tbuckley/cabot-search huggingface dataset:
miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer
Authors: Elvira D'Ippolito, Ilaria Plantamura, Lucia Bongiovanni, Patrizia Casalini, Sara Baroni, Claudia Piovan, Rosaria Orlandi, Ambra V. Gualeni, Annunziata Gloghini, Anna Rossini, Sara Cresta, Anna Tessari, Filippo De Braud, Gianpiero Di Leva, Claudio Tripodo, Marilena V. Iorio
Journal: Cancer Research (2016)

Abstract Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRβ has been identified as a key player of this process and is considered a promising target for breast cancer therapy. Thus, we aimed at investigating the role of miRNAs as a therapeutic approach to inhibit PDGFRβ-mediated vasculogenic properties of TNBC, focusing on miR-9 and miR-200. In MDA-MB-231 and MDA-MB-157 TNBC cell lines, miR-9 and miR-200 promoted and inhibited, respectively, the formation of vascular-like structures in vitro. Induction of endogenous miR-9 expression, upon ligand-dependent stimulation of PDGFRβ signaling, promoted significant vascular sprouting of TNBC cells, in part, by direct repression of STARD13. Conversely, ectopic expression of miR-200 inhibited this sprouting by indirectly reducing the protein levels of PDGFRβ through the direct suppression of ZEB1. Notably, in vivo miR-9 inhibition or miR-200c restoration, through either the generation of MDA-MB-231–stable clones or peritumoral delivery in MDA-MB-231 xenografted mice, strongly decreased the number of vascular lacunae. Finally, IHC and immunofluorescence analyses in TNBC specimens indicated that PDGFRβ expression marked tumor cells engaged in vascular lacunae. In conclusion, our results demonstrate that miR-9 and miR-200 play opposite roles in the regulation of the vasculogenic ability of TNBC, acting as facilitator and suppressor of PDGFRβ, respectively. Moreover, our data support the possibility to therapeutically exploit miR-9 and miR-200 to inhibit the process of vascular lacunae formation in TNBC. Cancer Res; 76(18); 5562–72. ©2016 AACR.
Quantitative Assessment of the Impact of Ex Vivo Manipulation on the In Vivo Functionality of Human T Cells in RAG2−/− γc−/− mice.
Authors: Rozemarijn S. van Rijn, Elles R. Simonetti, Gert Storm, Mark Bonyhadi, Anton Hagenbeek, Anton C.M. Martens, Saskia B. Ebeling
Journal: Blood (2004)
P2-016: Interactive effect of smoking and NQO1 for lung cancer risk
Authors: Jin Hee Kim, Soo-Hun Cho, Yun-Chul Hong, Heon Kim, Kye Young Lee, Kang-Hyeon Choe, Jeong-Seon Ryu, Sang Hoon Jheon, Sook Whan Sung
Journal: Journal of Thoracic Oncology (2007)
P-222 Analysis of tumour contours and radiotherapy planning of “on-trial” patients undergoing chemoradiotherapy (CRT) in SCALOP trial: does pre-trial Radiotherapy Quality Assurance (RTQA) improve the quality of “on-trial” radiotherapy?
Authors: E. Fokas, E. Spezi, N. Patel, C. Hurt, L. Nixon, K. Chu, G. Joseph, J. Staffurth, R. Abrams, S. Mukherjee
Journal: Annals of Oncology (2016)
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy
Authors: Bernard J. Gersh, Barry J. Maron, Robert O. Bonow, Joseph A. Dearani, Michael A. Fifer, Mark S. Link, Srihari S. Naidu, Rick A. Nishimura, Steve R. Ommen, Harry Rakowski, Christine E. Seidman, Jeffrey A. Towbin, James E. Udelson, Clyde W. Yancy
Journal: Journal of the American College of Cardiology (2011)
Dynamic changes of alkaline phosphatase as surrogate for best clinical benefit and overall survival during very early abiraterone therapy compared to PSA-changes in bone metastatic castration resistant prostate cancer.
Authors: Martin Boegemann, Phillip Mikah, Okyaz Eminaga, Edwin Herrmann, Philipp Marius Papavassilis, Reemt Hinkelammert, Axel Semjonow, Andres Jan Schrader, Laura-Maria Krabbe
Journal: Journal of Clinical Oncology (2015)

260 Background: Significant progress in treatment of metastatic castration resistant prostate cancer (mCRPC) has been made. Biomarkers to tailor therapy are scarce. To facilitate decision-making we evaluated dynamic changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) under Abiraterone acetate (AA). ALP-Bouncing can be observed during very early AA-therapy. Methods: Men with bone mCRPC (bmCRPC) on AA 12/2009-01/2014 were analyzed. Dynamic ALP-, LDH- and PSA-changes were analyzed as predictors of best clinical benefit (BCB) and overall survival (OS) with logistic-regression, Cox-regression and Kaplan-Meier-analysis. Results: 39 pre- and 45 post-chemotherapy patients with median follow up of 14.0 months were analyzed. In univariate analysis failure of PSA-reduction ≥50% (PSA-red≥50%) and failure of ALP-Bouncing were the strongest predictors of progressive disease (p=0.003 and 0.021). Rising ALP at 12 weeks (ALP12), no PSA-red≥50% and no ALP-Bouncing were strongest predictors of poor OS, (all p&lt;0.001). Kaplan-Meier-analysis showed worse OS for ALP12, no PSA-red≥50% and no ALP-Bouncing (p&lt;0.001). In subgroup-analysis of oligosymptomatic patients all parameters remained significant predictors of poor OS, no PSA-red≥50% and ALP12 being the strongest (p&lt;0.001). In multivariate analysis PSA-red≥50% remained independent predictor of OS for the whole cohort and for the oligosymptomatic subgroup (p=0.014). No patient with ALP-Bouncing had PD for BCB. Patients with ALP12 had no further benefit of AA. Conclusions: Dynamic changes of ALP, LDH and PSA during AA-therapy are associated with BCB and OS in bmCRPC. ALP-Bouncing occurring earlier than PSA-changes and rising ALP12 under AA may help to decide whether to discontinue AA.
The evaluation of the prognostic factors for locally advanced pancreatic cancer patients: A retrospective study from a single center.
Authors: Ryoji Takada, Tatsuya Ioka, Yutaro Abe, Kenji Hibino, Takeshi Tamura, Nobuyasu Fukutake, Reiko Ashida, Hiroyuki Uehara, Kazuyoshi Ohkawa, Takero Hirata, Yoshifumi Kawaguchi, Koji Konishi, Teruki Teshima, Kazuhiro Katayama
Journal: Journal of Clinical Oncology (2015)

e15225 Background: For the locally advanced pancreatic cancer (LAPC) patients (pts), both chemo-radiation therapy (CRT) and chemotherapy (CT) alone are recommended. It is unknown what pts should be selected to receive the CRT and what timing is better to do the CRT. We evaluated the prognostic factors and the timing of CRT for LAPC pts who received CRT. Methods: This is a retrospective study of LAPC pts who were underwent CRT between Jan. 2001 and Oct. 2013. We collected data regarding age, sex, types of the combination chemotherapy, tumor location, tumor size, Hb, Alb, LDH, WBC, CA19-9 and CEA. We evaluated progression free survival (PFS) and overall survival (OS) for these and timing of CRT. Results: A total of 246 pts were included. The median age was 65 (33-85), males 59%. The median OS in the whole was 516 days. By the univariate analysis, serum CA19-9 levels of less than 1,000 were significant in OS (p = 0.04). The tumor location and sizes were not significant (p = 0.09, 0.33, respectively) and induction CT did not influence on OS (p = 0.37). By the multivariate analysis, pancreatic head cancer were independent poor prognostic factor (p = 0.04). Conclusions: This study is one of the biggest analyses. So these evaluations are important in considering the treatment strategy for LAPC and we need further investigation.
David Oliver: End of life care in hospital is everyone’s business
Authors: David Oliver
Journal: BMJ (2016)

Palliative care: do we need more specialist clinicians, or more generalist staff better trained in it? My answer is both.

About 500 000 people die each year in England and Wales.1 Yet the United Kingdom has only an estimated 519 specialist palliative medicine consultants and fewer than 5000 crucial specialist palliative care nurses.2 1

A national audit of end of life care in hospital by the Royal College of Physicians found a median of one palliative medicine consultant and five nurse specialists for every 1000 adult hospital beds.3

Some of us will die …
In situ forming hydrogels based on chitosan for drug delivery and tissue regeneration
Authors: Li Liu, Qi Gao, Xuemin Lu, Huifang Zhou
Journal: Asian Journal of Pharmaceutical Sciences (2016)

In situ forming hydrogels with simple sol–gel transition are more practicable as injectable hydrogels for drug delivery and tissue regeneration. State-of-the-art in situ gelling systems can easily and efficiently be formed by different mechanisms in situ. Chitosan is a kind of natural polysaccharide that is widely exploited for biomedical applications due to its good biocompatibility, low immunogenicity and specific biological activities. Chitosan-based in situ gelling systems have already gained much attention as smart biomaterials in the development of several biomedical applications, such as for drug delivery systems and regeneration medicine. Herein, we review the typical in situ gelling systems based on chitosan and mechanisms involved in hydrogel forming, and report advances of chitosan-based in situ gels for the applications in drug delivery and tissue regeneration. Finally, development prospects of in situ forming hydrogels based on chitosan are also discussed in brief.
Update on a phase I study of the selective PI3Kδ inhibitor idelalisib (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory CLL.
Authors: Jacqueline Claudia Barrientos, Richard R. Furman, John Leonard, Ian Flinn, Kanti Roop Rai, Sven De Vos, Marshall T. Schreeder, Nina D. Wagner-Johnston, Jeff Porter Sharman, Thomas E. Boyd, Nathan Hale Fowler, Leanne Holes, David Michael Johnson, Daniel Li, Roger D. Dansey, Thomas Michael Jahn, Steven E. Coutre
Journal: Journal of Clinical Oncology (2013)

7017 Background: PI3K-delta signaling is critical for proliferation, survival, homing and tissue retention of malignant B cells. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that has shown considerable monotherapy activity in pts with heavily pretreated CLL. Methods: This phase I study evaluated idelalisib continuously given at 150 mg BID in combination with rituximab (R, 375 mg/m 2 every wk x 8), bendamustine (B, 70 or 90 mg/m 2 x 2, every 4 wks x 6) or BR (every 4 wks x 6) for relapsed/refractory CLL. Pts still on treatment after 48 weeks were eligible to continue idelalisib on an extension study. Clinical response was evaluated according to published criteria (Hallek 2008; Cheson 2012). Results: 52 pts (23F/29M) with a median (range) age of 64 (41-87) years were enrolled. Adverse disease characteristics included bulky lymphadenopathy (62%), refractory disease (50%), multiple prior therapies (median 3, range: 1-14) with 96% receiving prior R and 44% receiving prior B. As of 14 Jan 2013, the median (range) treatment duration was 18 (1-33) months. 31/52 (60%) pts enrolled into the extension study; of those, 24/52 (46%) pts are continuing idelalisib treatment on the extension study. The ORR was 81%, with 1 CR, and a median (range) time to response of 1.9 (1.5-8.3) months. The 2-year PFS and OS were 62% and 85%, respectively. At 2 years follow up, 71% of responses were still enduring. There was no difference in outcomes for pts with &lt;3 prior treatments (n=21) vs ≥3 prior treatments (n=31). The most common TEAEs (any Grade/≥Gr 3, independent of causality) included pyrexia (44%/6%), diarrhea (40%/14%), cough (31%/2%), fatigue (29%/2%), nausea (29%/0%). Pneumonia (any Gr/≥Gr 3) occurred in 15%/12% and rash was seen in 15%/0%. 10% of patients experienced ≥Gr 3 ALT/AST elevation based on laboratory values. Conclusions: A lack of overlapping toxicities allowed idelalisib to be co-administered with R, B, or BR, and all 3 combination regimens were highly active, resulting in durable tumor control in pts with heavily pretreated relapsed/refractory CLL. Phase III trials evaluating the efficacy of idelalisib in combination with R or BR are ongoing. Clinical trial information: NCT01088048.
Abstract 9908: Three-dimensional Optical Coherence Tomographic Analysis of Eccentric Morphology of the Jailed Side-branch Ostium in Coronary Bifurcation Lesions
Authors: Sungsoo Cho, Jung-Sun Kim, Jinyong Ha, Dong-Ho Shin, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, Myeong-Ki Hong
Journal: Circulation (2015)

Introduction: Using the 3D-OCT, morphologic changes in the jailed side- branch ostium were evaluated before and after a single stent crossover at coronary bifurcation lesions. Hypothesis: The severity of angiographic diameter stenosis of the jailed side-branch ostium is usually overestimated over the three-dimensional (3D) optical coherence tomography (OCT)-measured actual stenosis. Methods: In 109 patients who received a single stent crossover at coronary bifurcation lesions, the pre- and post-intervention minimal lumen area (MLA) and the eccentricity of the jailed side-branch ostium were measured with 3D-OCT. The eccentricity index was defined as the ratio of maximal diameter/minimal diameter of the jailed side-branch ostium. When the eccentricity index was &lt;1.5, the shape of the jailed side-branch ostium was defined as circular. The MLA of the jailed side-branch ostium was also calculated from the quantitative coronary angiography (QCA) minimal lumen diameter assuming a circular lumen. Results: The 3D-OCT-measured MLA of the jailed side-branch ostium decreased from 2.91±1.65 mm2 pre-intervention to 2.37±1.48 mm2 post-intervention (p&lt;0.01). The QCA- derived MLA also decreased from 2.35±1.71 mm2 pre-intervention to 1.68±1.56 mm2 post- intervention (p&lt;0.01). However, the 3D-OCT-measured MLA was significantly larger than the QCA-derived MLA (p&lt;0.01). The shape of the jailed side-branch ostium changed from circular to elliptical after the stent implantation (eccentricity index: 1.40±0.33 pre- intervention; 1.71±0.60 post-intervention, p&lt;0.01). Conclusions: Compared to QCA measurements, 3D-OCT analysis could be useful to guide decision for additional intervention or not after stent implantation across coronary bifurcation lesions.
Impact Assessment of Immunogenicity of Romiplostim In Subjects with Immune Thrombocytopenic Purpura (ITP)
Authors: Rupinderjit Pamma, Meghana Deshpande, Martha Hokom, Shalini Gupta, Yao Zhuang, Naren Chirmule, Steve Swanson, Vibha Jawa
Journal: Blood (2010)
Significant numbers of consultant obstetricians and gynaecologists report bullying
Authors: Jacqui Wise
Journal: BMJ (2016)

A substantial proportion of consultants in obstetrics and gynaecology say that they have experienced bullying and undermining behaviour and in many cases the behaviour has persisted for years, according to a survey published in BMJ Open .1

The Royal College of Obstetricians and Gynaecologists (RCOG) carried out an email survey of all obstetric and gynaecology consultants and fellows working in the UK. There was a 28% response rate (664 replies) with 44% saying that they had been persistently bullied or undermined. The 290 that reported themselves as victims of bullying represent 14% of the …
Gemcitabine, Vinorelbine and Dexamethasone (GVDexa) As Second-Line Salvage Regimen in Relapsed and Refractory Hodgkin's Lymphoma
Authors: Anjana Joel, Prasanth Ganesan, Tenali Gnana Sagar, Krishnarathnam Kannan, Trivadi Ganesan, Venkatraman Radhakrishnan, Rejiv Rajendranath, Shirley Sundersingh, Vandana Vikas
Journal: Blood (2015)
Ibrutinib combined with bendamustine and rituximab (BR) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): First results from a randomized, double-blind, placebo-controlled, phase III study.
Authors: Asher Alban Akmal Chanan-Khan, Paula Cramer, Fatih Demirkan, Graeme Fraser, Rodrigo Santucci Silva, Halyna Pylypenko, Sebastian Grosicki, Ann Janssens, Alexander Pristupa, Jiri Mayer, Marie-Sarah Dilhuydy, Javier Loscertales, Nancy L. Bartlett, Abraham Avigdor, Simon Rule, Steven Sun, Michelle Mahler, Mariya Salman, Angela J. Howes, Michael J. Hallek
Journal: Journal of Clinical Oncology (2015)

LBA7005 Background: The phase III HELIOS study evaluated the first-in-class, oral covalent BTK inhibitor ibrutinib in combination with BR (BR+ibr) vs BR plus placebo (BR+plb) in patients (pts) with previously treated CLL/SLL. The preplanned interim analysis reported here showed that the primary end point was met, upon which the IDMC recommended unblinding the study. Methods: Pts received BR ( ≤ 6 cycles) and were randomized 1:1 to ibr (420 mg daily) or plb. Purine analog refractoriness was a stratification factor. Pts with del17p ( &gt; 20% of cells) were excluded. Primary end point was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR) per IRC. Results: 578 pts were randomized (289 per arm); median age 64 yrs; 38% Rai Stage III/IV; median 2 prior therapies. 6 cycles of BR were completed in 83% and 78% of pts in the ibr and plb arms, respectively. At a median follow-up of 17.2 months, IRC-assessed PFS was significantly longer with BR+ibr vs BR+plb (median not reached vs 13.3 months; HR: 0.203, 95% CI: 0.150-0.276, P&lt; 0.0001); PFS results were consistent across high-risk subgroups. ORR and CR/CRi rates were 82.7% vs 67.8% (P&lt; 0.0001) and 10.4% vs 2.8%. Median OS was not reached. 90 pts (31%) in the BR+plb arm with confirmed PD crossed over to receive ibr, as permitted per the protocol. Incidence of most AEs was similar between arms. The most common all-grade AEs with BR+ibr and BR+plb were neutropenia (58.2% vs 54.7%) and nausea (36.9% vs 35.2%); most common grade 3/4 AEs were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15.0% each arm). Rates of grade 3/4 atrial fibrillation were 2.8% and 0.7%, and major hemorrhage were 2.1% and 1.7%. Fatigue (FACIT-Fatigue) was improved with BR+ibr vs BR+plb. Conclusions: The addition of ibr to BR reduced the risk of progression or death by 80% compared with BR+plb. ORR was also significantly improved. Safety of BR+ibr was consistent with the known profiles for BR and ibr. The data further support ibr as an important treatment option for pts with previously treated CLL/SLL. Clinical trial information: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745.
Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma
Authors: Peter Johnson, Massimo Federico, Amy Kirkwood, Alexander Fosså, Leanne Berkahn, Angelo Carella, Francesco d'Amore, Gunilla Enblad, Antonella Franceschetto, Michael Fulham, Stefano Luminari, Michael O'Doherty, Pip Patrick, Thomas Roberts, Gamal Sidra, Lindsey Stevens, Paul Smith, Judith Trotman, Zaid Viney, John Radford, Sally Barrington
Journal: New England Journal of Medicine (2016)

We tested interim positron-emission tomography–computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin’s lymphoma.
Maintenance of Genome Stability
Authors: Jiadong Wang, Tomas Lindahl
Journal: Genomics Proteomics & Bioinformatics (2016)

It was ever thought that genomic information is transmitted faithfully from generation to generation.But our current knowledge does not indicate that it is the case.For example, genomic variations can be generated from DNA replication infidelity and unequal chromosome segregation.Natural decay of DNA molecules is also a fundamental source of changing genomic information.In addition, cellular and organismal exposure to exogenous genotoxic agents such as ultraviolet (UV) light, oxidative stress, chemical mutagens, and radiation can lead to a variety of modifications on DNA constituents, resulting in genome alterations.Fortunately, cells have evolved several response systems to tackle numerous DNA lesions in order to maintain their genome integrity.Among them, checkpoint control is probably the most well-known one.For example, checkpoint responds to replication stress, replication fork stalling, double-strand DNA breaks, and various other types of DNA lesions.Increasing experimental evidence indicates that genomic instability is probably the fundamental reason for carcinogenesis.Genomic instability is also found to be a main etiological factor of neurodegenerative diseases, aging, immunodeficiency, etc.Thus, to understand how cells regulate to maintain their genomic stability is of fundamental importance.
Access, quality, and costs of care at physician owned hospitals in the United States: observational study
Authors: Daniel M Blumenthal, E John Orav, Anupam B Jena, David M Dudzinski, Sidney T Le, Ashish K Jha
Journal: BMJ (2015)

<b>Objective</b> To compare physician owned hospitals (POHs) with non-POHs on metrics around patient populations, quality of care, costs, and payments. <b>Design</b> Observational study. <b>Setting</b> Acute care hospitals in 95 hospital referral regions in the United States, 2010. <b>Participants</b> 2186 US acute care hospitals (219 POHs and 1967 non-POHs). <b>Main outcome measures</b> Proportions of patients using Medicaid and those from ethnic and racial minority groups; hospital performance on patient experience metrics, care processes, risk adjusted 30 day mortality, and readmission rates; costs of care; care payments; and Medicare market share. <b>Results</b> The 219 POHs were more often small (&lt;100 beds), for profit, and in urban areas. 120 of these POHs were general (non-specialty) hospitals. Compared with patients from non-POHs, those from POHs were younger (77.4 <i>v</i> 78.4 years, P&lt;0.001), less likely to be admitted through an emergency department (23.2% <i>v</i>. 29.0%, P&lt;0.001), equally likely to be black (5.1% <i>v</i> 5.5%, P=0.85) or to use Medicaid (14.9% <i>v</i> 15.4%, P=0.75), and had similar numbers of chronic diseases and predicted mortality scores. POHs and non-POHs performed similarly on patient experience scores, processes of care, risk adjusted 30 day mortality, 30 day readmission rates, costs, and payments for acute myocardial infarction, congestive heart failure, and pneumonia. <b>Conclusion</b> Although POHs may treat slightly healthier patients, they do not seem to systematically select more profitable or less disadvantaged patients or to provide lower value care.
Politics and the Medical Profession
Authors: T G Pickering
Journal: JAMA (2017)

For most of this century--particularly in the '40s, '50s and '60s--the emphasis among politicians and social planners has been on the provision of more and better health services. However, in the '70s a dramatic change of emphasis occurred and today most discussion of health care policy seems to relate to cost containment. Inevitably this has led to conflict. Aspects of conflict relating to the provision of health care will be discussed.
Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B- cell non-Hodgkin lymphoma
Authors: B Hertenstein, B Wagner, D Bunjes, C Duncker, A Raghavachar, R Arnold, H Heimpel, H Schrezenmeier
Journal: Blood (1995)