tbuckley/cabot-search huggingface dataset:
Primary central nervous system lymphoma: The influence of radiotherapy on patient outcome in an unselected population.
Authors: Scheryll Paula Alken, MinYuen Teo, Richard Martin Bambury, Mohd Syahizul Nuhairy Mohd Sharial, Connor O'Leary, Anuradha Jayaram, Francesca Brett, Louise Catherine Connell, Michael Anthony Farrell, Catherine Keohane, Clare Faul, Eugene J. Moylan, Derek Gerard Power, William Grogan, Oscar S. Breathnach, Maccon M. Keane, Seamus O'Reilly, Patrick Glyn Morris
Journal: Journal of Clinical Oncology (2014)

2044 Background: Treatment strategies for newly diagnosed PCNSL typically combine high dose methotrexate with whole-brain radiotherapy (WBRT). However, although WBRT is associated with neurotoxicity, its omission may compromise disease control. To address these issues, we report a retrospective, population-based study of high dose methotrexate with or without WBRT. Methods: We included patients (pts) with newly diagnosed PCNSL treated in three major medical oncology centers in Ireland between 2001 and 2011, which included 57% of cases diagnosed in Ireland over the same period. Medical records were examined for clinicopathologic characteristics, administered treatment and survival. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. For the primary endpoint, PFS was compared by receipt of WBRT using the log-rank test and Cox proportional hazard test. Results: A total of 70 pts were included in the study, median age of 60 years (range 17–78); 39 (53%) were male. In total, 66 (94%) received high dose methotrexate and 25 (36%) received WBRT. Distribution of demographics and clinical features including MSKCC RPA were comparable by receipt of WBRT (table). At a median follow up of 25 months for survivors, 33% have no evidence of disease and 46% are alive. For the primary endpoint, PFS was similar for pts who received WBRT or not (HR 0.95, 95%CI 0.39–2.32) (Table). Similarly, there were no differences in OS by receipt of WBRT (HR 0.92, 95%CI 0.44 – 1.51). Conclusions: In this retrospective study of older patients with newly diagnosed PCNSL the omission of WBRT did not adversely affect patient outcomes though selection bias cannot be outruled. Randomized studies are ongoing to examine if WBRT can be omitted from first line treatment without compromising outcome. WBRT No WBRT N % N % P Age (Median) 56 64 0.35 Range 25 - 78 17 - 76 Gender (males) 15 52 24 59 0.63 ECOG PS 0 - 1 15 52 27 66 0.88 ≥2 12 41 12 29 Unknown 2 7 2 5 MSKCC RPA I 9 31 10 24 0.71 II 12 41 15 37 III 6 21 10 24 Unknown 2 7 6 15 PFS (months) Median 20.8 22.3 0.91 OS (months) Median 33.7 32.1 0.42
The ABC-transporter genes Mdr1/Mdr1b, Mrp1, and Mrp3 are highly expressed in hepatic progenitor cells.
Authors: JE Ros, Tania Roskams, M Geuken, R Havinga, H Moshage, BE Petersen, F Kuipers, M Muller, PL Jansen
Journal: Hepatology (2001)
Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution
Authors: Adel Boueiz, Sharon M. Lutz, Michael H. Cho, Craig P. Hersh, Russell P. Bowler, George R. Washko, Eitan Halper-Stromberg, Per Bakke, Amund Gulsvik, Nan M. Laird, Terri H. Beaty, Harvey O. Coxson, James D. Crapo, Edwin K. Silverman, Peter J. Castaldi, Dawn L. DeMeo
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe–predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown.Objectives: To identify the genetic influences of emphysema distribution in non–alpha-1 antitrypsin–deficient smokers.Methods: A total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism–, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed.Measurements and Main Results: We identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution.Conclusions: This multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic approaches in chronic obstructive pulmonary disease.Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).
Blood Measurement of Carcinoembryonic Antigen Level for Detecting Recurrence of Colorectal Cancer
Authors: Brian D. Nicholson, Bethany Shinkins, David Mant
Journal: JAMA (2016)

<h3>Clinical Question</h3> What is the trade-off between sensitivity and specificity at specific carcinoembryonic antigen (CEA) thresholds for detecting recurrent colorectal cancer? <h3>Bottom Line</h3> To detect colorectal cancer recurrence, the sensitivity of CEA ranges from 68% for a threshold of 10 µg/L to 82% for a threshold of 2.5 µg/L and the specificity ranges from 97% for a threshold of 10 µg/L to 80% for a threshold of 2.5 µg/L.
Copolymer-Mediated Cell Aggregation Promotes a Proangiogenic Stem Cell Phenotype In Vitro and In Vivo
Authors: Spencer W. Crowder, Daniel A. Balikov, Timothy C. Boire, Devin McCormack, Jung Bok Lee, Mukesh K. Gupta, Melissa C. Skala, Hak‐Joon Sung
Journal: Advanced Healthcare Materials (2016)

Material-induced cell aggregation drives a proangiogenic expression profile. Copolymer substrates containing cell-repellent and cell-adhesive domains force the aggregation of human mesenchymal stem cells, which results in enhanced tubulogenesis in vitro and stabilization of vasculature in vivo. These findings can be used to design instructive biomaterial scaffolds for clinical use.
Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer
Authors: K. J. Ruddy, A. H. Partridge, S. Gelber, L. Schapira, M. Abusief, M. Meyer, E. P. Winer, E. S. Ginsburg
Journal: Journal of Clinical Oncology (2008)

9571 Background: Studies of fertility among breast cancer survivors have used continued menses as an indicator of ovarian function despite the fact that menstruation is a poor surrogate for fertility, especially as women age. Ovarian reserve testing predicts response to fertility treatments, but to date has not been well studied in women exposed to chemotherapy. Methods: We evaluated markers of ovarian reserve in breast cancer survivors with continued menses after receiving adjuvant chemotherapy compared to age-matched, parity- matched premenopausal controls. All survivors were ≥1yr from dx, with no evidence of recurrence. Ovarian reserve was measured on day 2, 3, or 4 of a menstrual cycle by antral follicle count (AFC) and serum follicle stimulating hormone (FSH), estradiol (E2), anti- Müllerian hormone (AMH) and inhibin B (InB) levels. The Wilcoxon sign rank test was used to calculate the pairwise differences; Spearman’s correlation coefficients were used to evaluate the relationship between the AFC and the serum values. Results: Twenty survivors and 20 controls were evaluated. Mean age was 36 years for both groups; 85% of survivors had received AC or AC-T chemotherapy, and 50% were currently on tamoxifen. Median AFC for survivors was 6, compared to 10 for controls. There were significant differences between the two groups in their AFC (p=0.004), InB (p=0.02), FSH (p=0.02) and AMH (p=0.0004) values, all indicating better ovarian reserve in controls. Only E2 failed to distinguish between the two groups (p=0.14). AFC and AMH, which reflect the remaining pool of immature oocytes, were highly correlated (r = 0.78, p<0.0001). Survivors on tamoxifen had lower AFC, InB, AMH, and higher E2 than non-tamoxifen treated survivors, but the small size of our sample precludes formal analysis. Conclusions: Premenopausal breast cancer survivors have diminished ovarian reserve compared to controls. The largest differences between survivors and controls were seen in AFC and AMH. These findings may have important implications for women who are interested in having children after cytotoxic chemotherapy. Prospective studies are needed to determine the predictive value of these tests for pregnancy after chemotherapy. (This study was supported by the Lance Armstrong Foundation) No significant financial relationships to disclose.
Temsirolimus (TEM) in metastatic renal cell carcinoma (mRCC): Safety and efficacy in patients (pts) previously treated with VEGF-targeted therapy
Authors: L. Wood, R. M. Bukowski, R. Dreicer, P. Elson, J. A. Garcia, T. Gilligan, T. Mekhail, B. I. Rini
Journal: Journal of Clinical Oncology (2008)

16067 Background: TEM is a selective inhibitor of mTOR, a regulator of cell proliferation, growth and survival, approved for advanced RCC based on a phase III trial in untreated poor-risk mRCC. TEM is now used widely, including pts with prior VEGF-targeted therapy in whom no safety or efficacy data is available. Methods: A retrospective review of VEGF-targeted treatment-refractory mRCC pts treated with TEM. Results: Nineteen pts (median age, 60 [42–74]; male/female, 84%/16%) were identified. All pts were previously treated with ≥ 1 VEGF-targeted therapies (84% sunitinib, 74% sorafenib, 16% bevacizumab, 16% axitinib). 84% pts had prior nephrectomy, clear cell histology (63%), ECOG status 1 (53%) and ≥ 3 sites of metastatic disease (68%). MSKCC prognostic group classification was favorable (11%), intermediate (58%) and poor risk (31%). Cleveland Clinic VEGF-targeted therapy prognostic group classification (Choueiri et al. Cancer 2007) was favorable (26%), intermediate (26%) and unfavorable (48%). 16% had previously treated brain metastasis. Median number prior therapies 2 (range, 1–7). Median 10 doses (range, 1–22); median 2 cycles (8 weeks) (range, 1+-6+); mean dose intensity of 21 mg/week. Most common treatment-related adverse events (all grades) were anemia (89%), fatigue (79%), hypertriglyceridemia (74%), hyperglycemia (74%), elevated creatinine (58%), rash (53%), thrombocytopenia (53%), hypercholesteremia (42%), pruritis (37%), anorexia (32%), and clinical mucositis (21%). 56% had doses held due to toxicity: 32% of pts had grade 3 adverse events (fatigue, hyperkalemia, neutropenia, creatinine, triglycerides). Nine pts discontinued therapy for disease progression and 3 for adverse events. Response assessment includes stable disease (47%); disease progression (47%); too early to assess (1 pt). Median PFS is 5.0 months. Conclusions: Administration of TEM is feasible in met RCC pts who have received prior VEGF-targeted treatment, with a higher incidence of fatigue, thrombocytopenia, and rash. Clinical efficacy in this setting requires further follow up. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech, Novartis, Pfizer, Wyeth Bayer, Genentech, Novartis, Onyx, Pfizer, Wyeth Bayer, Bristol-Myers Squibb, Genentech, Pfizer
Glycerophosphodiesterase GDE2 Promotes Neuroblastoma Differentiation through Glypican Release and Is a Marker of Clinical Outcome
Authors: Elisa Matas-Rico, Michiel van Veen, Daniela Leyton-Puig, Jeroen van den Berg, Jan Koster, Katarzyna M. Kedziora, Bas Molenaar, Marjolein J.A. Weerts, Iris de Rink, René H. Medema, Ben N.G. Giepmans, Anastassis Perrakis, Kees Jalink, Rogier Versteeg, Wouter H. Moolenaar
Journal: Cancer Cell (2016)

Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. A better understanding of neuroblastoma differentiation is essential for developing new therapeutic approaches. GDE2 (encoded by GDPD5) is a six-transmembrane-domain glycerophosphodiesterase that promotes embryonic neurogenesis. We find that high GDPD5 expression is strongly associated with favorable outcome in neuroblastoma. GDE2 induces differentiation of neuroblastoma cells, suppresses cell motility, and opposes RhoA-driven neurite retraction. GDE2 alters the Rac-RhoA activity balance and the expression of multiple differentiation-associated genes. Mechanistically, GDE2 acts by cleaving (in cis) and releasing glycosylphosphatidylinositol-anchored glypican-6, a putative co-receptor. A single point mutation in the ectodomain abolishes GDE2 function. Our results reveal GDE2 as a cell-autonomous inducer of neuroblastoma differentiation with prognostic significance and potential therapeutic value.
The journey from cancer patient to cancer survivor: A 5-year longitudinal study
Authors: C. F. Snyder, C. C. Earle, R. J. Herbert, B. A. Neville, K. D. Frick
Journal: Journal of Clinical Oncology (2007)

6501 Background: The appropriate care for cancer survivors after active treatment ends is unclear. This study explores the mix of physician specialties survivors see and how this mix affects their receipt of preventive care. Methods: We conducted a retrospective, longitudinal cohort study of stage 1–3 colorectal cancer survivors age 65+ diagnosed in 1997. The cohort was followed for a 5-year survivorship period, starting 365 days after diagnosis. Using the SEER-Medicare database, we examined physician visits and preventive care services for each year during the five year survivorship period. We investigated how receipt of preventive services relates to the mix of physician specialties seen: primary care provider (PCP) only, oncologist only, both PCP and oncologist, neither PCP nor oncologist. Results: 1,541 patients met the eligibility criteria (mean age 76, 43% male, 85% White). Over the five years of survivorship, the mean numbers of PCP visits increased (4.2, 4.1, 4.5, 4.6, 4.7) while the mean number of oncology visits decreased (1.3, 1.0, 0.8, 0.7, 0.5). In year 1 of survivorship, 37% of patients saw both a PCP and oncologist, 44% only a PCP, and 8% only an oncologist. By year 5, the respective numbers were 21%, 62%, and 4%. The rates of cholesterol screening (33%), mammography (43%), and cervical cancer screening (19%) were highest during the first year of survivorship. Compared to patients who saw only a PCP, only an oncologist, or neither, patients who had visits to both a PCP and oncologist were more likely to get flu shots, cholesterol screening, mammograms, cervical cancer screening, and bone densitometry (all p&lt;.0001). Conclusions: The mix of providers seen and preventive care received evolves during the first 5 years of survivorship. As shared care between PCPs and oncologists shifts to care by PCPs only, the rate of preventive care drops, particularly for cancer screenings. These results support the need for a survivorship care plan that explicitly outlines the roles of PCPs and oncologists and ensures proper preventive care. No significant financial relationships to disclose. [Table: see text]
MRD Monitoring in AML Patients with MLL-MLLT4 by Quantification of Fusion Gene Transcripts and Genomic Chromosomal Breakpoint Sequences
Authors: Grigory Tsaur, Anna Ivanova, Olga Plekhanova, Tatyana Riger, Yulia Yakovleva, Alexander Popov, Yulia Svechnikova, Olga Makarova, Egor Shorikov, Leonid Saveliev, Claus Meyer, Rolf Marschalek, Larisa Fechina
Journal: Blood (2008)
Pulmonary endarterectomy for calcified amorphous tumour-related pulmonary hypertension
Authors: Peter I Bonta, Harm J Bogaard, Inge van den Berk, Hans W M Niessen, Allard van der Wal, Petr Symersky
Journal: Thorax (2016)

A 42-year-old patient presenting with exertional dyspnoea was diagnosed with functional class II pulmonary hypertension (PH) with severe tricuspid valve insufficiency due to cardiac and pulmonary artery obstruction by calcified amorphous tumour (paCAT). Bilateral (sub)segmental perfusion defects were seen on ventilation/perfusion scan (see online supplementary figure S1), while the CT angiogram showed large amounts of calcified radio-opaque material in absence of radiological characteristics of chronic thromboembolic pulmonary hypertension (CTEPH), such as webs, stenosis or pouches (figure 1A, C). After multi-institutional (Amsterdam, NL and Papworth, Cambridge, UK) assessment of the case, a decision was made to perform a complete, bilateral, pulmonary endarterectomy (PEA) combined with tricuspid valve replacement. During PEA bone-hard material was retrieved that lacked the (sub)segmental pulmonary …
CMV Specific Immunotherapy: How Many Patients Will Benefit?.
Authors: Russell J. Garland, Paraskevi Diamanti, Samantha E. West, Ann Green, David Carrington, Sarah J. Groves, Kerri L. Winship, Stephen P. Robinson, Anthony Oakhill, Jacqueline M. Cornish, Derwood H. Pamphilon, David I. Marks, Nicholas J. Goulden, Allison G. Blair, Colin G. Steward
Journal: Blood (2004)
A phase II study of erlotinib and sorafenib in chemotherapy-naive patients with locally advanced/metastatic non-small cell lung cancer (NSCLC)
Authors: J. S. Lind, A. C. Dingemans, H. J. Groen, E. F. Smit
Journal: Journal of Clinical Oncology (2009)

8018 Background: This multicentre, phase II study evaluates efficacy and safety of erlotinib, an EGFR inhibitor, and sorafenib, a multi-kinase inhibitor, in advanced NSCLC. In addition circulating endothelial cell (CEC) numbers, plasma VEGF, tumor metabolic activity ( 18 FDG-PET), and tumor blood flow (H 2 15 O-PET) were measured. Methods: Chemotherapy-naive patients (≥ 18 years; performance status 0–1) with pathologically proven irresectable stage IIIB or IV NSCLC were eligible. Pts received erlotinib (150 mg/od) and sorafenib (400 mg/bd) until disease progression or unacceptable toxicity. The planned sample size was 48. The primary endpoint was the rate of non-progression (NPR) at 6 weeks. Secondary endpoints: objective response rate (RECIST), time to progression (TTP), overall survival (OS) and adverse events (AEs). CECs, characterized by CD45 neg /CD34 bright , and plasma VEGF were measured in blood samples on days (D)0, 7, 21. 18 FDG-PET and H 2 15 O-PET were performed on D0, 21. Results: 50 pts were enrolled: 22 females; median age 60 yrs (range 41–78); 30 PS 0; 37 stage IV; 34 adenocarcinoma; 11 never smokers; 10/33 EGFR mutations (exons 19 (n=5), 20 (n=1), 21 (n=4)); 3/33 K-Ras mutations. Median FU is 3.3 mo (range 0.2–10.8) with 20 pts on therapy. The NPR at 6 weeks was 76%: 13 PR, 25 SD, 8 PD, 4 NE. Median TTP is 4.6 mo (95% CI 2.6–6.6). Median OS has not been reached. Grade ≥ 3 AE: anorexia (n=1), acneiform rash (n=5), diarrhoea (n=6), fatigue (n=4), hand-foot skin reaction (n=6), nausea (n=2), oral mucositis (n=2), rash (n=5), vomiting (n=1) and fatal hemoptysis (n=1). Median CECs (n=24) and plasma VEGF (n=25) increased from 41cells/ml D0 to 124 D7 (p=0.001) to 148 D21 (p=0.000) and 44pg/ml D0 to 60 D7 (p= 0.024), respectively. 18 FDG SUV (n=28) decreased by median 35% (p=0,000). 18 FDG SUV decreased more in clinical (RECIST) responders than non-responders (-51% vs -18.5%, p=0.031). Tumor blood flow (n=14) decreased by median 11% (n.s). Relations of these biomarkers with TTP and survival will be provided. Conclusions: The combination of sorafenib and erlotinib is safe and has clinically significant anti-tumor activity in chemotherapy-naive patients with stage IIIB/IV NSCLC, with significant changes in CECs, VEGF, and metabolic tumor activity. No significant financial relationships to disclose.
Mitral regurgitation in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: Prognostic significance and relation to ventricular size and function
Authors: M Amigoni, D Mangalat, M Bourgoun, EJ Velazquez, Frans Van de Werf, J Ghali, Jjv McMurray, L Kober, MA Pfeffer, SD Solomon
Journal: Journal of the American College of Cardiology (2005)
Adjunctive abciximab to reperfusion therapy in patients with acute st-segment elevation myocardial infarction: A meta-analysis of randomized trials
Authors: G De Luca, H Suryapranata, GW Stone, D Antoniucci, JE Tcheng, FJ Neumann, Frans Van de Werf, EM Antman, EJ Topol
Journal: Journal of the American College of Cardiology (2005)
The beta-3 adrenoreceptor inhibits cardiac hypertrophy through nitric oxide synthase and activation of AMP-activated protein kinase
Authors: J Hammond, B Manoury, E Dubois, J Hamelet, B Demeulder, A Vanderper, Paul Herijgers, D Langin, Luc Bertrand, J. L Balligand
Journal: Cardiovascular Research (2012)
Uptake mechanisms of EGFR-targeted TiO2 nanoparticles.
Authors: Y. Yuan, T. Paunesku, J. Ward, S. Vogt, G. Woloschak
Journal: Journal of Clinical Oncology (2010)

e13583 Background: We are developing TiO2 nanoconjugates (NCs) that can be used as therapeutic and diagnostic agents. Nanoscale TiO2 can be surface conjugated with various molecules and has the unique ability to induce reactive oxygen species after radiation activation. The two major questions that we wish to answer are (1) how are NCs internalized by cells and (2) is targeting of NCs using a small peptide achievable. To address these questions, we have created NCs targeted to epidermal growth factor receptor (EGFR) which is enriched in many epithelial cancers. Methods: 3 nm TiO2 nanoparticles (NPs) were synthesized by low temperature alkaline hydrolysis. EGFR targeted NCs were created by conjugating an eleven amino acid EGF peptide to NPs through a dopamine linker. Cell growth and immunocytochemistry were done as usual. X-ray Fluorescence Microscopy (XFM) was performed at the 2-ID-E beamline of the Advanced Photon Source at Argonne National Laboratories. Results: Previous reports have shown that a part of epidermal growth factor (EGF) known as the B-loop is required for binding EGFR. We selected eleven amino acids from this region and synthesized FITC-labeled, dopamine-conjugated peptides. These peptides were then used to treat two isogenic colon cancer cell lines, one with high EGFR expression (SW480) and one with low EGFR expression (SW620). Immunofluorescent imaging of treated cells showed that FITC-labeled peptides colocalized with EGFR labeled with fluorescent antibodies on the cell surface and within the cytoplasm. The synthetic EGF peptides were then conjugated to NPs via dopamine to create EGFR targeted NCs. These NCs also colocalized with EGFR in treated cells by immunofluorescence imaging. This was confirmed using XFM which allows for direct detection of titanium as well as gold. These images showed that EGFR labeled with gold conjugated antibodies colocalized with titanium at the cell surface. Conclusions: TiO2 NCs are a promising vehicle for the delivery of therapeutic and diagnostic agents to certain cell types. Conjugating biomolecules that promote specific uptake and retention in tumor cells will allow for controlled drug delivery. In fact, we have shown that EGFR targeted NCs can successfully colocalize with EGFR on the surface of colon cancer cells. No significant financial relationships to disclose.