tbuckley/cabot-search huggingface dataset:
The potent histone deacetylase inhibitor vorinostat, in combination with melphalan, markedly enhances the anti-myeloma effects of chemotherapy in vitro and in vivo
Authors: Richard Campbell, Eric Sanchez, Jeffrey Steinberg, Michael Share, Mingjie Li, Haiming Chen, Benjamin Bonavida, James Berenson
Journal: Cancer Research (2008)

733  Histone deacetylase (HDAC) inhibitors represent a new targeted class of anti-cancer therapeutics and have been shown to exert anti-proliferative and apoptotic effects on cancer cells (including drug resistance subtypes), inhibit angiogenesis and sensitize cancer cells when combined with other anti-cancer therapies. Vorinostat (suberoylanilide hydroxamic acid) is a novel investigational small molecule drug that selectively inhibits HDAC enzymes resulting in acetylation of nucleosomal histones and activates gene transcription. In this study, we first evaluated the in vitro anti-myeloma effects of vorinostat alone and in combination with melphalan using the multiple myeloma (MM) cell lines RPMI8226, U266 and MM1S. Cells treated with the combination of vorinostat + melphalan showed marked synergistic anti-MM proliferative effects as determined by MTS assay. Next, we evaluated the anti-MM effects of vorinostat alone and in combination with melphalan in vivo using LAGκ-1B, one of our SCID-hu models of human MM. Each immunodeficient (SCID) mouse was implanted with a fragment (20 - 40 mm3) of the LAGκ-1B tumor into the left hind limb muscle. The tumors were allowed to grow for 14 days at which time human IgG levels were detectable in the mouse serum, and mice were blindly assigned into one of four treatment groups. Tumor-bearing mice were treated in groups consisting of vehicle only, vorinostat alone (100 mg/kg), melphalan alone (1 or 3 mg/kg), or vorinostat (100 mg/kg) + melphalan (1 and 3 mg/kg). Vorinostat was injected once daily for five consecutive days weekly (M-F) via intraperitoneal injection.Melphalan was injected once weekly (W) via intraperitoneal injection. Mice treated with vorinostat (100 mg/kg) and low-dose melphalan (1 mg/kg) combination therapy showed slight inhibition of tumor growth compared to mice receiving vehicle (P = 2 x10-5) or single agent vorinostat (P = 0.014) and single agent melphalan (P = 0.0016). In contrast, mice treated with the combination of vorinostat (100 mg/kg) and a higher dose of melphalan (3 mg/kg) showed markedly smaller tumors and decreased hIgG levels compared to treatment with vehicle alone (tumor volume P = 4 x10-5; hIgG P = 2 x10-5), vorinostat (tumor volume P = 0.02; hIgG P = 0.04) and melphalan alone (tumor volume P = 0.0091; hIgG P = 0.0035). Combination treatment with vorinostat and melphalan at these doses was not associated with any observed toxicity. These findings support the further clinical development of the combination of vorinostat + melphalan for MM patients and suggest that combining this HDAC inhibitor with low-dose chemotherapy may enhance the efficacy of both vorinostat and melphalan in relapsed/refractory myeloma.
A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Authors: D.P. Hurkmans, E.A. Basak, T. van Dijk, D. Mercieca, M.W.J. Schreurs, A.J.M. Wijkhuijs, S. Bins, E. Oomen-de Hoop, R. Debets, M. Joerger, A. Odink, A.A.M. Van der Veldt, C.H. Van Der Leest, J.G. Aerts, R.H.J. Mathijssen, S.L. Koolen
Journal: Annals of Oncology (2019)
Abstract P238: Sociodemographic Factors Associated With Under- and Overweight Among Women of Reproductive Age in Sub-Sahara Africa
Authors: Jason Were, Irena Creed, Saverio Stranges
Journal: Circulation (2019)

Introduction: In the last three decades, many countries in SSA have undergone rapid epidemiological and nutritional transitions, with an ever-increasing prevalence of cardio-metabolic conditions. Because of these changes, health care systems in the sub-region are faced with the simultaneous challenge of handling both underweight and overweight related sequelae. There is still limited epidemiological evidence on the drivers of this phenomenon within and across countries in SSA. Hypotheses: We assessed the following hypotheses: 1) SSA countries vary in terms of the type and extent of malnutrition; 2) Macro (country level) and micro (individual level) sociodemographic factors are associated with the double burden of malnutrition (i.e. under- and overweight) in SSA. Methods: Macro- and micro-level data for 34 SSA countries were acquired from the World Bank data base and Demographic and Health (DHS) surveys respectively. A total of 247,691 eligible participants (women between the age of 15 and 49) from the DHS surveys were analyzed. We first determined malnutrition categories in SSA from country level prevalence estimates of underweight and overweight using statistically defined logic expressions. Second, we used random forest analysis to investigate the association between the malnutrition groups and macro-level variables. Third, we used random forest analysis and multivariable multinomial logistic regression models to investigate the association between micro level variables and the three BMI categories i.e. underweight (BMI &lt;18.5), normal weight (BMI 18.5 to 24.9) and overweight (BMI≥25). Results: Out of the 34 countries studied, the prevalence of underweight was greater than 10% in 3 countries, whereas 13 countries had both underweight and overweight prevalence exceeding 10%. Overweight (BMI 25 to 29.9) prevalence exceeded 10% in 7 countries, while the obese (BMI≥30) prevalence was at least 10% in 11 countries. Macro level random forest analysis showed that fertility rate and gross domestic product (GDP) were key correlates of the malnutrition groups found in SSA. However, age, wealth and parity were key correlates of women’s nutritional status at the micro level. Old age and wealth were consistently associated with overweight across all the countries. However, parity was a risk factor for underweight in underweight countries, and a risk factor for overweight in overweight countries. Conclusion: In conclusion, we observed consistent cross-sectional associations between measures of fertility, wealth and age and the dual forms of malnutrition (under- and overweight) among women in SSA.
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome: Effect of Transplant Conditioning Regimen Intensity on Outcomes
Authors: Mary Eapen, Ruta Brazauskas, Michael T. Hemmer, Waleska S Pérez, Patricia Steinart, Mary M. Horowitz, H. Joachim Deeg
Journal: Blood (2017)
Randomised evaluation of active control of temperature versus ordinary temperature management (REACTOR) trial
Authors: Paul J. Young, Michael J. Bailey, Frances Bass, Richard W. Beasley, Ross C. Freebairn, Naomi E. Hammond, Frank M. P. van Haren, Meg L. Harward, Seton J. Henderson, Diane M. Mackle, Colin J. McArthur, Shay P. McGuinness, John A. Myburgh, Manoj K. Saxena, Anne M. Turner, Steve A. R. Webb, Rinaldo Bellomo
Journal: Intensive Care Medicine (2019)
Combined immunoscore for prognostic stratification of early stage NSCLC patients
Authors: G. Pasello, A. Boscolo, F. Fortarezza, F. Lunardi, L. Urso, S. Frega, G. Comacchio, L. Bonanno, V. Guarneri, F. Rea, F. Calabrese, P.F. Conte
Journal: Annals of Oncology (2019)
Lymphomas in Rheumatoid Arthritis Patients Treated with Anti-TNF Therapy: A Report from the Swedish Biologics Register (ARTIS) and the ARTIS Study Group 1998–2006
Authors: Eva Baecklund, Carin Backlin, Johan Askling, Gunilla Enblad, Christer Sundstrom, Richard Rosenquist, Nils Feltelius
Journal: Blood (2008)
Home Office makes U turn over threat to remove GP trainee after public pressure
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The Home Office is reconsidering the case of a GP trainee who has lived and studied in the UK for the past 13 years, who was told that she must leave the UK after her visa application was rejected because of a minor issue with her bank account.

Mu-Chun Chiang, who lives in Liverpool, received a letter from the Home Office on 25 September saying that she had to leave the UK or face being “detained and removed.” However, the Home Office has now told The BMJ that it is “reconsidering” her application after public pressure.

The U turn comes after a petition was set up by a fellow trainee to try to stop Chiang being forced to leave. It has so far received over 39 000 signatures.1 …
Advanced clear-cell renal cell carcinoma (accRCC): Association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome
Authors: A.T.L. Verbiest, V. Van Hoef, D. Lambrechts, C. Rodriguez Antona, O. Grana-Castro, L. Inglada-Perez, M. Albersen, M. Baldewijns, A. Laenen, P. Schoeffski, A. Wozniak, G. Couchy, S. Caruso, J. Zucman-Rossi, B. Beuselinck
Journal: Annals of Oncology (2019)
Basal NK activity and early Treg function inhibition predicts Nivolumab responsiveness in metastatic renal cancer patients (REVOLUTION) trial
Authors: S. Santagata, A.M. Trotta, G. Rea, M. Napolitano, C. D’Alterio, M Di Napoli, S. Rossetti, S. Pignata, S. Scala
Journal: Annals of Oncology (2019)
POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients
Authors: Richard D. Baird, Annelot G.J. van Rossum, Mafalda Oliveira, Karin Beelen, Meiling Gao, Mariette Schrier, Ingrid A.M. Mandjes, Javier Garcia-Corbacho, Anne-Laure Vallier, Greig Dougall, Erik van Werkhoven, Constanza Linossi, Sanjeev Kumar, Harm van Tinteren, Maurizio Callari, Emma Beddowes, José-Manuel Perez-Garcia, Hilde Rosing, Else Platte, Petra Nederlof, Margaret Schot, Aurelia de Vries Schultink, René Bernards, Cristina Saura, William Gallagher, Javier Cortès, Carlos Caldas, Sabine C. Linn
Journal: Clinical Cancer Research (2019)

The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor.
GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
Authors: P.P. Vitiello, L. Mele, C. Prisco, C. Cardone, D. Ciardiello, L. Poliero, C. Borrelli, N. Zanaletti, P. Vitale, V. Tirino, G. Papaccio, T. Troiani, F. Ciardiello, F. Marampon, V. Desiderio, E. Martinelli
Journal: Annals of Oncology (2019)
In search for the ideal anatomical composition of vascularised human skin equivalents for systemic sclerosis translational research: should we recruit the telocytes?
Authors: Mirko Manetti, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2019)

to the progressive loss of the normal tissue structure. 9 10At the moment, the protocols for selective telocyte purification are still at an early stage and more work is needed to definitively establish primary cultures.When this will be, telocytes cultured in vitro could represent an added value to improve the reliably building of vascularised human skin equivalents as suitable models for SSc translational research.
The clearance of EGF by tumor-associated macrophages is suppressed by chemotherapeutic agent cisplatin
Authors: I.V. Larionova, T. Liu, V. Riabov, D.M. Mossel, M.R. Patysheva, A.M. Kiselev, E.O. Kazakova, N.V. Cherdyntseva, J. Kzhyshkowska
Journal: Annals of Oncology (2019)
Abstract 14326: Inefficient Ventriculoarterial Coupling in Fontan Patients Measured Noninvasively Using Cardiac Magnetic Resonance
Authors: Max E Godfrey, Rahul H Rathod, Ellen M Keenan, Tal Geva, Kimberlee Gauvreau, Andrew J Powell, Ashwin Prakash
Journal: Circulation (2015)

Introduction: The ventriculoarterial coupling (VAC) ratio, defined as the ratio of arterial elastance (Ea) to ventricular end-systolic elastance (Ees), reflects the mechanoenergetic efficiency of the cardiovascular system. Extreme high or low values of VAC ratio imply inefficient energy transfer. Despite increasing rates of morbidity and mortality in patients with Fontan circulation, little is known about VAC ratio in this population. We used a previously described cardiac magnetic resonance (CMR) method to assess VAC in a large Fontan cohort and examined its relation to outcomes. Methods and Results: We retrospectively measured VAC from CMR and noninvasive blood pressure data on 195 Fontan patients (age 19.6±10.7 years) and 42 controls (age 15.2±2.2 years). VAC was calculated as Ea/Ees (Ea= mean arterial blood pressure (MBP)/ventricular stroke volume; Ees= MBP/end-systolic volume). Compared with controls, Fontan patients had lower body surface area (BSA) adjusted median Ees (1.54 vs. 2.4, p&lt;0.001) and Ea (1.35 vs. 1.48, p=0.01) and a higher median VAC ratio (0.88 vs 0.62, p&lt;0.001) (Figure). After a median follow-up of 4 years (range 1-10), 20 patients reached a composite endpoint of death or heart transplant listing. As seen in the Figure, extreme values of the VAC ratio were associated with higher risk of reaching the endpoint. In a multivariable Cox regression model controlling for EDV/BSA, which has been shown to be a risk factor, being in the highest tertile of the VAC was no longer a risk factor, but patients in the lowest tertile of VAC ratio showed a trend towards being more likely to reach the endpoint (Hazard Ratio 4.06 vs middle tertile, p=0.08). Conclusion: In this cohort, Fontan patients demonstrated inefficient VAC as compared with controls. A lower VAC ratio tended to be associated with death or transplantation listing even when controlling for ventricular size. Further investigation of CMR-derived VAC in the Fontan circulation is warranted.
Polatuzumab Vedotin Alone or in Combination with Obinutuzumab Synergistically Enhances In-Vitro Cytotoxicity and Cytokine Release Against CD20+/ CD79b+ Burkitt Lymphoma (BL) /Primary Mediastinal Large B Cell Lymphoma (PMBL)
Authors: Aradhana Tiwari, Dina Edani, Janet Ayello, Christian Klein, Dean Anthony Lee, Mitchell S. Cairo
Journal: Blood (2017)
Landolfi’s Sign
Authors: Jorge Aceituno, Pamela Ramírez
Journal: New England Journal of Medicine (2019)

A 73-year-old man presented with shortness of breath. On ocular exam, pupil dilation and constriction that were synchronized with his heartbeat were noted, a finding known as Landolfi’s sign (shown in a video). He was found to have severe aortic regurgitation.
What If Miró’s Dots and Lines Are Not Simply Dots and Lines?
Authors: Elena Guardiola, Josep-E. Baños
Journal: JAMA Internal Medicine (2019)

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Abstract 10941: Hepatic Overexpression of Endothelial Lipase Induces a Markedly Low HDL-Cholesterol but Maintains Macrophage Reverse Cholesterol Transport in Mice in an ABCA1-dependent Fashion
Authors: Shunichi Takiguchi, Makoto Ayaori, Harumi Uto-Kondo, Emi Yakushiji, Kazuhiro Nakaya, Makoto Sasaki, Tomohiro Komatsu, Masumi Kamiyama, Takafumi Nishida, Katsunori Ikewaki
Journal: Circulation (2015)

We previously showed that hepatic overexpression of endothelial lipase (EL) by adenoviral vectors markedly reduced plasma HDL levels but maintained macrophage reverse cholesterol transport (RCT) in an SR-BI-dependent fashion in mice. In the present study, we further investigated roles of ABCA1 using probucol, an ABCA1 inhibitor, under EL overexpression. In vivo RCT assay demonstrated that hepatic EL overexpression reduced macrophages-derived 3H-cholesterol in plasma, especially HDL fractions but maintained fecal 3H-cholesterol excretion as compared with the control under normal chow. Probucol diet reduced both 3H- and non-radiolabeled-cholesterol levels in HDL fraction, which were further exacerbated by EL overexpression. Interestingly, probucol diet combined with EL overexpression clearly promoted fecal excretion of macrophages-derived 3H-cholesterol, indicating that EL overexpression and ABCA1 inhibition synergistically enhanced macrophage RCT despite of extremely low HDL levels.
AB0681 Hidden generalized edema in inflammatory myopathy; generalized edema is an unrecognized clinical feature of myositis?
Authors: Y Namiki, K Kurasawa, A Tanaka, R Yamazaki, H Okada, S Arai, T Owada, R Maezawa, M Arima
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Dermatomyositis (DM)/ polymyoitis (PM) are systemic diseases characterized by muscle inflammation, which shows varieties of clinical symptoms and signs. We have experienced cases of DM/PM with generalized edema as reported previously by others (1). Moreover, we found that there were many myositis patients who lost their body weight (BW) after starting of high dose glucocorticoid (GC) therapy. Thus, we hypothesized that hidden generalized edema is a characteristic clinical feature of myositis. <h3>Objectives</h3> To determine whether generalized edema is a hidden clinical feature of myositis. If so, what myositis patients have the feature. <h3>Methods</h3> The study was a retrospective observation study. The subjects were consecutive 67 of DM/PM and 53 of SLE patients who diseases for the first time, admitted our department from April 2007 to September 2016 and received immunosuppressive therapy including over 30mg/day GC. The patients were excluded who had cardiogenic or nephrogenic edema or whose BW data was not available. To detect hidden generalized edema caused by inflammation, we examined the change in BW within 2 weeks after starting immunosuppressive therapy. The clinical features of DM/PM patients with/without BW change were examined through reviewing medical record. <h3>Results</h3> The included subjects were DM/PM 66 patients (M/F; 18/48 with a mean age of 59.4 y.) and SLE 40 patients (M/F;14/26 with a mean age of 49.8 y.). The body weight of DM/PM and SLE were 56.4±14.0 and 54.7±10.9 kg, respectively. Decrease in BW within 2weeks after starting the therapy were 3.02±2.99kg of DM/PM and 0.85±2.87 kg of SLE, which was larger in DM/PM compared to SLE (Fig A). The numbers of patients who lost BW more than 2kg within the 2 weeks were 42 in DM/PM (64%) and 14 in SLE (35%). Serum albumin levels were slightly decreased by 0.18 g/ dl (0.06 to 0.30; 95% CI) in DM/PM, while no significant change was detected in SLE. In myositis, change in BW was similar among DM, amyopathic DM (ADM) and PM (Fig.B). Moreover, no differences were found in the change of BW between patients with and without male sex, malignancy, interstitial pneumonia, anti-ARS Ab and anti-MDA5Ab. Additionally, between patients with and without BW loss more than 2kg, no differences were found in age, serum TP, Alb and CRP levels before and after treatment and prognosis. <h3>Conclusions</h3> DM/PM patients lose BW by immunosuppressive therapy including GC, which indicates the existence of hidden generalized edema that might be a characteristic clinical feature in inflammatory myopathy. <h3>References</h3> Tu J1, McLean-Tooke A, Junckerstorff R. Increasing recognition of dermatomyositis with subcutaneous edema - is this a poorer prognostic marker? Dermatol Online J. 2014;20:21244. <h3>Disclosure of Interest</h3> None declared
The role of AXL as mechanism of resistance to trastuzumab and a prognostic factor in breast cancer HER2 positive: A translational approach
Authors: A. Adam-Artigues, E. Tormo, F. Rojo, J.A. Perez-Fidalgo, S. Zazo, P. Gonzalez-Alonso, C. Hernando, M.T. Martínez, V. Gambardella, J. Poveda, S. Simón, S. Moragon, E. Alonso, J. Albanell, O. Burgues, B. Bermejo, P. Eroles, A. Lluch, J.M. Cejalvo, A. Rovira
Journal: Annals of Oncology (2019)
Randomized, phase Ib/II study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Authors: S. Banerjee, I. Vergotte, N. Colombo, M. Barve, R. Grisham, K.T. Mehr, M. Falk, F. Beier, M. Hennessy, A. Schroeder, M. Birrer
Journal: Annals of Oncology (2019)
Results of the ASCEND-7 phase II study evaluating ALK inhibitor (ALKi) ceritinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) metastatic to the brain
Authors: L.Q. Chow, F. Barlesi, E.M. Bertino, M.J. van den Bent, H. Wakelee, P.Y. Wen, C.-H. Chiu, S. Orlov, M. Majem, R. Chiari, M. McKeage, C.-J. Yu, F.K. Hurtado, P Cazorla Arratia, Y. Song, F. Branle, M. Shi, D.-W. Kim
Journal: Annals of Oncology (2019)
A prospective, multicenter case control study of risk factors for acquisition and mortality in Enterobacter species bacteremia
Authors: Rocío Álvarez-Marín, Dolores Navarro-Amuedo, Oriol Gasch-Blasi, José Manuel Rodríguez-Martínez, Jorge Calvo-Montes, Rosario Lara-Contreras, José Antonio Lepe-Jiménez, Fe Tubau-Quintano, María Eliecer Cano-García, Fernando Rodríguez-López, Jesús Rodríguez-Baño, Miquel Pujol-Rojo, Julián Torre-Cisneros, Luis Martínez-Martínez, Álvaro Pascual-Hernández, Manuel Enrique Jiménez-Mejías
Journal: Journal of Infection (2019)
Genome-wide germline correlates of the epigenetic landscape of prostate cancer
Authors: Kathleen E. Houlahan, Yu-Jia Shiah, Alexander Gusev, Jiapei Yuan, Musaddeque Ahmed, Anamay Shetty, Susmita G. Ramanand, Cindy Q. Yao, Connor Bell, Edward O’Connor, Vincent Huang, Michael Fraser, Lawrence E. Heisler, Julie Livingstone, Takafumi N. Yamaguchi, Alexandre Rouette, Adrien Foucal, Shadrielle Melijah G. Espiritu, Ankit Sinha, Michelle Sam, Lee Timms, Jeremy Johns, Ada Wong, Alex Murison, Michèle Orain, Valérie Picard, Hélène Hovington, Alain Bergeron, Louis Lacombe, Mathieu Lupien, Yves Fradet, Bernard Têtu, John D. McPherson, Bogdan Pasaniuc, Thomas Kislinger, Melvin L. K. Chua, Mark M. Pomerantz, Theodorus van der Kwast, Matthew L. Freedman, Ram S. Mani, Housheng H. He, Robert G. Bristow, Paul C. Boutros
Journal: Nature Medicine (2019)
Phase II study of preoperative radiotherapy combined with S-1 plus cisplatin in clinically resectable type 4 or large type 3 gastric cancer: OGSG1205
Authors: S. Endo, M. Imano, H. Furukawa, M. Yokokawa, Y. Nishimura, M. Shinkai, T. Yasuda, T. Nakagawa, S. Adachi, S.W. Lee, M. Goto, T. Kii, K. Uchiyama, H. Kawakami, T. Shimokawa, D. Sakai, Y. Kurokawa, T. Satoh
Journal: Annals of Oncology (2019)
Pharmacokinetic (PK) assessment of BT1718: A phase I/II a study of BT1718, a first in class bicycle toxin conjugate (BTC), in patients (pts) with advanced solid tumours
Authors: N. Cook, U. Banerji, J. Evans, A. Biondo, T. Germetaki, M. Randhawa, L. Godfrey, S. Leslie, P. Jeffrey, M. Rigby, G. Bennett, S. Blakemore, M. Koehler, A. Niewiarowski, M. Pittman, S.N. Symeonides
Journal: Annals of Oncology (2019)