tbuckley/cabot-search huggingface dataset:
Mammary Carcinogenesis by 3-Methylcholanthrene. I. Hormonal Aspects in Tumor Induction and Growth
Authors: Dao, Thomas L., Sunderland, Henry
Journal: JNCI Journal of the National Cancer Institute (1959)

Journal Article Mammary Carcinogenesis by 3-Methylcholanthrene. I. Hormonal Aspects in Tumor Induction and Growth Get access Thomas L. Dao, Thomas L. Dao Roswell Park Memorial Institute, Buffalo, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry Sunderland Henry Sunderland Roswell Park Memorial Institute, Buffalo, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 23, Issue 3, September 1959, Pages 567–585, https://doi.org/10.1093/jnci/23.3.567 Published: 01 September 1959 Article history Received: 05 March 1959 Published: 01 September 1959
Computed tomography-derived pathological phenotypes in COPD
Authors: William MacNee
Journal: European Respiratory Journal (2016)

Chronic obstructive pulmonary disease (COPD) is considered to be a complex, multicomponent, heterogeneous disease, the pathology, clinical and functional presentation of which vary greatly between individual patients despite similar degrees of airflow limitation [1]. COPD has therefore been considered to have distinct phenotypes that represent a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes such as symptoms, exacerbations, rate of disease progression or death [2]. Importantly, these phenotypes of COPD may require different targeted treatment strategies [3]. There is a need to reach a consensus on the most appropriate method for quantifying emphysema and airways by CT <http://ow.ly/YCKP300tQQi>
A systematic review of patient‐reported outcomes in patients with cutaneous lupus erythematosus
Authors: M.E. Ogunsanya, S.J. Kalb, A. Kabaria, S. Chen
Journal: British Journal of Dermatology (2016)

Cutaneous lupus erythematosus (CLE) is a chronic dermatological autoimmune disease marked by photosensitive lesions that can lead to hyperpigmentation changes, scarring and hair loss. Health-related quality of life (HRQoL) in patients with CLE is severely impaired. Given the heterogeneous nature of CLE, health perceptions of patients can differ significantly from those of clinicians. It is important to use subjective measures, such as patient-reported outcomes (PROs), to capture HRQoL data in patients with CLE. We conducted a systematic review of published PRO instruments used in measuring HRQoL in patients with CLE. Also, we examined the disease burden on HRQoL in patients with CLE. To identify studies, PubMed/MEDLINE, Web of Science and CINAHL were searched using 'CLE/cutaneous lupus erythematosus' in combination with PRO-related keywords such as 'quality of life', 'self-report' and 'instrument'. English-language articles published between 2003 and 2014 were identified. A total of 482 citations were identified in the initial search. Eleven studies met our inclusion criteria, and five PRO instruments were found to be used: Skindex (versions 16 and 29), Dermatology Life Quality Index, 36-Item Short-Form Health Survey, and visual analogue scales for pain and pruritus. Patients with CLE reported having poor quality of life and experienced symptoms ranging from pain, pruritus and fatigue to photosensitivity. There is a limited number of studies examining PRO in patients with CLE. While our findings suggest that quality of life in patients with CLE is poor, further studies are needed to understand better the impact of CLE from patients' perspectives.
Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines
Authors: Ghaith Bakdash, Sonja I. Buschow, Mark A.J. Gorris, Altuna Halilovic, Stanleyson V. Hato, Annette E. Sköld, Gerty Schreibelt, Simone P. Sittig, Ruurd Torensma, Tjitske Duiveman-de Boer, Christoph Schröder, Evelien L. Smits, Carl G. Figdor, I. Jolanda M. de Vries
Journal: Cancer Research (2016)

The tumor microenvironment is characterized by regulatory T cells, type II macrophages, myeloid-derived suppressor cells, and other immunosuppressive cells that promote malignant progression. Here we report the identification of a novel BDCA1(+)CD14(+) population of immunosuppressive myeloid cells that are expanded in melanoma patients and are present in dendritic cell-based vaccines, where they suppress CD4(+) T cells in an antigen-specific manner. Mechanistic investigations showed that BDCA1(+)CD14(+) cells expressed high levels of the immune checkpoint molecule PD-L1 to hinder T-cell proliferation. While this BDCA1(+)CD14(+) cell population expressed markers of both BDCA1(+) dendritic cells and monocytes, analyses of function, transcriptome, and proteome established their unique nature as exploited by tumors for immune escape. We propose that targeting these cells may improve the efficacy of cancer immunotherapy. Cancer Res; 76(15); 4332-46. ©2016 AACR.
Effects of text generation on P300 brain-computer interface performance
Authors: Jane E. Huggins, Ramses E. Alcaide-Aguirre, Katya Hill
Journal: Brain-Computer Interfaces (2016)

Brain-computer interfaces (BCIs) are intended to provide independent communication for those with the most severe physical impairments. However, development and testing of BCIs is typically conducted with copy-spelling of provided text, which models only a small portion of a functional communication task. This study was designed to determine how BCI performance is affected by novel text generation. We used a within-subject single-session study design in which subjects used a BCI to perform copy-spelling of provided text and to generate self-composed text to describe a picture. Additional off-line analysis was performed to identify changes in the event-related potentials that the BCI detects and to examine the effects of training the BCI classifier on task-specific data. Accuracy was reduced during the picture description task; (t(8) = 2.59 p = .0321). Creating the classifier using self-generated text data significantly improved accuracy on these data; (t(7) = −2.68, p = .0317), but did not bring performance up to the level achieved during copy-spelling. Thus, this study shows that the task for which the BCI is used makes a difference in BCI accuracy. Task-specific BCI classifiers are a first step to counteract this effect, but additional study is needed.
Screening of Conditionally Reprogrammed Patient-Derived Carcinoma Cells Identifies ERCC3–MYC Interactions as a Target in Pancreatic Cancer
Authors: Natalya Beglyarova, Eugenia Banina, Yan Zhou, Ramilia Mukhamadeeva, Grigorii Andrianov, Egor Bobrov, Elena Lysenko, Natalya Skobeleva, Linara Gabitova, Diana Restifo, Max Pressman, Ilya G. Serebriiskii, John P. Hoffman, Keren Paz, Diana Behrens, Vladimir Khazak, Sandra A. Jablonski, Erica A. Golemis, Louis M. Weiner, Igor Astsaturov
Journal: Clinical Cancer Research (2016)

Even when diagnosed prior to metastasis, pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with almost 90% lethality, emphasizing the need for new therapies optimally targeting the tumors of individual patients.We first developed a panel of new physiologic models for study of PDAC, expanding surgical PDAC tumor samples in culture using short-term culture and conditional reprogramming with the Rho kinase inhibitor Y-27632, and creating matched patient-derived xenografts (PDX). These were evaluated for sensitivity to a large panel of clinical agents, and promising leads further evaluated mechanistically.Only a small minority of tested agents was cytotoxic in minimally passaged PDAC cultures in vitro Drugs interfering with protein turnover and transcription were among most cytotoxic. Among transcriptional repressors, triptolide, a covalent inhibitor of ERCC3, was most consistently effective in vitro and in vivo causing prolonged complete regression in multiple PDX models resistant to standard PDAC therapies. Importantly, triptolide showed superior activity in MYC-amplified PDX models and elicited rapid and profound depletion of the oncoprotein MYC, a transcriptional regulator. Expression of ERCC3 and MYC was interdependent in PDACs, and acquired resistance to triptolide depended on elevated ERCC3 and MYC expression. The Cancer Genome Atlas analysis indicates ERCC3 expression predicts poor prognosis, particularly in CDKN2A-null, highly proliferative tumors.This provides initial preclinical evidence for an essential role of MYC-ERCC3 interactions in PDAC, and suggests a new mechanistic approach for disruption of critical survival signaling in MYC-dependent cancers. Clin Cancer Res; 22(24); 6153-63. ©2016 AACR.
PD3-1-4: Enzastaurin (LY317615.HCl), a selective PKC beta inhibitor, suppresses human lung cancer cells in vitro and in vivo: a pharmacodynamic study
Authors: Daniel C. Chan, Victor J. Chen, Zhiyong Zhang, Di Zheng, Alexandra Dulude, Eji Nakajima, Barbara Helfrich, Fred Hirsch, Michael P. Clay, Doreen Ma, Paul A. Bunn
Journal: Journal of Thoracic Oncology (2007)
Toxicity of prolonged treatment with eribulin (E) in metastatic breast cancer (MBC) patients: Results of the EXTER study.
Authors: Francisco Ayala, Margarita Feijoo, Noelia Martinez, Jesús Florián Gericó, Amalia Gomez, Pedro Sánchez Rovira, Valero Pedro Jimenez, Coralia Bueno, Francisco Carabantes, Ignacio Delgado, Elena Galve Calvo, Jose Angel Garcia Saenz, Juan Lao, Ramon Pérez-Carrión, Pedro Salinas, Margarita Rodriguez Moral, María Valero Arbizu
Journal: Journal of Clinical Oncology (2015)

e11528 Background: Treatment with eribulin, the first halichondrin derivative for human use, is an emergent option for the second and third-line treatment of MBC. The EXTER study has included MBC patients with long-lasting ( > 7 months) response to eribulin. Since median duration of treatment for pivotal studies of E is around 3 months, availability of toxicity data for longer treatments is limited. We studied the adverse events profile of patients included in the EXTER study, in order to evaluate whether any cumulative toxicity may limit prolonged treatment. Methods: We analyzed the toxicity of MBC patients receiving E for at least 7 months and included in an observational, retrospective study in 30 hospitals. Toxicity was categorized according to CTCAE 4.0 criteria and classified into two categories: adverse events (any grade from 1 to 4) (AE) and severe adverse event (corresponding to grade 3-4 extra-hematologic toxicity or grade 4 hematologic toxicity). Results: Median duration of treatment was 8.5 months in the 45 patients recruited for the study. At least one AE of any grade occurred in 37 patients (82.2%). The most frequent AE were hematologic (leucopenia: 20%; neutropenia: 46.7%; anemia: 35.5%; thrombopenia: 8.9%) followed by asthenia (66.7%), neurotoxicity (33.3%), alopecia (29%), diarrhea (26.7%), nausea (22.2%) and fever (13.3%). Eleven patients presented severe adverse events: neutropenia (11.1%), leucopenia (4.4%), febrile neutropenia (4.4%), fever (2.2%) and asthenia (2.2%). Neither toxic death nor abandonment or interruption of treatment due to toxicity was observed. Dose reductions, dose delays or both occurred at least once in 4 (8.9%), 18 (40%) and 9 (20%) patients, respectively. No cases of severe neurotoxicity were observed, and only 2 dose reductions and 1 dose delay were related to peripheral neuropathy. Conclusions: Toxicity of prolonged treatment with E was mainly hematological, and did not differ from that reported for MBC patients treated with short-term eribulin. The low rate of treatment delays or suspension and the limited cumulative side effects make feasible the prolongation of treatment with eribulin in responding MBC patients.
Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity
Authors: Steven P. Broadley, Ann Plaumann, Raffaele Coletti, Christin Lehmann, Andreas Wanisch, Amelie Seidlmeier, Knud Esser, Shanshan Luo, Patrick C. Rämer, Steffen Massberg, Dirk H. Busch, Menno van Lookeren Campagne, Admar Verschoor
Journal: Cell Host & Microbe (2016)
P-175 Effectiveness of sorafenib in the treatment of hepatocellular carcinoma
Authors: P. Salamanca, H. Magalhães, F. Carneiro, D. Marques, C. Faustino, N. Sousa, M. Machado, P. Ferreira, A. Raimundo, M. Fragoso, L. Lara Santos, D. Pereira
Journal: Annals of Oncology (2016)
Abstract 16919: MicroRNA-26b Reduces Sarcomericactin and Disrupts the Sarcomere during Myocyte Hypertrophy
Authors: Mingyue Han, Minzhen He, Maha Abdellatif
Journal: Circulation (2010)

MicroRNA-26b (miR-26b) is downregulated during cardiac hypertrophy. We have previously reported that it inhibits GATA4 and compromises myocyte survival. The objective of this study was to further d...
T<scp>ranslational</scp> A<scp>dvances</scp> <scp>in</scp> <scp>the</scp> F<scp>ield</scp> <scp>of</scp> P<scp>ulmonary</scp> H<scp>ypertension</scp> Molecular Medicine of Pulmonary Arterial Hypertension. From Population Genetics to Precision Medicine and Gene Editing
Authors: Eric D. Austin, James West, James E. Loyd, Anna R. Hemnes
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

An improved understanding of the molecular causes and modifiers of pulmonary arterial hypertension (PAH) has emerged during the last several decades.However, the survival of patients with PAH remains poor, and there is no curative therapy (1-6).Further, specific molecular information to directly inform decisionmaking at the individual level regarding prognosis and therapeutic decision-making remains insufficient.The next decade and beyond should see major advances in our capacity to precisely define the factors involved in PAH, and all forms of pulmonary hypertension, using traditional and novel approaches to personalized care.Traditional molecular medicine approaches have been invaluable in the expansion of our knowledge of PAH, including but not limited to the application of traditional genetic approaches, genetic epidemiology studies, molecular signaling and structural analyses, and the use of molecular pharmacology and gene modification techniques.But more recently, advanced experimental techniques and systems analyses have emerged to shed light on the genomic, transcriptomic, epigenomic, metabolomic, proteomic, and other domains of molecular activity, and their interactions, that contribute to PAH pathogenesis and progression (7)."Omics" and related advances are crucial, but must be integrated with alternative data sources.The resultant synergy of traditional and novel molecular approaches will facilitate the personalization of PAH risk, treatment, and cure.
Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer
Authors: Lingxi Xing, Qiusheng Shi, Kailiang Zheng, Ming Shen, Jing Ma, Fan Li, Yang Liu, Lizhou Lin, Wenzhi Tu, Yourong Duan, Lianfang Du
Journal: Theranostics (2016)

Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer.
Case 41-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Robert M. Neer, Austin L. Vickery
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 77-year-old man was admitted to the hospital because of collapse.There was a long history of obesity and heavy smoking. Twenty-one years before admission the patient had a myocardial infarct and retired from his work as a police officer. He subsequently experienced occasional episodes of chest pain, which was relieved by nitroglycerin. Three years before entry he began to have postprandial epigastric pain, nausea, and vomiting every three to four days. An upper gastrointestinal series, performed elsewhere, showed a large gastric ulcer; an antacid was prescribed, with improvement. Three months before entry be began to have . . .
Enestpath: A Phase III Study to Assess the Effect of Nilotinib Treatment Duration on Treatment-Free Remission (TFR) in Chronic Phase-Chronic Myeloid Leukemia (CP-CML) Patients (pts) Previously Treated with Imatinib: Interim Analysis from the First Year of Induction Phase
Authors: Delphine Rea, Gianantonio Rosti, Nicholas C.P. Cross, Andrzej Hellman, Dietger Niederwieser, Ester Pungolino, Franca Falzetti, Patrizia Pregno, Ester Maria Orlandi, Antonio Medina Almeida, Arpad Illes, Cristalina Fernandez, Luca Dezzani, Angela Pellegrino, Chiara Costantini, Claudia Walasek, Giuseppe Saglio, Juan Luis Steegmann, Michele Baccarani
Journal: Blood (2015)
Case 34-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, R. H. Meade, K. H. Proppe
Journal: New England Journal of Medicine (1980)

Presentation of CaseAn 18-year-old man was admitted to the hospital because of fever and cough.He was well until five weeks earlier, when he abruptly became febrile, with weakness, malaise, and substernal pain. A diagnosis of streptococcal pharyngitis was made at another hospital. Penicillin and tetracycline were administered for five days, without improvement. Three weeks before admission a physician found that a screening test for infectious mononucleosis was positive; microscopical examination of the peripheral blood showed 65 per cent lymphocytes, many of them atypical. Rest was advised. During the next three weeks a large mass developed in the right . . .
A phase 1 study evaluating ABT-414 in combination with temozolomide (TMZ) for subjects with recurrent or unresectable glioblastoma (GBM).
Authors: Hui Kong Gan, Lisa Fichtel, Andrew B. Lassman, Ryan Merrell, Martin J. Van Den Bent, Priya Kumthekar, Andrew Mark Scott, Michelle Pedersen, Erica Gomez, JuDee Fischer, William Ames, Hao Xiong, Matthew W. Dudley, Wijith Munasinghe, Lisa Roberts-Rapp, Peter Ansell, Kyle D. Holen, David A. Reardon
Journal: Journal of Clinical Oncology (2014)

2021 Background: Patients (pts) with recurrent GBM have few treatment options and a very poor prognosis. GBM tumors often exhibit aberrant epidermal growth factor receptor (EGFR) proliferative signaling. ABT-414 is an antibody drug conjugate consisting of a unique antibody targeting active EGFR or mutant EGFRvIII linked to a potent, toxic anti-microtubule agent monomethylauristatin F (MMAF). ABT-414 has demonstrated high antitumor activity in preclinical GBM tumor models harboring either wild type EGFR or EGFRvIII. Methods: Objectives were to evaluate the toxicities, pharmacokinetics (PK), and the recommended phase 2 dose of ABT-414 when administered every other week (QOW) in combination with TMZ in pts with recurrent or unresectable GBM. Assessments include adverse events (AEs, NCI-CTCAE), PK parameters, objective response (RANO criteria) and tumor tissue EGFR biomarkers. Results: As of Jan 1, 2014, safety data was compiled for 12 pts (6/6, Male/Female, median age 48). Common (≥ 3 pts) adverse events include blurred vision (n=5), corneal deposits (n=4), foreign body sensation in the eye, nausea, pyrexia, and headache (n=3 each). Grade 3/4 AEs include lymphopenia, corneal deposits, skin infection, and blood cholesterol increase (n=1 each). Three cohorts have been treated to date (0.5, 1.0, 1.5 mg/kg). One dose limiting toxicity of grade 3 corneal deposits was reported at 1.0 mg/kg with improvement of symptoms after a dose reduction. ABT-414 PK results in 7 pts appeared to be dose proportional from 0.5-1.0 mg/kg, with mild accumulation using QOW dosing, and a half-life of 7-8 days. As of Jan 9, best responses for 9 pts with measurable disease at baseline include 1 complete response (CR) and 2 partial responses (33%). Patient samples are being evaluated for EGFR amplification, EGFR VIII status and expression of EGFR mRNA to determine which marker best associates with clinical response. Conclusions: Preliminary safety data demonstrate a unique toxicity pattern related to MMAF-induced corneal epithelial microcysts. Preliminary responses in 3/9 pts with TMZ refractory GBM, including 1 CR, warrant further study. Phase 2 studies with ABT-414 in GBM are being planned. Clinical trial information: NCT01800695.