tbuckley/cabot-search huggingface dataset:
Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) administered twice weekly
Authors: A. J. Murgo, S. Kummar, E. R. Gardner, W. Figg, X. Chen, M. Yancey, P. Ivy, B. Conley, J. H. Doroshow, M. E. Gutierrez
Journal: Journal of Clinical Oncology (2007)

3566 Background: 17-DMAG binds to heat-shock protein 90, leading to degradation of oncogene client proteins, inhibiting tumor growth. Preclinically, 17-DMAG has potent antitumor activity. Methods: 17-DMAG was given by 1–2 hour infusion twice weekly for 4 weeks/28-day cycle. Starting dose: 1mg/m 2 /dose. Eligibility: ECOG = 2, adequate organ function. Exclusions: prolonged QTc/uncontrolled illness. An accelerated titration escalation design was used; one patient (pt)/dose level was entered until a single pt experienced dose-limiting toxicity (DLT) or 2 pts have grade (gr) = 2 toxicity during the first cycle. Ending the accelerated phase, it converts to a standard 3–6 pt/cohort design. Objectives: To determine the toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD) and MTD of twice weekly 17-DMAG. Plasma samples collected before and up to 48 hours after 17-DMAG infusion were analyzed by LC-MS. Results: 23 pts were accrued and treated; Diagnosis: renal cell-1, pancreatic-2, medullary thyroid-1, NSCLC-3, colorectal -5, peritoneal mesotelioma-1 adrenocortical carcinoma-1, pheochromocytoma-2, malignant thymoma-1, melanoma-2, sarcoma-1, hepatocarcinoma-1 and head &amp; neck -1 and ovary-1. 2 DLTs (gr 3 peripheral neuropathy and renal failure) were observed at 27 mg/m 2 /dose. Toxicities at the MTD dose (21 mg/m 2 /dose) have been acceptable: Myalgias/arthralgias being the most common. Other gr 1–2 toxicities included: diarrhea, weight loss, fatigue, elevated transaminases, hair loss, electrolyte abnormalities (hyponatremia and hypo/hyper-magnesemia) and leukocytopenia. PK is linear, with AUC and C max increasing as dose was escalated. Drug clearance is independent of dose, but highly variable (10.75 ± 5.56 L/hr/m 2 ). Half-life: 10.0 to 31.7 h, with a median of 17.2 h. At the MTD: C max was 523.6 ± 265.3 ng/mL; Very high interindividual variability (CV = 70.3%) and a mean AUCinf of 2467.5 ± 1733.8 hr*ng/mL. Disease stabilization was achieved in a pt with mesothelioma (19 mos +) and another with head and neck cancer (8 mos +). Conclusions: We recommend 21mg/m 2 /dose twice weekly as the Phase II dose. The study continues to accrue at the MTD to collect paired biopsies for proteomic evaluation on Hsp90 client proteins analysis. No significant financial relationships to disclose.
Impact of Different Mobilization Methods on Graft Composition and Outcome after Autologous Stem Cell Transplantation: Implications for Upfront Use of Plerixafor
Authors: LaQuisa Hill, Oluchi C. Ukaegbu, Bipin N. Savani, Salyka Sengsayadeth, Stacey Goodman, Stephen J. Brandt, Wichai Chinratanalab
Journal: Blood (2014)
The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study
Authors: Wyndham H. Wilson, John F. Gerecitano, Andre Goy, Sven de Vos, Vaishalee P. Kenkre, Paul M. Barr, Kristie A. Blum, Andrei R. Shustov, Ranjana H. Advani, Jason Lih, Mickey Williams, Roland Schmitz, Yandan Yang, Stefania Pittaluga, George Wright, Lori A. Kunkel, Jesse McGreivy, Sriram Balasubramanian, Mei Cheng, Davina Moussa, Joseph J. Buggy, Louis M. Staudt
Journal: Blood (2012)
Minimal Residual Disease (MRD) By 8-Color Flow Cytometry (Flow-MRD) and IGH Clonospecific Quantitative PCR (ASO RQPCR) Reached Similar Performances for Evaluation of CLL Treatment in a Phase II Clinical Trial: Cross Validation of the Methods
Authors: Remi Letestu, Guillaume Cartron, Stephane Lepretre, Magali Le Garff-Tavernier, Francoise Solly, Lydia Campos, Michel Ticchioni, Claire Quiney, Abdelmalek Dahmani, Marouane Boubaya, Vincent Levy, Florence Cymbalista, Marie-Helene Delfau-Larue
Journal: Blood (2014)
Leptin-Induce Proliferation Mediated by JAK/STAT and MAPK Activation in Acute Myelogenous Leukemia Cells.
Authors: Hyun Ki Park, Ju Young Kim, Jin Sun Yoon, Eun Shil Kim, Kwang Sung Ahn, Sung Soo Yoon, Byoung Kook Kim, Young Yiul Lee
Journal: Blood (2005)
GW26-e1255 Genetic Polymorphisms of PXR and POR are Associated with Increased Warfarin Maintenance Dose in Han Chinese
Authors: Wutao Zeng, Qishan Zheng, Chenghsun Li, Jiali Li, Xiuyu Leng, Hanjing Cen, Lizi Zhao, Min Huang
Journal: Journal of the American College of Cardiology (2015)
GW26-e4476 Administration of intracoronary verapamil via self-made perfusion balloon to Treat No-Reflow Phenomenon following PCI in patients with Acute Coronary Syndromes
Authors: Jincheng Guo, Wenming Chen, Guozhong Wang, Fuli Zhu, Rong Xu, Zhenghai Zhang, Shunjin Gan
Journal: Journal of the American College of Cardiology (2015)
GW26-e4684 Sphingosine-1-Phosphate Lyase Overexpression Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension
Authors: Shihao Zhao, Wenjun Yan, Fuyang Zhang, Yunlong Xia, Wei Wang, Ling Tao
Journal: Journal of the American College of Cardiology (2015)
A comparison of BRCA1 and BRCA2 risk assessment models
Authors: S. Panchal, M. Ennis, H. Yee, V. Contiga, L. J. Bordeleau
Journal: Journal of Clinical Oncology (2006)

10034 Background: A number of models of varying complexity are available to calculate the risk of carrying a BRCA1 or BRCA2 mutation causing hereditary breast and ovarian cancer. A &gt;10% risk of carrying a BRCA1 or BRCA2 mutation is commonly used to establish testing eligibility in North America (testing threshold). We have compared these risk assessment models to ascertain their utility in patients from a large breast cancer program in our tertiary referral center. Methods: Risk assessment calculations were performed using the BRCAPRO, Myriad, Manchester, and UPennII models for all new probands referred to our clinic at Mount Sinai Hospital, Toronto (Canada), between May and October 2005. Individuals with a known familial mutation were excluded. Pearson correlation coefficients and pairwise scatterplots were performed for each pair of models. Regression analyses were developed to explore how well the BRCAPRO model can be predicted by other models. Results: 103 probands were included in our analyses (97% female, mean age: 50 yrs, 22% of Ashkenazi Jewish descent, 52.4% affected with breast cancer, 67% with ≥ one 1st degree relative affected with breast or ovarian cancer). The proportion of probands meeting the testing threshold based on each model was: BRCAPRO (34.0%), Myriad (33.0%), Manchester (55.3%), and UPennII (46.6%). Correlations calculated for each pair of models were large (range: 0.48–0.86). In comparing two of the most clinically relevant models (BRCAPRO and UPennII), the proportion of probands meeting the testing threshold was significantly higher using the UPennII model (p=0.0036). Between these two models, a higher correlation was observed for BRCA1 than for BRCA2 (R=0.76, R=0.58, respectively). The UPennII model was the strongest univariate predictor of the BRCAPRO results. Conclusions: All risk assessment models predicted a substantial proportion of patients referred to our clinic to be eligible for testing (≥ 33% of probands). A significantly higher proportion of probands were eligible for testing when using the UPennII model compared to the BRCAPRO model. This difference is in part due to the differential inclusion of prostate/pancreatic cancers and of third degree relatives with cancer in these models. An exploration of the sensitivity and specificity of these models will be presented. No significant financial relationships to disclose.
経皮的冠動脈インターベンションを施行した患者の院内転帰に対する危険因子 日本全国における調査(Risk factors for in-hospital outcomes for patients undergoing percutaneous coronary intervention: A nationwide Japanese survey)
Authors: Tsuchihashi Miyuki, Tsutsui Hiroyuki, Shihara Miwako, Tada Hideo, Shigematsu Hideaki, Takeshita Akira
Journal: Circulation (2002)
Epidemiology Data of Patients with Chronic Lymphocytic Leukemia in West Central Mexico
Authors: Virgina Campos-Cabrera, Gregorio Campos-Cabrera, Salvador Campos-Cabrera, Alicia Rivera-Trujillo, Sonia Hernandez-Rodriguez, Miguel-Angel Gomez-Guijosa, Maria Mora-Torres, Maria-Luisa Pedraza-Colin, Sergio Cuin-Macedo, Luis Pita-Ramirez, Jose-Luis Campos-Villagomez
Journal: Blood (2015)
HHV8-Negative Body Cavity-Based Lymphoma Is Mature Large B-Cell Lymphoma That Affects Elderly and Displays Favorable Prognosis: A Multi-Center Retrospective Study of 50 Patients in Japan
Authors: Daisuke Kaji, Yasunori Ota, Yasuharu Sato, Koji Nagafuji, Masataka Okamoto, Yasushi Terasaki, Naoko Tsuyama, Tomohiro Kinoshita, Shuichi Taniguchi, Koichi Ohshima, Koji Izutsu
Journal: Blood (2014)
18F-Fluorocholine PET/CT of Incidental Male Breast Cancer
Authors: Alexis Hugentobler, Laurent Gilbeau, Jean-Noel Talbot, Mathieu Gauthé
Journal: Clinical Nuclear Medicine (2016)

Breast cancer is approximately 100 times less common among men. Estrogen-related receptor α was detected in human prostate cancer tissue, and androgen receptors are expressed in both normal and malignant breast tissue. Thus, prostate cancer hormonal therapy may increase breast cancer risk. A 67-year-old man with prostate cancer history presented with rising prostate-specific antigen level. F-Fluorocholine PET/CT showed intense uptake in his right breast and moderate uptake in right axillary lymph node. Complementary F-FDG PET/CT demonstrated more intense tracer uptakes in both the right breast and axillary lymph node. Breast histological findings were invasive ductal cancer, with axillary lymph node invasion.
Prevalence, incidence and survival of smoldering multiple myeloma in the United States
Authors: A Ravindran, A C Bartley, S J Holton, W I Gonsalves, P Kapoor, M A Siddiqui, S K Hashmi, A L Marshall, A A Ashrani, A Dispenzieri, R A Kyle, S V Rajkumar, R S Go
Journal: Blood Cancer Journal (2016)
Eliminating malaria: following Sri Lanka’s lead
Authors: Erika Larson, Roly Gosling, Rabindra Abeyasinghe
Journal: BMJ (2016)

Crossborder collaboration is an essential component of any elimination strategy 

In September, the World Health Organization certified that Sri Lanka had eliminated malaria after it sustained zero local transmission for over three years.1 The long history of Sri Lanka’s fight against the disease,2 the country’s natural receptivity to malaria transmission,3 and the context of a 30 year civil conflict4 make this important public health achievement remarkable. Factors that contributed to Sri Lanka’s success include strong leadership, evidence driven policy, strong domestic funding, an ability to adapt to new circumstances, support of international partners, and the maintenance of services in conflict zones.5

Sri Lanka is only the second country in South East Asia to be certified malaria-free. Many more countries in Asia and elsewhere are on the cusp of elimination, however, and WHO estimates that over 20 countries will eliminate malaria by 2020.6

Success in achieving and sustaining malaria elimination requires the collaboration of neighbouring countries. In 2015, Sri Lanka reported 36 cases of malaria imported from other countries.7 To prevent an imported case …
P0660 : A specific KIR/HLA-C genotype is associated with immune activity and response to peginterferon and adefovir in HBeAg-positive chronic hepatitis B patients
Authors: F. Stelma, L. Jansen, M.J. Sinnige, E.M. van Leeuwen, N.A. Kootstra, H.W. Reesink
Journal: Journal of Hepatology (2015)
Allogeneic Hematopoietic Stem Cell Transplantation for Secondary Acute Myeloid Leukemia- a Report from the Acute Leukemia Working Party of the EBMT
Authors: Bipin N. Savani, Myriam Labopin, Ariane Boumendil, Gerhard Ehninger, Arnold Ganser, Francis Ayuk, Matthias Stelljes, Jürgen Finke, Dietrich W. Beelen, Dietger Niederwieser, Gernot Stuhler, Bertram Glass, Renate Arnold, Emmanuelle Polge, Norbert Claude Gorin, Jordi Esteve, Fabio Ciceri, Frederic Baron, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
Journal: Blood (2015)
AMP-Activated Protein Kinase α2 in Neutrophils Regulates Vascular Repair via Hypoxia-Inducible Factor-1α and a Network of Proteins Affecting Metabolism and Apoptosis
Authors: Randa Abdel Malik, Nina Zippel, Timo Frömel, Juliana Heidler, Sven Zukunft, Barbara Walzog, Nariman Ansari, Francesco Pampaloni, Susanne Wingert, Michael A. Rieger, Ilka Wittig, Beate Fisslthaler, Ingrid Fleming
Journal: Circulation Research (2016)

The AMP-activated protein kinase (AMPK) is stimulated by hypoxia, and although the AMPKα1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPKα2 subunit in vascular repair.To determine the role of the AMPKα2 subunit in vascular repair.Recovery of blood flow after femoral artery ligation was impaired (>80%) in AMPKα2-/- versus wild-type mice, a phenotype reproduced in mice lacking AMPKα2 in myeloid cells (AMPKα2ΔMC). Three days after ligation, neutrophil infiltration into ischemic limbs of AMPKα2ΔMC mice was lower than that in wild-type mice despite being higher after 24 hours. Neutrophil survival in ischemic tissue is required to attract monocytes that contribute to the angiogenic response. Indeed, apoptosis was increased in hypoxic neutrophils from AMPKα2ΔMC mice, fewer monocytes were recruited, and gene array analysis revealed attenuated expression of proangiogenic proteins in ischemic AMPKα2ΔMC hindlimbs. Many angiogenic growth factors are regulated by hypoxia-inducible factor, and hypoxia-inducible factor-1α induction was attenuated in AMPKα2-deficient cells and accompanied by its enhanced hydroxylation. Also, fewer proteins were regulated by hypoxia in neutrophils from AMPKα2ΔMC mice. Mechanistically, isocitrate dehydrogenase expression and the production of α-ketoglutarate, which negatively regulate hypoxia-inducible factor-1α stability, were attenuated in neutrophils from wild-type mice but remained elevated in cells from AMPKα2ΔMC mice.AMPKα2 regulates α-ketoglutarate generation, hypoxia-inducible factor-1α stability, and neutrophil survival, which in turn determine further myeloid cell recruitment and repair potential. The activation of AMPKα2 in neutrophils is a decisive event in the initiation of vascular repair after ischemia.
Colorectal Cancer Screening
Authors: Øyvind Holme, Geir Hoff, Magnus Løberg
Journal: JAMA (2016)

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Pegylated Liposomal Doxorubicin in Primary Cutaneous Lymphomas: Efficacy, Safety, and Low Rate of Palmar-Plantar Erythrodysesthesia
Authors: Stefano Pulini, Serena Rupoli, Nicola Pimpinelli, Annalisa Natale, Gaia Goteri, Anna Rita Scortechini, Paola Picardi, Simonetta Mulattieri, Pietro Leoni, Giuseppe Fioritoni
Journal: Blood (2008)
Evolution and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens during the first 2 decades of life
Authors: Daniela Posa, Serena Perna, Yvonne Resch, Christian Lupinek, Valentina Panetta, Stephanie Hofmaier, Alexander Rohrbach, Laura Hatzler, Linus Grabenhenrich, Olympia Tsilochristou, Kuan-Wei Chen, Carl-Peter Bauer, Ute Hoffman, Johannes Forster, Fred Zepp, Antje Schuster, Ulrich Wahn, Thomas Keil, Susanne Lau, Susanne Vrtala, Rudolf Valenta, Paolo Maria Matricardi
Journal: Journal of Allergy and Clinical Immunology (2016)
A phase I/II study of INCB018424, an oral, selective JAK inhibitor, in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF)
Authors: S. Verstovsek, H. M. Kantarjian, A. Pardanani, D. A. Thomas, J. E. Cortes, R. Mesa, W. Hogan, J. Redman, R. Levy, K. Vaddi, A. Tefferi
Journal: Journal of Clinical Oncology (2008)

7004 Background: Mutations in JAK2 and MPL have been recognized in Philadelphia chromosome-negative myeloproliferative disorders, including PV, ET and PMF, making Janus associated kinase (JAK) a therapeutic target for these diseases. INCB018424 is a potent, selective and orally bioavailable JAK inhibitor with an excellent safety profile supporting its clinical evaluation. Methods: A phase I/II trial of INCB018424 given orally BID is being conducted in patients with PMF and Post-PV/ET MF. Primary end points in this study are responses according to the International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia (IWG-MRT). Results: Overall characteristics of the 32 patients enrolled include median age of 65 yrs; 67% males; 47% PMF, 38% post-PV and 15% post ET; and 87% with JAK2V617F mutation. The starting dose of 25 mg PO BID was demonstrated to be the maximum tolerated dose (MTD) (N = 6 pts). Two patients had grade 4 thrombocytopenia in the 50 mg PO BID cohort (N = 5 pts) which defined the dose limiting toxicity. No other significant drug-related toxicities were noted. An expanded cohort of 21 additional patients has also been enrolled at the MTD, all of whom completed at least 1 month of therapy. A rapid and significant reduction in splenomegaly was observed in the patients with palpable spleens at baseline with reductions of 53% at 1 month (N = 24), and 76% at 3 months (N = 7). In addition, the majority of patients had improvement in their ECOG PS to 0 and their constitutional symptoms resolved or were significantly reduced. Additional drug- related improvements included transfusion independence in the initial patient enrolled on the study, significant reduction in JK2V617F allele burden, marked reduction in proinflammatory and angiogenic cytokines, significant increases in hematopoietic growth factors and normalization of phosphorylated Stat3. Conclusions: Treatment with INCB018424 results in unprecedented clinical activity in PMF and post-PV/ET MF without significant toxicity. Clinical improvements occurred regardless of mutation status or MPD diagnosis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Incyte Corporation Incyte Corporation Incyte Corporation Incyte Corporation
Pharmacokinetics of Single-Agent Lumiliximab (Anti-CD23 Antibody) in Patients with Chronic Lymphocytic Leukemia.
Authors: James Woodworth, Bryan R. Leigh, Susan O’Brien, Ian Flinn, Thomas J. Kipps, Mark A. Weiss, Kanti Rai, Aron Thall, Dee Wynne, John C. Byrd
Journal: Blood (2004)
Relationship between glutathione-S-transferase P1 <i>Ile<sup>105</sup>Val</i> polymorphism and docetaxel neurosensory toxicity
Authors: O. Mir, J. Alexandre, A. Tran, F. Rabillon, V. Girre, V. Dieras, G. Pons, J. M. Treluyer, F. Goldwasser
Journal: Journal of Clinical Oncology (2007)

2527 Background: Glutathione-S-transferases (GST) regulate the cellular response to oxidative stress and various anticancer agents. We recently underlined the importance of oxidative stress in the side effects of taxanes [Alexandre et al,J Natl Cancer Inst 2006;98:236–44], and investigated the relationship between the GST isoforms M1, T1 and P1 genes polymorphisms and docetaxel-induced peripheral neuropathy. Methods: We retrospectively analysed GST polymorphisms in a cohort of cancer patients (pts) treated with docetaxel and entered in a clinical trial database. A clinical neurologic evaluation (according to the NCI-CTC v2.0) was performed at baseline and at each treatment cycle. The GST M1 (null genotype), GST T1 (null genotype), and GST P1 (Ile 105 Val and Ala 114 Val) polymorphisms were determined using PCR, followed by either sequencing or RFLP techniques. The relationship between GST polymorphisms and grade = 2 neurosenrory toxicity (NST) as primary endpoint was studied, using the Chi2-square (with Yates correction) and the Fischer’s two-tailed exact test. Results: Fifty-eight pts were included : F/M: 29/29; median age: 61 years (range: 47–75). Primary tumor: 27.6% breast, 27.6% prostate, 24.1% lung and 20.7% other cancers. Pts received docetaxel 75–100 mg/m 2 given as single-agent. A total of 261 cycles were administered (median/pt: 4, range 2–12). Ten pts developed grade = 2 NST. Twenty-seven pts (47%) were homozygous for the GST P1 105 Ile allele, and 31 pts were either homozygous or heterozygous for the GST P1 105 Val allele. Grade = 2 NST was significantly more common in pts with GST P1 105 Ile/ 105 Ile genotype (8/27 pts, 30%) compared with patients with 105 Ile/ 105 Val or 105 Val/ 105 Val GSTP1 genotype (2/31 pts, 6,5%; P = 0.047). Pts who were genotyped as GST P1 105 Ile/ 105 Ile had a higher risk of developing a grade = 2 NST than did those with other GSTP1 genotypes (OR 6.11; 95% CI, 1.17–31.94; P &lt; 0.05). Conclusions: We found a significant correlation between GST P1 105 Ile homozygous genotype and the development of a docetaxel-induced peripheral neuropathy. No significant financial relationships to disclose.