tbuckley/cabot-search huggingface dataset:
A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in Chronic Obstructive Pulmonary Disease
Authors: Francesca Polverino, Maria E. Laucho-Contreras, Hans Petersen, Vanesa Bijol, Lynette M. Sholl, Mary E. Choi, Miguel Divo, Victor Pinto-Plata, Alfredo Chetta, Yohannes Tesfaigzi, Bartolomé R. Celli, Caroline A. Owen
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia.Objectives: To determine whether (1) cigarette smoke (CS)-induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress–advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs–RAGE pathway in endothelial cells in both organs.Methods: In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, and measured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice.Measurements and Main Results: Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions.Conclusions: Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal and lung function by reducing endothelial injury.
Bendamustine/Mitoxantrone/Rituximab (BMR): A Very Effective and Well Tolerated Immuno-Chemotherapy for Relapsed and Refractory Indolent Lymphomas - Results of a Multicentre Phase-II-Study of the German Low Grade Lymphoma Study Group (GLSG).
Authors: Rudolf Weide, Hubert Koeppler, Jochen Heymanns, Joerg Thomalla, Georg Hess, Heinhold Gamm, Ali Aldaoud, Stephan Schmitz, Ursula Haak, Dirk Plewe, Oswald Burkhard, Bernd Gaede, Fokke Hinrichs, Karl-Heinz Pflueger, Martin Dreyling, Michael Unterhalt, Wolfgang Hiddemann
Journal: Blood (2004)
Effectiveness of Interventions to Maintain Penicillin Allergy Label Removal As Part of an Inpatient Penicillin Allergy Testing Protocol
Authors: Sheenal V. Patel, Scott A. Tarver, Kristin S. Alvarez, Kristin E. Lutek, James Schlebus, David A. Khan
Journal: Journal of Allergy and Clinical Immunology (2017)
Brain metastases (BM) in colorectal cancer (CRC): Prognostic factors and survival analysis
Authors: L. Pl Carpio De Huerta, M. Tobeña, A.C. Virgili Manrique, J. Szafranska, M. Martín-Richard, D. Paez, I. Espinoza, A. Sebio Garcia, P. Gomila Pons, M. Andrés Granyo, A. Barba Joaquín, N. Dueñas Cid, A. Vethencourt Casado, M.S. García-Cuerva
Journal: Annals of Oncology (2016)
A randomised phase II study of perioperative epirubicin, cisplatin and capecitabine (ECX) ± lapatinib for operable, HER-2 positive gastric, oesophagogastric junctional (OGJ) or lower oesophageal adenocarcinoma: Results from the UK MRC ST03 lapatinib feasibility study (ISRCTN 46020948)
Authors: E. Smyth, S. Rowley, W. Allum, S. Stenning, A. Wotherspoon, C. Robb, H. Grabsch, D. Alderson, T. Crosby, R. Mason, M. Griffin, W. Mansoor, S. Darby, M. Seymour, J. Thompson, S. Sothi, K. Sumpter, J. Blazeby, R. Langley, D. Cunningham
Journal: Annals of Oncology (2016)
Circulating Angiopoietin-2 Predicts Time to Relapse after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.
Authors: Christian Koenecke, Philipp Kümpers, Alexander Lukasz, Hartmut Hecker, Elke Dammann, Willem Verhagen, Sascha David, Gudrun Göhring, Stefanie Buchholz, Eva Weissinger, Jürgen Krauter, Matthias Eder, Hermann Haller, Arnold Ganser
Journal: Blood (2008)
Abstract #4391: The Raf/MEK/ERK pathway can mediate androgen receptor downregulation and growth arrest independently of ERK1/2 kinase activity in LNCaP cells
Authors: Seung-Keun Hong, Seunghee Yoon, Jong-In Park
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Although Ras or Raf mutations are rarely detected in prostate tumor, activation of the Raf/MEK/ERK pathway is correlated with some aspects of prostate tumorigenesis including loss of androgen receptor (AR) expression in prostate tumors upon androgen withdrawal. We investigated the effect of activation of the Raf/MEK/ERK pathway on AR expression in the androgen-dependent human prostate tumor cell line, LNCaP. Activation of the Raf/MEK/ERK pathway, using an inducible Raf or constitutively active MEK1/2, induced downregulation of AR and c-MYC, which is accompanied by growth arrest and morphological changes. This indicated that activation of the Raf/MEK/ERK pathway alone is sufficient to mediate AR downregulation and prompted us to further investigate involved mechanisms of ERK1/2 signaling. Surprisingly, we found that Raf/MEK/ERK-induced AR downregulation and growth arrest can be mediated via a novel ERK signaling mechanism for which ERK1/2 kinase activity is not necessary. Ablation of ERK1/2 by RNA interference abrogated the effects of Raf activation on downregulation of AR and c-MYC, growth arrest as well as morphological changes. However, overexpression of ERK1-K71R, a kinase-deficient ERK1 that competitively inhibited activation of endogenous ERK1/2, could not block Raf-induced AR downregulation and growth arrest although it effectively blocked morphological changes, c-MYC downregulation, and phosphorylation of the ERK1/2 catalytic activity readouts, p90RSK and ELK1. Since this indicated non-catalytic signaling potential of ERK1/2, we generated LNCaP lines in which both ERK1 and ERK2 were stably knocked down, and further determined the non-catalytic ERK signaling using ERK2-K52R, a rat-derived kinase-deficient ERK2, which is not targeted in the stable cell lines. Indeed, ERK2-K52R selectively restored cellular ability to undergo Raf-induced AR downregulation and growth arrest without affecting cellular morphology and c-MYC levels. Kinase activity is the key biochemical property of the MAP kinase, ERK1/2. However, these results suggest that ERK1/2 can also mediate non-catalytic signaling in cells. Our finding of kinase activity-independent ERK1/2 signaling may provide a foundation to investigate the molecular background of AR downregulation during prostate tumorigenesis.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4391.
A phase I trial of tumor-associated antigen-pulsed dendritic cell immunotherapy for patients with brain stem glioma and glioblastoma
Authors: S. Phuphanich, J. Rudnick, R. Chu, M. Mazer, H. Wang, N. Serrano, M. Francisco, C. Wheeler, M. Singh, J. S. Yu
Journal: Journal of Clinical Oncology (2009)

2032 Background: Previous immunotherapy trials for malignant glioma (Yu, J.,et al, Cancer Res. 2001;61:842–7 and 2004;64;4973–9) have demonstrated efficacy in generating a tumor specific immune response. Here we set out to determine feasibility and immunogenecity of dendritic vaccination with specific glioma-associated antigens. Methods: The goal of this study is to use tumor associated antigens (TAA) known to be expressed on gliomas and pulse dendritic cells with these antigens in an MHC compatible fashion using epitopes of HER-2, TRP-2, gp100, MAGE-1, IL13R alpha, and AIM-3. In this phase I trial, HLA-A1 and/or HLA-A2-positive patients with newly diagnosed or recurrent glioblastoma were eligible. Leukapheresis was used to isolate mononuclear cells which were differentiated into dendritic cells in culture, pulsed with tumor peptide, and then administered intradermally three times at 2-week intervals. Results: Twenty patients, 15 males and five females, were enrolled between November 2006 and December 2008 with one screen failure. The median patient age was 47 years (range: 26–65) and patients had a median Karnofsky performance status of 90% (range: 90–100). There were 16 newly diagnosed and three recurrent glioblastoma multiforme (GBM) patients, who underwent surgery prior to vaccination. Our data on 19 patients and 54 courses of dendritic cell vaccines demonstrate zero grade 3 /4 toxicities that were attributable to the vaccination. Thirteen patients continue to have stable disease (ranging from 15 to 115 weeks), six patients have demonstrated tumor progression. Median survival from surgery was 60 weeks (ranging from 26 to 115 weeks). Of 15 patients tested to date, six patients demonstrated an antigen-specific cytotoxic T-cell response to at least one antigen after vaccination. Only 17% of CTL responders (1/6) demonstrated tumor progression compared to 56% (5/9) of nonresponders to date. Conclusions: This phase I study demonstrated the feasibility, safety, and bioactivity of a TAA-pulsed dendritic cell vaccine for patients with glioblastoma progression free survival correlated with CTL response. [Table: see text]
Advancing the Health of Lesbian, Gay, and Bisexual Adults—Reply
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2017)

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GDC-0980, a novel PI3K/mTOR kinase inhibitor, is effective in HER2 positive gastric cancer (GC) cell lines resistant to Trastuzumab
Authors: J. Ventriglia, M.M. laterza, A. Capasso, V. Belli, B. Savastano, A. Petrillo, G. Tirino, L. Pompella, A. Diana, M. Orditura, F. Ciardiello, F. De Vita
Journal: Annals of Oncology (2016)
Maternal Vitamin E Plasma Isoform Concentrations and Association with Child Wheezing and Asthma Outcomes
Authors: Cosby A. Stone, Joan A. Cook-Mills, Tebeb Gebretsadik, Emma K. Larkin, Christian Rosas-Salazar, Alexandra Connolly, Theresa Rogers, Zhouwen Liu, Kaitlin Costello, Tina V. Hartert
Journal: Journal of Allergy and Clinical Immunology (2017)
Component-resolved diagnostics in keratoconjunctivitis
Authors: Jessica Luna Junqueira Vasconcelos, Carolina S. Aranda, Fabio Zanini, Renata Rodrigues Cocco, Gustavo F. Wandalsen, Marcia C. Mallozi, Felipe Pierotti, Myrna Serapião dos Santos, Denise de Freitas, Natalia Dias, Gabriele Moreira Camilo, Dirceu Solé
Journal: Journal of Allergy and Clinical Immunology (2017)
Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice
Authors: Christopher R. Chapple, Jameel Nazir, Zalmai Hakimi, Sally Bowditch, Francis Fatoye, Florent Guelfucci, Amine Khemiri, Emad Siddiqui, Adrian Wagg
Journal: European Urology (2017)

Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β3-adrenoceptor agonist with a different adverse event profile.To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period.Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date.Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride.The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching.The study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; p<0.0001) and other antimuscarinics (range 30-78 d; adjusted HR range 1.24-2.26, p<0.0001 for all comparisons). The 12-mo persistence rates and MPR were also significantly greater with mirabegron than with all the antimuscarinics. Limitations include the retrospective design, use of prescription records to estimate outcomes, and inability to capture reasons for discontinuation.Persistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK.This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics.
DRES-06. COMBINATION THERAPY OF LDK378 AND INC280 (INCB028060) ENHANCES TEMOZOLOMIDE SENSITIVITY IN MGMT UNMETHYLATED GLIOBLASTOMA: PRE-CLINICAL ASSESSMENT
Authors: Arabinda Das, Pierre Giglio, William Alexander Vandergrift, Naren L Banik, Abhay K. Varma, Michele L Decandio, Bruce M Frankel, Sunil J. Patel, Jeffrey Raizer, Scott M. Lindhorst, David Cachia
Journal: Neuro-Oncology (2016)

Temozolomide (TMZ) therapy is the standard of care for patients with glioblastoma (GB), and resistance to this drug is at least partly modulated by the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Expression of MGMT is silenced by promoter methylation in approximately half of GB tumors, and clinical studies have shown that elevated MGMT protein levels or lack of MGMT promoter methylation is associated with TMZ resistance in some, but not all, GB tumors. Another reason for treatment failure in GB management is signal redundancy due to coactivation of several functionally linked receptor tyrosine kinases (RTKs), including anaplastic lymphoma kinase (ALK), and c-Met (hepatocyte growth factor receptor). As such, these could be attractive targets for GB therapy. Thus, we tested two novel drugs: LDK378 (highly selective anaplastic lymphoma kinase-ALK inhibitor) and INC280 (INCB028060: highly selective c-Met receptor tyrosine kinase-RTK inhibitor), aiming to overcome TMZ resistance in MGMT unmethylated GB cells in in vitro and ex vivo slice culture models. Treatments were examined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot analysis, caspases assay, and PCR assay. Results obtained from our experiments demonstrated that combination of LDK378 and INC280 statistically significantly enhances the efficacy of TMZ, and also strongly inhibited the proliferation of GB cells via suppression of ALK and c-Met expression. The use of these drugs resulted in a decrease in expression of the mismatch repair (MMR) proteins, MSH6 and MLH1. Also, they induced apoptosis by modulating downstream mediators such as STAT3, AKT, and ERK. Taken together, this data indicates that co-inhibition of ALK and c-MET can enhance growth inhibitory effects in MGMT unmethylated cells and augment TMZ sensitivity in-vitro, suggesting the potential value for ALK inhibitors combined with c-MET-targeting for therapeutic benefit in MGMT unmethylated GB patients.
Latino Patients With Chronic Rhinosinusitis (CRS) Have a Distinct Nasal Microbiome Associated with Poor Disease Outcome
Authors: Sherlyana Surja, Ferry Gunawan, Pete S. Batra, Philip A. Engen, Phillip S. LoSavio, Ali Keshavarzian, Mahboobeh Mahdavinia
Journal: Journal of Allergy and Clinical Immunology (2017)
Fertility Attitudes and Cancer Treatment Study (FACTS).
Authors: Dina M Flink, Yvonne Kellar-Guenther, Jeanelle Sheeder, Laxmi A Kondapalli
Journal: Journal of Clinical Oncology (2016)

112 Background: Approximately 140,000 people under 45 year old are diagnosed with cancer annually in the US. Survivorship is high and many of these individuals desire future fertility. Although fertility preservation (FP) services are increasing, utilization rates remain low. Methods: We conducted a 2-phase study to identify factors for FP decisions among newly diagnosed males and females receiving fertility consultation, 18-45 years old. Phase 1 was a chart review; Chi-square and t-tests were used to determine potential factors associated with FP decision. Phase 2 consisted of face-to-face interviews. Content analysis was used to identify relevant themes associated with reasons, priorities, support, and satisfaction for FP decision. Results: In Phase 1, 108 charts were reviewed; FP utilization rate was 50%. Those who chose FP were more likely to be male (73.6% vs. 26.4%, p &lt; 0.001), Caucasian (90.6% vs. 9.4%, p = 0.042), have a solid tumor (98.1% vs. 1.9% p = 0.032), and a shorter time from diagnosis to fertility consult (29.5 vs. 58.8 days, p = 0.017). Age, relationship, education, parity, or treatment plan did not differ with FP decision. In phase 2, we assessed reasons why patients chose FP; 27 participants were interviewed. Primary reasons for choosing FP were: future fertility and access to FP services. Main reasons for not choosing FP were: concerns with future conception and lack of access to FP services. Cost ranked 4 th among reasons to not choose FP; however 50% of patients overcame the cost to prioritize future fertility. Males top priorities were: future parenthood, cancer treatment, and survivorship QOL. Females top priorities were: future parenthood, decisional conflict, and cancer treatment. Patients greatest concerns with FP were: birth defects, future conception, and success of FP. Conclusions: Future fertility is a priority for newly diagnosed young adults. All patients should receive a referral to a reproductive specialist, regardless of patient factors or diagnosis. While patients expressed feeling well-informed to make FP decisions following fertility consult, some still had concerns with the safety and success of FP. Adequate FP consultation should include discussion of all treatment options and concerns for FP.
Progression-free survival (PFS) with lanreotide autogel/depot (LAN) in enteropancreatic NETs patients: The CLARINET extension study.
Authors: Martyn E. Caplin, Philippe B. Ruszniewski, Marianne E. Pavel, Jaroslaw B. Cwikla, Alexandria T. Phan, Markus Raderer, Eva Sedlackova, Guillaume Cadiot, Lucy R. Wall, Guido Rindi, Alison Langley, Joelle Blumberg
Journal: Journal of Clinical Oncology (2014)

4107^ Background: The CLARINET core study showed that the long-acting somatostatin analog (SSA) LAN 120 mg significantly prolonged PFS vs placebo (PBO) in patients (pts) with metastatic enteropancreatic NETs (p=0.0002). Median PFS not reached with LAN vs 18.0 months with PBO. This study was the first randomized PBO-controlled trial investigating PFS with an SSA in a population that included pts with pancreatic NETs and pts with grade G2 tumors (Ki-67 <10%). Here, we report PFS data and safety findings from the open-label extension (OLE) to CLARINET. Methods: Pts enrolled in CLARINEThad: well/moderately differentiated non-functioning enteropancreatic NETs with Ki-67 <10%; no prior SSAs, or other medical therapies in last 6 months; metastatic disease. In CLARINET, pts were randomized to LAN 120 mg (n=101) or PBO (n=103) every 28 days for 96 wks or until death/disease progression (PD; according to RECIST 1.0). LAN pts with stable disease and PBO pts with/without PD could then enter the single-arm (LAN) OLE (NCT00842348, max. expected duration 5 yrs). The primary objective of the OLE was safety (safety population). The main efficacy endpoint was PFS (i.e. time from randomization in core study to death/PD) for the core study intent-to-treat population, using survival analysis based on Kaplan–Meier estimates. Results: 88 pts from the CLARINET core study (LAN arm, 41; PBO arm, 47) participated in OLE. At core study enrollment, 96% of OLE patients did not have tumor progression; 38% had pancreatic primary tumors, 39% had midgut, and 8% hindgut. The median PFS for LAN was reached during the OLE: 32.8 months. For subset of pts who had PD while on PBO in the core study, median time to further PD with LAN in the OLE was 14.0 months. During the OLE, 27% who continued LAN vs 40% switched to LAN had treatment-related adverse events (TRAE); most frequent TRAE was diarrhea. No new safety concerns were identified in the extension. Conclusions: CLARINET extension data suggest there were antitumor effects with LAN 120 mg in enteropancreatic NET patients with progressive disease. Long-term safety/tolerability of lanreotide in the extension was consistent with its known profile. Clinical trial information: NCT00842348.
Stroma-Derived Factors Significantly Impact the Drug Response Profiles of Patient-Derived Primary AML Cells: Implications for Drug Sensitivity Testing
Authors: Riikka Karjalainen, Tea Pemovska, Muntasir Mamun Majumder, David Tamborero, Bhagwan Yadav, Mika Kontro, Bjørn Gjertsen, Alun Parsons, Minna Suvela, Tero Aittokallio, Kimmo Porkka, Olli Kallioniemi, Krister Wennerberg, Caroline A Heckman
Journal: Blood (2014)
Meta-analysis of Mepolizumab Global Studies Suggest Consistent Therapeutic Response Across a Range of Demographic Sub-groups
Authors: Steven W. Yancey, Necdet B. Gunsoy, Eric S. Bradford, Frank C. Albers, Charlene M. Prazma, Richard Follows, Oliver N. Keene, Ian Pavord
Journal: Journal of Allergy and Clinical Immunology (2017)
Transdermal granisetron plus dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (cinv) in patients with locally advanced head-neck squamous cell cancer (hnscc) treated with radiotherapy plus concomitant administration of cisplatin
Authors: A. Rozzi, M. Corona, P.T. Falbo, C. Spoto, A. Iannace, L. De Filippis, G. Lanzetta
Journal: Annals of Oncology (2016)