tbuckley/cabot-search huggingface dataset:
Proteomic Profiling of 150 Proteins in 511 Acute Myelogenous Leukemia (AML) Patient Samples Using Reverse Phase Proteins Arrays (RPPA) Reveals Recurrent Proteins Expression Signatures with Prognostic Implications
Authors: Steven M. Kornblau, YiHua Qiu, Wenjing Chen, Phillip Chou, Lance Blau, Ha Nashino, Farhad Ravandi, Michael Andreeff, Hagop Kantarjian, Shannon Neeley, Zhenlin Ju, Nianxiang Zhang, Kevin R. Coombes
Journal: Blood (2008)
ZM447439, a Novel Aurora Kinase Inhibitor, Induces Growth Arrest and Apoptosis of Human Leukemia Cells.
Authors: Takayuki Ikezoe, Chie Nishioka, Taizo Tasaka, Ayuko Taniguchi, Naoki Komatsu, Yoshio Kuwayama, Kazuto Togitani, H. Phillip Koeffler, Hirokuni Taguchi
Journal: Blood (2006)
Update from the Hgb-205 Phase 1/2 Clinical Study of Lentiglobin Gene Therapy: Sustained Clinical Benefit in Severe Hemoglobinopathies
Authors: Jean-Antoine Ribeil, Salima Hacein-Bey-Abina, Emmanuel Payen, Michaela Semeraro, Magrin Elisa, Laure Caccavelli, Fabien Touzot, Francois Lefrere, Felipe Suarez, Olivier Hermine, Valentine Brousse, Catherine Poirot, Benedicte Neven, Philippe Bourget, Wassim El Nemer, Pablo Bartolucci, Leslie Weber, Hervé Puy, Jean-François Méritet, David Grevent, Yves Beuzard, Stany Chrétien, Thibaud Lefebvre, Mohammed Asmal, Marcelyne Joseney-Antoine, Mariane De Montalembert, Stephane Blanche, Philippe Leboulch, Marina Cavazzana
Journal: Blood (2016)
Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma
Authors: Henrike Julich-Haertel, Sabine K. Urban, Marcin Krawczyk, Arnulf Willms, Krzysztof Jankowski, Waldemar Patkowski, Beata Kruk, Maciej Krasnodębski, Joanna Ligocka, Robert Schwab, Ines Richardsen, Sebastian Schaaf, Angelina Klein, Sebastian Gehlert, Hanna Sänger, Markus Casper, Jesus M. Banales, Detlef Schuppan, Piotr Milkiewicz, Frank Lammert, Marek Krawczyk, Veronika Lukacs-Kornek, Miroslaw Kornek
Journal: Journal of Hepatology (2017)
Abstract P5-06-05: Preclinical characterization of VX-984, a selective DNA-dependent protein kinase (DNA-PK) inhibitor in combination with doxorubicin in breast and ovarian cancers
Authors: D Boucher, D Newsome, D Takemoto, S Hillier, Y Wang, R Arimoto, J Maxwell, P Charifson, SZ Fields, K Tanner, MS Penney
Journal: Cancer Research (2017)

Abstract Background: The efficacy of chemotherapeutic agents such as doxorubicin, which cause lethal DNA double-strand breaks (DSBs), is diminished by efficient repair of the damaged DNA in cancer cells. DNA-PK is a key regulator of the non-homologous end joining (NHEJ) pathway, which is responsible for repairing DSBs. Studies of nonselective inhibitors of DNA-PK have shown that cancer cells depend on DNA-PK for survival following treatment with DSB-inducing agents. However, a comprehensive characterization of DNA-PK inhibition has been hampered by a lack of selective inhibitors. Here we describe VX-984, a potent and selective inhibitor of DNA-PK, and its preclinical profile in combination with doxorubicin both in vitro and in vivo. Methods: VX-984 was examined as a single agent and in combination with doxorubicin or pegylated liposomal doxorubicin (PLD) in a panel of breast cancer cell lines and in mouse xenograft models, respectively. Results: In vitro, inhibition of DNA-PK by VX-984 enhanced the cytotoxic activity of doxorubicin in established breast cancer cell lines and in primary ovarian tumor explants. Notably, mean Bliss DE &amp;gt;10% (strong synergy) were observed for doxorubicin in the presence of VX-984 in 22 of 35 breast cancer cell lines and 21 of 44 ovarian cancer cell lines in a broad cancer cell line screen. Further, the efficacy observed with VX-984 was associated with increased DNA damage as measured by phosphorylated histone H2AX (gamma-H2AX) and phosphorylated Kruppel-associated protein (pKAP1) in DU4475, MDA-MB-436 and MDA-MB-468 breast cancer cell lines, which is consistent with diminished DSB repair. In vivo, VX-984 significantly enhanced the efficacy of PLD in ovarian cancer patient-derived xenograft models and in cell line xenograft models. Conclusions: These data provide evidence that inhibition of DNA-PK by VX-984 enhances the efficacy of doxorubicin in preclinical models and support the use of VX-984 in combination with DSB agents such as anthracyclines including PLD for the treatment of breast and ovarian cancers. VX-984 is currently in a Phase 1 clinical trial in combination with PLD. Sponsored by Vertex Pharmaceuticals Incorporated. Citation Format: Boucher D, Newsome D, Takemoto D, Hillier S, Wang Y, Arimoto R, Maxwell J, Charifson P, Fields SZ, Tanner K, Penney MS. Preclinical characterization of VX-984, a selective DNA-dependent protein kinase (DNA-PK) inhibitor in combination with doxorubicin in breast and ovarian cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-06-05.
A Study in Trypanosomiasis—Carlos Chagas and His Unique Approach
Authors: Raghav Gupta, Christopher Kim, Arpan V. Prabhu, Thomas G. Benedek
Journal: JAMA Dermatology (2017)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
A Randomised Comparison of the Sequential Addition of the FLT3 Inhibitor Lestaurtinib (CEP701) to Standard First Line Chemotherapy for FLT3-Mutated Acute Myeloid Leukemia: The UK Experience
Authors: Steven Knapper, Robert K Hills, James D Cavenagh, Lars Kjeldsen, Ann E. Hunter, Richard E Clark, Michael Dennis, Donald Milligan, Mark J Levis, Nigel Russell, Alan K. Burnett
Journal: Blood (2014)
Abstract P6-07-28: The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study
Authors: J Gligorov, N Dohollou, JL Mouysset, P Laplaige, A Fignon, A Lafuma, P Michaud
Journal: Cancer Research (2017)

Abstract BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in breast cancer (BC). The 21-gene assay test is used to estimate the risk of recurrence and to predict the benefit of adjuvant chemotherapy (ACT) at an early stage of hormone-receptor-positive (ER+) BC. This study aims to examine the implications of RecurrenceScore (RS) testing within the routine clinical practices in France. METHODS: We conducted a prospective multicentert study, with voluntary participation, involving women with ER+, HER2-, BC. Performing the assay was left at the discretionof the physicians. The final treatment decision was discussed pre and post assay among tumor board (TB). The therapeutic changes after knowledge of RS were collected. RS and classical BC prognostic markers were investigated in parallel including an estimate of the budget impact of the assay. RESULTS: 603 patients were included in this analysis (tumor size ≤ 20 mm: 70.6%; node-negative patients: 61.2%; SBR 2: 74.9%). After the first TB, ACT was recommended for 529 patients (88.0%) and hormonotherapy (HT) alone for 74 patients (12.0%). The RS was low for 59.7% of the cases, intermediate for 34.0% and high for 6.3%. Based on RS results, second TB changed treatment decision for 70.48% of patients, avoiding CT in 64 % of cases. Only 24% received ACT while 76% received HT alone. The calculated budget impact as a minimal estimate according to the French healthcare payer perspective is estimated at a savings of € 570 per patient, corresponding to a global cost-saving of € 221,730. CONCLUSION: The results of this “real life” study confirm that the 21-gene assay had a significant impact on therapeutic decision. These findings warrant further consideration for the use of this genomic assay in patients with early stage BC in France. Citation Format: Gligorov J, Dohollou N, Mouysset JL, Laplaige P, Fignon A, Lafuma A, Michaud P. The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-28.
Azacytidine and Vorinostat in Patients with Chronic Lymphocytic Leukemia (CLL) Diagnosed with Therapy-Related Myelodysplastic Syndromes/Acute Myeloid Leukemia (t-MDS/AML)
Authors: Yesid Alvarado, Michael J Keating, Susan O'Brien, Hagop M. Kantarjian, William G. Wierda, Troy Sneed, Nitin Jain, Guillermo Garcia-Manero
Journal: Blood (2014)
Polyvalent vaccine-KLH conjugate and OPT-821 with bevacizumab (BEV) in patients with ovarian cancer in second or greater remission.
Authors: Roisin Eilish O'Cearbhaill, Alexia Iasonos, Qin Zhou, Robert Durany, Carol Aghajanian, Martee Leigh Hensley, Jason A. Konner, Vicky Makker, William P. Tew, Martin Fleisher, Paul Sabbatini
Journal: Journal of Clinical Oncology (2013)

5550 Background: We previously completed a phase I study of a polyvalent vaccine containing GM2, Globo-H, Le Y , Tn-MUC1, Tn(c), STn(c) and TF(c) antigens (AGs) individually conjugated to KLH and mixed with adjuvant OPT-821. We showed safe induction of antibody (ab) responses to 5 of the 7 vaccine AGs. Data has shown that tumor vaccine efficacy may be enhanced through disruption of angiogenesis thus providing a rationale for combining BEV with the polyvalent vaccine. We conducted an IRB-approved pilot study to evaluate the safety and immunogenicity of the poly-KLH-vaccine when given with BEV in OC in remission. Methods: Pts with recurrent OC in ≥2nd complete or partial remission were enrolled from 12/2010-03/2012. Pts received 6 vaccines and BEV over 17 weeks. BEV was continued beyond the vaccination phase. Treatment was continued until disease progression or toxicity. Serologic IgM and IgG responses were measured by ELISA against each AG. Wilcoxon signed rank test was used to test changes in cytokines (CKs): FGFβ, IL-8, PDGF, VEGF measured by angio multiplex assay. Results: n=21 Median age 56yrs (51-70). 2, 8, 8, 3 pts were in 2 nd , 3 rd , 4 th , 5 th remission, respectively. 1 DLT (gr 4 fever post vaccine #2). Immune Results: n=19 IgG +/or IgM: ≥3 AGs in 17pts. IgM: ≥1 AG in 19pts, ≥3 AGs in 15pts. IgG: ≥1 AG in 17pts, ≥3 AGs in 3pts. CK Results: In 10 pts who completed 6 vaccines there was a mean (median) decrease in VEGF of 144 (111) pg/ml at the 17-week timepoint compared to baseline (p=0.05). For 8 pts who did not complete all 6 vaccines there was a mean (median) increase of 76 (69) pg/ml compared to baseline at the off-study visit (p=0.16). There was no statistically significant change in the other CKs compared to baseline values. At last follow-up, 18 pts had recurred and 3 pts had died. The median PFS was 5.6mths. Conclusions: 89% of pts responded to ≥3 AGs comparable to the 89% response in our prior phase I trial without BEV. BEV and polyvalent-KLH vaccine can be safely administered together with retention of the vaccine’s immunogenicity. Serum VEGF levels decreased in patients on continued BEV therapy. Clinical trial information: NCT01223235. [Table: see text]
Transfusion-Dependency Is the Most Important Prognostic Factor for Survival in 1000 Newly Diagnosed MDS Patients with Low- and Intermediate-1 Risk MDS in the European LeukemiaNet MDS Registry
Authors: Louise de Swart, Alex Smith, Pierre Fenaux, David Bowen, Guillermo Sanz, Eva Hellström-Lindberg, Argyris Symeonidis, Jaroslav Cermak, Ulrich Germing, Reinhard Stauder, Otilia Georgescu, Marius MacKenzie, Luca Malcovati, Mette Skov Holm, Sophie Park, Odile Beyne-Rauzy, Jackie Droste, Theo de Witte
Journal: Blood (2011)
Pharmacogenetic Outcomes of Pediatric Acute Lymphoblastic Leukemia in Korea
Authors: Hyoung Jin Kang, Hyery Kim, Young Jin Seo, Mi Kyung Jang, Yongtaek Oh, Byoung-Don Han, Kyung Duk Park, Chul Woo Kim, Hee Young Shin, Hyo Seop Ahn
Journal: Blood (2008)
LBH589, a Novel Deacetylase Inhibitor (DACi), Treatment of Patients with Cutaneous T-Cell Lymphoma (CTCL). Skin Gene Expression Profiles in the First 24 Hours Related to Clinical Response Following Therapy.
Authors: Miles Prince, D.J. George, R. Johnstone, C. McCormack, L. Ellis, R. Williams-Truax, P. Atadja, C. Zhao, M. Dugan, K. Culver
Journal: Blood (2006)
MRI ventilation abnormalities predict quality-of-life and lung function changes in mild-to-moderate COPD: longitudinal TINCan study
Authors: Miranda Kirby, Rachel L Eddy, Damien Pike, Sarah Svenningsen, Harvey O Coxson, Don D Sin, David G McCormack, Grace Parraga
Journal: Thorax (2017)

<h3></h3> COPD biomarkers are urgently required for clinical trials of new therapies. We evaluated the longitudinal change and relationship of MRI and CT biomarkers of COPD with St. George9s Respiratory Questionnaire (SGRO) and FEV<sub>1</sub> worsening over 30 months. Among imaging biomarkers, only the longitudinal change in MRI ventilation defect percent (VDP) was greater in ever-smoker (n=34/p&lt;0.05) and COPD (n=48/p&lt;0.0001) subgroups compared with never-smokers (n=42). Only the longitudinal change in VDP was correlated with change in SGRQ (r=0.26/p=0.03), and only baseline VDP predicted longitudinal change in SGRQ&gt;minimum clinically important difference (p=0.047) in mild-to-moderate COPD. These data strongly support the use of MRI intermediate endpoints in COPD studies. <h3>Trial Registration Number</h3> NCT02723474; Status: Recruiting.
Lenalidomide (LEN) in INT 2 and High Risk MDS with DEL 5q. Interim Results of a Phase II Trial by the GFM.
Authors: S. Burcheri, T. Prebet, O. Beyne-Rauzy, R.M. Mbida, N. Hoarau, L. Legros, C. Ravoet, F. Dreyfus, A. Stamatoullas, M.P. Chaury, J. Delaunay, G. Laurent, N. Vey, L. Ades, C. Gardin, Pierre Fenaux
Journal: Blood (2007)
Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities
Authors: Yan Huang, Michael M Bornstein, Ivo Lambrichts, Hai-Yang Yu, Constantinus Politis, Reinhilde Jacobs
Journal: International Journal of Oral Science (2017)

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal mechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma (PRP) therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field. Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and (pre-)clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of injured peripheral nerves around dental implants is discussed. Platelet-rich plasma (PRP) therapy offers potential for nerve regeneration, particularly peripheral nerve recovery around dental implants. Regeneration of nerve fibers and restoration of sensory feedback can present problems following dental implant placement. Owing to its safety and applicability, PRP therapy has shown promise in treating musculoskeletal injuries. Reinhilde Jacobs (University of Leuven, Belgium), Haiyang Yu (Sichuan University, China) and and coworkers reviewed basic research studies and preliminary clinical trials on the biological efficacy of PRP in peripheral nerve regeneration. The authors concluded that various growth factors released by PRP may indeed modify and promote sensory feedback around a dental implant. However, further research is necessary before using PRP with dental implants can be advocated as safe, effective treatment. Among the authors' recommendations for future studies are optimizing the clinical efficacy of growth factors within PRP.
Connective Tissue Growth Factor (CTGF) Is Essential for Self Renewal and Proliferation of Mesenchymal Stromal Cells (MSCs) and Affects Leukemia-Stromal Interactions.
Authors: Venkata Lokesh Battula, Maria da Graca Cabreira, Zhiqiang Wang, Wencai Ma, Juliana Benito, Peter P. Ruvolo, Richard Eric Davis, Marina Konopleva, Michael Andreeff
Journal: Blood (2010)
Biomarker analyses and association with clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib with or without erlotinib in the phase III SEARCH trial.
Authors: Andrew X. Zhu, Yoon-Koo Kang, Olivier Rosmorduc, T.R. Jeffry Evans, Armando Santoro, Paul J. Ross, Edward Gane, Arndt Vogel, Michael Jeffers, Gerold Meinhardt, Carol Elaine Pena
Journal: Journal of Clinical Oncology (2014)

4028^ Background: Sorafenib (S) is the current standard therapy for advanced HCC but validated biomarkers predicting its clinical outcome are lacking. The present study aimed to identify biomarkers predicting prognosis and/or response to S ± erlotinib (E) in HCC patients from the randomized phase III SEARCH trial. Methods: A total of 720 patients were randomized to receive oral S 400 mg bid plus either E 150 mg qd or placebo (P). VEGF-A, VEGF-C, PDGF-BB, KIT (extracellular domain), HGF, bFGF, IGF-2, amphiregulin, betacellulin, EGF, epigen, epiregulin, heregulin, hbEGF, and TGF-a were measured in baseline plasma samples. Mutations in 19 oncogenes were analyzed in archival biopsies (Sequenom OncoCarta). Results: Baseline plasma biomarker data were available for 494 (69%) patients; n=243 S/E and 251 S/P. Treatment-independent analyses (combining both treatment arms) indicated that elevated HGF was associated with poor overall survival (OS; HR=0.598 [low vs high expression], multiplicity adjusted (adj) p=0.0007). Elevated plasma VEGF-A levels and low levels of KIT showed a similar trend towards poor survival (VEGF-A: HR=0.722 [low vs high expression], p=0.03, adj-p=0.39; KIT: HR=0.713 [high vs low expression], p=0.05, adj-p=0.60). High levels of plasma VEGF-C correlated with longer time to tumor progression (HR=0.626 [high vs low expression], adj-p=0.0042). Finally, in 67% of evaluable patients (339/494), a multi-marker composite signature consisting of HGF, VEGF-A, KIT, epigen, and VEGF-C correlated with improved OS: median OS 349 vs 184 days, HR=0.505, p=0.00002. None of the 15 baseline plasma biomarkers predicted efficacy from E in biomarker-treatment interaction analyses. Oncogenic mutations were detected in only 2 patient samples. Conclusions: HGF, VEGF-A, KIT, and VEGF-C baseline plasma levels were associated with clinical outcomes in HCC patients treated with S ± E, and these biomarkers plus epigen constituted a multi-marker composite signature for improved OS. Because S was used in both arms, whether these biomarkers are prognostic or also predictive of benefit from S alone in this population remains to be determined. Clinical trial information: NCT0901901.
Imatinib Mesylate in the Treatment of Systemic Mastocytosis with Wild-Type c-Kit Codon 816.
Authors: Fred H. Hsieh, Alan E. Lichtin, Hary T. Katz, Susan Lubell, Dorothy Vasas, Aridth Gibbons, Pankaj Sharma, S.J. Haque
Journal: Blood (2006)
Gunmen disguised as doctors kill 30 at Afghan hospital
Authors: Owen Dyer
Journal: BMJ (2017)

Terrorists who concealed weapons under doctors’ white coats have killed at least 30 people and wounded 70 at Afghanistan’s biggest hospital in Kabul.

The attack began at 9 am on Wednesday 8 March with a suicide bomb detonating at the front gate, at which point a gunman already inside the building began firing at the main entrance from the second floor, killing a security guard.

Soon afterwards, four gunmen were prowling through the building, firing at everyone they encountered, as staff and patients scrambled to escape through lower floor windows. Some people trapped on upper floors could be seen from the street hiding …
High Resolution Karyotyping of Large Granular Lymphocyte Leukemia by SNP Arrays Reveals Clonal Defects Leading to LOH at Loci Integral to Lymphocyte Function.
Authors: Aaron D. Viny, Hideki Makashima, Jungwon Huh, Karl S. Theil, Lukasz Gondek, Jaroslaw Maciejewski
Journal: Blood (2008)
Prognostic Impact of Bone Marrow B Lymphocyte Precursors (hematogones) Detection in 95 Acute Lymphoblastic Leukemia Cases
Authors: Sylvain P Chantepie, Audrey Emmanuelle Dugué, Patrice Chevallier, Aline Schmidt-Tanguy, Véronique Salaün, Richard Garand, Marion Eveillard, Oumedaly Reman
Journal: Blood (2012)