tbuckley/cabot-search huggingface dataset:
Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection
Authors: Kris V. Kowdley, Vinay Sundaram, Christie Y. Jeon, Kamran Qureshi, Nyan L. Latt, Amandeep Sahota, Stephen Lott, Michael P. Curry, Naoky Tsai, Nathorn Chaiyakunapruk, Yoori Lee, Jorg Petersen, Peter Buggisch
Journal: Hepatology (2016)

Eight weeks duration of ledipasvir/sofosbuvir (LDV/SOF) can be considered in genotype 1 hepatitis C virus–infected patients who are treatment‐naive, do not have cirrhosis, and have a pretreatment viral load &lt;6,000,000 IU/mL. The effectiveness of this regimen, however, has not been fully confirmed by real‐world experience. Using data from real‐world cohorts, we aimed to determine the effectiveness of 8 weeks of LDV/SOF treatment, examine variables associated with relapse after treatment with this regimen, and compare the effectiveness of 8 weeks and 12 weeks of LDV/SOF treatment. To evaluate the effectiveness of 8 weeks of therapy and characteristics associated with relapse, we used individual patient data from the IFI (Institut für Interdisziplinäre Medizin), Burman's Pharmacy, and Kaiser Permanente Southern California. All patients had fibrosis staging assessed with biopsy, transient elastography, or serum biomarkers. We also performed a systematic review and meta‐analysis of six additional real‐world cohorts, to compare effectiveness of 8 weeks to 12 weeks duration. In our pooled data analysis, 634 patients were treated for 8 weeks with LDV/SOF, of whom all had outcomes of cure or relapse without loss to follow‐up. Per protocol rates of sustained virologic response at 12 weeks were 98.1% (622/634) in the full cohort and 97.9% (571/583) among treatment‐eligible patients. Exact logistic regression revealed no specific patient characteristics associated with relapse. Our meta‐analysis of six additional real‐world cohorts, comprised of 5,637 patients, demonstrated similar risk for relapse between 8 weeks and 12 weeks of LDV/SOF (relative risk = 0.99, 95% confidence interval 0.98‐1.00). Conclusion : An 8‐week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (H epatology 2017;65:1094‐1103)
In Vitro Expansion of Blood γδ T Cells in Patients with Myeloma/Lymphoma and Anti-Tumor Cytotoxicity of the Expanded γδ T Cells.
Authors: Anri Saito, Miwako Narita, Norihiro Watanabe, Nozomi Tochiki, Yumi Hiroi, Takayoshi Shirasaki, Jun Takizawa, Tatsuo Furukawa, Ken Toba, Sadao Aoki, Yoshifusa Aizawa, Masuhiro Takahashi
Journal: Blood (2006)
Analysis of B-CLL with Discordant ZAP-70 Expression and IgVH Mutational Status.
Authors: Remi Letestu, Magali Le Garff-Tavernier, Dominique Vaur, Michel Ticchioni, Fanny Baran-Marszak, Frederic Davi, Veronique Salaun, Franck Genevieve, Virginie Eclache, Dina Naguib, Florence N’Guyen, Xavier Troussard, Helene Merle-Beral, Florence Ajchenbaum-Cymbalista
Journal: Blood (2005)
Abstract 4283: Anticancer effects obtained against A20 lymphomas following treatment with LTX-315 (Oncopore®) in combination with low-dose cyclophosphamide
Authors: Ketil André Camilio, Liv-Marie Eike, Øystein Rekdal, Baldur Sveinbjornsson
Journal: Cancer Research (2015)

Abstract Background: Host defense peptides (HDPs) are naturally occurring molecules found in most eukaryotic species, where they play a significant role in the first line of defense against pathogens. Several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on the HDP bovine lactoferricin has resulted in the design of LTX-315, a short chemically modified peptide that induces immunogenic dell death. Previous animal studies have demonstrated that intratumoral (i.t.) treatment of syngeneic murine A20 B-cell lymphomas, CT26WT colon carcinomas and B16F1 melanomas with LTX-315 resulted in complete tumor regression and tumor specific immune responses. In the present study, we investigated the antitumor effects of LTX-315 in combination with low-dose cyclophosphamide (CY) against A20 lymphomas. Methods: A20 lymphoma cells (5 × 106) were intradermally inoculated into the abdomen of syngeneic Balb/c mice. Established tumors were treated i.t. with LTX-315 in combination with low-dose CY. Results: Intratumoral (i.t.) administration of LTX-315 in a suboptimal setting resulted in a synergistic antitumor effect when combined with low-dose CY, compared to CY and LTX-315 alone. In the combination therapy group the treatment induced a complete regression of the tumor in the majority of the animals (6 out of 9 animals), compared to LTX-315 alone (1 out of 8 animals) and no regression in the two control groups (CY alone and vehicle). Conclusions: Our results demonstrate that treatment with LTX-315 in combination with low-dose CY results in a synergistic antitumor effect in vivo. Thus, local treatment with the immunogenic cell death inducer LTX-315 combined with systemic chemotherapy may represent a promising combination strategy in future cancer therapy. Citation Format: Ketil André Camilio, Liv-Marie Eike, Øystein Rekdal, Baldur Sveinbjornsson. Anticancer effects obtained against A20 lymphomas following treatment with LTX-315 (Oncopore®) in combination with low-dose cyclophosphamide. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4283. doi:10.1158/1538-7445.AM2015-4283
Venous thromboembolic events in critically ill traumatic brain injury patients
Authors: Markus B. Skrifvars, Michael Bailey, Jeffrey Presneill, Craig French, Alistair Nichol, Lorraine Little, Jacques Duranteau, Olivier Huet, Samir Haddad, Yaseen Arabi, Colin McArthur, D. James Cooper, Rinaldo Bellomo
Journal: Intensive Care Medicine (2016)
Phase 1 Study of PKC412, an Oral FLT3 Kinase Inhibitor, in Sequential and Concomitant Combinations with Daunorubicin and Cytarabine (DA) Induction and High-Dose Cytarabine (HDAra-C) Consolidation in Newly Diagnosed Patients with AML.
Authors: Francis Giles, C. Schiffer, H. Kantarjian, T. Fischer, R. Paquette, D. M. Pelov, D. J. Resta, P. S. Cohen, Y. F. Wang, R. Stone
Journal: Blood (2004)
668. Platelets Engineered to Express Interleukin-24 Inhibited Melanoma Tumor Growth in Mice
Authors: Juan Fang, Ming Yao, Weiqing Jing, Beicheng Sun, Bryon D. Johnson, David A. Wilcox
Journal: Molecular Therapy (2016)

Background: Activated platelets secrete agents (e.g., cytokines) that can promote solid tumor growth & cancer metastasis. Previous studies showed that hematopoietic stem cells (HSC) can be genetically modified to induce platelets to express & secrete proteins to establish hemostasis in animal models of bleeding disorders. Interleukin-24 (IL-24) is a cytokine (normally produced by activated monocytes, macrophages & Thelper cells) with cytotoxic & anti-angiogenic activity preferentially towards cancer cells. Thus, we hypothesized it may be feasible use HSC gene transfer to target platelet synthesis, storage & secretion of IL-24 to inhibit tumor growth. Aims: To investigate if HSC gene transfer targeting IL-24 synthesis, storage & secretion from platelets can inhibit melanoma in mice. Methods: C57BlL/6 mice were transplanted with bone marrow transduced with a lentiviral construct encoding a megakaryocytespecific ITGA2B gene promoter driving synthesis of IL-24 gene. Four weeks after transplant, IL-24 protein was characterized in platelets by flow cytometry. Murine melanoma cells (1×106) were implanted in mice at 5 weeks after transplant. Tumor size was measured in IL24 & control groups using a digital caliper periodically for 4 weeks. Then mice were sacrificed to record tumor mass. Results: Flow cytometry showed that HSC gene transfer of murine bone marrow led to synthesis & storage of IL-24 in platelets. An elisa assay showed that activated platelets could secrete IL-24 in vitro. At 30 days after implant of melanoma cells, platelet IL24 mice displayed significantly smaller (≈50%) tumor size (550 ± 101mm3) & weight (599 ± 120 mg) compared to control mice with larger tumor size (1120 ± 114 mm3) & weight (1391 ± 134 mg) n≈5 mice/group (p<0.05) indicating that platelet IL24 inhibited tumor growth in vivo. Conclusion: HSC gene transfer can be utilized to induce synthesis, storage and secretion of anti-oncogenic agent IL24 in platelets. Melanoma tumor challenge in mice with platelet IL24 showed a significant decrease in tumor growth suggesting that platelets may serve as an ideal therapeutic vehicle to treat cancer.
P230 Evaluation of a novel dysfunctional breathing service
Authors: CP Winfield, C Moffat, R Hurst, JP Fuld
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Despite multiple trials, there remains a lack of consensus on the optimum management of dysfunctional breathing patients.<sup>1</sup> This service evaluation considers the effectiveness of a novel, multi-factorial intervention, consisting of cardiopulmonary exercise testing (CPET), explanation of physiological findings and breathing retraining, for those suffering from dysfunctional breathing. <h3>Methods</h3> Patients who had a history of likely dysfunctional breathing combined with CPET evidence of dysfunctional breathing, hyperventilation or lack of underlying pathology were invited to attend a joint consultation with a respiratory physician and a physiotherapist. To date, fourteen patients have attended initial consultation and six patients have completed full follow up. All patients received chest consultant clinical consultation where their CPET findings were reviewed with them, with particular emphasis on fitness, evidence of underlying disease and breathing pattern. Initial physiotherapist consultation was followed by a bespoke breathing retraining programme. The Nijmegan questionnaire and the self-evaluation of breathing questionnaire formed the main outcome measures. Patients also completed a service satisfaction questionnaire, rating 6 aspects of the service on a scale of 1–5, with 5 being most satisfied. Paired t-tests were used to calculate significance of pre and post values. <h3>Results</h3> Fourteen patients have so far been assessed in the initial consultation. Their diagnosis and breathing patterns, demonstrated on CPET, are described in Table 1. Average pre-trial Nijmegan Questionnaire scores demonstrated an improvement post-intervention from the 6 patients who have completed the intervention (26.5 pre to 21.2 post, p = 0.0465). Patients also completed the self-evaluation of breathing questionnaire, before and after the intervention. The average score decreased from 27.2 pre-trial to 15.0 post-trial (p = 0.0098). No changes in functional residual capacity controlled pause (10.0s pre to 11.8s post, p &gt; 0.05) or total lung capacity breath hold (11.8s pre to 21.0s post, p &gt; 0.05) were evident. The average patient satisfaction score was 28.6/30. <h3>Conclusion</h3> A novel combined physiological and physiotherapist based intervention may be effective in supporting symptoms in people with dysfunctional breathing. <h3>Reference</h3> Stanton AE, Vaughn P, Carter R, Bucknall CE. An observational investigation of dysfunctional breathing and breathing control therapy in a problem asthma clinic. <i>Journal of Asthma</i> 2008;<b>45</b>(9):758–765.
Abstract 3758: A combined machine learning and bioinformatic analysis approach identifies biological pathways that predict clinical stage and survival outcome in neuroblastoma patients
Authors: Alex Carlisle, Ivan Caceres, Sonali Mehta, Jay Schindler, Jonathan Sharma
Journal: Cancer Research (2015)

Abstract Neuroblastoma is an aggressive pediatric cancer that displays tremendous clinical and biological heterogeneity. Approximately 40% of patients present with metastatic disease and have poor outcome; new biomarkers that improve risk classification and prognostication are desperately needed. Applying a machine learning-based approach to analyzing transcriptome-wide signals in multiple populations of neuroblastoma patients spanning clinical stage we identified a combined set of 14 clinical and molecular variables that predicted survival outcome and tumor stage with over 87% accuracy. A systems biology-based analysis of the molecular variables from our predictive set identified 5 major networks with hubs defining 3 major ontological processes: apoptosis, nucleotide biosynthesis, and RNA metabolism. Citation Format: Alex Carlisle, Ivan Caceres, Sonali Mehta, Jay Schindler, Jonathan Sharma. A combined machine learning and bioinformatic analysis approach identifies biological pathways that predict clinical stage and survival outcome in neuroblastoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3758. doi:10.1158/1538-7445.AM2015-3758
Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study
Authors: Wai‐Kay Seto, Thomas Sau‐Yan Chan, Yu‐Yan Hwang, Danny Ka‐Ho Wong, James Fung, Kevin Sze‐Hang Liu, Harinder Gill, Yuk‐Fai Lam, Eric H.Y. Lau, Ka‐Shing Cheung, Albert K.W. Lie, Ching‐Lung Lai, Yok‐Lam Kwong, Man‐Fung Yuen
Journal: Hepatology (2016)

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–negative, antibody to hepatitis B core antigen (anti‐HBc)–positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg‐negative, anti‐HBc–positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg‐negative, anti‐HBc–positive, of whom 62 were recruited and monitored for a median of 48 (4‐104) weeks. The 2‐year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8‐100) weeks. Multivariate analysis showed that age ≥50 years ( P = 0.004, hazard ratio = 8.2) and chronic graft‐versus‐host disease ( P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients &lt;50 years old and without chronic graft‐versus‐host disease, compared with the remaining patient cohort, had a significantly lower 2‐year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. Conclusion : HBsAg‐negative, anti‐HBc–positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft‐versus‐host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (H epatology 2017;65:1451‐1461).
Noninvasive Measurement of mTORC1 Signaling with 89Zr-Transferrin
Authors: Charles Truillet, John T. Cunningham, Matthew F.L. Parker, Loc T. Huynh, Crystal S. Conn, Davide Ruggero, Jason S. Lewis, Michael J. Evans
Journal: Clinical Cancer Research (2016)

Abstract Purpose: mTOR regulates many normal physiological processes and when hyperactive can drive numerous cancers and human diseases. However, it is very challenging to detect and quantify mTOR signaling noninvasively in clinically relevant animal models of disease or man. We hypothesized that a nuclear imaging tool measuring intracellular mTOR activity could address this unmet need. Experimental Design: Although the biochemical activity of mTOR is not directly amenable to nuclear imaging probe development, we show that the transferrin receptor can be used to indirectly measure intracellular changes in mTOR activity. Results: After verifying that the uptake of radiolabeled transferrin (the soluble ligand of the transferrin receptor) is stimulated by active mTORC1 in vitro, we showed that 89Zr-labeled transferrin (Tf) can measure mTORC1 signaling dynamics in normal and cancerous mouse tissues with PET. Finally, we show that 89Zr-Tf can detect the upregulation of mTORC1 by tumor cells to escape the antitumor effects of a standard-of-care antiandrogen, which is to our knowledge the first example of applying PET to interrogate the biology of treatment resistant cancer. Conclusions: In summary, we have developed the first quantitative assay to provide a comprehensive measurement of mTOR signaling dynamics in vivo, in specific normal tissues, and during tumor development in genetically engineered animal models using a nuclear imaging tool that is readily translatable to man. Clin Cancer Res; 23(12); 3045–52. ©2016 AACR.
Serum Levels of Apolipoproteins and Incident Type 2 Diabetes: A Prospective Cohort Study
Authors: Adela Brahimaj, Symen Ligthart, M. Arfan Ikram, Albert Hofman, Oscar H. Franco, Eric J.G. Sijbrands, Maryam Kavousi, Abbas Dehghan
Journal: Diabetes Care (2016)

We aimed to investigate the role of serum levels of various apolipoproteins on the risk for type 2 diabetes (T2D).We used data from 971 individuals from the prospective population-based Rotterdam Study. We studied the association of HDL cholesterol (HDL-C), apoA1, apoCIII, apoD, and apoE as well as the ratios of apolipoproteins with apoA1 with the risk of T2D. All apolipoproteins, ratios, and HDL-C levels were naturally log-transformed to reach normal distribution. First, their cross-sectional associations with fasting glucose and insulin were investigated by using linear regression. Second, Cox proportional hazard models were used to examine whether apolipoproteins predict the risk for T2D among individuals free of diabetes at baseline. We also studied the apolipoproteins jointly by calculating the apolipoproteinic score from the first step and then performing Cox regression with it.During a median follow-up of 13.5 years, diabetes developed in 110 individuals. After adjustment for age, sex, BMI, parental history of diabetes, hypertension, alcohol use, smoking, prevalent cardiovascular disease, and serum lipid-reducing agents, HDL-C (per 1 SD naturally log-transformed hazard ratio 0.74 [95% CI 0.57, 0.97], apoCIII (1.65 [1.42, 1.91]), apoE (1.36 [1.18, 1.55]), apoCIII-to-apoA1 ratio (1.72 [1.51, 1.95]), apoE-to-apoA1 ratio (1.28 [1.13, 1.45]), and apolipoproteinic score (1.60 [1.39, 1.83]) remained significant. Only apoCIII (1.42 [1.03, 1.96]) and apoCIII-to-apoA1 ratio (1.56 [1.04, 2.36]) survived the adjustment for triglycerides in the last model.Serum apoCIII levels as well as apoCIII-to-apoA1 ratio are associated with incident T2D. They are associated independent of known risk factors and stronger than HDL-C levels.
Chromatin Texture and Molecular Features Are Independent Prognostic Factors In AML
Authors: Mariana Rezende Bandeira Mello, Dulcinéia Martins Albuquerque, Krizzia Borges Albanez, Randall L. Adam, Fernanda Gonçalves Pereira-Cunha, Katia B. Pagnano, Fernando Ferreira Costa, Konradin Metze, Irene Lorand-Metze
Journal: Blood (2010)
Abstract A2-33: Molecular profiling of patient-derived xenograft models across cancers
Authors: Zhengyan Kan, Edward Rosfjord, James Hardwick, Ying Ding, Xianxian Zheng, Julio Fernandez, Stephanie Shi, Mark Ozeck, Hui Wang, Gabriel Troche, Eric Upeslacis, Amy Jackson-Fisher, Keith Ching, Shibing Deng, Xie Tao, John Chionis, Maruja Lira, Xiaorong Li, Konstantinos Tsaparikos, Patrick Lappin, Pamela Vizcarra, David Shields, Judy Lucas, Paul Rejto
Journal: Cancer Research (2015)

Abstract Patient-Derived Xenograft (PDX) provides important preclinical model for pharmacological testing of oncology drug candidates. Molecular profiling of PDX tumors contributes to many areas of drug discovery from target discovery to development of clinical biomarker hypotheses and clinical trial design. We established a work flow to perform genomic and histopathology analyses of large numbers of PDX tumor models being made available for Pfizer internal research. To date we have generated whole-genome sequencing (WGS), whole-exome sequencing (WES) and whole transcriptome sequencing (RNA-Seq) data on PDX models spanning six cancer types including colon, pancreatic and breast cancers. Bioinformatics pipelines were developed to quantify gene expression and detect genetic alterations including mutation, copy number variations and gene fusions. A controlled evaluation study demonstrated that in silico classification of NGS reads into human/mouse origins is more effective than laboratory-based methods for removing mouse tissue contamination. Comparative analyses of molecular profiles from PDX and primary tumors of the same cancer origins suggest that important patterns of gene expression are retained by PDX models. An integrative genomic classifier was developed using the random forest algorithm, trained on primary tumor data, and shown to identify PDX cancer subtypes with high accuracy. Citation Format: Zhengyan Kan, Edward Rosfjord, James Hardwick, Ying Ding, Xianxian Zheng, Julio Fernandez, Stephanie Shi, Mark Ozeck, Hui Wang, Gabriel Troche, Eric Upeslacis, Amy Jackson-Fisher, Keith Ching, Shibing Deng, Xie Tao, John Chionis, Maruja Lira, Xiaorong Li, Konstantinos Tsaparikos, Patrick Lappin, Pamela Vizcarra, David Shields, Judy Lucas, Paul Rejto. Molecular profiling of patient-derived xenograft models across cancers. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-33.
Biomarkers associated with sedentary behaviour in older adults: A systematic review
Authors: Katharina Wirth, Jochen Klenk, Simone Brefka, Dhayana Dallmeier, Kathrin Faehling, Marta Roqué i Figuls, Mark A. Tully, Maria Giné-Garriga, Paolo Caserotti, Antoni Salvà, Dietrich Rothenbacher, Michael Denkinger, Brendon Stubbs
Journal: Ageing Research Reviews (2016)

Pathomechanisms of sedentary behaviour (SB) are unclear. We conducted a systematic review to investigate the associations between SB and various biomarkers in older adults. Electronic databases were searched (MEDLINE, EMBASE, CINAHL, AMED) up to July 2015 to identify studies with objective or subjective measures of SB, sample size ≥50, mean age ≥60 years and accelerometer wear time ≥3 days. Methodological quality was appraised with the CASP tool. The protocol was pre-specified (PROSPERO CRD42015023731). 12701 abstracts were retrieved, 275 full text articles further explored, from which 249 were excluded. In the final sample (26 articles) a total of 63 biomarkers were detected. Most investigated markers were: body mass index (BMI, n = 15), waist circumference (WC, n = 15), blood pressure (n = 11), triglycerides (n = 12) and high density lipoprotein (HDL, n = 15). Some inflammation markers were identified such as interleukin-6, C-reactive protein or tumor necrosis factor alpha. There was a lack of renal, muscle or bone biomarkers. Randomized controlled trials found a positive correlation for SB with BMI, neck circumference, fat mass, HbA1C, cholesterol and insulin levels, cohort studies additionally for WC, leptin, C-peptide, ApoA1 and Low density lipoprotein and a negative correlation for HDL. Most studied biomarkers associated with SB were of cardiovascular or metabolic origin. There is a suggestion of a negative impact of SB on biomarkers but still a paucity of high quality investigations exist. Longitudinal studies with objectively measured SB are needed to further elucidate the pathophysiological pathways and possible associations of unexplored biomarkers.