tbuckley/cabot-search huggingface dataset:
Targeting the Complement Alternative Pathway Permits Graft Versus Leukemia Activity while Preventing Graft Versus Host Disease
Authors: Hung Nguyen, Ali Alawieh, David Bastian, Sandeepkumar Kuril, Min Dai, Anusara Daenthanasanmak, Mengmeng Zhang, Supinya Iamsawat, Steven D. Schutt, Yongxia Wu, M. Mahdi Sleiman, Akshay Shetty, Carl Atkinson, Shaoli Sun, Juan Carlos Varela, Stephen Tomlinson, Xue-Zhong Yu
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Application of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with hematologic disorders is limited by the development of GVHD. Separation of GVHD and graft-versus-leukemia (GVL) remains a great challenge in the field. We investigated the contribution of individual pathways involved in the complement cascade in GVH and GVL responses to identify specific targets by which to separate these two processes. Experimental Design: We used multiple preclinical murine and human-to-mouse xenograft models involving allo-HCT recipients lacking components of the alternative pathway (AP) or classical pathway (CP)/lectin pathway (LP) to dissect the role of each individual pathway in GVHD pathogenesis and the GVL effect. For translational purposes, we used the AP-specific complement inhibitor, CR2-fH, which localizes in injured target organs to allow specific blockade of complement activation at sites of inflammation. Results: Complement deposition was evident in intestines of mice and patients with GVHD. In a preclinical setting, ablation of the AP, but not the CP/LP, significantly improved GVHD outcomes. Complement activation through the AP in host hematopoietic cells, and specifically dendritic cells (DC), was required for GVHD progression. AP deficiency in recipients decreased donor T-cell migration and Th1/Th2 differentiation, while increasing the generation of regulatory T cells. This was because of decreased activation and stimulatory activity of recipient DCs in GVHD target organs. Treatment with CR2-fH effectively prevented GVHD while preserving GVL activity. Conclusions: This study highlights the AP as a new therapeutic target to prevent GVHD and tumor relapse after allo-HCT. Targeting the AP by CR2-fH represents a promising therapeutic approach for GVHD treatment.
Inotuzumab Ozogamicin in B-Cell Non-Hodgkin's Lymphoma Refractory to Rituximab + Chemotherapy or Radioimmunotherapy
Authors: M. Ogura, J. Leach, M. Egyed, K. Ando, K. Hatake, K. Tobinai, T. Feldman, S. Hua, A. Volkert, E. Vandendries, A. Goy
Journal: Annals of Oncology (2012)
P3.10 Microrna Profiling in Gastric Cancer
Authors: V. Canu, A. Sacconi, F. Biagioni, F. Mori, A. di Benedetto, L. Lorenzon, S. di Agostino, A. Cambria, S. Germoni, G. Grasso, R. Blandino, V. Panebianco, V. Ziparo, O. Federici, P. Muti, S. Strano, F. Carboni, M. Mottolese, M.G. Diodoro, E. Pescarmona, A. Garofalo, G. Blandino
Journal: Annals of Oncology (2012)
BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial–Mesenchymal Transition
Authors: Masaki Sato, Mitsuyo Matsumoto, Yuriko Saiki, Mahabub Alam, Hironari Nishizawa, Masahiro Rokugo, Andrey Brydun, Shinji Yamada, Mika K. Kaneko, Ryo Funayama, Mamoru Ito, Yukinari Kato, Keiko Nakayama, Michiaki Unno, Kazuhiko Igarashi
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the cancers with the poorest prognoses due to its highly malignant features. BTB and CNC homology 1 (BACH1) has been implicated in RAS-driven tumor formation. We focused on the role of BACH1 in PDAC, more than 90% of which have KRAS mutation. Knockdown of BACH1 in PDAC cell lines reduced cell migration and invasion, in part, by increasing E-cadherin expression, whereas its overexpression showed opposite effects. BACH1 directly repressed the expression of FOXA1 that is known to activate the expression of CDH1 encoding E-cadherin and to inhibit epithelial-to-mesenchymal transition. BACH1 also directly repressed the expression of genes important for epithelial cell adhesion including CLDN3 and CLDN4. In a mouse orthotopic implantation model, BACH1 was required for the high metastatic ability of AsPC-1 cells. IHC analysis of clinical specimens with a newly developed anti-BACH1 mAb revealed that high expression of BACH1 is a poor prognostic factor. These results suggest that the gene regulatory network of BACH1 and downstream genes including CDH1 contribute to the malignant features of PDAC by regulating epithelial-to-mesenchymal transition. Significance: Greater understanding of the gene regulatory network involved in epithelial-to-mesenchymal transition of pancreatic cancer cells will provide novel therapeutic targets and diagnostic markers.
Use of Biosimilar G-CSF for Prevention of Chemotherapy-Induced Neutropenia: Pooled Analysis of Clinical Usage Studies
Authors: P. Gascon, H. Tesch, K. Verpoort, M.S. Rosati, N. Salesi, H. Barker, S. Agrawal, M. Muenzberg, M. Turner
Journal: Annals of Oncology (2012)
Mouthguard use in youth ice hockey and the risk of concussion: nested case–control study of 315 cases
Authors: Dirk A Chisholm, Amanda Marie Black, Luz Palacios-Derflingher, Paul H Eliason, Kathryn J Schneider, Carolyn A Emery, Brent E Hagel
Journal: British Journal of Sports Medicine (2020)

Concussion is the most common injury in youth ice hockey. Whether mouthguard use lowers the odds of concussion remains an unanswered question.To determine the association between concussion and mouthguard use in youth ice hockey.Nested case-control design. Cases and controls were identified from two prospective cohort studies using valid injury surveillance methods. Cases were players concussed during a game or practice; controls were players who sustained a non-concussion injury during a game or practice. The primary exposure was mouthguard use at time of injury; mouthguard type (dental custom fit or off the shelf) was a secondary exposure. Physician-diagnosed or therapist-suspected concussion was the primary outcome. Dental injury was a secondary outcome. Multilevel logistic regression with random effect at a team level was used to obtain ORs for the mouthguard effect, adjusted for level of play, age group, position, concussion history, mechanism of injury, cohort, session type and body checking policy.Among cases, 236/315 (75%) were wearing a mouthguard at time of injury, while 224/270 (83%) controls were wearing a mouthguard at time of injury. Any mouthguard use was associated with an adjusted OR for concussion of 0.36 (95% CI 0.17 to 0.73). Off-the-shelf mouthguards were associated with a 69% lower odds of concussion (adjusted OR: 0.31; 95% CI 0.14 to 0.65). Dental custom-fit mouthguards were associated with a non-significant 49% lower odds of concussion (adjusted OR: 0.51; 95% CI 0.22 to 1.10). No dental injuries were identified in either cohort.Mouthguard use was associated with lower odds of concussion. Players should be required to wear mouthguards in youth ice hockey.
Vinorelbine in Mesothelioma (VIM): A Randomised Phase II Trial of Oral Vinorelbine as Second-Line Therapy for Patients with Malignant Pleural Mesothelioma (MPM) Expressing Brca1 – a Study in Progress
Authors: D.A. Fennell, A. Casbard, L. Nixon, J. Lester, G. Griffiths
Journal: Annals of Oncology (2012)
Evaluation of a Novel Flow Cytometry-Based System for the Detection of Circulating Tumor Cells
Authors: J. Hashimoto, M. Watanabe, Y. Uehara, N. Yamashita, Y. Fujimura, K. Nishio, M. Nakamichi, Y. Fujiwara, S. Kanda, H. Horinouchi, H. Nokihara, N. Yamamoto, Y. Koh, T. Tamura, F. Koizumi
Journal: Annals of Oncology (2012)
Influence of Baseline Oxidative Stress Level on Changes in Left Ventricle Echocardiographic Parameters in Patients with Breast Cancer Receiving Anthracycline Chemotherapy
Authors: L. Petruzelka, M. Kocik, M. Zimovjanova, J. Kodytkova, L. Vavrova, O. Mestek, K. Gorican, A. Zak
Journal: Annals of Oncology (2012)
Preliminary safety, product parameters, and immune response assessments from a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy (ACI), in patients (pts) with surgically resected HER2+ urothelial cancer (UC) at high risk for recurrence.
Authors: Dean F. Bajorin, Padmanee Sharma, Seth P. Lerner, Robert Brownell Sims, Amanda Sanders, Todd DeVries, Nadeem A. Sheikh, Leonard G. Gomella
Journal: Journal of Clinical Oncology (2013)

4547^ Background: DN24-02 is a HER2-targeted ACI, consisting of antigen presenting cells (APC) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to GM-CSF; DN24-02 is based on the same manufacturing platform as sipuleucel-T, approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. NeuACT (N10E1; NCT01353222) is an open-label, randomized phase 2 trial comparing adjuvant DN24E02 to surveillance in HER2+ UC pts at high risk of relapse following cystectomy or nephroureterectomy. The primary endpoint is overall survival. Here we report preliminary evaluation of adverse events (AE), product potency, and immune response. Methods: Pts randomized to DN24-02 underwent leukapheresis followed by infusion of DN24-02 (total of 3 infusions with 2 wk intervals). AEs were assessed at each visit. Product potency was assessed for each infusion by measuring CD54 upregulation on APCs, a marker of APC activation. Antigen-specific immune responses were evaluated by ELISA to HER500 and BA7072. Results: As of November 2012, 13 pts had received ≥1 DN24-02 infusion. The most commonly reported AEs within 1 day after DN24-02 infusion were mild–moderate chills (54%), nausea (31%) and fatigue (23%). Ten pts completed all DN24-02 infusions and were assessed for product potency. Increased median APC activation at infusions 2 and 3 compared with infusion 1 was indicative of an immunological prime-boost effect; this effect was also seen in the 7/10 pts with prior neoadjuvant chemotherapy. Median anti-BA7072 and anti-HER500 titers (IgM) were 128- and 256-fold higher at week 6 vs baseline, respectively. The emergence of IgG indicated a memory antibody phenotype. Conclusions: Preliminary data indicate that DN24-02 product potency (CD54 upregulation) is comparable to sipuleucel-T. DN24-02 appears to be well tolerated in UC. Favorable immune responses were observed, including in pts with prior neoadjuvant chemotherapy. Updated results, including preliminary T-cell immune response data, will be presented. Clinical trial information: NCT01353222.
OUTSMART HF
Authors: D. Ian Paterson, George Wells, Fernanda Erthal, Lisa Mielniczuk, Eileen O’Meara, James White, Kim A. Connelly, Juhani Knuuti, Miroslaw Radja, Mika Laine, Benjamin J.W. Chow, Riina Kandolin, Li Chen, Alexander Dick, Carole Dennie, Linda Garrard, Justin Ezekowitz, Rob Beanlands, Kwan-Leung Chan, Peter Brown, Juha Kartikainen, Marja Hedman, Eric Larose, Philippe Pibarot, Jean-Claude Tardif, Jonathan Leipsic, Marla Kiess, Andrew Howarth, Helena Hanninen, Lloyd Duchesne, Michael Freeman, Howard Leong-Poi, Graham Wright, Heikki Ukkonen
Journal: Circulation (2020)

Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF); however, there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Our primary hypothesis was that routine use of CMR will yield more specific diagnoses in nonischemic HF. Our secondary hypothesis was that routine use of CMR will improve patient outcomes.Patients with nonischemic HF were randomized to routine versus selective CMR. Patients in the routine strategy underwent echocardiography and CMR, whereas those assigned to selective use underwent echocardiography with or without CMR according to the clinical presentation. HF causes was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months.A total of 500 patients (344 male) with mean age 59±13 years were randomized. The routine and selective CMR strategies had similar rates of specific HF causes at 3 months clinical follow-up (44% versus 50%, respectively; P=0.22). At image interpretation, rates of specific HF causes were also not different between routine and selective CMR (34% versus 30%, respectively; P=0.34). However, 24% of patients in the selective group underwent a nonprotocol CMR. Patients with specific HF causes had more clinical events than those with nonspecific caused on the basis of imaging classification (19% versus 12%, respectively; P=0.02), but not on clinical assessment (15% versus 14%, respectively; P=0.49).In patients with nonischemic HF, routine CMR does not yield more specific HF causes on clinical assessment. Patients with specific HF causes from imaging had worse outcomes, whereas HF causes defined clinically did not. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01281384.
The Case for Removing Race From the American Academy of Pediatrics Clinical Practice Guideline for Urinary Tract Infection in Infants and Young Children With Fever
Authors: Rachel H. Kowalsky, Ashley C. Rondini, Shari L. Platt
Journal: JAMA Pediatrics (2020)

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
Outcomes Six Months after Delivering 100% or 70% of Enteral Calorie Requirements during Critical Illness (TARGET). A Randomized Controlled Trial
Authors: Adam M. Deane, Lorraine Little, Rinaldo Bellomo, Marianne J. Chapman, Andrew R. Davies, Suzie Ferrie, Michael Horowitz, Sally Hurford, Kylie Lange, Edward Litton, Diane Mackle, Stephanie O’Connor, Jane Parker, Sandra L. Peake, Jeffrey J. Presneill, Emma J. Ridley, Vanessa Singh, Frank van Haren, Patricia Williams, Paul Young, Theodore J. Iwashyna
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared with a lesser amount of calories are unknown.Objectives: Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality-of-life scores, return to work, and key life activities and reduce death and disability 6 months later.Methods: We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3,957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition.Measurements and Main Results: Participants assigned energy-dense nutrition received more calories (percent recommended energy intake, mean [SD]; energy-dense: 103% [28] vs. usual: 69% [18]). Mortality at Day 180 was similar (560/1,895 [29.6%] vs. 539/1,920 [28.1%]; relative risk 1.05 [95% confidence interval, 0.95-1.16]). At a median (interquartile range) of 185 (182-193) days after randomization, 2,492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality-of-life questionnaire visual analog scale, median [interquartile range]: 75 [60-85]; group difference: 0 [95% confidence interval, 0-0]). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n = 818). There was no observed difference in disability (n = 1,208) or participation in key life activities (n = 705).Conclusions: The delivery of approximately 100% compared with 70% of recommended calorie intake during critical illness does not improve quality of life or functional outcomes or increase the number of survivors 6 months later.
A Prospective Data Audit of the Management of Chemotherapy-Induced Anemia With Darbepoetin Alfa – the Apriori Study
Authors: P. Boguradzki, K. Boér, A. Cipková, E. Wojciechowska-Lampka, M. Schützová, J. Ocvirk, E. Tóth
Journal: Annals of Oncology (2012)
P16(INK4A) Gene Hypermethylation and Kras Mutation are Independent Predictors of FolFiri and Cetuximab Chemotherapy in Patients with Metastatic Colorectal Cancer (MCRC)
Authors: S.H. Kim, K.H. Park, S.J. Shin, K.Y. Lee, T.I. Kim, N.K. Kim, S.Y. Rha, J.K. Roh, J.B. Ahn
Journal: Annals of Oncology (2012)
Professional Attitudes Towards Treatment of Rare Histological Subtypes of Carcinomas of the Breast: An International Practice Survey (Paris Study)
Authors: Z. Fadoukhair, D. Lefeuvre, K. Hofert, E. Lanoy, R. Rahhali, M. Mathieu, C. Mazouni, S. Delaloge
Journal: Annals of Oncology (2012)
Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation
Authors: Tobias Becher, Dario F. Riascos-Bernal, Daniel J. Kramer, Vanessa M. Almonte, Jingy Chi, Tao Tong, Gustavo H. Oliveira-Paula, Issam Koleilat, Wei Chen, Paul Cohen, Nicholas E.S. Sibinga
Journal: Circulation Research (2020)

Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms.We used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models.Adipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated.We present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume. Visual Overview: An online visual overview is available for this article.
Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial
Authors: A.S. Mansfield, A. Każarnowicz, N. Karaseva, A. Sánchez, R. De Boer, Z. Andric, M. Reck, S. Atagi, J.-S. Lee, M. Garassino, S.V. Liu, L. Horn, X. Wen, C. Quach, W. Yu, F. Kabbinavar, S. Lam, S. Morris, R. Califano
Journal: Annals of Oncology (2020)

The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen.Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13.Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm.In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting.NCT02763579.
Temporal and region-specific effects of sleep fragmentation on gut microbiota and intestinal morphology in Sprague Dawley rats
Authors: Judy Triplett, David Ellis, Amber Braddock, Erin Roberts, Katherine Ingram, Eric Perez, Amanda Short, Dominique Brown, Victoria Hutzley, Chelsey Webb, Armando Soto, Victor Chan
Journal: Gut Microbes (2020)

Sleep is a fundamental biological process, that when repeatedly disrupted, can result in severe health consequences. Recent studies suggest that both sleep fragmentation (SF) and dysbiosis of the gut microbiome can lead to metabolic disorders, though the underlying mechanisms are largely unclear. To better understand the consequences of SF, we investigated the effects of acute (6 days) and chronic (6 weeks) SF on rats by examining taxonomic profiles of microbiota in the distal ileum, cecum and proximal colon, as well as assessing structural and functional integrity of the gastrointestinal barrier. We further assayed the impact of SF on a host function by evaluating inflammation and immune response. Both acute and chronic SF induced microbial dysbiosis, more dramatically in the distal ileum (compared to other two regions studied), as noted by significant perturbations in alpha- and beta-diversity; though, specific microbial populations were significantly altered throughout each of the three regions. Furthermore, chronic SF resulted in increased crypt depth in the distal ileum and an increase in the number of villi lining both the cecum and proximal colon. Additional changes were noted with chronic SF, including: decreased microbial adhesion and penetration in the distal ileum and cecum, elevation in serum levels of the cytokine KC/GRO, and depressed levels of corticotropin. Importantly, our data show that perturbations to microbial ecology and intestinal morphology intensify in response to prolonged SF and these changes are habitat specific. Together, these results reveal consequences to gut microbiota homeostasis and host response following acute and chronic SF in rats.