tbuckley/cabot-search huggingface dataset:
Pooled mutation analysis for the NP28673 and NP28761 studies of alectinib in <i>ALK+</i> non-small-cell lung cancer (NSCLC).
Authors: Oscar Puig, James Chih-Hsin Yang, Sai-Hong Ignatius Ou, Alberto Chiappori, Bo H Chao, Chandra Prakash Belani, Alexander I. Spira, Alessandra Bearz, Michael Duruisseaux, John Allard, Fabian Birzele, Frederic Boisserie, Ulrika Lonngren, Walter Bordogna, Daniel M. Klass, Aaron M. Newman, Ali Hassan Zeaiter, Alice Tsang Shaw
Journal: Journal of Clinical Oncology (2016)

9061 Background: TheALK inhibitor alectinib is FDA-approved for the treatment of patients (pts) with ALK+ NSCLC who have progressed on, or are intolerant to, crizotinib, based on the NP28673 (NCT01801111) and NP28761 (NCT01871805) trials. Long-term effectiveness of ALK inhibitors can be limited by ALK resistance mutations that occur on treatment. This mutation analysis assessed the efficacy of alectinib on different ALK point mutations using pooled data from these two pivotal studies. Methods: The global NP28673 and North American NP28761 studies enrolled pts with ALK+ NSCLC who had progressed on crizotinib. All pts received 600 mg oral alectinib twice daily. Optional tissue and plasma samples were collected for exploratory ALK mutation analyses using next-generation sequencing methods including CAPP-Seq. Results: For most pts, tissue samples were available at baseline (after crizotinib, before alectinib), with only two tissue samples obtained after progression on alectinib. For NP28673, tissue was available for 94/138 pts; for NP28761, tissue was available for 35/134 pts. Plasma samples were available for all pts at baseline and for ~50% of pts at progression. Preliminary data from tissue and plasma from 51 pts are reported here. At baseline, 13 functional ALK mutations were identified (5 were previously unreported in the literature); at end of treatment, 3 new mutations (known resistance mutations) were seen (I1171N, I1171S, G1202R; n = 1 for each mutation). PFS > 3 months was seen in pts with baseline F1174V, L1196M, S1157F, R1231W, G1128A, G1269A or C1156F mutations, suggesting alectinib activity with these variants. Median PFS was similar in pts with or without ALK mutations. Resistance mutations I1171S/N and G1202R developed during treatment. Allele frequency for ALK sensitive mutations (e.g. C1156F) decreased after alectinib therapy in plasma samples. Conclusions: These data suggest that alectinib is clinically active against native ALK and several ALK variants that can cause resistance to crizotinib. Resistance mutations including I1171S/N and G1202R may occur during treatment with alectinib. Tumor DNA in plasma may be a non-invasive way to monitor resistance mutations during therapy. Clinical trial information: NCT01801111 and NCT01871805.
Novel APC-like properties of human NK cells directly regulate T cell activation
Authors: Jacob Hanna, Tsufit Gonen-Gross, Jonathan Fitchett, Tony Rowe, Mark Daniels, Tal I. Arnon, Roi Gazit, Aviva Joseph, Karoline W. Schjetne, Alexander Steinle, Angel Porgador, Dror Mevorach, Debra Goldman-Wohl, Simcha Yagel, Michael J. LaBarre, Jane H. Buckner, Ofer Mandelboim
Journal: Journal of Clinical Investigation (2015)

A number of figure irregularities in this article were recently brought to the attention of the editorial board by the first author and corresponding author.In Figure 1, the ANK and UaNK sample labels were switched.In Figure 2C, the RT-PCR gel shown is identical to an RT-PCR gel shown in the original version of another publication (1).In Figure 3D, the panel showing DR0401-ospA incubated with ANK cells pulsed with HA protein (top left) is identical to the panel showing DR0401-HA pulsed with HA (bottom middle).Also in Figure 3D, the panel showing DR0401-HA incubated with UaNK cells pulsed with HA protein (top right) is identical to the panel showing DR0401-HA incubated with ANK cells pulsed with BSA protein (bottom left).In Figure 8, multiple flow cytometry panels shown were duplicated in the original version of another publication (2).The samples for these panels were labeled differently in the two publications, and in several cases, different antibodies were indicated.The authors have stated that the errors were inadvertently introduced and further that recent experiments support their original findings.Moreover, they also note that their conclusions are supported by other work in the field (3, 4).However, the original data for this article are no longer available, and it is evident that a number of serious mistakes were made in the preparation of this article.Thus, the JCI editorial board is retracting this article due to the numerous errors in data reporting, misrepresentation of data, and image duplication.1.
Novel Exon 2 Alpha Spectrin Mutation in a Caucasian Family with Pyropoikilocytosis, Elliptocytosis, and Normal Morphology: Three Phenotypes Due to Decreased Spectrin mRNA and Intragenic Crossover
Authors: Neeraj Agarwal, Sabina Swierczek#, Filipe R. Lorenzo, Kubendran Naidoo, Archana M. Agarwal, Roberto H Nussenzveig, Jonathan Whisenant, Theresa L. Coetzer, Josef T. Prchal
Journal: Blood (2008)
Extraluminal migration of an esophageal metal stent causing splenic injury
Authors: Saad Khan, Nayana George, Benjamin Tharian
Journal: Endoscopy (2016)

A 47-year-old woman developed a large area of anastomotic dehiscence ([Fig. 1 a]) 3 months after sleeve gastrectomy for obesity. A 15-cm fully covered self-expanding metal stent (SEMS) was deployed to cover the anastomotic leak, as a bridge to surgery. This was anchored to the esophageal wall by endosuture ([Fig. 1 b]). The patient presented again 6 weeks later with distal SEMS migration through the gastric defect into the splenic parenchyma ([Fig. 2]), causing splenic laceration and hematoma. There was active extravasation of contrast at the distal end of the stent while the proximal end remained within the stomach. She underwent urgent embolization of the left gastric, splenic, and left inferior phrenic arteries, followed by total splenectomy and Roux-en-Y gastrojejunostomy.
TCT-711 Moderately Elevated Mean Mitral Gradient after MitraClip Repair of Mitral Regurgitation Is Not Associated with Increased Mortality
Authors: Richard Cheng, Emily Tat, Reza Arsanjani, Mamoo Nakamura, Robert Siegel, Moody Makar, Saibal Kar
Journal: Journal of the American College of Cardiology (2015)
Tie2 Expression on Macrophages Is Required for Blood Vessel Reconstruction and Tumor Relapse after Chemotherapy
Authors: Lin Chen, Jie Li, Fei Wang, Chengliang Dai, Fan Wu, Xiaoman Liu, Taotao Li, Rainer Glauben, Yi Zhang, Guangjun Nie, Yulong He, Zhihai Qin
Journal: Cancer Research (2016)

Abstract Tumor relapse after chemotherapy is a major hurdle for successful cancer therapy. Chemotherapeutic drugs select for resistant tumor cells and reshape tumor microenvironment, including the blood supply system. Using animal models, we observed on macrophages in tumor tissue a close correlation between upregulated Tie2 expression and tumor relapse upon chemotherapy. Conditional deletion of Tie2 expression in macrophages significantly prohibited blood supply and regrowth of tumors. Tie2+ macrophages were derived from tumor-infiltrating Tie2−CD11b+ cells and hypoxia-induced Tie2 expression on these cells. Mechanistically, expression of Tie2 prevented macrophages from apoptosis in stress conditions via the AKT-dependent signaling pathway. Together, these results demonstrate that Tie2 expression by macrophages is necessary and sufficient to promote the reconstruction of blood vessels after chemotherapy, shedding new light on developing novel strategies to inhibit tumor relapse. Cancer Res; 76(23); 6828–38. ©2016 AACR.
TCT-775 Rates, Predictors, and Risk Stratification of Mortality after Endovascular and Surgical Revascularization for Octogenarian Patients with Critical Limb Ischemia due to Infrainguinal Artery Disease
Authors: Tatsuya Shiraki, Osamu Iida, Yoshimitsu Soga, Terutoshi Yamaoka, Yoshiaki Shintani, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2015)
Incidence and Outcomes of Treatment Refractory Diffuse Large B-Cell Lymphoma in the Immunochemotherapy Era
Authors: Matthew J Maurer, Carrie A. Thompson, Umar Farooq, Tasha Lin, Grzegorz S. Nowakowski, Yi Lin, Ivana Micallef, Anne Novak, William Macon, Sergei Syrbu, James Cerhan, Thomas E. Witzig, Thomas M. Habermann, Stephen Ansell, Brian K Link
Journal: Blood (2015)
The effect of changes in PSA kinetics on metastasis-free survival (MFS) in patients with PSA-recurrent prostate cancer (PC) treated with nonhormonal agents: Combined analysis of three randomized trials.
Authors: E. S. Antonarakis, J. Lin, D. Keizman, M. A. Carducci, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2010)

4549 Background: A number of phase II trials in men with noncastrate PSA-recurrent PC have assessed the impact of novel nonhormonal agents on PSA kinetics. However, it is unknown whether changes in PSA kinetics are related to clinical outcomes. Methods: We performed a retrospective post hoc analysis of 121 men treated on randomized phase II trials using one of three investigational drugs: lenalidomide (an antiangiogenic/immunomodulatory drug; n=60), marimastat (a matrix metalloproteinase inhibitor; n=39), and ATN-224 (a Cu/Zn superoxide dismutase inhibitor; n=22). We examined factors influencing MFS, including within-subject changes in PSA kinetics (log PSA slope, PSA doubling time [PSADT], PSA velocity) before and after treatment initiation. Results: After a median follow-up of 16.6 mo (range, 0.9-121.4), 58 of 121 men had developed metastases. In univariate Cox regression analysis, five factors were predictive of MFS: baseline PSADT, Gleason sum, decrease in log PSA slope, increase in PSADT, and decrease in PSA velocity (Table). In the multivariate model, only PSADT, Gleason sum and decrease in log PSA slope emerged as independent predictors. In Kaplan-Meier analysis, median MFS for men with any decrease in log PSA slope on treatment was 40.6 mo (95% CI 23.5 69.5) vs. 13.7 mo (95% CI 6.5-22.9) for men with no decrease in log PSA slope. Conclusions: This hypothesis-generating study suggests for the first time that within-subject changes in log PSA slope after initiation of experimental therapy may correlate with MFS in men with PSA-recurrent PC. If validated in prospective trials using MFS as the primary endpoint, change in log PSA slope may represent a reasonable intermediate endpoint for screening new agents in these patients. Variable Univariate Multivariate HR (95% CI) P HR (95% CI) P PSADT ≥ 6 mo 0.22 (0.09-0.51) <0.001 0.25 (0.10-0.61) 0.002 < 6 mo 1 1 Gleason sum ≤ 7 0.42 (0.25-0.70) 0.001 0.56 (0.33-0.96) 0.036 > 7 1 1 Δ in log PSA slope Decrease 0.37 (0.20-0.67) 0.001 0.32 (0.11-0.96) 0.042 No decrease 1 1 Δ in PSADT Increase 0.43 (0.23-0.82) 0.011 0.77 (0.25 -2.43) 0.660 No increase 1 1 Δ in PSA velocity Decrease 0.41 (0.24-0.71) 0.001 0.71 (0.39 -1.32) 0.281 No decrease 1 1 No significant financial relationships to disclose.
Successful Treatment of Intractable Gastrointestinal Hemorrhage with Low Dose of Recombinant FVIIa (Novoseven®) in Pediatric Patient without Coagulation Deficiencies.
Authors: Ji Yoon Kim, Kun Soo Lee, Soon Hak Kwon, Byung Ho Choe, Sang Kyun Sohn
Journal: Blood (2004)
A Retrospective Real-Life Analysis of Chronic Myeloid Leukemia Patients in Suboptimal Response to Imatinib
Authors: Dario Ferrero, Elena Crisà, Marco Cerrano, Mario Boccadoro, Francesca Pirillo, Maura Nicolosi, Umberto Vitolo, Giovanna Rege Cambrin, Carmen Fava, Giuseppe Saglio, Monia Lunghi, Gioacchino Catania, Alessandro Levis, Patrizia Pregno
Journal: Blood (2012)
Insights from the Shell Proteome: Biomineralization to Adaptation
Authors: Jaison Arivalagan, Tejaswi Yarra, Benjamin Marie, Victoria A. Sleight, Evelyne Duvernois-Berthet, Melody S. Clark, Arul Marie, Sophie Berland
Journal: Molecular Biology and Evolution (2016)

Bivalves have evolved a range of complex shell forming mechanisms that are reflected by their incredible diversity in shell mineralogy and microstructures. A suite of proteins exported to the shell matrix space plays a significant role in controlling these features, in addition to underpinning some of the physical properties of the shell itself. Although, there is a general consensus that a minimum basic protein tool kit is required for shell construction, to date, this remains undefined. In this study, the shell matrix proteins (SMPs) of four highly divergent bivalves (The Pacific oyster, Crassostrea gigas; the blue mussel, Mytilus edulis; the clam, Mya truncata, and the king scallop, Pecten maximus) were analyzed in an identical fashion using proteomics pipeline. This enabled us to identify the critical elements of a "basic tool kit" for calcification processes, which were conserved across the taxa irrespective of the shell morphology and arrangement of the crystal surfaces. In addition, protein domains controlling the crystal layers specific to aragonite and calcite were also identified. Intriguingly, a significant number of the identified SMPs contained domains related to immune functions. These were often are unique to each species implying their involvement not only in immunity, but also environmental adaptation. This suggests that the SMPs are selectively exported in a complex mix to endow the shell with both mechanical protection and biochemical defense.
First next-generation sequencing full-genome characterization of a hepatitis C virus genotype 7 divergent subtype
Authors: M. Salmona, A. Caporossi, P. Simmonds, M.-A. Thélu, K. Fusillier, S. Mercier-Delarue, N. De Castro, J. LeGoff, M.-L. Chaix, O. François, F. Simon, P. Morand, S. Larrat, S. Maylin
Journal: Clinical Microbiology and Infection (2016)
TCT-559 Optical coherence tomography (OCT) guided percutaneous coronary intervention : clinical impact of acute abnormal findings after drug-eluting stent implantation detected only by OCT
Authors: Seung Hun Lee, Jae Young Cho, Hyung Joon Joo, Jae Hyoung Park, Soonjun Hong, Cheol Woong Yu, Do Sun Lim
Journal: Journal of the American College of Cardiology (2016)
Acute Myeloid Leukemia Cells Acquire Chemo-Resistance By Inducing Osteoblast Differentiation in Mesenchymal Stem Cells through up-Regulation of RUNX2
Authors: Venkata Lokesh Battula, Phuong M Le, Jeffrey Sun, Teresa McQueen, Anitha Somanchi, Rui-Yu Wang, Dirk Strunk, Elizabeth J Shpall, Peter P. Ruvolo, Hagop M. Kantarjian, Marina Konopleva, Michael Andreeff
Journal: Blood (2014)
Signal-Oriented Pathway Analyses Reveal a Signaling Complex as a Synthetic Lethal Target for p53 Mutations
Authors: Songjian Lu, Chunhui Cai, Gonghong Yan, Zhuan Zhou, Yong Wan, Vicky Chen, Lujia Chen, Gregory F. Cooper, Lina M. Obeid, Yusuf A. Hannun, Adrian V. Lee, Xinghua Lu
Journal: Cancer Research (2016)

Abstract Defining processes that are synthetic lethal with p53 mutations in cancer cells may reveal possible therapeutic strategies. In this study, we report the development of a signal-oriented computational framework for cancer pathway discovery in this context. We applied our bipartite graph–based functional module discovery algorithm to identify transcriptomic modules abnormally expressed in multiple tumors, such that the genes in a module were likely regulated by a common, perturbed signal. For each transcriptomic module, we applied our weighted k-path merge algorithm to search for a set of somatic genome alterations (SGA) that likely perturbed the signal, that is, the candidate members of the pathway that regulate the transcriptomic module. Computational evaluations indicated that our methods-identified pathways were perturbed by SGA. In particular, our analyses revealed that SGA affecting TP53, PTK2, YWHAZ, and MED1 perturbed a set of signals that promote cell proliferation, anchor-free colony formation, and epithelial–mesenchymal transition (EMT). These proteins formed a signaling complex that mediates these oncogenic processes in a coordinated fashion. Disruption of this signaling complex by knocking down PTK2, YWHAZ, or MED1 attenuated and reversed oncogenic phenotypes caused by mutant p53 in a synthetic lethal manner. This signal-oriented framework for searching pathways and therapeutic targets is applicable to all cancer types, thus potentially impacting precision medicine in cancer. Cancer Res; 76(23); 6785–94. ©2016 AACR.
BMI at Age 17 Years and Diabetes Mortality in Midlife: A Nationwide Cohort of 2.3 Million Adolescents
Authors: Gilad Twig, Amir Tirosh, Adi Leiba, Hagai Levine, Dana Ben-Ami Shor, Estela Derazne, Ziona Haklai, Nehama Goldberger, Michal Kasher-Meron, Dror Yifrach, Hertzel C. Gerstein, Jeremy D. Kark
Journal: Diabetes Care (2016)

The sequelae of increasing childhood obesity are of major concern. We assessed the association of BMI in late adolescence with diabetes mortality in midlife.The BMI values of 2,294,139 Israeli adolescents (age 17.4 ± 0.3 years), measured between 1967 and 2010, were grouped by U.S. Centers for Disease Control and Prevention age/sex percentiles and by ordinary BMI values. The outcome, obtained by linkage with official national records, was death attributed to diabetes mellitus (DM) as the underlying cause. Cox proportional hazards models were applied.During 42,297,007 person-years of follow-up (median, 18.4 years; range <1-44 years) there were 481 deaths from DM (mean age at death, 50.6 ± 6.6 years). There was a graded increase in DM mortality evident from the 25th to the 49th BMI percentile group onward and from a BMI of 20.0-22.4 kg/m2 onward. Overweight (85th to 94th percentiles) and obesity (the 95th percentile or higher), compared with the 5th to 24th percentiles, were associated with hazard ratios (HRs) of 8.0 (95% CI 5.7-11.3) and 17.2 (11.9-24.8) for DM mortality, respectively, after adjusting for sex, age, birth year, height, and sociodemographic variables. The HR for the 50th through 74th percentiles was 1.6 (95% CI 1.1-2.3). Findings persisted in a series of sensitivity analyses. The estimated population-attributable fraction for DM mortality, 31.2% (95% CI 26.6-36.1%) for the 1967-1977 prevalence of overweight and obesity at age 17, rose to a projected 52.1% (95% CI 46.4-57.4%) for the 2012-2014 prevalence.Adolescent BMI, including values within the currently accepted "normal" range, strongly predicts DM mortality up to the seventh decade. The increasing prevalence of childhood and adolescent overweight and obesity points to a substantially increased future adult DM burden.
Effectiveness of a Mindfulness-Based Mental Health Promotion Program Provided by Health Coaches: A Controlled Multisite Field Trial
Authors: Lisa Lyssenko, Gerhard Müller, Nikolaus Kleindienst, Christian Schmahl, Mathias Berger, Georg Eifert, Alexander Kölle, Siegmar Nesch, Jutta Ommer-Hohl, Michael Wenner, Martin Bohus
Journal: Psychotherapy and Psychosomatics (2016)
Ex Vivo Gene Therapy of a Preadolescent with X-Linked Severe Combined Immunodeficiency.
Authors: Javier Chinen, Jennifer M. Puck, Joie Davis, Gilda F. Linton, Narda L. Whiting-Theobald, Patricia C. Woltz, Rebecca H. Buckley, Harry L. Malech
Journal: Blood (2004)
GW27-e0325 Effect of Different Concentrations of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits
Authors: Maoxiao Nie, Yunfeng Yan, Xinhe Li, Tingting Feng, Xin Zhao, Mingduo Zhang, Quanming Zhao
Journal: Journal of the American College of Cardiology (2016)
Mircrorna-550 Functions As a Critical Tumor Suppressor in Acute Myeloid Leukemia
Authors: Chao Hu, Xi Jiang, Bryan Ulrich, Yungui Wang, Rui Su, Hengyou Weng, Huilin Huang, Jennifer Strong, Ping Chen, Shenglai Li, Jianjun Chen, Jie Jin
Journal: Blood (2015)
TCT-525 Clinical outcomes following percutaneous coronary intervention using small bioresorbable scaffolds
Authors: Akihito Tanaka, Azeem Latib, Neil Ruparelia, Hiroyoshi Kawamoto, Francesco Giannini, Alessandro Sticchi, Mauro Carlino, Alaide Chieffo, Matteo Montorfano, Antonio Colombo
Journal: Journal of the American College of Cardiology (2015)
TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells
Authors: Hung C. Tran, Zesheng Wan, Michael A. Sheard, Jianping Sun, Jeremy R. Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S. Kim, Shahab Asgharzadeh, Robert C. Seeger
Journal: Clinical Cancer Research (2016)

Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma.TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis. The ability of galunisertib to inhibit SMAD activity induced by neuroblastoma patient blood and bone marrow plasmas in neuroblastoma cells was tested. The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined.Neuroblastomas express TGFB1 and TGFBR1 mRNA. Galunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice. In NK cells treated in vitro with exogenous TGFβ1, galunisertib suppressed SMAD2 phosphorylation and restored the expression of DNAM-1, NKp30, and NKG2D cytotoxicity receptors and the TRAIL death ligand, the release of perforin and granzyme A, and the direct cytotoxicity and ADCC of aNK cells against neuroblastoma cells. Addition of galunisertib to adoptive cell therapy with aNK cells plus dinutuximab reduced tumor growth and increased survival of mice injected with two neuroblastoma cell lines or a patient-derived xenograft.Galunisertib suppresses activation of SMAD2 in neuroblastomas and aNK cells, restores NK cytotoxic mechanisms, and increases the efficacy of dinutuximab with aNK cells against neuroblastoma tumors. Clin Cancer Res; 23(3); 804-13. ©2016 AACRSee related commentary by Zenarruzabeitia et al., p. 615.
Retrospective Analysis Of 204 Patients With Polycythemia VERA: The International Working Group For Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) Prognostic Score Is A Good Predictor Of Survival and Prognosis
Authors: Giulia Benevolo, Elena Crisà, Barbara Nicolino, Patrizia Pregno, Eloise Beggiato, Andrea Evangelista, Dario Ferrero, Laura Godio, Mario Boccadoro, Umberto Vitolo
Journal: Blood (2013)
Molecular Subtype Characterization of Formalin-Fixed, Paraffin-Embedded Diffuse Large B-Cell Lymphoma Samples on the Iceplex® System.
Authors: Angela M. B. Collie, Jork Nolling, Jeffrey J. Lin, Brian T. Hill, Tomas Radivoyevitch, Lilly Kong, Eric D. Hsi
Journal: Blood (2012)