tbuckley/cabot-search huggingface dataset:
Clofarabine in previously untreated elderly (&gt;65 yrs) AML patients with an unfavourable cytogenetic profile who are considered unfit for standard intensive chemotherapy
Authors: A. K. Burnett, M. Baccarani, P. Johnson, J. Yin, N. Russell
Journal: Journal of Clinical Oncology (2006)

6513 Background: Elderly AML patients (&gt;65 yrs) are a very poor prognostic population. Standard treatment achieves an 18% overall response (OR) rate (low dose Ara-C, U.K. AML 14 trial) with no little or no responses observed in high-risk cytogenetic patients. BIOV-121 is a Phase II non-randomized study of clofarabine, a novel, next generation purine nucleoside analogue, in older patients (&gt;65 yrs) with previously untreated acute myeloid leukemia (AML) for whom standard intensive chemotherapy is not considered suitable. Methods: 66 patients aged &gt; 65 yrs with untreated AML were enrolled in study BIOV-121. All patients were considered unfit for standard intensive chemotherapy based primarily on age (&gt; 65 years) and/or performance status. All patients received clofarabine 30mg/m2 for 5 consecutive days repeated every 28 days (1 course) for a maximum of 6 courses. The primary study endpoint was overall response rate (ORR) defined as the number of patients achieving a CR, CRi, or PR according to the international working group guidelines. A preliminary analysis was conducted on both patients with an unfavourable cytogenetic profile (11/44 patients), for whom data was available, and on patients &gt; 70 years of age (36/66 patients). Unfavourable cytogenetic prognostic risk was defined as the presence of a complex karyotype, monosomies of chromosome 5 (del [5q]/5q-), or 3q abnormalities as reported by Grimwade et al (U.K. MRC AML 10 trial). Results: Of 44 patients for whom cytogenetic data was available, 25% (11/44) had an unfavourable cytogenetic prognostic risk profile. The median number of clofarabine courses administered in this patient group was one. With a median age of 68 years the overall response rate (ORR) in this unfavourable cytogenetic patient group was 36% (4/11) with a 27% complete response (CR) rate. 55% (36/66) of patients were aged &gt;70 years. The ORR and CR rate was 56% and 44% respectively in patients aged &gt;70 years. The toxicity of clofarabine was acceptable and manageable in elderly AML patients. Conclusions: Clofarabine appears superior to current standard treatment (low-dose Ara-C) in both unfavourable cytogenetic AML (&gt;65 years) and AML patients &gt; 70 years (all cytogenetic risk groups). [Table: see text]
Use of PSA threshold to identify an increased 4-year risk of a prostate cancer diagnosis in U.S. men
Authors: E. D. Crawford, J. Moul
Journal: Journal of Clinical Oncology (2009)

5051 Background: Recent studies have shown that prostate specific antigen (PSA) values can be used to predict risk of developing prostate cancer (PCa) in the future. In the European Randomized Study of Screening for PCa (ERSPC) subjects with PSA of ≥1.5 ng/mL had a significantly greater risk of developing PCa after 4 years than subjects with PSA of &lt;1.5 ng/mL (9.2% vs 1.5%, respectively; OR = 7.466; p &lt; 0.001). This current analysis aimed to validate the ability of PSA of ≥1.5 ng/mL to predict the future risk of PCa in a US population of men within the Henry Ford Healthcare System (HFHS). Methods: This is a retrospective analysis of men enrolled in the Health Alliance Plan of the HFHS between 1997–2004 with at least 4 years of follow-up data. Men ≥40 years of age, with a baseline PSA value between 0–4.0 ng/mL, not receiving 5-alpha reductase inhibitors were included. Men were followed for 4 years after their first PSA value. The risk of 4-year PCa diagnosis was evaluated based on a 1.5 ng/mL PSA threshold, and was assessed by logistic regression, controlling for age and race. Results: A total of 21,502 patients were included in the analysis. At baseline, patients had a mean age of 55 years and a mean PSA of 1.0 ng/mL. Overall, 7.9% of patients with baseline PSA of 1.5–4 ng/mL were diagnosed with PCa after 4 years, compared to 0.5% of patients with a baseline PSA of &lt;1.5 ng/mL. In a multivariate analysis (controlling for race and age), patients with a baseline PSA of 1.5–4 ng/mL were 12 times more likely to be diagnosed with PCa over 4 years than patients with baseline PSA of &lt;1.5 ng/mL (OR = 12.4; 95% CI: 9.7–15.9; p &lt; 0.0001). African Americans (n = 6,367) with baseline PSA 1.5–4 ng/mL vs baseline PSA&lt;1.5 ng/mL had an even higher risk of being diagnosed with PCa over 4 years (OR = 17.0; 95% CI: 11.0–26.1; p &lt; 0.0001). Conclusions: This analysis validates that men with PSA values 1.5 to 4 ng/mL are at a significantly increased risk for developing future prostate cancer compared to those with a PSA value below the 1.5 threshold. This threshold also confers increased 4-year risk in African American men. [Table: see text]
A Phenotype of Atopy in Schoolchildren Is Associated with New Development of Allergic Rhinitis and Asthma in a Prospective Study
Authors: Si Hyeon Lee, Eun Lee, Hyun-Ju Cho, Ji-Won Kwon, Young Ho Kim, Yean Jung Choi, Song-I Yang, Young Ho Jung, Ho-Jang Kwon, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2016)
Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups
Authors: Simon Rothwell, Robert G Cooper, Ingrid E Lundberg, Frederick W Miller, Peter K Gregersen, John Bowes, Jiri Vencovsky, Katalin Danko, Vidya Limaye, Albert Selva-O'Callaghan, Michael G Hanna, Pedro M Machado, Lauren M Pachman, Ann M Reed, Lisa G Rider, Joanna Cobb, Hazel Platt, Øyvind Molberg, Olivier Benveniste, Pernille Mathiesen, Timothy Radstake, Andrea Doria, Jan De Bleecker, Boel De Paepe, Britta Maurer, William E Ollier, Leonid Padyukov, Terrance P O'Hanlon, Annette Lee, Christopher I Amos, Christian Gieger, Thomas Meitinger, Juliane Winkelmann, Lucy R Wedderburn, Hector Chinoy, Janine A Lamb
Journal: Annals of the Rheumatic Diseases (2015)

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and extramuscular manifestations such as skin rashes and interstitial lung disease. We genotyped 2566 IIM cases of Caucasian descent using the Immunochip; a custom array covering 186 established autoimmune susceptibility loci. The cohort was predominantly comprised of patients with dermatomyositis (DM, n=879), juvenile DM (JDM, n=481), polymyositis (PM, n=931) and inclusion body myositis (n=252) collected from 14 countries through the Myositis Genetics Consortium.The human leucocyte antigen (HLA) and PTPN22 regions reached genome-wide significance (p<5×10(-8)). Nine regions were associated at a significance level of p<2.25×10(-5), including UBE2L3, CD28 and TRAF6, with evidence of independent effects within STAT4. Analysis of clinical subgroups revealed distinct differences between PM, and DM and JDM. PTPN22 was associated at genome-wide significance with PM, but not DM and JDM, suggesting this effect is driven by PM. Additional suggestive associations including IL18R1 and RGS1 in PM and GSDMB in DM were identified. HLA imputation confirmed that alleles HLA-DRB1*03:01 and HLA-B*08:01 of the 8.1 ancestral haplotype (8.1AH) are most strongly associated with IIM, and provides evidence that amino acids within the HLA, such as HLA-DQB1 position 57 in DM, may explain part of the risk in this locus. Associations with alleles outside the 8.1AH reveal differences between PM, DM and JDM.This work represents the largest IIM genetic study to date, reveals new insights into the genetic architecture of these rare diseases and suggests different predominating pathophysiology in different clinical subgroups.
Zoladex with or without Flutamide in the Treatment of Locally Advanced or Metastatic Prostate Cancer: Interim Analysis of an Ongoing PONCAP Study
Authors: F Boccardo, A Decensi, D Guarneri, A Rubagotti, F Oneto, G Martorana, L Giuliani, U Delli Ponti, S Petracco, P Cortellini
Journal: European Urology (1990)
A preliminary report of biweekly oxaliplatin plus continuous ufur therapy for metastatic colorectal cancer patients
Authors: C.-P. Lin, I. Y. Chang, C. Cheng, W.-Y. Wang
Journal: Journal of Clinical Oncology (2004)

3669 Background: The aim of this study is to define the safety and efficacy of biweekly oxaliplatin therapy combined with continuous oral ufur therapy in colorectal cancer. Biweekly therapy in outpatient is more acceptable and supplemented with Ufur(tegafur+uracil)) may maintain the dose intensity of drug therapy. Methods: patients of metastatic colorectal cancer with one or more measurable metastatic lesion, who have ECOG performance status ≤ 2, and with adequate bone marrow, liver, renal function were enrolled . Treatment plans: Oxaliplatin 85 mg/m2 IV in 2 hrs with premedication of MgSO4(2 gm) Calcium gluconate (1gm) were given biweekly in out-patient . Ufur 200mg p.o. BID daily, until disease progress or totally 12 course of oxaliplatin. Results: twenty-one patients were enrolled in this trial (M/F=12/9), median age was 58 years (33–71), primary tumor site: colon 14 cases, rectum 7 cases, medium number of metastatic site was 2, and 57% of the patient had 2 or more sites (Liver 71%, LN 48%, Lung 14%, Peritoneum 14%, skin 4%). The grade III/IV toxicity of nausea 24%,neutropenia 14%, thrombocytopenia 19%, peripheral neuropathy 24%. Efficacy: 2 patients dropped out due to intolerance to continuous ufur therapy, but still received oxaliplatin, and more than 76% (16 patients) received more than 6 courses( 3 months) oxaliplatin therapy. One patient reached CR and continued oral Ufur therapy, she remains CR for more than 11 months. Two patients had PR, and one received liver segmental resection, remains healthy. Five patients (26%) had stable disease, and 11 patients( 58%) had progress disease. Conclusions: our data suggest that biweekly oxaliplatin plus ufur therapy is a active and tolerable regimen in treating metastatic colorectal cancer patients. No significant financial relationships to disclose.
Intracrine VEGF Signaling Mediates the Activity of Prosurvival Pathways in Human Colorectal Cancer Cells
Authors: Rajat Bhattacharya, Xiang-Cang Ye, Rui Wang, Xia Ling, Madonna McManus, Fan Fan, Delphine Boulbes, Lee M. Ellis
Journal: Cancer Research (2016)

Abstract The effects of vascular endothelial growth factor-A (VEGF-A/VEGF) and its receptors on endothelial cells function have been studied extensively, but their effects on tumor cells are less well defined. Studies of human colorectal cancer cells where the VEGF gene has been deleted suggest an intracellular role of VEGF as a cell survival factor. In this study, we investigated the role of intracrine VEGF signaling in colorectal cancer cell survival. In human colorectal cancer cells, RNAi-mediated depletion of VEGF decreased cell survival and enhanced sensitivity to chemotherapy. Unbiased reverse phase protein array studies and subsequent validation experiments indicated that impaired cell survival was a consequence of disrupted AKT and ERK1/2 (MAPK3/1) signaling, as evidenced by reduced phosphorylation. Inhibition of paracrine or autocrine VEGF signaling had no effect on phospho-AKT or phospho-ERK1/2 levels, indicating that VEGF mediates cell survival via an intracellular mechanism. Notably, RNAi-mediated depletion of VEGF receptor VEGFR1/FLT1 replicated the effects of VEGF depletion on phospho-AKT and phospho-ERK1/2 levels. Together, these studies show how VEGF functions as an intracrine survival factor in colorectal cancer cells, demonstrating its distinct role in colorectal cancer cell survival. Cancer Res; 76(10); 3014–24. ©2016 AACR.
Phase II trial of ketoconazole, hydrocortisone, and dutasteride (KHAD) for castration resistant prostate cancer (CRPC)
Authors: M. Taplin, Y. Ko, M. M. Regan, T. M. Beer, M. A. Carducci, P. Mathew, G. Bubley, W. K. Oh, P. W. Kantoff, S. P. Balk
Journal: Journal of Clinical Oncology (2008)

5068 Background: Recent studies indicate that intratumoral androgen synthesis and levels are increased CRPC and may contribute to androgen receptor reactivation. Ketoconazole (K) and hydrocortisone (H) have been used in CRPC to suppress adrenal androgen synthesis, but residual weak androgens may still be converted to DHT by 5α-reductases (with type 1 5α-reducatse being increased in CRPC). Based on these observations, we conducted a single-arm phase II trial to assess combination therapy with KH and dutasteride (D) (KHAD), a dual type 1 and type 2 5α-reductase inhibitor, in CRPC. Methods: Eligible men were castrate, had rising PSA, and no prior K therapy (prior chemotherapy was allowed). Treatment was K 400mg TID, H 30mg AM/10mg PM and D 0.5 mg daily. Target accrual was 57. Primary endpoint was response rate (decline in PSA >50% or measurable disease). Results: 57 participants were accrued over a two year period. Baseline mean PSA was 24 (3.7–2,671). Disease was measurable in 61%, evaluable in 23% and 14% had only rising PSA. Gleason score was 7 in 28% and 8–9 in 35%. At this report 13 patients remain on study and 40 are off study (22/40 due to progressive disease and 18 for toxicity/patient preference). PSA declined > 50% in 30/57, > 80% in 24/57 and > 90% in 14/57. Median time to progression was 13.7 months (95% CI 4.1 to 15.7 months). Conclusions. The response rate was equivalent or superior to historical controls, and time to progression was prolonged compared to published durations of 3.5–8.6 months for K/H. These data indicate that addition of D to further suppress intratumor androgen synthesis may result in improved responses, and support a randomized trial to compare KHAD with standard K/H. Updated data and correlative androgen levels will be available. No significant financial relationships to disclose.
Phase I study of oral etoposide in children with refractory solid tumors.
Authors: P Mathew, R C Ribeiro, D Sonnichsen, M Relling, C Pratt, H Mahmoud, L Bowman, W Meyer, L Avery, W Crist
Journal: Journal of Clinical Oncology (1994)

To determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and plasma concentrations of orally administered etoposide (VP-16) in pediatric oncology patients.In a phase I study, 20 children with refractory solid tumors received oral VP-16 (the intravenous preparation diluted with sodium chloride) three times daily for 21 days. Daily dose levels studied were 50 mg/m2 (n = 5), 60 mg/m2 (n = 7), and 75 mg/m2 (n = 8). VP-16 concentrations were measured in blood samples collected on days 1, 7, 14, and 21.Grade 3 to 4 thrombocytopenia and/or neutropenia causing interruption of the 21-day course or persisting for more than 7 days after the last day of chemotherapy was seen at all dose levels, but was not dose-limiting. One patient treated at the 50-mg/m2 daily dose died of sepsis. At the 75-mg/m2 dose level, diarrhea was dose-limiting. Estimated plasma VP-16 concentrations were greater than 1 micrograms/mL for median periods of 9.4, 15.4, and 13.5 hours per day at daily doses of 50, 60, and 75 mg/m2, respectively. Responses were observed in seven of 14 patients who received at least one additional course of etoposide after a rest period of 7 days. There was one complete and two objective responses. Four patients were considered to have stable disease.The intravenous preparation of VP-16 administered orally appears to be well tolerated by heavily pretreated pediatric patients. On the three-times daily, 21-day schedule, a daily dose of 75 mg/m2 exceeds the MTD, with diarrhea as the dose-limiting toxicity. The recommended dose for oral etoposide is 60 mg/m2/d administered every 8 hours.
Abstract 15459: Calcium Intake and Source Effects on Soft Tissue Calcification in Ossabaw Miniature Swine
Authors: Alyssa Phillips, Berdine Martin, Meryl Wastney, George Jackson, Scott Radcliffe, William Van Alstine, Mikaela McKenney, Martin Bahls, Sean Newcomer, Michael Sturek, Connie Weaver
Journal: Circulation (2013)

Concern over calcium supplementation for elevating risk of cardiovascular disease has led to a calcium controversy because calcium is a shortfall essential nutrient. Understanding cardiovascular ri...
A new 3D-printed overtube system for endoscopic submucosal dissection: first results of a randomized study in a porcine model
Authors: Eugen Zizer, Daniel Roppenecker, Felix Helmes, Sebastian Hafner, Yannick Krieger, Tim Lüth, Alexander Meining
Journal: Endoscopy (2016)

<b>Background and study aim:</b> Endoscopic therapy of early malignant alterations can be difficult and cumbersome. Our research study group took advantage of new methods for rapid prototyping (i. e. 3D printing) to design and test an overtube system with two manipulator arms at the tip. Both arms can be steered independently from each other by a dedicated user platform. <b>Methods:</b> This animal study involved a randomized evaluation of the new overtube device for endoscopic submucosal dissection (ESD) compared with a conventionally performed ESD. In total, 12 ESDs in six pigs were performed. Six ESDs were performed in the stomach and six in the colon. Size (in cm<sup>2</sup>) of resected specimens, the time needed to perform endoscopic resection, and adverse events were assessed. <b>Results:</b> The overtube-assisted ESD was faster and therefore more effective than the conventional ESD technique (0.45 ± 0.24 cm<sup>2</sup>/min vs. 0.22 ± 0.11 cm<sup>2</sup>/min; <i>P = </i>0.029). Only one adverse effect was recorded in the conventional group. <b>Conclusions:</b> The overtube-assisted ESD was feasible in an animal model. ESD can be performed more quickly and potentially more effectively with the newly designed overtube device compared with the conventional ESD technique.
Anagliptin, a dipeptidyl peptidase-4 inhibitor, decreases macrophage infiltration and suppresses atherosclerosis in aortic and coronary arteries in cholesterol-fed rabbits
Authors: Tsutomu Hirano, Satoko Yamashita, Masaki Takahashi, Hiroyuki Hashimoto, Yusaku Mori, Moritaka Goto
Journal: Metabolism (2016)
Reply to Nicola Fossati, Giorgio Gandaglia, Alberto Bossi, Francesco Montorsi, Alberto Briganti's Letter to the Editor re: Stephen J. Freedland, Voleak Choeurng, Lauren Howard, et al. Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy After Radical Prostatectomy. Eur Urol 2016;70:588–96
Authors: Stephen J. Freedland, Robert B. Den
Journal: European Urology (2016)
Viral evasion of DNA-stimulated innate immune responses
Authors: Maria H Christensen, Søren R Paludan
Journal: Cellular and Molecular Immunology (2016)

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.
Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways
Authors: David C. Gibbs, Irene Orlow, Jennifer I. Bramson, Peter A. Kanetsky, Li Luo, Anne Kricker, Bruce K. Armstrong, Hoda Anton-Culver, Stephen B. Gruber, Loraine D. Marrett, Richard P. Gallagher, Roberto Zanetti, Stefano Rosso, Terence Dwyer, Ajay Sharma, Emily La Pilla, Lynn From, Klaus J. Busam, Anne E. Cust, David W. Ollila, Colin B. Begg, Marianne Berwick, Nancy E. Thomas
Journal: JNCI Journal of the National Cancer Institute (2016)

Background:Solar elastosis and neval remnants are histologic markers characteristic of divergent melanoma pathways linked to differences in age at onset, host phenotype, and sun exposure. However, the association between these pathway markers and newly identified low-penetrance melanoma susceptibility loci remains unknown.
Imaging Mass Spectrometry of Novel Drug in Human Tumor Specimens: Distribution of Unlabeled Drugs to Support Early Phase Clinical Trial
Authors: T. Shimoi, A. Hamada, K. Yonemori, S. Shimma, S. Osawa, Y. Tanabe, J. Hashimoto, M. Kodaira, M. Yunokawa, H. Yamamoto, C. Shimizu, Y. Fujiwara, K. Tamura
Journal: Annals of Oncology (2014)
Pancreatic neuroendocrine tumors: Can the WHO staging system be simplified
Authors: C. Ferrone, L. H. Tang, J. Tomplinson, D. S. Klimstra, D. G. Coit, M. F. Brennan, P. J. Allen
Journal: Journal of Clinical Oncology (2007)

15038 Background: The current World Health Organization (WHO) classification system for well-differentiated pancreatic endocrine neoplasms (PENs) is complex, and incorporates both stage- and grade-specific information. The aim of this study was to compare separately the prognostic value of stage and grade in a large single institution study of PENs. Methods: A prospectively maintained database from a single institution identified 183 patients who underwent operative treatment for a PEN between 1982–2005. Tumors were staged (&lt;2 cm primary, =2 cm primary, metastatic disease) and graded (Low: no necrosis and &lt;2 mitoses/50 high-power fields - HPF. Intermediate: presence of necrosis and/or =2 mitoses/50 HPF) with a simplified schema. The influence of tumor stage and grade on disease recurrence and disease-specific survival (DSS) was assessed. Results: Median age of the 183 patients was 56 years and 53% were women. Median length of follow-up was 44 months. At the time of presentation 35 patients (19%) had tumors &lt;2 cm without evidence of metastatic disease (&lt;2 cm), 96 patients (52%) had tumors =2 cm without metastases (=2 cm), and 52 patients (29%) were found to have nodal or distant metastatic disease (mets). Size of the primary tumor was not associated with the presence of nodal metastases (mean diameter: N0, 4.8 cm vs. N1, 4.7 cm: p=0.96) and 5/19 patients with tumors =2 cm had positive nodes. Grade was determined in 98% of patients (n=180). Low-grade tumors were present in 102 patients (56%) and intermediate grade tumors in 78 patients (42%). Earlier stage tumors were more likely to have low grade disease (% Low grade: &lt;2 cm, 83%; =2 cm, 61%; mets, 28%: p &lt;0.001). For all patients, tumor stage and grade were associated with survival (5-yr DSS: Stage: &lt;2 cm, 100%; =2 cm, 90%; mets, 70%: p&lt;0.001. Grade: Low, 98%; Intermediate, 70%: p&lt;0.001). For patients with tumors =2 cm or with mets, grade was associated with survival within each sub-group (5-yr DSS =2 cm: Low 97% vs. Intermediate 80%: p&lt;0.001, Mets: Low 93% vs. Intermediate 62%: p=0.05). Discussion: Stage and grade are important independent prognostic factors in patients with PENs. More accurate prognostic information can be provided by combining tumor size and metastases with simple grading information based on necrosis and mitotic rate. No significant financial relationships to disclose.