tbuckley/cabot-search huggingface dataset:
Weekly oxaliplatin (OXA), 5-fluorouracil (FU) and leucovorin (LV) as first line treatment for advanced colorectal cancer (CRC) –A phase II study
Authors: D. Tsavdaridis, A. Athanasiadis, N. Pissanidis, M. Saleh, A. Moshidis, A. Chatzichristou, N. Makrantonakis, P. Kamentsidis, I. Natsiopoulos, C. Christakis
Journal: Journal of Clinical Oncology (2004)

3712 Background: OXA has previously shown high efficacy in metastatic colorectal cancer when combined with 5FU/LV, mainly as a FOLFOX schedule. This phase II clinical study was designed to evaluate the efficacy and toxicity of a different OXA-5FU/LV schedule, as first line treatment of advanced colorectal cancer. Methods: Forty-five patients with advanced CRC (median age 69 years, range 50–80, 34 males, 11 females were included. Sites of metastases included liver 25 (55.6%), lymph nodes 14 (31.1%), pelvis 12 (26.7%), peritoneum 11 (24.4%), other 9 (20.0%). Eleven patients had received prior adjuvant chemotherapy, and two radiotherapy outside of the target lesions. The regimen consisted of 200 mg/m2 LV (2h i.v.), 450 mg/m2 5-FU (bolus), and 45 mg/m2 OXA (2h i.v.), weekly for 6 weeks as induction therapy and then weekly for 3 weeks with 1 week rest until progression or unacceptable toxicity. Results: All patients were evaluable for response and toxicity. Grade 3–4 toxicities were: neurotoxicity (4%), diarrhea (4%), leucopenia (2%), nausea/vomiting (2%) and allergy (2%). Dose reductions were necessary in 14 of 45 patients (31.1%) and treatment was early interrupted in 3 of 45 patients (2 progressive disease and 1 death due to acute myocardial infarction). Complete response was observed in 4/45 (8.9%), partial response in 11/45 (24.4%) for a response rate of 33.3%. At a median follow-up of 19 months, 29 patients had relapsed (64.5%). Median time to progression was 13.4 months [95% CI: 10.6–18.2], and median survival 20.4 months [95% CI: 17.2–28.2]. Conclusions: This schedule is highly effective as first line treatment for advanced CRC. It is a feasible, well-tolerated regimen, with low incidence of G3–4 toxicities. Further evaluation is warranted. No significant financial relationships to disclose.
Participation in cancer pharmacogenomic studies in 8,456 patients registered to Cancer and Leukemia Group B (Alliance) clinical trials.
Authors: Lynn G. Dressler, Allison Mary Deal, Dorothy Watson, Donna Hollis, Kouros Owzar, Kathleen Donohue, Paula N. Friedman, Mark J. Ratain, Howard L. McLeod
Journal: Journal of Clinical Oncology (2013)

6501 Background: Clinically annotated specimens from cancer clinical trial participants offer an opportunity for discovery and validation of pharmacogenomic findings. This observational study assessed patient (pt) and institutional factors that may contribute to participation in pharmacogenomic components of prospective cancer clinical trials. No trial in the study used pharmacogenomic results to guide therapy, but germline DNA was collected from consenting pts for future study of potential heritable variations associated with clinical outcome. Methods: Pt demographic data (age, sex, diagnosis, self-reported race) and institutional characteristics (CALGB/CTSU site, diversity, accrual rate) were evaluated for 8546 pts enrolled in 7 CALGB phase III trials with a pharmacogenomic component. Participation was defined as pt consent specific to this component documented in the CALGB database. Results: Most pts (81%) enrolled on the clinical trials consented to participate in the pharmacogenomic component. In a multivariable analysis, site (CALGB vs CTSU), self-reported race (non-white vs white) and institutional diversity (% minority cancer pts on national trials) were significantly associated with participation. Pts from CALGB sites were more likely to participate than pts at CTSU sites (OR 2.09, CI 1.60-2.73, p&lt;0.0001). Non-white pts were less likely to participate than white pts (OR 0.48, CI 0.41-0.56, p&lt;0.0001). A significant interaction between site and race was observed (OR 0.41, CI 0.37-0.47, p&lt;0.0001). As institutional diversity increased, likelihood of participation in the pharmacogenomic component decreased for both white (p=0.0001) and non-white pts (p=0.054). Conclusions: Pharmacogenomic studies are achievable in the context of multicenter cancer clinical trials, but optimization of pt and institution participation is needed. Institutional factorsappear to be more important than pt demographics. To promote equitable pt benefit, prospective studies should be conducted to understand barriers and incentives to participation in pharmacogenomic research at the patient, clinician and institutional levels.
Special Report: The American Academy of Ophthalmology Task Force Consensus Statement on Adverse Events with Intraocular Lenses
Authors: Samuel Masket, Eva Rorer, Walter Stark, Jack T. Holladay, Scott MacRae, Michelle E. Tarver, Adrian Glasser, Don Calogero, Gene Hilmantel, Tieuvi Nguyen, Malvina Eydelman
Journal: Ophthalmology (2016)
A new method for estimating left ventricular dP/dt by continuous wave Doppler echocardiography (I: Reply)
Authors: G. S. Bargiggia, C. Bertucci, F. Recusani, A. Raisaro, S. De Servi, L. M. Valdes-Cruz, D. J. Sahn, L. Tronconi
Journal: Circulation (1990)
NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis
Authors: S Struski, S Lagarde, P Bories, C Puiseux, N Prade, W Cuccuini, M-P Pages, A Bidet, C Gervais, M Lafage-Pochitaloff, C Roche-Lestienne, C Barin, D Penther, N Nadal, I Radford-Weiss, M-A Collonge-Rame, B Gaillard, F Mugneret, C Lefebvre, E Bart-Delabesse, A Petit, G Leverger, C Broccardo, I Luquet, M Pasquet, E Delabesse
Journal: Leukemia (2016)
Pretherapeutic prognostic impact of FDG-PET in high-grade gliomas: A multivariate analysis including all consensual prognostics factors
Authors: C. Colavolpe, E. Guedj, J. Mancini, C. Bequet-Boucard, P. Metellus, M. Barrie, D. Taieb, D. Figarella-Branger, O. Mundler, O. L. Chinot
Journal: Journal of Clinical Oncology (2008)

2080 Background: The prognostic value of positron emission tomography with [18F]-fluoro-2-deoxy-D-glucose (FDG-PET) has been previously reported in high-grade gliomas (HGG) with inconstant results using different statistical methods in nonhomogeneous population. Indeed, most of these studies are based on univariate or limited multivariate analysis, not including all consensual prognostics factors. The objective of this study was to determine the independent prognostic value of pretherapeutic FDG-PET on overall (OS) and event-free survival (EFS) in HGG. Methods: We retrospectively included 41 histologically-proven HGG: 31 glioblastomas multiforme, WHO grade IV (GBM) and 10 anaplasic gliomas, WHO grade III (AG). Pretherapeutic FDG-PET was performed on hybrid PET/computerized tomography. The uptake of FDG was assessed by a five visual-step metabolic grading (MG), and the ratio between tumour and controlateral maximal standardized uptake value (T/CL). OS and EFS following PET were determined by Kaplan-Meier analysis and correlated with FDG uptake by univariate and multivariate analysis (MVA) using log-rank test and Cox Regression. MVA included FDG uptake, age, Karnofsky performance status (KPS), extend of surgery, histologic grade (HG), and first-line chemotherapy in GBM. A second MVA was performed with FDG uptake and RPA (recursive partitioning analysis) classification of the RTOG. Results: Median OS and EFS of were respectively 18.4 and 9.2 months, significantly higher for AG than GBM (respectively p=0.040 and p=0.027). MG was nearly correlated with OS in the whole group and in the GBM (respectively p=0.077 and 0.059). T/CL ratio was significantly correlated with OS (p=0.003) and nearly significantly with EFS (p=0.052), independently from age, KPS, histological grade, surgery and RPA classification. In GBMs subgroup, T/CL ratio still predicted OS (p=0.018), independently from age, KPS, surgery, RPA classification and 1st-line chemotherapy. Conclusions: On preoperative FDG-PET, the ratio between tumour and controlateral uptake can provide additional prognostic information in the management of HGG, independently from consensual prognostic factors. No significant financial relationships to disclose.
Plasma Concentrations of Asymmetric Dimethylarginine, an Endogenous Nitric Oxide Synthetase Inhibitor, Are Elevated in Sickle Cell Patients but Do Not Increase during Painful Crises.
Authors: Pearl Landburg, Tom Teerlink, Sigrid de Jong, Frits A. Muskiet, Ashley J. Duits, John-John B. Schnog
Journal: Blood (2006)
Granulocyte Transfusions at Appropriate Doses Improve Survival in Hematological Patients with Febrile Neutropenia
Authors: Luciana Teofili, Caterina Giovanna Valentini, Nicola Piccirillo, Roberta De Blasi, Patrizia Chiusolo, Rossana Putzulu, Stefan Hohaus, Marco Lai, Luana Fianchi, Maria Bianchi, Gina Zini, Simona Sica, Livio Pagano
Journal: Blood (2015)
The role of critical care nurses in euthanasia and assisted suicide. by David A. Asch
Authors: David A Asch
Journal: New England Journal of Medicine (1996)

tag=1 data=The role of critical care nurses in euthanasia and assisted suicide. by David A. Asch

tag=2 data=Asch, David A.

tag=3 data=New England Journal of Medicine,

tag=4 data=334

tag=5 data=21

tag=6 data=23 May 1996

tag=7 data=1374-1379.

tag=8 data=EUTHANASIA

tag=11 data=1996/2/4

tag=12 data=96/0174

tag=13 data=CAB
A Phase 1b Dose Escalation Safety Analysis of Lenalidomide and Azacitidine Maintenance Therapy for Poor Risk AML,
Authors: Andrew H Wei, Peter T. Tan, Patricia A. Walker, Sharon Avery, Sushrut S. Patil, Anthony P. Schwarer, Elchanan H. Januszewicz, Simon J. Harrison, Wai Khoon Ho, Constantine S. Tam, Andrew Spencer
Journal: Blood (2011)
Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen
Authors: Heather M. Brechbuhl, Jessica Finlay-Schultz, Tomomi M. Yamamoto, Austin E. Gillen, Diana M. Cittelly, Aik-Choon Tan, Sharon B. Sams, Manoj M. Pillai, Anthony D. Elias, William A. Robinson, Carol A. Sartorius, Peter Kabos
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Antiendocrine therapy remains the most effective treatment for estrogen receptor–positive (ER+) breast cancer, but development of resistance is a major clinical complication. Effective targeting of mechanisms that control the loss of ER dependency in breast cancer remains elusive. We analyzed breast cancer–associated fibroblasts (CAF), the largest component of the tumor microenvironment, as a factor contributing to ER expression levels and antiendocrine resistance. Experimental Design: Tissues from patients with ER+ breast cancer were analyzed for the presence of CD146-positive (CD146pos) and CD146-negative (CD146neg) fibroblasts. ER-dependent proliferation and tamoxifen sensitivity were evaluated in ER+ tumor cells cocultured with CD146pos or CD146neg fibroblasts. RNA sequencing was used to develop a high-confidence gene signature that predicts for disease recurrence in tamoxifen-treated patients with ER+ breast cancer. Results: We demonstrate that ER+ breast cancers contain two CAF subtypes defined by CD146 expression. CD146neg CAFs suppress ER expression in ER+ breast cancer cells, decrease tumor cell sensitivity to estrogen, and increase tumor cell resistance to tamoxifen therapy. Conversely, the presence of CD146pos CAFs maintains ER expression in ER+ breast cancer cells and sustains estrogen-dependent proliferation and sensitivity to tamoxifen. Conditioned media from CD146pos CAFs with tamoxifen-resistant breast cancer cells are sufficient to restore tamoxifen sensitivity. Gene expression profiles of patient breast tumors with predominantly CD146neg CAFs correlate with inferior clinical response to tamoxifen and worse patient outcomes. Conclusions: Our data suggest that CAF composition contributes to treatment response and patient outcomes in ER+ breast cancer and should be considered a target for drug development. Clin Cancer Res; 23(7); 1710–21. ©2016 AACR.
Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness
Authors: Julie Leca, Sébastien Martinez, Sophie Lac, Jérémy Nigri, Véronique Secq, Marion Rubis, Christian Bressy, Arnauld Sergé, Marie-Noelle Lavaut, Nelson Dusetti, Céline Loncle, Julie Roques, Daniel Pietrasz, Corinne Bousquet, Stéphane Garcia, Samuel Granjeaud, Mehdi Ouaissi, Jean Baptiste Bachet, Christine Brun, Juan L. Iovanna, Pascale Zimmermann, Sophie Vasseur, Richard Tomasini
Journal: Journal of Clinical Investigation (2016)

The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk. Formation of the ANXA6/LRP1/TSP1 complex was restricted to cancer-associated fibroblasts (CAFs) and required physiopathologic culture conditions that improved tumor cell survival and migration. Increased PDA aggressiveness was dependent on tumor cell-mediated uptake of CAF-derived ANXA6+ EVs carrying the ANXA6/LRP1/TSP1 complex. Depletion of ANXA6 in CAFs impaired complex formation and subsequently impaired PDA and metastasis occurrence, while injection of CAF-derived ANXA6+ EVs enhanced tumorigenesis. We found that the presence of ANXA6+ EVs in serum was restricted to PDA patients and represents a potential biomarker for PDA grade. These findings suggest that CAF-tumor cell crosstalk supported by ANXA6+ EVs is predictive of PDA aggressiveness, highlighting a therapeutic target and potential biomarker for PDA.
Prognostic Impact of Deletions of Derivative Chromosome 9 on Patients (PTS) with Chronic Myelogenous Leukemia (CML) in Chronic Phase Treated with Nilotinib or Dasatinib.
Authors: Alfonso Quintas-Cardama, Hagop M. Kantarjian, Susan O’Brien, Gautam Borthakur, Srdan Verstovsek, William Wierda, Jenny Shan, Jorge Cortes
Journal: Blood (2008)
Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and meta-analysis
Authors: F. Petrelli, K. Borgonovo, M. Cabiddu, A. Coinu, M. Ghilardi, V. Lonati, S. Barni
Journal: British Journal of Dermatology (2016)

Topical and systemic prophylactic measures, which are administered before the development of epidermal growth factor receptor (EGFR)-related acneiform rash, are appropriate interventions to mitigate the intensity of skin toxicity. We have performed a systematic review and meta-analysis to evaluate whether prophylactic antibiotics may reduce the occurrence and severity of anti-EGFR drug-related skin rashes. A systematic review was performed by searching Medline, Scopus, Embase, CINAHL, LILACS, Web of Science and the Cochrane Library from inception until March 2016 for publications regarding the pre-emptive role of antibiotics for EGFR-induced skin rashes. Fixed- or random-effects meta-analyses, according to heterogeneity, were used to summarize odds ratios of skin toxicity with antibiotic use. Of the 827 citations found in the search, 13 studies comprising 1073 patients were included in the analysis. In 12 studies, patients in the prophylactic antibiotic arms had a lower risk of developing a skin rash (odds ratio 0·53, 95% confidence interval 0·39-0·72, P < 0·01) than patients without antibiotic prophylaxis. In particular, moderate-to-severe toxicities (grades 2-4) were reduced by nearly two-thirds (odds ratio 0·36, 95% confidence interval 0·22-0·60, P < 0·01) in 13 studies. This translated to a 26% absolute difference of high-grade skin rash compared with the control arms (from 50% to 24%). The results of this meta-analysis show that the risk of skin rash after treatment with anti-EGFR agents for solid tumours was significantly lower in patients taking prophylaxis with antibiotics than in those who were not. Therefore, taking pre-emptive tetracyclines for several weeks at the start of anti-EGFR treatment can significantly reduce the incidence and severity of cutaneous acneiform rash.
FOLFIRI-3/bevacizumab induction, then capecitabine/bevacizumab maintenance as front-line strategy for metastatic colorectal cancer: A phase II trial.
Authors: Stefano Chong Hun Kim
Journal: Journal of Clinical Oncology (2012)

e14007 Background: Bevacizumab with FOLFIRI or FOLFOX regimen is the standard of care in metastatic colorectal cancer (mCRC). As second line regimen after FOLFOX, FOLFIRI-3 has showed a significantly better PFS in comparison with other irinotecan-based regimen. We therefore evaluated the safety, efficacy and possible predictive factors for FOLFIRI-3 in combination with bevacizumab as initial treatment for mCRC. Secondarily, we evaluated the feasibility of Capecitabine-Bevacizumab maintenance. Methods: We conducted a phase II, multicentric trial of FOLFIRI-3 regimen (irinotecan 100mg/m2 day 1, LV 200mg/m 2 day 1, 5-FU bolus 400 mg/m 2 day 1 followed by a 36-h 5-FU continuous infusion 2400 mg/m 2 , irinotecan 100mg/m 2 day 3) with bevacizumab (5mg/kg day 1) repeated every 2 weeks, as first-line treatment in mCRC for 6 months, followed by maintenance treatment with bevacizumab (7.5 mg/kg day 1) and capecitabine (1000 mg/m 2 day 1 to 14), repeated every 3 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints were PFS, overall survival (OS), and biologic analysis of potential predictive factors of response to treatment. Results: From October 2007 to July 2009, 61 patients were enrolled for treatment. The ORR was 66.7% (8.3% of complete response and 58.3% of partial response). Stable disease was observed in 25% of patients (disease control rate of 91.7%). PFS was 12 months, and OS was 33 months. Forty patients entered to maintenance phase. Favorable tolerance profile was observed. Median PFS was 14 months, and OS was 36 months. Its efficacy was maintained in patients recently exposed to oxaliplatin. Conclusions: As front-line regimen in mCRC, FOLFIRI3-bevacizumab is maybe the best among irinotecan-5FU-bevacizumab based regimens to obtain objective response rate. PFS and OS are high but it can be secondary to high complete resection rate in our trial. In recently oxaliplatin-exposed patients, FOLFIRI3-bevacizumab regimen should be considered as first line treatment. Capecitabine-bevacizumab maintenance is clearly feasible and its encouraging result should be validated in a large phase III trial.
Safety and pharmacokinetics of intravenous VEGF Trap in a phase I clinical trial of patients with advanced solid tumors
Authors: J. Dupont, M. L. Rothenberg, D. R. Spriggs, J. M. Cedarbaum, E. S. Furfine, D. P. Cohen, I. Dancy, H. S. Lee, W. Cooper, A. C. Lockhart
Journal: Journal of Clinical Oncology (2005)

3029 Background: VEGF Trap is a potent angiogenesis inhibitor comprising portions of human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (KDR) extracellular domains fused to the Fc portion of human IgG. VEGF Trap binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. This study was designed to evaluate the safety and pharmacokinetics (PK) of VEGF Trap administered intravenously. Methods: Successive cohorts of patients (pts) with relapsed or refractory solid tumors received intravenous VEGF Trap on Days 1 and 15. Pts without dose-limiting toxicity subsequently entered a long-term extension study. Study endpoints included safety, PK, and immunogenicity. Antitumor activity was assessed by CT scan, and tumor vascular response was assessed by DCE-MRI. Results: Sixteen pts have been treated across 3 dose levels (0.3, 1.0, 2.0 mg/kg every 2 weeks) to date. In the 10 pts treated at the first 2 dose levels, the most common adverse events (AEs) were fatigue (n=9), pain (n=4), and constipation (n=4). Two of these 10 pts had potentially drug-related grade 3 AEs (dose-limiting arthralgia/fatigue/voice changes; non-dose-limiting transient ALT elevation). No grade 4 or 5 AEs were encountered. Peak total VEGF Trap concentrations increased approximately proportionally to dose from 0.3 to 1.0 mg/kg; PK analysis of higher dose levels is ongoing. No pts have developed anti-VEGF Trap antibodies. Fifteen (94%) pts had DCE-MRI scans that were evaluable for tumor vascular response analysis, which is ongoing. One pt with metastatic renal cell carcinoma has maintained stable disease for over 6 months, and 1 pt with advanced uterine leiomyosarcoma had a minor response (both at the 1.0 mg/kg dose level). Conclusions: VEGF Trap has a manageable safety and tolerability profile at the dose levels studied. The maximum tolerated dose has not yet been reached, and dose escalation continues. Updated safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy results from this ongoing study will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Regeneron, sanofi-aventis, tbc sanofi-aventis tbc sanofi-aventis, tbc tbc
P2.46 (also presented as PD1.01): LCSS as a Marker of Treatment Benefit With Nivolumab vs Docetaxel in Pts With Advanced Non-Squamous NSCLC From Checkmate 057
Authors: Richard J. Gralla, David Spigel, Bryan Bennett, Fiona Taylor, John R. Penrod, Michael Derosa, Homa Dastani, Lucinda Orsini, Clarissa Mathias, Martin Reck
Journal: Journal of Thoracic Oncology (2016)
Rabbit Antithymocyte Globulin in Treatment of Children with Severe Aplastic Anemia.
Authors: Katarzyna Pawelec, Michal J. Matysiak, Edyta Niewiadomska, Kowalczyk Jerzy, Jolanta Stefaniak, Walentyna Balwierz, Ewa Zaleska-Czepko, Alicja Chybicka, Krzysztof Szmyd, Danuta Sonta-Jakimczyk, Halina Bubala, Mariusz Wysocki, Andrzej Kurylak, Jacek Wachowiak, Malgorzata Kaczmarek-Karnold, Malgorzata Stolarska, Maryna Krawczuk-Rybak, Elzbieta Leszczynska, Tomasz Urasinski, Jaroslaw Peregud-Pogorzelski, Anna Balcerska, Marek Wlazlowski
Journal: Blood (2007)