR axis is well-characterized, Gαs signaling inhibits ETAR-mediated OC cell migration, wound healing, proliferation and colony formation on soft agar while inducing OC cell apoptosis. Mechanistically, ET-1/ETAR is coupled to Gαs/cAMP signaling in the same ovarian carcinoma-derived cell line. Gαs/cAMP/PKA activation inhibits ETAR-mediated β-arrestin activation of angiogenic/metastatic Calcrl and Icam2 expression. Consistent with our findings, Gαs overexpression is associated with improved survival in OC patients in the analysis of the Cancer Genome Atlas data. In conclusion, our results indicate a novel function for Gαs signaling in ET-1/ETAR-mediated OC oncogenesis and may provide a rationale for a biased signaling mechanism, which selectively activates Gαs-coupled tumor suppressive pathways while blocking Gαq-/β-arrestin-mediated oncogenic pathways, to improve the targeting of the ETAR axis in OC. Citation Format: Jian-peng Teoh, Kyoung-mi Park, Yongchao Wang, Qiuping Hu, Sangmi Kim, Guangyu Wu, Shuang Huang, Nita Maihle, Il-man Kim. Endothelin-1/endothelin a receptor-mediated biased signaling is a new player in modulating human ovarian cancer cell tumorigenesis [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1328.
Safe and Effective Treatment of Graft Versus Host Disease with Platelet Lysate-Expanded Human Mesenchymal Stromal Cells: A Phase 1 Study On 47 Adult and Pediatric Patients
Authors: Martino Introna, Giovanna Lucchini, Erica Dander, Attilio Rovelli, Adriana Balduzzi, Daniela Longoni, Fabio Pavan, Francesca Masciochi, Alessandra Algarotti, Caterina Micò, Anna Grassi, Irene Cavattoni, Sara Deola, Giuseppe Gaipa, Daniela Belotti, Paolo Perseghin, Matteo Parma, Enrico Maria Pogliani, Josée Golay, Elisa Gotti, Chiara Capelli, Sergio Cortelazzo, Giovanna D'Amico, Andrea Biondi, Alessandro Rambaldi, Ettore Biagi
Journal: Blood (2012)
Occurrence of Painless Acute Surgical Disorders in Psychotic Patients
Authors: Walter E. Marchand, Benjamin Sarota, Henry C. Marble, Theodore M. Leary, Charles B. Burbank, Martin J. Bellinger
Journal: New England Journal of Medicine (1959)

THE lack of complaint of pain by psychotic patients when afflicted by painful disorders has been an observation of every physician practicing in a mental institution. Despite this the phenomenon has not been thought of as having clinical significance and worthy of comment in the medical literature. The reason for this has been the lack of information regarding the actual frequency of the phenomenon in relation to various medical or surgical disorders. To supply the necessary data about a medical disorder — namely, acute myocardial infarction — a report,1 which soon thereafter was corroborated by Lieberman,2 was published in 1955. . . .
Nature of Virus-Producing Rous Sarcoma Cells in Hamsters Treated With Antilymphocyte Serum: Immunochemical, Cytogenetical, and Electron Microscopic Observations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Francis de Halleux, Herman van den Berghe, Alain Decleve
Journal: JNCI Journal of the National Cancer Institute (1972)

Bryan-strain chicken Rous sarcoma cells produced tumors in newborn hamsters treated with heterologous antilymphocyte serum (ALS), but not in untreated animals. These tumors contained both chick and hamster antigens and cells. Mitotic figures displayed the chromosome complement of both chick and hamster cells, the latter being more numerous. However, combined histologic and immunofluorescence studies clearly established the chicken origin of tumor cells, whereas hamster cells appeared to be mostly adventitious nontumorous cells. Unlike mammalian cells transformed by Rous sarcoma virus, tumors yielded abundant infectious virus. Ultrastructure of tumor cells was similar to that of chicken sarcoma cells. C-type particles similar to avian oncornaviruses were more abundant in hamster tumors than in the original chicken sarcoma. ALS treatment of newborn hamsters thus provides immunosuppression which permits some proliferation of xenografted tumor cells. The procedure may increase the chances of detecting viruses in such tumors.
Is exhaled nitric oxide a marker of air pollution effect?
Authors: Isabella Annesi-Maesano, Anh Tuan Dinh-Xuan
Journal: European Respiratory Journal (2016)

Exhaled nitric oxide, measured through noninvasive breath testing with a portable device [1], is an established biomarker of airway inflammation [2]. This relies on the fact that NO is a gaseous molecule produced in a type of inflammatory response. Specifically, in humans, NO is produced from l-arginine, an α-amino acid that is used in the biosynthesis of proteins, by three enzymes called NO synthases (NOS), namely inducible NOS (iNOS), endothelial NOS and neuronal NOS [3]. In the state of inflammation, several cells, including eosinophils, use iNOS to produce NO. Due to these properties, exhaled NO has been used as a biomarker for the diagnosis and follow-up of asthma, and as a guide to therapy in asthmatics [4, 5]. It is open to debate whether F eNO is a biomarker of the effects of air pollution <http://ow.ly/ZrSke>
Surgery for ascending aortic aneurysm with aortic regurgitation.
Authors: Soichiro Kitamura, Kenji Ohnishi, Susumu Nakano, Choken Oyama, Kanji Kawachi, Yoshiaki Koh, Yasunaru Kawashima
Journal: Circulation (1982)

We reviewed 22 consecutive patients undergoing surgery during 13 years from 1968 to 1981 for ascending aortic aneurysms associated with aortic regurgitation due primarily to idiopathic medionecrosis resulting in annuloaortic ectasia. Chronic aortic dissection was accompanied in 45% of the patients. The operative period was divided into 2 stages, the first from 1968 to 1976, and the second from 1977 to 1981. In the earlier period, the operative mortality was 42%, and it improved significantly to 0% (P < 0.05) in the later period. The reasons for improved surgical results are 1 ) the employment of the Bentall operation with some technical modifications and 2) the use of better myocardial protection method with cold potassium cardioplegia. The postoperative hemodynamic and clinical improvements were significant. The left ventricular end-diastolic pressure and left ventricular dimension were significantly improved toward normal (p < 0.05 and p < 0.001). Operative survivors showed a clinical improvement from NYHA class 3 to 1.3 on an average. The actuarial survival rate at 6 years after operation was 64.3% in the entire series, and 71.1% in patients with the Bentall operation. In patients with type I aortic dissection, a false lumen remained patent after operation and may progress to cause late morbidity or mortality. Surgery should be performed earlier than aortic dissection takes place whenever feasible. The Bentall operation can now be performed with a low risk, and can improve the clinical and hemodynamic states and very possibly prolong the longevity of the patients.
Abstract 433: Disrupting the Interaction Between CaM Kinase II and Histone Deacetylase 4 - an Epigenetic Therapy for Heart Failure?
Authors: Johannes Backs, Tao He, Lorenz H Lehmann, Andrea Schmidt, Jan Beckendorf, Joe Lewis, Vasileios Askoxylakis, Hugo A Katus
Journal: Circulation Research (2015)

CaM Kinase II (CaMKII) critically drives adverse cardiac remodeling. During the process of remodeling, CaMKII binds and phosphorylates Histone Deacetylase 4 (HDAC4), resulting in activation of the transcription factor MEF2. However, it remained unclear whether binding between CaMKII and HDAC4 causes heart failure and whether this interaction represents a novel therapeutic target. We used mouse genetics, HDAC4-based peptides and chemical biology to address these questions. First, we generated CaMKII-resistant HDAC4 mutant mice (CrH) by replacing Arg-598 (corresponds to Arg-601 in humans) of HDAC4 with Phe, because we found Arg-598 to be essential for the CaMKII-HDAC4 interaction. CrH were protected from cardiac dysfunction, hypertrophy and fibrosis in response to both pathological pressure overload or ischemia/reperfusion injury. CrH showed reduced CaMKII binding and less MEF2 activation. These data provided a proof-of-principle that the disruption of the CaMKII-HDAC4 interaction may have therapeutic potential. Thus, in a second step we engineered an HDAC4-derived peptide with homology to the CaMKII binding domain of HDAC4. This peptide competed with HDAC4 for binding with CaMKII, resulting in decreased MEF2 activation and attenuated agonist-induced cardiomyocyte hypertrophy. These data encouraged us to carry the translational pipeline one step further and we screened for small molecules that disrupt the CaMKII-HDAC4 interaction in an in vitro ALPHAScreen Assay (medium-throughput format using 78000 compounds). After a stringent validation process, 38 compounds showed &gt; 40% inhibition. Out of these, 13 compounds effectively inhibited MEF2 activity in a cell-based assay without obvious signs for cellular toxicity, providing now potential cell permeable drug-like candidates. Chemical optimization and in vivo validation strategies are currently ongoing. In summary, we show that the CaMKII-HDAC4 interaction contributes to the development of heart failure and we identified drug-like molecules that specifically disrupt this protein-protein interaction. These findings lay the ground for a novel epigenetic therapeutic approach to combat heart failure.
Treating heart disease
Authors: J. Rawles
Journal: BMJ (1995)

high.This approach has presumably been used in at least two articles in which individual rates were analysed with non-parametric rank sum tests, indicating that the assumption of normality was not met.2'Obviously, sample size calculations are possible for this kind of variable, and the sample size needed is clearly smaller than that needed in the first approach.The third method, survival analysis, can cause problems from the clinical point of view.For example, the exact time of occurrence of vertebral fractures is usually unknown.Additionally, the treatment regimens used do not generally affect patients immediately.Thus, fractures during the first months of the study may unnecessarily be regarded as being due to failures of treatment, leading to wrong conclusions and possible loss of relevant data.Recently a lot of statistical research has been conducted to allow for many events in the same patient during follow up and to take different times to the end points into account.These methods include, for example, random effects models for binary or counted data.4To our knowledge, how- ever, these techniques have not yet been included in widely used statistical programs.While waiting for the above models we prefer to choose the second alternative (individual event rate adjusted for follow up time), which fulfils the statistical assumptions, has a clear clinical interpretation, and includes information about all events.
Anatomic segmentectomy for stage I non-small cell lung cancer: Comparison of outcomes with the VATS versus open approach
Authors: M. J. Schuchert, B. L. Pettiford, T. A. d’Amato, S. Keeley, R. Santos, A. Kilic, H. C. Fernando, J. D. Luketich, R. J. Landreneau
Journal: Journal of Clinical Oncology (2007)

7616 Background: Anatomic segmentectomy for early-stage NSCLC has been proposed as a means of achieving a complete resection in high-risk patients with poor lung function, who might not otherwise tolerate conventional lobectomy. Historically, anatomic segmentectomy has been associated with increased recurrence rates and postoperative air leaks. In the current study, we present our experience with VATS versus open segmentectomy for stage I NSCLC. Methods: A total of 181 consecutive anatomic segmentectomies (114 Open, 67 VATS) were performed for Stage IA (n=110) or IB (n=71) NSCLC from 2002–2006. A VATS approach was employed in 67 patients, and an open approach in 114 patients. Outcome variables include hospital course, complications, mortality, recurrence patterns and survival. Results: The mean age was 70 years (range: 45–100). Average tumor size was 2.3 cm (2.0 cm VATS; 2.4 cm open, NS). Lymph node sampling or dissection was performed in 169 (93%) of patients with an average node harvest of 8.2 nodes (Open = 9.2; VATS = 6.2, p=0.006). There were two perioperative deaths (1.1%), both open. Complications occurred in 59 patients (33%). Median length of stay was 6 days (VATS=5, Open=7). Mean follow-up was 15.6 months. There were fewer major (7 vs. 31, p=0.005) and infectious (3 vs. 12%, p=0.026) complications in the VATS group, with no significant difference in pulmonary complications or air leaks. Twenty-nine recurrences (16%; VATS=7, Open=22) occurred at a mean of 12.7 months [11 locoregional (6%), 18 distant (10%)]. Overall mortality, complications, recurrence and two-year actuarial survival (78%) were similar between VATS and open segmentectomy. Conclusions: VATS segmentectomy can be performed safely with acceptable morbidity, mortality, recurrence and survival. The VATS approach affords a shorter length of stay and fewer postoperative complications (major and infectious) compared with open techniques. The potential benefits of segmentectomy will need to be further validated by prospective, randomized trials (ACOSOG Z4032). Sublobar resection techniques represent an important adjunct in treating compromised patients with early stage NSCLC. No significant financial relationships to disclose.
TCTAP A-065 Long-Term Comparison of Percutaneous Coronary Intervention Using Drug-Eluting Stents and Coronary Artery Bypass Grafting for Chronic Total Occlusion Revascularization
Authors: Hee-soon Park, Jae Seok Bae, Seung-Jung Park, Seong-Wook Park, Cheol Whan Lee, Young-Hak Kim, Seung-Whan Lee, Duk-Woo Park, Soo-Jin Kang, Jung-Min Ahn, Pil Hyung Lee, Se Hun Kang, Cheol Hyun Lee, Min Soo Cho, Yu Na Kim, Sung Han Yoon, Do-Yoon Kang, Mineok Chang
Journal: Journal of the American College of Cardiology (2016)
Hand hygiene
Authors: L. Teare, B. Cookson, S. Stone
Journal: BMJ (2001)

It is two years since the hand washing liaison group, a group of professionals interested in reducing the transmission of infection, drew attention in the BMJ to the importance of hand washing in reducing hospital acquired infections.1 The issue has again received prominence in Britain with the recent publication of the “Epic” evidence based guidelines on hand hygiene, commissioned by the Department of Health.2 The challenge now is to ensure implementation of the guidelines in daily practice. In recognition of the fact that washing with soap and water is not the only (or even the most effective) way of reducing the transmission of organisms our group has changed its name to the hand hygiene liaison group and has some practical recommendations on easy ways of improving hygiene.

Publication of the Epic guidelines on preventing hospital acquired infection follows reports 3 4 documenting the seriousness of hospital acquired infection and antimicrobial resistance in the NHS. Hospital acquired infections in the United Kingdom cost around £1bn a year3 and affect nearly 10% of …
Notch and Jak/STAT signaling pathways in breast carcinoma of luminal and basal/triple-negative immunophenotypes.
Authors: E. Adrover, L. Sanchez-Tejada, G. Peiro, D. Giner, E. Lerma, F. I. Aranda, F. J. Gutierrez-Aviño
Journal: Journal of Clinical Oncology (2010)

618 Background: Notch and Jak/STAT pathways have a role in normal cell growth and development, but activation has been reported in several neoplasms. A relationship with positive hormonal receptor (HR) breast carcinomas (BC) has been suggested. We studied the Notch and Jak/STAT pathways in a series of BC of luminal and basal/triple negative (TN) immunophenotypes to determine their involvement. Methods: 170 invasive BC of luminal A (ER and PR ≥ 50% positive nuclei; and p53 < 20% or Ki67 < 20%), luminal B (ER and/or PR <50%, and p53 ≥ 20% or Ki67 ≥ 20%), and basal/TN (ER/PR/HER2-negative ± CK5/6 ± EGFR) immunophenotypes were analyzed. Total RNA was isolated from 2-3 paraffin-embedded cylinders from preselected tumor areas, and retrotranscripted to cDNA. RT-PCR was performed by Syber Green to study the expression of Notch1, 2, 4; Jagged1 (Notch pathway), and STAT3 (Jak/STAT pathway). The primers were tested in triplicate; RT minus controls and two commercial positive controls (total human and BC RNA) were included. The quantification was normalized to β-actin gene (Spearman rank correlation coefficient: r = 0.82; p < 0.05). Relative mRNA expression levels were carried out using the ΔΔCT method. A pool of normal breast tissues was used as calibrator for luminal BC, (similar gene expression levels were found in the adjacent tissue to all luminal BC). Each basal/TN BC was correlated with their corresponding normal breast tissue. The results were analyzed statistically by Chi-square and Fisher's exact test. Results: Similar overexpression in all analyzed genes was found in both luminal subtypes. In contrast, in the basal/TN group Notch1 and Jagged1 were down-regulated (Notch1 p < 0.000, OR: 2.849 -1.492-5.439-; Jagged1 p = 0.024, OR: 1.583 -0.964- 2.600-); and no differences were found for Notch4 and Notch2. Regarding STAT3, overexpression was detected in both phenotypes. Conclusions: The Notch pathway is activated in BC of luminal phenotype but not in the basal/TN group, in which down-regulation predominates, supporting its role in HR-positive BC. Nevertheless, up-regulation of the Jak/STAT pathway is present in all analyzed subtypes. Supported by grant FIS 03/1411and FCVI- HGUA/2006. No significant financial relationships to disclose.
Cost-effectiveness analysis of oncotype DX-guided treatment in early breast cancer
Authors: D. T. Tsoi, M. Inoue, C. M. Kelly, S. Verma, K. Pritchard
Journal: Journal of Clinical Oncology (2009)

e11536 Background: Some early breast cancer patients with hormone receptor positive (HR+) disease may benefit from adjuvant chemotherapy in addition to hormonal therapy. Most guidelines recommend the addition of adjuvant chemotherapy for majority of women, leading to overtreatment causing considerable morbidity and cost. There has been recent incorporation of gene expression analysis to help aid in adjuvant chemotherapy decision making. We evaluated the cost-effectiveness of Oncotype DX-guided treatment as compared to treatment guided by Adjuvant! Online program. Methods: A Markov model was developed to compare the cost- effectiveness of treatment guided by either Oncotype DX or Adjuvant! Online in a cohort of 50-year-old women with HR+, lymph node negative breast cancer over a lifetime horizon. We assumed women assessed to be high risk all received chemotherapy followed by tamoxifen, and that those assessed to be low risk received tamoxifen only. The model took a health care payer's perspective with results reported in 2008 Canadian dollars ($). Event rates, costs and utilities were derived from the literature. Both costs and benefits were discounted at 5%. Sensitivity analysis for key parameters in the model was conducted. Outcome measures were life year gained, quality- adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Results: For a 50-year-old woman, Oncotype DX-guided treatment was associated with an incremental lifetime cost of $4,200 and a gain in 0.067 QALY, with an ICER of $61,800/QALY compared with treatment guided by Adjuvant! ICER was positively correlated to the cost of Oncotype DX and the age of patients. Results were most sensitive to probabilities relating to risk categorization and recurrence rate. Conclusions: Relative to Adjuvant!-guided treatment, Oncotype DX-guided treatment appears cost-effective with an ICER of $61,800/QALY from a Canadian health care perspective. [Table: see text]