tbuckley/cabot-search huggingface dataset:
Comparison of High-Throughput Sequencing and Flow Cytometry for Measuring Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia: A Children's Oncology Group Cohort
Authors: Charles Gawad, Michael J. Borowitz, Gary V. Dahl, Meenakshi Devidas, Malek Faham, Martin Moorhead, Brent L. Wood, Jianbiao Zheng, Mignon L. Loh, Norman J. Lacayo
Journal: Blood (2012)
Clinicopathologic factors associated with PET/CT results in early breast cancer.
Authors: C. M. Noblia, C. E. Cresta, M. A. Castro, M. E. Azar, E. G. Gonzalez, E. G. Armanasco, D. Montoya, J. M. Ipiña, G. Bruno, C. Gonzalez, A. M. Alvarez, Y. Blumenkrantz, M. D. Pereira
Journal: Journal of Clinical Oncology (2011)

e11580 Background: Increasing data support the questionable role for 18-FDG PET/CT scan in early BC assessment. We evaluated prospectively, the impact of the main clinicopathological factors of early breast cancer on (18) fluorodeoxyglucose (FDG) uptake in the breast. Methods: 60 stage 1 (n:38) and stage 2 (n:22) BC.Of these, 16 were pre-menopausal and 44 peri-menopausal.Median age was 59 yr (range, 37-83). Mean tumor size: 18.95± 9.97 mm (range, 5-40).18-FDG PET/CT took place 15 days before surgery. Results: Forty-four (72.3%) were PET/CT positive (PP) and 16 (27.7%) were PET/CT negative ( PN). Significant association between PET/CT results and clinicopathologic factors were observed for: Tumor size: 19 (32%) ≤ 10mm (T1a and T1b) (10PP and 9 PN, median SUV 1.7); 20 (33%) 10.1-20 mm (T1c) (14PP and 6 PN, median SUV 3) and 21 (35%) 20.1 -50 mm( T2) (20 PP and 1 PN;median SUV 5.6)(p= 0.009) and histologic subtype: 44 (80%) invasive ductal carcinoma (39 PP and 9 PN; median SUV 3.4), 6 (10%) invasive lobular carcinoma (3 PP and 3 PN; median SUV 2.1) and 6 (10%) other subtypes (2PP and 4 PN; median SUV 1.7) (p= 0.017). Menopausal status,age,sentinel node macro or micrometastases,nuclear grade, histologic grade and mitotic index were not significantly correlated with PET results. Multivariate logistic regresion demonstrated that small tumor size and non invasive ductal carcinoma histologic subtype were independently associated with PN results [OR: 3.13, 95%CI:1.21-8.08 (p=0.007) and OR: 3.57, 95%CI:1.40-9.10 (p=0.018), respectively]. Conclusions: Our data encourages the need to be cautious with interpretation of 18-FDG PET/CT negative results in early breast cancer population. There is a need for improving PET/CT scan accuracy, specially for non-ductal invasive carcinomas and small tumors whom are at high risk of having a PN result.
HOXB9, a gene promoting tumor angiogenesis and proliferation, as a prognostic factor in breast cancer.
Authors: H. Seki, T. Hayashida, H. Jinno, S. Hirose, M. Takahashi, M. Mukai, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

33 Background: We demonstrated that HOXB9, a member of homeobox genes, expression promoted tumor neovascularization and metastasis in vitro and in vivo assay. These findings imply that overexpression of HOXB9 contributes to tumor progression through activation of signaling pathways that alter both tumor-specific cell fates and tumor-stromal microenvironment, leading to increased invasion and metastasis. (Hayashida et al., PNAS 2010) We sought to determine whether these results could be extended to the clinical application. In this study, we evaluated the correlation between HOXB9 expression, clinical outcomes, and the clinicopathological variables in breast cancer patients, and the contribution of HOXB9 expression to tumor cell proliferation and angiogenesis. Methods: A consecutive series of 141 patients with invasive ductal carcinoma who underwent surgical treatment were examined. HOXB9 protein expression was analyzed immunohistochemically using the anti-human HOXB9 polyclonal antibody. Immunostaining of Ki-67, CD31, and CD34 were performed to evaluate the association of proliferation and tumor angiogenesis with HOXB9 expression. Results: Of 141 tumor specimens immunostained for HOXB9, 69 specimens (48.9%) were positive staining. Univariate logistic regression revealed ER and PgR negativity, HER2 positivity, high nuclear grade, and large pathological tumor size as significant variables associated with HOXB9 expression. Moreover, 12 (92.3%) out of 13 triple negative breast cancer showed HOXB9 expression. The disease-free survival (DFS) and the overall survival were significantly different between the HOXB9 positive and negative group; HR=20.714, p=0.001, HR 9.206, p=0.003, respectively. A Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for DFS (HR=15.532, p=0.009). In subgroup analysis, HOXB9 positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio in comparison with HOXB9 negative. Conclusions: Our results suggest that HOXB9 expression promoting the tumor proliferation and the angiogenesis is a significant prognostic factor in breast cancer.
Prostate-specific antigen (PSA) progression-free survival (PFS): A comparison of degarelix versus leuprolide in patients with prostate cancer.
Authors: N. D. Shore, J. W. Moul, E. Crawford, E. van der Meulen, T. Olesen, B. Persson
Journal: Journal of Clinical Oncology (2011)

12 Background: Comparative effectiveness of the gonadotropin-releasing hormone (GnRH) blocker, degarelix, vs the GnRH agonist, leuprolide, was evaluated during a 1-year phase III trial (CS21); data have been presented. We now report long-term data from an ongoing 5-year extension study (CS21A). Methods: In CS21, patients with prostate cancer (all stages) were randomized to degarelix (240 mg for 1 month, then monthly maintenance doses of 80 mg [n=207] or 160 mg [n=202]), or leuprolide 7.5 mg/month (n=201). Leuprolide patients could receive bicalutamide. Of the 504 patients who completed the 1-year trial, 384 chose to continue in an extension study; those on leuprolide were re-randomized to degarelix 240/80 mg or 240/160 mg. PSA PFS was defined as time to first PSA failure (two consecutive increases in PSA of 50% and ≥5 ng/mL above nadir) or death. Time for 25% of patients to experience PSA PFS (TTP25%) was analyzed using Weibull estimates. Results: Up to 1 year, the risk of PSA PFS was significantly lower with degarelix 240/80 mg vs leuprolide (p=0.05, log-rank). At 27.5 months' median follow-up, hazard rate of PSA PFS significantly decreased in leuprolide patients switched to degarelix compared with before the switch (0.20 vs 0.08; p=0.003). Similar improvements occurred in patients with baseline PSA &gt;20 ng/mL. During the first year, TTP25% for patients with baseline PSA &gt;20 ng/mL was numerically longer with degarelix vs leuprolide (407 vs 303 days; p=0.085); the difference was even greater when degarelix data were analyzed beyond 1 year (514 vs 303 days; p=0.01). Conclusions: Patients receiving degarelix had a significantly lower risk of PSA failure or death vs leuprolide during the first year of treatment. After switching to degarelix, patients who initially received leuprolide experienced a significantly lower rate of PSA failure or death. In patients with baseline PSA &gt;20 ng/mL, TTP25% was significantly longer for degarelix patients. These data support the durability of the significant PSA PFS benefit of degarelix vs monthly leuprolide observed during the first year and the use of degarelix as first-line androgen deprivation therapy. [Table: see text]
Sole Trisomy 8 In Patients (pts) with De Novo Acute Myeloid Leukemia (AML) Is Associated with Age-Independent Poor Outcome That Is Modified by Molecular Markers and with Unique Gene- and Microrna (miR)-Signatures: a Cancer and Leukemia Group B (CALGB) Study
Authors: Heiko Becker, Kati Maharry, Michael D. Radmacher, Dean Margeson, Krzysztof Mrózek, Susan P. Whitman, Yue-Zhong Wu, Klaus H. Metzeler, Sebastian Schwind, Kelsi B. Holland, Jonathan E. Kolitz, Andrew J. Carroll, Michael A. Caligiuri, Maria R. Baer, Richard A. Larson, Guido Marcucci, Clara D. Bloomfield
Journal: Blood (2010)
Fatigue, the Un-Addressed Curse of Myeloproliferative Diseases (MPD): Results of an International Internet Based QOL Survey of 830 MPD Patients.
Authors: Ruben A. Mesa, Martha Wadleigh, Joyce Niblack, D. G. Gilliland, Srdan Verstovsek, John Camoriano, Lawrence Solberg, Sunni Barnes, Jeffrey Sloan, P. Atherton, A. Tan, Ayalew Tefferi
Journal: Blood (2005)
Low-Dose Deguelin, Selective Targeting of Mt NPM1, Induces Differentiation in NPMc+ AML Cells By Regulation the Axis of SIRT1/CEBPβ/G-CSFR, Instead of HDAC1/3
Authors: Youping Wang, Zichu Zhao, Jingyu Hu, Fei Zhao, Jing He, Jun Fang, Chun Zhang, Guohui Cui, Yan Chen
Journal: Blood (2014)
Differential Expression of Adhesion Molecules and Chemokine Receptors Confers Increased Migrative Capacity to ZAP-70-Positive Subclones in CLL Primary Cells,
Authors: Marta Crespo, Cecilia del Carmen Carpio, Eva Calpe, Pau Abrisqueta, Carlos Palacio, Noelia Purroy, Francesc Bosch
Journal: Blood (2011)
The Incidence of Heparin-Induced Thrombocytopenia (HIT) After Prophylactic Heparin Exposure in Pediatric Intensive Care and Congenital Cardiology Patients: A Single Center, Prospective and Phase-IV Study: Turkish Experience
Authors: Kaan Kavakli, Gabil Mursalov, Bulent Karapinar, Ruhi Ozyurek, Deniz Yilmaz Karapinar, Can Balkan, Nihal Ozdemir Karadas
Journal: Blood (2012)
APL-2, a Complement C3 Inhibitor for the Potential Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH): Phase I Data from Two Completed Studies in Healthy Volunteers
Authors: Federico V Grossi, Pauline Bedwell, Pascal Deschatelets, Lil Edis, Cedric G Francois, Patrick J Johnson, Helen J Richardson, Lisa Tan, Carolina A Vega, Jason Lickliter
Journal: Blood (2016)
Development of a real-time multiplex PCR assay for the detection of FGFR3 mutations in urine.
Authors: J. Millholland, S. G. Patel, C. A. Fernandez, A. P. Shuber
Journal: Journal of Clinical Oncology (2011)

271 Background: We have recently reported the development of a Multi-Analyte Diagnostic Readout (MADR) non-invasive assay using urinary matrix metalloproteinases (MMPs) and FGFR3 as triage monitors in high-risk bladder cancer populations. This concept combines the marker performance characteristics of protein and DNA biomarkers into one assay for optimal performance. Eight common FGFR3 mutations in 3 exons have been associated with bladder cancer. Analysis of mutational status for each single mutation required 8 amplification steps, which were costly and time consuming. We have now developed a real-time multiplexed FGFR3 assay, generating a cost-effective, clinically applicable assay for the detection of FGFR3 mutations in urine. Methods: Our approach involves a two-step PCR amplification process. The initial round generates exon specific PCR products, which are then used as template for real-time PCR mutation detection utilizing locked nucleic acid (LNA) oligonucleotides. The LNA suppress wild-type DNA amplification. To convert our existing FGFR3 assay to a multiplex format, primary amplifications of exons 7, 10, and 15 were combined into a single real-time PCR assay for exon specific amplification and DNA quantitation. The LNA-mediated mutation detection was then converted from 4 reactions to 2 duplex amplifications. All multiplex assays were carried out on the Roche LC 480 real-time PCR platform. Results: To validate the new multiplex format, FGFR3 multiplex analysis was performed on DNA isolated from 50 Ta stage bladder tumors. FGFR3 mutations were detected in 90% (48/50) of the tumors. To directly compare performance with single mutation analysis, 40 urine samples previously analyzed using the singleplex format were again tested using the multiplex FGFR3 assay. 100% concordance was seen between the two assay formats. Conclusions: By multiplexing the FGFR3 mutation analysis we reduced the number of amplification steps, improving assay turnaround time and throughput, without compromising assay performance. The FGFR3 multiplex analysis provides a robust, cost-effective DNA assay that in combination with MMP protein analysis delivers a clinically applicable assay with optimal performance. [Table: see text]
Phase II study of single-agent volasertib (BI 6727) for second-line treatment of urothelial cancer (UC).
Authors: W. M. Stadler, D. J. Vaughn, G. Sonpavde, N. J. Vogelzang, S. T. Tagawa, P. J. Rosen, C. Lin, J. F. Mahoney, C. Zhao, M. A. Carducci
Journal: Journal of Clinical Oncology (2011)

253 Background: Polo-like kinase 1 (Plk1) controls multiple essential steps of mitosis. Volasertib (BI 6727) is a first-in-class, selective inhibitor of Plk1. In vitro, Plk1 depletion in cancer cells leads to activation of the mitotic checkpoint, prolonged mitotic arrest, and eventually apoptosis. No standard therapy exists for metastatic urothelial cancer (UC) progressing after initial chemotherapy. Thus, there is an urgent need for novel treatment options. Interim efficacy and tolerability results are presented from an open-label, single-arm, multi-center phase II trial of volasertib in patients (pts) with previously treated advanced UC. Methods: Pts progressing after one prior systemic chemotherapy for locally advanced or metastatic UC or relapsing within 2 years of adjuvant/ neoadjuvant treatment received 300 mg volasertib (2-hour intravenous infusion) on day 1 every 21 days. If well tolerated, dose escalation to 350 mg in cycle 2 was encouraged. Primary endpoint was objective tumor response, defined by RECIST. The trial follows a modified Gehan-two-stage design with an early stopping rule based on the observed response rate of the first 20 pts receiving up to 4 courses of treatment. A minimum response rate of 10% (2/20) was required to recommend additional study. Results: This trial is ongoing: 31 pts (median age 67) were treated between December 2009 and August 2010. All pts were eligible for interim safety/efficacy analysis. As of August 2010, 6 pts (19%) demonstrated a partial response, 7 pts (23%) had stable disease and 16 (52%) progressed between 3-6 weeks after study initiation. Thirteen (42%) pts remain on trial between 13-41 weeks (median time on trial 5 months) without disease progression. Major grade 3 or 4 adverse events (irrespective of drug relatedness) were neutropenia (10 pts, 32%), thrombocytopenia (7 pts, 23%), anemia (5 pts, 16%), hyponatremia (3 pts, 10%), dehydration (2 pts, 7%), and urinary tract infection (2 pts, 7%). Conclusions: Single-agent volasertib was well tolerated and demonstrates clinical activity in the second-line treatment of pts with advanced UC. The early signs of clinical benefit allows proceeding per protocol to the second stage of the trial. [Table: see text]
PAX5/TEL Has An Opposite Dominant Effect on Endogenous PAX5, Affecting Its Transcriptional Regulation, B Cell Adhesion and BCR Signaling In Murine Pre-BI Cells
Authors: Grazia Fazio, Valeria Cazzaniga, Chiara Palmi, Marta Galbiati, Marco Giordan, Truus te Kronnie, Antonius Rolink, Andrea Biondi, Giovanni Cazzaniga
Journal: Blood (2010)
A pilot study of the decision-making process of seeking medical care in women diagnosed with large breast tumors.
Authors: J. M. Eggar, C. S. Lea, L. S. Bellin, R. E. Raab, J. H. Wong, L. P. Burke
Journal: Journal of Clinical Oncology (2011)

237 Background: Twelve percent of women diagnosed with invasive breast cancer in eastern NC present with large tumors (≥ 4 cm). The reasons for presentation with advanced cancer are not known and may include both social factors and tumor characteristics. Methods: The objective of this qualitative pilot study was to investigate the decision-making process of seeking medical care in women diagnosed with ≥ 4 cm breast tumors through in-depth interviews. Six female breast cancer patients treated at Brody School of Medicine completed in-depth qualitative semistructured interviews along with demographic questionnaires. The interviews, designed to uncover barriers and motivators to seeking breast cancer diagnosis and care, were recorded and transcribed verbatim. Results: Six women (aged 44-68) completed the interview process, three African Americans and three Caucasians. Mean tumor at diagnosis size was 11.2 cm (range 4-18 cm). Three women who lived alone hid breast cancer symptoms from their family; of these, two women had fungating tumors and one had nipple drainage for more than 1 year prior to diagnosis. Four women had health insurance. Two women reported being without insurance for more than 10 years and cited this as the primary reason for delaying care. Both insured and uninsured subjects delayed care due to fear of being a burden to family, financially or support wise. One woman delayed care due to fear of chemotherapy and radiation. Three women reported regular mammograms; two presented with fast-growing tumors, one had a chest wall tumor that was missed on mammography. Conclusions: Three of six patients presenting with locally advanced disease stated that they made a decision to delay medical care. Subjects’ lack of insurance, fear of cancer and cancer treatments, and concern for family were among reasons for delays. Qualitative approaches may be useful in studying factors that affect patient access to care. More research is needed on ways to improve access and empower women to seek care.
Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Authors: Andrew T Drysdale, Logan Grosenick, Jonathan Downar, Katharine Dunlop, Farrokh Mansouri, Yue Meng, Robert N Fetcho, Benjamin Zebley, Desmond J Oathes, Amit Etkin, Alan F Schatzberg, Keith Sudheimer, Jennifer Keller, Helen S Mayberg, Faith M Gunning, George S Alexopoulos, Michael D Fox, Alvaro Pascual-Leone, Henning U Voss, BJ Casey, Marc J Dubin, Conor Liston
Journal: Nature Medicine (2016)
TAS-117, a Novel Selective Akt Inhibitor Demonstrates Significant Growth Inhibition in Multiple Myeloma Cells in Vitro and in Vivo
Authors: Naoya Mimura, Hiroto Ohguchi, Diana Cirstea, Francesca Cottini, Gullu Topal Gorgun, Jiro Minami, Rikio Suzuki, Toshiyasu Shimomura, Teruhiro Utsugi, Teru Hideshima, Kenneth C. Anderson
Journal: Blood (2012)
A Single Institution’s Experience with Allogeneic Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia: Analysis of Factors Leading to Improved Outcome
Authors: Pawel A Kaczmarek, Michael N Potter, Mark E Ethell, Jennifer G Treleaven, Faith E Davies, Claire E Dearden, Gareth J Morgan, Bronwen E Shaw
Journal: Blood (2008)
Low-Density Lipoprotein Levels and Risk of Major Cardiovascular Events—Reply
Authors: Morton Leibowitz, Chandra J. Cohen-Stavi, Ran D. Balicer
Journal: JAMA Internal Medicine (2016)

In Reply We thank Dr Rott for his comments and agree with his concluding statement that guidelines have not and should not be determined by observational studies. They can, however, supplement randomized studies by assessing effects on broader, less rigidly specific populations.1
The Gene Expression Profile of Nodal T-Cell Lymphomas Identifies a Molecular Link between Angioimmunoblastic T-Cell Lymphoma (AITL) and Follicular Helper T Cells (TFH), and between CD30+ Peripheral T-Cell Lymphoma and ALK-Negative Anaplastic Large Cell Lymphoma (ALCL).
Authors: Laurence de Leval, David Rickman, Caroline Thielen, Aurélien de Reynies, Yen-Lin Huang, Georges Delsol, Laurence Lamant, Thierry Molina, Françoise Berger, Christian Gisselbrecht, Luc Xerri, Philippe Gaulard
Journal: Blood (2006)
Interleukin-2 and Granulocyte-Macrophage Colony Stimulating Factor Is an Alternative to Donor Lymphocyte Infusion for Relapse after Allogeneic Stem Cell Transplantation and Is Associated with Increase Immune Effector Cells and Polarization to Type 2 Dendritic Cells.
Authors: Carlos R. Bachier, Paul Shaughnessy, Brad Smith2, Richard Salinas, Charles F. LeMaistre
Journal: Blood (2007)
Brivanib (BMS-582664) in advanced soft-tissue sarcoma (STS): Biomarker and subset results of a phase II randomized discontinuation trial.
Authors: G. K. Schwartz, R. G. Maki, M. J. Ratain, S. D. Undevia, R. L. Jones, C. M. Rudin, L. L. Siu, B. Brockstein, D. Khayat, T. Gil, M. J. De Jonge, M. B. Sawyer, T. R. J. Evans, J. Medioni, P. J. O'Dwyer, C. Hartman, V. Poulart, I. B. Walters
Journal: Journal of Clinical Oncology (2011)

10000 Background: Pts with sarcomas, a family of >70 types of cancer, have limited options once cytotoxic agents fail. Brivanib (B) is an oral once daily selective dual inhibitor of FGF and VEGF signaling currently in phase III. Data from a phase II trial were analyzed to evaluate the potential utility of biomarkers and STS subtypes in predicting response to B. Methods: Pts aged ≥18 y with unresectable STS and no other treatment options received open-label B 800 mg qd for a 12-wk lead-in period and were assessed by CT/MRI. Pts with RECIST response continued on open-label B, those with progressive disease (PD) went off study. Pts with stable disease (SD) were randomized 1:1 to B or placebo (P), stratified by FGF2 expression (IHC + or -), until PD or unacceptable toxicity. Pts with PD on P could crossover to resume open-label B. The primary endpoint was PFS for B vs P in FGF2+ pts; secondary endpoints included ORR, DCR (ORR+SD), and exploratory biomarkers. Results: Of 251 pts (52% with ≥2 prior systemic regimens; subtypes: leiomyosarcoma, n=60; liposarcoma, n=61; angiosarcoma, n=20; other, n=110) enrolled from 21 centers, 76 were randomized. PFS from wk 12 was significantly (prespecified 10% alpha level) prolonged for B vs P in randomized FGF2+ pts (n=53): median 2.8 vs 1.4 m (HR 0.58, 90% CI 0.34–0.97; P=.08). HR for the smaller FGF2- subset (n=23) was 0.80 (90% CI 0.36–1.79, P=.69). At wk 12, ORR was 2.8% (7 PR) and DCR 30% overall, with 3 PR in angiosarcomas (15% ORR for subtype). Exploratory analyses (eg, mPFS, HR, PFS rate) showed no apparent differences between subtypes. Of 38 patients randomized to P, 30 crossed over to B at PD; median PFS for these pts from crossover was 4.1 m (95% CI, 2.8–6.2). Most common AEs were as expected; grade 3-4 AEs ≥5% were hypertension (15%), fatigue (10%), dyspnea (5%), and abdominal pain (5%). Conclusions: Single-agent B significantly improved PFS vs P in pts with heavily pretreated advanced FGF2+ STS (benefit in FGF2- not excluded), with most common AEs as expected. All STS subtypes appeared to potentially benefit, with possibly increased activity in angiosarcoma. Further investigation is warranted, potentially in combination with other agents.