tbuckley/cabot-search huggingface dataset:
Dose finding study of the intratumoral administration of the oncolytic polio/rhinovirus recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG).
Authors: Annick Desjardins, John H. Sampson, Gordana Vlahovic, Katherine B. Peters, Dina Randazzo, Stevie Threatt, James Emmett Herndon, Chevelle A Bullock, Elizabeth S Miller, Susan Boulton, Denise Lally-Goss, Frances McSherry, Eric S Lipp, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, Matthias Gromeier
Journal: Journal of Clinical Oncology (2017)

e13533 Background: The live attenuated oral poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We report results of the dose finding trial evaluating PVSRIPO delivered intratumorally by convection-enhanced delivery (CED). Methods: Eligible patients were adults with recurrent supratentorial WHO grade IV MG; solitary tumor 1-5.5cm in diameter; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS≥70%; and positive anti-polio titer. The original two-step continual reassessment method dose escalation was amended to decrease to dose level(DL) -1 and DL -2 after observing prolonged steroid use in patients treated on higher DLs. Results: As of 2/01/2017, 52 pts were treated on study (1 each at DL1 and DL3, 7 at DL2, 2 at DL4, 4 at DL5, 24 at DL -1 and 13 at DL -2). Only one DLT was observed, a grade 4 intracranial hemorrhage at the time of catheter removal on DL5. Grade 3 or higher adverse events possibly, probably or definitely related to PVSRIPO include: lymphopenia (grade 3, n = 1), steroid myopathy (grade 3, n = 1), cerebral edema (grade 4, n = 1), headache (grade 3, n = 1), dystonia (grade 3, n = 1), pyramidal tract syndrome (grade 3, n = 6), seizure (grade 3, n = 1; grade 4, n = 1), delusions (grade 3, n = 1), hypertension (grade 3, n = 1), and thromboembolic events (grade 3, n = 2). At a median follow-up of 20.1 months, 20.8% of pts remain alive at 36-month post PVSRIPO infusion, compared to 4% of an historical control. Four pts remain alive more than 22 months post treatment without having received any additional intervention following PVSRIPO at 57.5+, 56.4+, 27.9+ and 23.2+ months. Conclusions: Infusion of PVSRIPO via CED is safe and encouraging efficacy results are observed. The dose finding study is now completed and we are initiating clinical trials evaluating combination of PVSRIPO with other therapies. Clinical trial information: NCT01491893.
Time to progression and time to treatment failure in patients with triple-negative metastatic breast cancer receiving eribulin mesylate in a community oncology setting.
Authors: Claudio Faria, James Jackson, Orsolya Lunacsek, Kristin L. Hennenfent
Journal: Journal of Clinical Oncology (2014)

e12039 Background: Triple-negative breast cancer (TNBC) is an aggressive heterogeneous group of tumors that accounts for 15-20% of all breast cancers. These patients are currently without an option for targeted therapy and effective treatment remains elusive. Eribulin mesylate has demonstrated benefit in TNBC patients in phase 3 trials, including a non-significant trend toward improved overall survival. The purpose of this study was to evaluate time to treatment progression (TTP) and time to treatment failure (TTF) in triple-negative (TN) compared with endocrine receptor positive/HER2-negative (NTN) MBC patients receiving eribulin therapy in a real-world practice setting. Methods: Patients with TN (ER/PR–/HER2–) and NTN (ER/PR+/ HER2–) MBC initiating eribulin (November 2010-January 2013) were identified in an electronic medical record (EMR) database of 21 US community oncology practices. TTP and TTF were compared between the TN and NTN cohorts using the Kaplan-Meier method and covariate-adjusted Cox proportional hazards modeling. Results: Of 173 patients meeting study criteria, 32% (n=55) were TN and 68% (n=118) were NTN. Mean age (60 years in both cohorts), presence of multiple metastatic sites (TN=76% vs NTN=80%), and median number of eribulin cycles (TN=3 vs NTN=4) were similar between cohorts (P>0.05 for all). Patients in the TN cohort received fewer prior metastatic lines of therapy (median 3 vs 5, P<0.0001). Median TTP (TN=2.8 mo vs NTN=3.7 mo; P=0.2626) and median TTF (TN=2.1 mo vs NTN=2.8 mo; P=0.1146) were not statistically different between cohorts, although they numerically favored NTN. Adjusted analyses did not show significant inter-cohort differences in the risk of progression (HR=1.231; 95% CI 0.795-1.908; P=0.3515; reference=NTN) or risk of treatment failure (HR=1.186; 95% CI 0.839-1.676; P=0.3351; reference=NTN). Conclusions: In this retrospective study of heavily pretreated HER2-negative MBC patients treated in a community oncology setting, patients with TNBC achieved similar treatment benefit from eribulin therapy compared with the NTN cohort. Erbulin may be a considered a treatment option for patients with TN MBC.
Resource Utilization in the Last Three Months of Life by Lung Cancer Patients in the Hamilton-Niagara-Haldimand-Brant Local Health Integration Network (Lhin)
Authors: Peter M. Ellis, Susan Schiff, Adrianne Van Dam, Claire Mcmillan, Marissa Slaven, Sally Hapke, Lorraine Martelli-Reid, Phillip Hughes, John R. Goffin, Jonathan Sussman
Journal: Journal of Thoracic Oncology (2013)
Abstract 5293: A New Animal Model of Hypercholesterolemia and Atherosclerosis: Mice Deficient in All Nitric Oxide Synthases
Authors: Masato Tsutsui, Yasuko Yatera, Hiroaki Shimokawa, Sei Nakata, Kiyoko Shibata, Tsuyoshi Morishita, Ken Sabanai, Hiromi Tasaki, Yasuhide Nakashima, Nobuyuki Yanagihara, Yutaka Otsuji
Journal: Circulation (2008)

We have recently developed mice lacking all three nitric oxide synthase (NOS) isoforms: nNOS, iNOS, and eNOS ( PNAS 2005). In this study, we examined the effects of a high-cholesterol (HC) diet on lipid metabolism and vascular lesion formation in those mice. Experiments were performed in 2-month-old male wild-type (WT) and singly, doubly, and triply NOS −/− mice (n=6–9). They were maintained on either a regular diet or a HC diet for 3 months. The HC feeding significantly increased plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) in all the genotypes studied as compared on the regular diet (all P &lt;0.05). These serum levels of TC and LDL on the HC diet (mg/dl) were both significantly higher in all the singly, doubly, and triply NOS −/− genotypes as compared with the WT genotype (singly nNOS −/− [371±61 and 205±65], iNOS −/− [559±62 and 350±62], eNOS −/− [619±22 and 395±25], doubly n/iNOS −/− [518±77 and 328±72], n/eNOS −/− [635±56 and 458.8±42], e/iNOS −/− [480±38 and 260±40], triply n/i/eNOS −/− [2316±704 and 1588±715], and WT [326±43 and 244±54]) (all P &lt;0.05). Notably, the extent of the dyslipidemia was by far severest in the triply n/i/eNOS −/− genotype among the NOS −/− genotypes, and intriguingly, the serum levels of TC and LDL in the triply n/i/eNOS −/− genotype were equivalent to those in apolipoprotein E −/− mice that exhibit severe hypercholesterolemia. Lipid accumulation in the aorta on the HC diet (lipid area, %, oil red O staining) was also significantly more accelerated in all the NOS −/− genotypes than in the WT genotype (singly nNOS −/− [6.6±1.5], iNOS −/− [6.7±2.2], eNOS −/− [5.5±2.3], doubly n/iNOS −/− [4.7±1.7], n/eNOS −/− [6.4±1.4], i/eNOS −/− [6.8±1.3], triply n/i/eNOS −/− [20.6±1.0], and WT [3.6±1.2]), while the extent of the aortic atherosclerosis was again by far severest in the triply n/i/eNOS −/− genotype (all P &lt;0.05). These results demonstrate that mice deficient in all NOSs manifest severe hypercholesterolemia and lipid-rich atherosclerotic lesion formation in response to a HC diet, indicating a pivotal role of the whole NOS system in preventing those disorders. Our triply NOS −/− mouse is a new experimental model of human hypercholesterolemia and atherosclerosis.
Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1–2 study
Authors: Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
Journal: The Lancet Oncology (2017)
Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: A qualitative analysis.
Authors: Albert Farias, India Ornelas, Sarah Hohl, Steven B. Zeliadt, Ryan N. Hansen, Christopher I. Li, Beti Thompson
Journal: Journal of Clinical Oncology (2016)

e12055 Background: Physicians play an important role in the on-going care of breast cancer survivors, particularly women who are actively taking adjuvant endocrine therapy (AET). The role of the physician can both positively and negatively affect medication adherence. Therefore, the objective of this study is to explore, from the breast cancer patient’s perspective, how physicians communicate with them about AET treatment. Methods: Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes. Results: We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self-management and monitoring potential side-effects, (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient’s health literacy regarding the benefits and knowledge of AET. Patients expressed trust and confidence in their physician. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side-effects. Conclusions: Women’s interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who communicate information about AET treatment benefits, purpose, and expectations in a way that patients understand may improve adherence.
The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study
Authors: Brett Ley, Chad A Newton, Isabel Arnould, Brett M Elicker, Travis S Henry, Eric Vittinghoff, Jeffrey A Golden, Kirk D Jones, Kiran Batra, Jose Torrealba, Christine Kim Garcia, Paul J Wolters
Journal: The Lancet Respiratory Medicine (2017)
Perirenal Extramedullary Hematopoiesis
Authors: Ying-Nan Cheng, I-Wen Ting
Journal: New England Journal of Medicine (2017)

A 69-year-old woman with chronic kidney disease and myelofibrosis presented with dyspnea and weakness. Imaging revealed lesions in both perirenal spaces, and extramedullary hematopoiesis was detected on biopsy.
Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury
Authors: Wei Eric Wang, Liangpeng Li, Xuewei Xia, Wenbin Fu, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, Cindy Zeng, Lin Zhou, Bin Zhou, Dayue Darrel Duan, Xiongwen Chen, Steven R. Houser, Chunyu Zeng
Journal: Circulation (2017)

Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts.β-Actin-green fluorescent protein transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a coculture system with neonatal rat ventricular myocytes, ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and 5-ethynyl-2-deoxyuridine incorporation analysis. Echocardiography was used to measure cardiac function, and histology was performed to determine infarction size.In vitro, mononucleated and bi/multinucleated ACMs were able to proliferate at a similar rate (7.0%) in the coculture. Dedifferentiation proceeded ACM proliferation, which was followed by redifferentiation. Redifferentiation was essential to endow the daughter cells with cardiomyocyte contractile function. Intercellular propagation of Ca2+ from contracting neonatal rat ventricular myocytes into ACM daughter cells was required to activate the Ca2+-dependent calcineurin-nuclear factor of activated T-cell signaling pathway to induce ACM redifferentiation. The properties of neonatal rat ventricular myocyte Ca2+ transients influenced the rate of ACM redifferentiation. Hypoxia impaired the function of gap junctions by dephosphorylating its component protein connexin 43, the major mediator of intercellular Ca2+ propagation between cardiomyocytes, thereby impairing ACM redifferentiation. In vivo, ACM proliferation was found primarily in the MI border zone. An ischemia-resistant connexin 43 mutant enhanced the redifferentiation of ACM-derived new cardiomyocytes after MI and improved cardiac function.Mature ACMs can reenter the cell cycle and form new cardiomyocytes through a 3-step process: dedifferentiation, proliferation, and redifferentiation. Intercellular Ca2+ signal from neighboring functioning cardiomyocytes through gap junctions induces the redifferentiation process. This novel mechanism contributes to new cardiomyocyte formation in post-MI hearts in mammals.
Partial Splenic Embolization For The Treatment Of Steroid-Resistant Chronic Idiopathic Thrombocytopenic Purpura
Authors: Chiaki Nakaseko, Emi Togasaki, Naomi Shimizu, Emiko Sakaida, Masahiro Takeuchi, Chikako Ohwada, Yusuke Takeda, Shio Sakai, Shokichi Tsukamoto, Takeharu Kawaguchi, Tomoya Muto, Tohru Iseki, Koutaro Yokote
Journal: Blood (2013)
A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups
Authors: C.R. Lindsay, V. Faugeroux, S. Michiels, E. Pailler, F. Facchinetti, D. Ou, M.V. Bluthgen, C. Pannet, M. Ngo-Camus, G. Bescher, C. Caramella, F. Billiot, J. Remon, D. Planchard, J.-C. Soria, B. Besse, F. Farace
Journal: Annals of Oncology (2017)
Dental implant treatment for renal failure patients on dialysis: a clinical guideline
Authors: Quan Yuan, Qiu-Chan Xiong, Megha Gupta, Rosa María López-Pintor, Xiao-Lei Chen, Dutmanee Seriwatanachai, Michael Densmore, Yi Man, Ping Gong
Journal: International Journal of Oral Science (2017)

Chronic kidney disease (CKD) is a worldwide public health problem that is growing in prevalence and is associated with severe complications. During the progression of the disease, a majority of CKD patients suffer oral complications. Dental implants are currently the most reliable and successful treatment for missing teeth. However, due to complications of CKD such as infections, bone lesions, bleeding risks, and altered drug metabolism, dental implant treatment for renal failure patients on dialysis is more challenging. In this review, we have summarized the characteristics of CKD and previous publications regarding dental treatments for renal failure patients. In addition, we discuss our recent research results and clinical experience in order to provide dental implant practitioners with a clinical guideline for dental implant treatment for renal failure patients undergoing hemodialysis. New clinical guidelines aim to ensure safer dental implant procedures for patients on dialysis for kidney failure. Chronic kidney disease is becoming more common, and 90% of patients experience oral symptoms that lead to early tooth loss. Dental implants can greatly improve quality of life, but carry increased risk of infections for dialysis patients because of their compromised immune systems. Dr. Yuan at Sichuan University, Chengdu, China, and experts from other 4 countries have produced comprehensive clinical guidelines for installing dental implants in dialysis patients. They stress that dentists should consult kidney specialists early in the process, systematically review patient history and perform extensive blood tests prior to surgery. The procedure itself should be as simple and non-invasive as possible, and prophylactic antibiotics should be taken post-operation to minimize infection risk and complications with dialysis.
Evaluation of VeriStrat, a serum proteomic test, in the randomized, open-label, phase 3 LUX-Lung 8 (LL8) trial of afatinib (A) versus erlotinib (E) for the second-line treatment of advanced squamous cell carcinoma (SCC) of the lung.
Authors: Glenwood D. Goss, Ki Hyeong Lee, Enriqueta Felip, Manuel Cobo, Konstantinos N. Syrigos, Erdem Göker, Vassilis Georgoulias, Salih Z. Guclu, Dolores Isla, Young J. Min, Alessandro Morabito, Sandra Close, Nicholas Dupuis, Vikram K. Chand, Flavio Solca, Nicole Krämer, Neil Gibson, Eva Ehrnrooth, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2016)

e20510 Background: Treatment (tx) options for patients (pts) with advanced SCC of the lung after progression on platinum-based chemotherapy are limited. In LL8, the irreversible ErbB family blocker, A, significantly improved OS, PFS and disease control rate vs E, a reversible EGFR TKI, in 795 pts with SCC of the lung. VeriStrat is a serum protein test that utilizes MALDI-TOF mass spectrometry to assign a ‘GOOD' (VS-G) or ‘POOR' (VS-P) classification and has demonstrated prognostic and predictive utility for EGFR targeted therapies in NSCLC.1 Here, the predictive ability of VeriStrat was tested in LL8; OS was the primary efficacy variable. Methods: Pre-tx serum samples, blinded to clinical outcome, were classified as VS-G or VS-P based on predefined reference groups. Clinical outcomes were analyzed with respect to VeriStrat status in the overall population (all pts with both clinical and VeriStrat data) and in predefined subgroups. Results: 675 pts were classified (VS-G: 412; VS-P: 263). In the VS-G group, median OS was 11.5 mo for A and 8.9 mo for E (HR [95% CI] 0.79 [0.63–0.98]; p = 0.03); median PFS was 3.3 mo for A and 2.0 mo for E (HR [95% CI] 0.73 [0.59–0.92]; p = 0.005). In the VS-P group, median OS was 4.7 mo for A and 4.8 mo for E (HR [95% CI] 0.90 [0.70–1.16]; p = n.s.); median PFS was 1.9 mo for both A and E (HR [95% CI] 0.96 [0.73–1.27]; p = n.s.). In pts treated with A, both OS (HR [95% CI] 0.40 [0.31–0.51]; p < 0.0001) and PFS (HR [95% CI] 0.56 [0.43–0.72]; p < 0.0001) were longer in the VS-G group vs the VS-P group. Multivariate analysis showed that VeriStrat was an independent predictor of OS and PFS in pts treated with A, regardless of ECOG PS, best response to first-line therapy, age and race. However, there was no interaction between VeriStrat classification and tx group for OS (pint = 0.53) or PFS (pint = 0.12). Conclusions: In LL8, VeriStrat has a strong independent stratification effect in pts with relapsed/refractory SCC of the lung treated with A. In these difficult to treat pts, A conferred significantly better OS and PFS than E in the VS-G group, with a median OS of 11.5 mo. 1. Gregorc V, et al. Lancet Oncol 2014;15:713‒21 Clinical trial information: NCT01523587.
Utilization of the 21-gene assay for breast cancer treatment decision-making in Alberta.
Authors: Gloria Beatriz Roldan Urgoiti, Kirsten Anna Smerdon, Hua Yang, Gilbert Bigras, Judith Hugh, Roger Y. Tsang, Karen M. King, Sasha M. Lupichuk
Journal: Journal of Clinical Oncology (2016)

e12024 Background: The 21-gene assay (Oncotype DX) was publicly funded in Alberta in March 2014. At the discretion of the consulting oncologist, testing was offered to eligible women to facilitate systemic therapy decision-making. Oncologists recorded their pre-test chemotherapy (CT) recommendation (no, yes, unsure). Methods: Retrospective chart review of patients age ≤ 70 with grade 2 or 3 estrogen receptor positive, HER-2 negative, lymph node negative breast cancer seen at the two tertiary cancer centers in Alberta, Canada (March 2014- June 2015). Patient, tumor, 21-gene assay, and treatment information was recorded. Logistic regression analyses exploring predictors of 21-gene assay use and CT recommendation will be performed. Results: Of 591 eligible patients, 590 were female. Most of the tumors were grade 2 (394; 67%), did not have lymph-vascular invasion (468; 79%) and were 10 to 20 mm in size (T1c; 295; 50%). One hundred and five patients (28%) had 21-gene assay testing completed. In 348 cases (59%) the treating oncologist made treatment recommendations based on patient/tumor characteristics only, 18 (4%) patients were not candidates for CT (3%), 51 (9%) refused CT and 9 (2%) requested CT. For those who had 21-gene assay testing, recurrence risk was low (RS 0-18) in 113 (68%) patients, intermediate (RS 19-30) in 37 (22%), and high ( ≥ 31) in 13 (8%). In two cases, the tissue sample was insufficient for analysis. CT was administered to 1/113 ( < 1%) patients with low risk, 9/37 (24%) with intermediate risk and 13/13 (100%) with high risk. Conclusions: Of eligible patients, 28% had 21-gene assay testing completed. The majority of those tested had a low or intermediate RS and did not receive CT. We will present impact of 21-gene assay results on oncologists’ CT recommendation and regression analyses for predictors of 21-gene assay use, results and CT recommendation. 21-gene assay completed (n = 165) 21-gene assay not done (n = 426) Median age (range) 55 (34-70) 59 (24-70) Local-regional treatment Breast conservation + radiation 99 (60%) 275 (65%) Mastectomy 66 (40%) 151 (35%) Hormonal therapy Yes 159 (96%) 363 (85%) No 6 (4%) 59 (14%) Unknown 0 4 (1%) Chemotherapy Yes 23 (14%) 140 (33%) No 142 (86%) 284 (67%) Unknown 0 2 ( < 1%)