tbuckley/cabot-search huggingface dataset:
Hematologic Responses in Patients with Aplastic Anemia Treated with Deferasirox: A Post-Hoc Analysis From the EPIC Study
Authors: Jong Wook Lee, Sung-Soo Yoon, Zhi Xiang Shen, Arnold Ganser, Hui-Chi Hsu, Ali El-Ali, Dany Habr, Bernard Roubert, John B. Porter
Journal: Blood (2011)
Concepts in Cancer Modeling: A Brief History
Authors: Renee M. Thomas, Terry Van Dyke, Glenn Merlino, Chi-Ping Day
Journal: Cancer Research (2016)

Modeling, an experimental approach to investigate complex biological systems, has significantly contributed to our understanding of cancer. Although extensive cancer research has been conducted utilizing animal models for elucidating mechanisms and developing therapeutics, the concepts in a good model design and its application have not been well elaborated. In this review, we discuss the theory underlying biological modeling and the process of producing a valuable and relevant animal model. Several renowned examples in the history of cancer research will be used to illustrate how modeling can be translatable to clinical applications. Finally, we will also discuss how the advances in cancer genomics and cancer modeling will influence each other going forward. Cancer Res; 76(20); 5921-5. ©2016 AACR.
AHRQ Director Sets Course for Agency’s Health Services Research
Authors: Joan Stephenson
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Determinants of low cell yield in random fine needle aspiration (rFNA) procedures of the breast in healthy women unselected by risk.
Authors: S. A. Khan, S. Sukumar, N. Khouri, L. K. Jacobs, A. Eiring, D. Ivancic, C. Shehata, C. M. Zalles, R. T. Chatterton, V. Stearns
Journal: Journal of Clinical Oncology (2010)

1569 Background: rFNA is a minimally invasive method of breast epithelial sampling in the research setting, but low cell yield is an important limiting feature. We are enrolling healthy women unselected by risk, with the goal of identifying novel breast cancer risk biomarkers. Here we report a preliminary analysis of factors predicting low epithelial cell yield (ECY). Methods: Participants undergo bilateral breast rFNA (Fabian et. al.) The Gail risk ratio (Gail-RR) is calculated as the ratio of the subject's Gail risk estimate/risk of an average peer (Gail-RR). rFNA samples are pooled, pelleted, resuspended, and aliquoted; 10% of the sample is used for cytomorphologic evaluation (Masood score) and assessment of ECY. Mammographic density is reported using the BIRADS class (1= fatty to 4 = extremely dense). Data analysis used the chi square test for categorical variables, the Kruskal-Wallis test for comparison of medians, and linear regression for testing relationships between continuous variables. Results: 92 evaluable women had the following median values: age 50.6 years (range 36-60), BMI 26 (IQ range 22.6-31.1); BIRADS density 3 (IQ range 2-3) and 5-year Gail risk estimate 1.8% (IQ range 1.3-2.7). Gail-RR was < 1 in 15 women (17%), it was 1-2 in 49 (54%), and was > 2 in 27 women (30%); it was non-significantly higher in women yielding > 6,000 cells (2.57 vs. 1.57, p = 0.123). Median ECY overall was 5,000 (IQ range 200-17,000), with 43 women (52%) yielding < 6,000 epithelial cells. ECY was higher in pre than in postmenopausal women (8,000 vs. 3,000, p = 0.0025), and was unrelated to mammographic density (p = 0.3), or to BMI (p = 0.22). However, 4/6 women (67%) with fatty breasts and BMI > 31 yielded < 6,000 epithelial cells. There was a strong correlation of ECY with cytological atypia (p = 0.0001) and with Masood score (p = 0.0001). Conclusions: We observed a trend for an association between low cell yield and low Gail risk, low BIRADS density, and high BMI. However, the correlation is not sufficiently strong to exclude women from trials using rFNA on the basis of any single parameter. The combination of fatty breasts and high BMI may identify a small subset of women who are unlikely to yield sufficient cells for biomarker analysis. No significant financial relationships to disclose.
Pneumoscrotum after ERCP-related duodenal perforation
Authors: Marco Milone, Michele Manigrasso, Katia Di Lauro, Benedetta Manzo, Francesco Maione, Francesco Milone, Giovanni De Palma
Journal: Endoscopy (2016)

The incidence of duodenal perforation after endoscopic retrograde cholangiopancreatography (ERCP) is lower than 1 %. When it does occur, intestinal gas usually tracks upward through the retroperitoneal space and mediastinum to present as surgical emphysema in the neck [1]. We describe a rare case of a young man developing pneumoscrotum following an ERCP-related duodenal perforation.
The Added Value of Circulating Tumor Cell Enumeration to Standard Markers in Assessing Prognosis in a Metastatic Castration-Resistant Prostate Cancer Population
Authors: Glenn Heller, Karim Fizazi, Robert McCormack, Arturo Molina, David MacLean, Iain J. Webb, Fred Saad, Johann S. de Bono, Howard I. Scher
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease for which better prognostic models for survival are needed. We examined the added value of circulating tumor cell (CTC) enumeration relative to common prognostic laboratory measures from patients with CRPC. Methods: Utility of CTC enumeration as a baseline and postbaseline prognostic biomarker was examined using data from two prospective randomized registration-directed trials (COU-AA-301 and ELM-PC4) within statistical models used to estimate risk for survival. Discrimination and calibration were used to measure model predictive accuracy and the added value for CTC enumeration in the context of a Cox model containing albumin, lactate dehydrogenase (LDH), PSA, hemoglobin, and alkaline phosphatase (ALK). Discrimination quantifies how accurately a risk model predicts short-term versus long-term survivors. Calibration measures the closeness of actual survival time to the predicted survival time. Results: Adding CTC enumeration to a model containing albumin, LDH, PSA, hemoglobin, and ALK (“ALPHA”) improved its discriminatory power. The weighted c-index for ALPHA without CTCs was 0.72 (SE, 0.02) versus 0.75 (SE, 0.02) for ALPHA + CTCs. The increase in discrimination was restricted to the lower-risk cohort. In terms of calibration, adding CTCs produced a more accurate model-based prediction of patient survival. The absolute prediction error for ALPHA was 3.95 months (SE, 0.28) versus 3.75 months (SE, 0.22) for ALPHA + CTCs. Conclusions: Addition of CTC enumeration to standard measures provides more accurate assessment of patient risk in terms of baseline and postbaseline prognosis in the mCRPC population. Clin Cancer Res; 23(8); 1967–73. ©2016 AACR.
TP, TS AND DPD as Potential Predictors of Outcome Following Capecitabine Plus Oxaliplatin (XELOX) vs. Bolus 5-Fluorouracil/Leucovorin (5-FU/LV) as Adjuvant Therapy for Stage III Colon Cancer: Updated Biomarker Findings from Study NO16968 (XELOXA)
Authors: H. Schmoll, J. Tabernero, J.A. Maroun, F. De Braud, T. Price, E. Van Cutsem, M. Hill, S. Hoersch, K. Rittweger, D. Haller
Journal: Annals of Oncology (2012)
Subcutaneous Alemtuzumab Is Safe and Effective for Treatment of Global or Single-Lineage Immune-Mediated Marrow Failure: A Pilot Study.
Authors: Antonio M. Risitano, Carmine Selleri, Bianca Serio, Ludovica Marando, Andrea Camera, Lucio Catalano, Giulia Scalia, Luigi Del Vecchio, Bruno Rotoli
Journal: Blood (2007)
CHK-2 expression in lung cancer and tumor sensitivity to DNA damage-inducing therapy
Authors: H. R. Mirshahidi, J. Rogers, R. Tallaksen, M. Szwerc, P. Zhang
Journal: Journal of Clinical Oncology (2005)

7247 Background: Check-point kinase-2 (CHK2 kinase) is a critical intermediate in DNA damage pathway that regulates cell cycle progression, DNA repair and apoptosis. CHK2 gene mutation has been linked to familial human cancer syndrome Li-Fraumeni syndrome. Genetically, CHK2 knockout mice are remarkably resistant to ionizing radiation. The main purpose of this study was to correlate the expression level of CHK2 kinase in non-small cell lung cancer (NSCLC) with tumor response to DNA damaging agents. Methods: We compared the CHK-2 expression levels in NSCLC, ovarian cancer, SCLC, normal pulmonary epithelial cell lines and studied the role of epigenetic mechanism in controlling CHK2 expression. In our in-vivo studies, we used tissue micro-arrays and IHC to quantify CHK2 expression in common carcinomas. We reviewed the clinical data of 46 patients with advanced NSCLC, quantified CHK2 and p53 expression by IHC method and assessed clinical response by radiographic imaging. We correlated the tumor sensitivity to DNA damage-inducing therapies, such as chemo and radiation therapy with the level of CHK2 kinase in these tumors. Results: We found that CHK2 kinase expression was low to absent in NSCLC cell line but present in other cell lines. The reduced CHK2 expression appears due to methylation of the CHK2 promoter. CHK2 expression was present in 88% of seminoma and in 17% of NSCLC samples, tumors known to be highly sensitive and resistant, respectively, to DNA damaging agents. Our data showed that the clinical responses of NSCLC were highly variable. There appeared to be no correlation between CHK2 and p53 expression and tumor sensitivity to chemotherapy and/or radiation. Conclusions: Although CHK2 kinase is aberrantly expressed in NSCLC, there appeared to be no correlation between the tumor response and the level of CHK2 expression. Genetic complexity of advanced NSCLC may abrogate the effect of single gene expression on tumor sensitivity to treatment. Further studies using combinatorial approach should be considered. No significant financial relationships to disclose.
Synergistic Targeting of Protein Translation and Inhibition of NOTCH Signaling in T-ALL
Authors: Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Luyao Xu, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Kim De Keersmaecker, Andrea Califano, Adolfo A. Ferrando
Journal: Blood (2015)
Cardiovascular research funding : European Molecular Biology Organization Awards
Authors: Jennifer Taylor, Carola Rintisch, Sonia Stefanovic, Jaakko L. O. Pohjoismaeki, Cedric Blanpain, Holger Gerhardt, Ralf H. Adams
Journal: Circulation (2012)

Recipients of European Molecular Biology Organization funding for cardiovascular research describe their awards and their work to Jennifer Taylor, BSc, MSc, MPhil.
P0154 : Differential leukocyte count as an adjunctive biomarker of outcome in patients with acute-on-chronic liver failure
Authors: M.J. McPhail, C. Bernsmeier, E. Fatourou, A. Dhar, G. Auzinger, C. Willars, W. Bernal, M. Thursz, C. Antoniades, J.A. Wendon
Journal: Journal of Hepatology (2015)
Assessment of preoperative liver function in patients with hepatocellular carcinoma: The albumin-indocyanine green evaluation (ALICE) grade.
Authors: Takashi Kokudo, Kiyoshi Hasegawa, Katsumi Amikura, Emilie Uldry, Chikara Shirata, Takamune Yamaguchi, Junichi Arita, Junichi Kaneko, Nobuhisa Akamatsu, Yoshihiro Sakamoto, Amane Takahashi, Hirohiko Sakamoto, Masatoshi Makuuchi, Yutaka Matsuyama, Nicolas Demartines, Massimo Malago, Nermin Halkic, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2016)

4066 Background: Most patients with hepatocellular carcinoma (HCC) have underlying liver disease, therefore, precise preoperative evaluation of the patient’s liver function is essential. Methods: We developed a simple grading system incorporating only two variables, namely, the serum albumin level and the indocyanine green retention rate at 15 minutes, to assess the preoperative liver function, based on the overall survival of 1868 patients with HCC who underwent liver resection. We then tested the model in a European cohort (n = 70) and analyzed the predictive power of the grading system for the postoperative short-term outcome in a Japanese cohort. Results: The Albumin-Indocyanine Green Evaluation (ALICE) grading system was developed in a randomly assigned training cohort: linear predictor = 0.663 × log10 ICG R15 (%) - 0.0718 × albumin (g/dL) (cut-off value: -2.20 and -1.39). This new grading system showed a predictive power for the overall survival similar to the Child-Pugh grading system in the validation cohort. Determination of the ALICE grade in Child-Pugh A patients allowed further stratification of the postoperative prognosis (median survival time: grade 1, 12.5 y; grade 2, 6.45 y; grade 3, 3.37 y). This result was reproducible in the European cohort. Determination of the ALICE grade allowed better prediction of the risk of postoperative liver failure and mortality (ascites: grade 1, 2.1%; grade 2, 6.5%; grade 3, 16.0%; mortality: grade 1, 0%; grade 2, 1.3%; grade 3, 5.3%) than the previously reported model based on the presence/absence of portal hypertension. The ALICE grade 2 was further divided into 2 groups (2a and2b) using the median linear predictor (-1.88) as a cut-off value. Although major resection did not affect the incidence of ascites or the mortality rate in the ALICE grade 2a group, major resection in the ALICE grade 2b group had a significantly higher incidence of ascites and mortality rate. Conclusions: This new grading system is a simple and objective method for prediction of the postoperative long-term and short-term outcomes. This new system could be potentially used worldwide for surgical decision making in patients with HCC.
Dynamic contrast enhanced MRI (DCE-MRI) to measure antiangiogenic therapy and predict treatment response in primary liver cancer (PLC).
Authors: A. C. Yopp, L. H. Schwartz, N. E. Kemeny, D. Gultekin, M. Gonen, Z. Bamboat, J. Shia, M. I. D'Angelica, R. P. DeMatteo, W. R. Jarnagin
Journal: Journal of Clinical Oncology (2010)

e14537 Background: Phase II trial of unresectable PLC (intrahepatic cholangiocarcinoma [ICC] or hepatocellular carcinoma [HCC]) using a regimen of hepatic artery infusion (HAI) of floxuridine (FUDR)/dexamethasone (dex) and systemic bevacizumab (bev) analyzes the ability of DCE-MRI to predict response and outcome. Methods: 17 patients with unresectable PLC (14 ICC, 3 HCC) were treated with HAI FUDR/dex for 14 days, followed by systemic bev alone for 14 days. DCE-MRI images and peripheral blood were obtained at baseline and after HAI/FUDR/dex and bev therapy. Dynamic MRI data were analyzed using a two-compartment model. Kinetic parameters related to perfusion (AUC90, AUC180) and permeability (Ktrans) of the tumor and adjacent liver parenchyma were measured. Tumor tissue obtained at baseline was immunostained (IHC) for HIF1α and VEGF. MRI kinetic parameters, serum angiogenesis markers and IHC data were correlated with time to progression (TTP). Results: With a median follow-up of 19 months, 10 patients had progressed, 3 patients were converted to resectable disease, 2 patients are stable and 2 patients died of unrelated causes. Median TTP was 8.3 months. Significant decreases in tumor perfusion (AUC90 [-26.5%], AUC180 [-25.5%]) and permeability (Ktrans ([-25.4]) were noted in the tumors after 14 days of bev (p < 0.05). HAI FUDR/dex did not induce significant changes. No vascular parameters in normal liver parenchyma were affected by either therapy. There was an inverse correlation between changes in AUC90 and AUC180 and TTP after bev (r = -0.78, p = 0.014 and r = -0.76, p = 0.017, respectively). Decreases in AUC90 and AUC180 were associated with positive baseline tumor expression of HIF1α, p = 0.02 and 0.03, respectively. VEGF(+) tumors were associated with a prolonged TTP compared to VEGF(−) tumors (median TTP = NR vs. 5.3 months, p = 0.013). Plasma levels of VEGF and CAIX were significantly decreased after bev (p = 0.01 and p = 0.008, respectively). Conclusions: In patients with PLC, bev induces early, marked changes in tumor perfusion kinetics as measured with DCE-MRI. These changes correlate with other biomarkers of angiogenesis inhibition and hypoxia and predict time to progression. No significant financial relationships to disclose.
A New Sequence Change in the Hs2-Lcr (G→A − 10.677) and Gg-Globin Gene Promoter Region (T→C − 157 and a 4 Bp Deletion − 222 to − 225) in Sickle Cell Anemia Patients with Fetal Hemoglobin Level and bS-Globin Gene Haplotypes Diversity.
Authors: Elisangela V. Adorno, Jose P. Moura Neto, Isa Lyra, Angela D. Zanette, Leandro F. Santos, Magda O. Seixas, Mitermayer G. Reis, Fernando F. Costa, Marilda S. Goncalves
Journal: Blood (2006)
Retrospective review of paclitaxel beyond second-line therapy in patients with small cell cancer.
Authors: Tricia L. Kalwar, Haralambos Raftopoulos, Doru Paul, Craig E. Devoe, Nina Kohn, Scott Z. Fields
Journal: Journal of Clinical Oncology (2014)

e18549 Background: Previous studies have evaluated paclitaxel (pac) in the second-line setting for relapsed/refractory small cell cancer (SCC) with response rates of 23.8% and a median survival of 5.8 months noted. There is limited data on the use of pac in patients that have disease progression after second line treatment and are fit for further treatment. This review serves as the first known dedicated evaluation of pac in the third line and beyond. Methods: Eligible patients were analyzed for response (complete and partial) according to the RECIST criteria with the associated two-sided 95% exact binomial confidence interval calculated. Due to the small sample size this study is descriptive in nature, evaluating toxicities, stage, previous treatments, and duration of pac. Results: Between 2010 and 2012, 10 patients with relapsed SCC were treated with pac as third line treatment or beyond at our institution. The median age was 53.5 (45-82); 60% were males; 80% of the cases were small cell of the lung (remaining were ampulla of vater and bladder). Of the lung cases 75% were extensive stage at diagnosis. The number of previous chemotherapy regimens received was 2, 3 and 4 (50%, 40% and 10% respectively). Of all 10 patients 90% received platinum/etoposide as first line treatment and eight patients received irinotecan prior to pac therapy. Eighty percent of patients received weekly pac . The partial response rate was 44%(CI95% 0.14- 0.79). Disease progression occurred in 44% of patients, 11% had a mixed response and there were no complete responses (One patient's response was unknown). Median survival after initiation of pac was 8.6 months. Neuropathy, myelosuppression and fatigue were assessed with no grade 3 or higher toxicities, with 67% of patients able to receive additional treatments after progression. Conclusions: Pac has activity in this patient population with acceptable toxicity and a prospective study may be appropriate to confirm. Nab-paclitaxel may offer a similar benefit with less toxicity. The results from our review would provide the background for the design of a prospective evaluation of nab-paclitaxel in heavily pretreated patients with small cell cancer.
Healthcare Resource Utilization Trends over Time with Continuous Lenalidomide Treatment (Tx) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM)
Authors: Katja Weisel, Dan T. Vogl, Michel Delforge, Kevin Song, Meletios Dimopoulos, Jamie Cavenagh, Cyrille Hulin, Philippe Rodon, Bertrand Arnulf, Robin Foá, Albert Oriol, Shien Guo, Mara Silvia Monzini, Jason Van Oostendorp, Annette Ervin-Haynes, Thierry Facon
Journal: Blood (2014)
DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study
Authors: Joanne Trinh, Emil K Gustavsson, Carles Vilariño-Güell, Stephanie Bortnick, Jeanne Latourelle, Marna B McKenzie, Chelsea Szu Tu, Ekaterina Nosova, Jaskaran Khinda, Austen Milnerwood, Suzanne Lesage, Alexis Brice, Meriem Tazir, Jan O Aasly, Laura Parkkinen, Hazal Haytural, Tatiana Foroud, Richard H Myers, Samia Ben Sassi, Emna Hentati, Fatma Nabli, Emna Farhat, Rim Amouri, Fayçal Hentati, Matthew J Farrer
Journal: The Lancet Neurology (2016)
Cost-effectiveness of rituximab, fludarabine, and cyclophosphamide (R-FC) in patients with previously untreated chronic lymphocytic leukemia (CLL).
Authors: J. C. Hornberger, C. M. Reyes, A. Shewade, M. Friedmann, L. Chan, H. Gutierrez, S. Satram-Hoang, S. Lerner, M. J. Keating
Journal: Journal of Clinical Oncology (2010)

e16500 Background: R-FC significantly increases progression-free survival (PFS) compared to FC in previously untreated CLL (phase III trial ML 17102-CLL-8). A cost-effectiveness analysis was conducted from a U.S. third-party payer perspective. Methods: We developed a decision- analytical model to project PFS and overall survival (OS) data over a time horizon of 15 years. Costs calculated in 2009 US dollars included chemotherapy drugs, administration, treatment of grade 3/4 adverse events, and salvage therapies after disease progression. Drug costs were based on the dose tables from the trial and were calculated using Medicare fee schedules. Utilities for stable and progressed disease were obtained from the literature. Main outcome measures were incremental cost-effectiveness ratio (ICER) for life-year and quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of the results. Results: Using the area under the curve approach, R-FC increased both PFS and OS by 1.9 years, and QALYs by 1.2 years compared with FC. R-FC incurred $28,000 higher costs for chemotherapy drugs and administration and $3,500 for treatment of adverse events. 16% of these increased costs for R-FC were offset by higher treatment and administration costs for FC after progression due to early relapse. The net difference in costs between R-FC and FC was $26,000, resulting in an ICER of $22,000 which compares well with the cost-effectiveness of oncology treatments in the United States. Results were sensitive to time horizon, cost of 100-mg vial of rituximab, and discount rate. The ICER exceeded $30,000 and $50,000 in 11% and 0.4% of probabilistic simulations, respectively. Conclusions: Among previously untreated patients with CLL, the chemotherapeutic regimen R-FC is a cost-effective use of medical resources compared to FC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech
Focal BTG1 Deletions Occur in Specific Precursor B-Cell Acute Lymphoblastic Leukemia Subtypes At Defined Hotspots Due to Aberrant V(D)J Recombination
Authors: Blanca Scheijen, Esmé Waanders, Simon V. van Reijmersdal, Laurens T. van der Meer, Liesbeth van Emst, Eugene Verwiel, Yvet Kroeze, Edwin Sonneveld, Peter M. Hoogerbrugge, Ad Geurts van Kessel, Frank N. van Leeuwen, Roland P. Kuiper
Journal: Blood (2011)