tbuckley/cabot-search huggingface dataset:
Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction
Authors: Caroline Fattah, Katrin Nather, Charlotte S. McCarroll, Maria P. Hortigon-Vinagre, Victor Zamora, Monica Flores-Munoz, Lisa McArthur, Lorena Zentilin, Mauro Giacca, Rhian M. Touyz, Godfrey L. Smith, Christopher M. Loughrey, Stuart A. Nicklin
Journal: Journal of the American College of Cardiology (2016)

Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI).The authors evaluated effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post-infarction.C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular pressure volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation/contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff-perfused whole-heart model.Gene delivery of Ang-(1-9) reduced sudden cardiac death post-MI. Pressure volume measurements revealed complete restoration of end-systolic pressure, ejection fraction, end-systolic volume, and the end-diastolic pressure volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism.Our novel findings showed that Ang-(1-9) gene therapy preserved left ventricular systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) directly affected cardiomyocyte calcium handling through a protein kinase A-dependent mechanism. These data emphasized Ang-(1-9) gene therapy as a potential new strategy in the context of MI.
The experimental study of bortezomib induce ovarian cancer SKOV-3,SKOV-3/DDP cell proliferation and drug resistance reversion.
Authors: Z. Liu, N. MA, Z. Jiang, G. Yang, J. Wang, D. Zhao
Journal: Journal of Clinical Oncology (2011)

e15547 Background: Ovarian cancer is the one of three malignant tumor in the department of gynecology. As the development of population aging, there is a trend of increasing ovarian cancer incidence rate.The traditional therapeutic tool of ovarian cancer lack tumor tissue specificity, so targeted therapy become a new tendency of the ovarian cancer therapy. Chemoresistance remains a major therapeutic problem. Researching new chemotherapeutics and overcoming drug resistance is a key to successful treatment of ovarian cancer. Methods: In this experiment the SKOV-3,SKOV-3/DDP cell growth inhibiting rates, the cellular apoptosis percentage, cell cycle phase and the expression of apoptosis relative protein were examined by MTT assay, Annextin V/PI assay, immunohistochemistry assay methods. Results: We found that Bortezomib can actively inhibit the growth of SKOV-3,SKOV-3/DDP cell line, induce them apoptosis, and together with DDP can effectively enhance the inhibiting effect to SKOV-3/DDP cell line. The mechanism of Bortezomib suppressing SKOV-3/DDP cell line growth is that the G2/M phase cell growth was blocked, and when Bortezomib was used with DDP together, the S phase cell growth was blocked. In addition, the mechanism of Bortezomib inducing SKOV-3,KOV-3/DDP cell line apoptosis maybe related with antiapoptotic proteins Bcl-2 expression level decrease, and proapoptotic proteins Bad expression level increase. Conclusions: Although we only did the relative research of Bortezomib treatment to ovarian cancer in vitro, confirmed that its effectiveness on ovarian cancer. This may provide the new treatment ideas and experiment support for ovarian cancer chemotherapy and recrudescent and refractory ovarian cancer treatment, and also may provide clinical guide for solid tumors treatment and multidrug resistance reversion.
35. Mesenchymal Stem Cells Reduce Endoplasmic Reticulum (ER) Stress and Correct Inappropriate Epithelial Mesenchyme Relation in Pulmonary Fibrosis Using Stanniocalcin-1
Authors: Shinya Ohkouchi, Manabu Ono, Hajime Kurosawa, Masakazu Ichinose
Journal: Molecular Therapy (2015)

Current hypotheses suggest that aberrant wound healing has a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). In these hypotheses, continuous TGF-b1 secretion by alveolar epithelial cells (AECs) in abnormal wound healing has a critical role in promoting fibroblast differentiation into myofibroblasts. Mesenchymal stem cells (MSCs) home to the injury site and reduce fibrosis by secreting multifunctional antifibrotic humoral factors in IPF. In this study, we show that MSCs can correct the inadequate communication between epithelial and mesenchymal cells through STC1 (Stanniocalcin-1) secretion in a bleomycin induced IPF model. Inhalation of recombinant STC1 shows the same effects as the injection of MSCs. Using STC1 plasmid, it was possible to enhance the ability of MSCs to ameliorate the fibrosis. MSCs secrete large amounts of STC1 in response to TGF-b1 in comparison to AECs and fibroblasts. The antifibrotic effects of STC1 include reducing oxidative stress, endoplasmic reticulum (ER) stress, and TGF-b1 production in AECs. The STC1 effects can be controlled by blocking uncoupling protein 2 (UCP2) and the secretion is affected by the PI3/AKT/mTORC1 inhibitors. Further we proved that the STC1 can reduce the secretion of TGF-b1 from alveolar macrophages (AMs) which is the another source of TGF-b1 in the pathogenesis of IPF using same mechanisms. Our findings suggest that STC1 tends to correct the inappropriate epithelial mesenchymal relationships and that STC1 plasmid transfected to MSCs or STC1 inhalation could become promising treatments for IPF. Summary of our study is shown in below figure.
Reduced-Intensity Conditioning (RIC) Followed by Allogeneic Transplantation in Relapsed Lymphomas: Evidence for Graft-Versus-Lymphoma Effect in Low and High Grade Histologies, but Not in Hodgkin Disease.
Authors: Paolo Corradini, Anna Dodero, Marco Bregni, Attilio Olivieri, Lucia Farina, Elena Rizzo, Raffaella Milani, Rosanna Scime, Alessandro Rambaldi, Francesca Bonifazi, Francesca Patriarca, Anna Locasciulli, Andrea Bacigalupo, Alessandro Massimo Gianni, Corrado Tarella
Journal: Blood (2004)
Psychosocial impact of HIV-related caregiving on health providers: a review and recommendations for the role of psychiatry
Authors: D C Silverman
Journal: American Journal of Psychiatry (1993)

The author considers current knowledge about the stresses of HIV-related care and assesses available evidence for the presence of major occupational, physical, and psychiatric morbidity in health care providers involved in intensive HIV-related caregiving.The review is based on anecdotal reports of AIDS-care-related psychosocial distress and the literature concerning caregivers' attitudes toward people with HIV illness and HIV-related caregiving, the psychosocial impact of HIV work, and stress related to the ethical and philosophical challenges facing HIV caregivers.Few of the current publications concerning HIV caregiver stress come from the psychiatric literature. Psychiatry appears to lack a strong clinical, educational, research, or policy presence regarding psychosocial stress in HIV care providers. The numerous studies in the nursing, medical, public health, and health education literature do not include any controlled investigations documenting the incidence and prevalence of physical, psychological, occupational, or interpersonal symptoms or disorders in health care professionals who devote a substantial amount of their clinical activities to patients with HIV illness.Major HIV-related stress in conjunction with other psychiatric morbidity, such as mood disorders, anxiety disorders, substance abuse, and relationship and occupational problems, seems likely in susceptible caregivers. Decisions about the structure and form of delivery of HIV-related care and programs for caregivers must be based on more carefully controlled psychiatric observations of occupational, physical, psychological, and social adaptation to HIV-related work. The author suggests several areas in which psychiatric clinicians, educators, researchers, and policy experts can make major contributions.
Long Term Effects on GVHD and Survival Following the Use of G-CSF Stimulated Bone Marrow Versus G-CSF Mobilized Peripheral Blood Stem Cells in HLA Matched Sibling Transplant.
Authors: Anne W. Beaven, Thomas C. Shea, Don A. Gabriel, Terrance Comeau, Robert Irons, Dominic T. Moore, Li Lin, Andrew Sharf, Carol Krasnov, Mark E. Brecher, Jonathan Serody
Journal: Blood (2005)
FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N 6 -Methyladenosine RNA Demethylase
Authors: Zejuan Li, Hengyou Weng, Rui Su, Xiaocheng Weng, Zhixiang Zuo, Chenying Li, Huilin Huang, Sigrid Nachtergaele, Lei Dong, Chao Hu, Xi Qin, Lichun Tang, Yungui Wang, Gia-Ming Hong, Hao Huang, Xiao Wang, Ping Chen, Sandeep Gurbuxani, Stephen Arnovitz, Yuanyuan Li, Shenglai Li, Jennifer Strong, Mary Beth Neilly, Richard A. Larson, Xi Jiang, Pumin Zhang, Jie Jin, Chuan He, Jianjun Chen
Journal: Cancer Cell (2016)
Allo-HLA Reactive CD8 T-Cells May Recognize Tissue Specific Peptides Explaining Tissue Restricted GVHD after HLA Mismatched SCT.
Authors: Avital Amir, Marieke Griffioen, Michel D.G. Kester, M. Willy Honders, Roelof Willemze, J.H. Frederik Falkenburg, Mirjam Heemskerk
Journal: Blood (2007)
Abstract CT318: Evaluation of salivary transcriptome markers for early detection of squamous cell cancer in a prospective blinded trial
Authors: Neil Gottehrer, Jack Martin
Journal: Cancer Research (2015)

Abstract Oral squamous cell cancer (OSCC) is often diagnosed in late stages. Informative biomarkers could play a key role in early diagnosis. Prior case-control studies identified discriminatory salivary mRNA markers for OSCC. The National Cancer Institute (NCI) recommends prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design study for rigorous biomarker identification and validation. A PRoBE design study enrolled 170 patients with lesions suspicious for OSCC. Saliva was collected before performing oral biopsy. Six mRNAs (IL1β, IL8, OAZ1, SAT1, S100P, and DUSP1) were measured by quantitative polymerase chain reaction (PCR) without knowledge of tissue diagnosis. A pre-specified multi-marker panel from prior NCI - Early Detection Research Network (EDRN) studies was evaluated in this new PRoBE dataset. Individual marker cycle thresholds (Ct) from PCR were also compared in cancer versus control and new discriminatory models were generated. The EDRN model was validated based on pre-specified statistical analysis plan. Ct values of individual mRNAs reflect an approximately two to nearly fourfold increase in concentration in invasive OSCC (p&amp;lt;0.01 for all). A new model from this intended use population demonstrates a maximal sum of sensitivity and specificity of 153.5% with an area under the receiver operating characteristic (ROC) curve of 0.81. The validation of six pre-specified individual salivary transcriptome markers of OSCC and a pre-specified multi-marker model in a new prospective population, support the robustness of these markers and the multi-marker methodology. New models generated in this intended use population have the potential to further enhance the decision process for early biopsy. Trial ID: NCT01587573 Citation Format: Neil Gottehrer, Jack Martin. Evaluation of salivary transcriptome markers for early detection of squamous cell cancer in a prospective blinded trial. [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 CT318. doi:10.1158/1538-7445.AM2015-CT318
Lack of Benefit for Liraglutide in Heart Failure—Reply
Authors: Kenneth B. Margulies, Steven E. McNulty, Thomas P. Cappola
Journal: JAMA (2016)

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Early tumor shrinkage (eTS) as a predictive and prognostic factor in metastatic renal cell carcinoma (mRCC).
Authors: Viktor Gruenwald, Xun Lin, Daniel Kalanovic, Ronit Simantov
Journal: Journal of Clinical Oncology (2015)

4551 Background: Tumor shrinkage (TS) has predictive value in mRCC, and early TS has been reported to be associated with prognosis in small series with mRCC, but the optimal cut-off has not been defined. We therefore quantitated the degree of tumor shrinkage at first scan that has predictive or prognostic value in mRCC. Methods: Data from Pfizer-sponsored clinical trials with sunitinib, axitinib, sorafenib, IFN or temsirolimus in mRCC were included for this posthoc analysis (A6181006, A6181034, A6181061, A6181065, A6181110, RTKC-0511-014, A4061032, A4060146, A4061051, 3066K1-304, 3066K1-3311, 3066K1-404). Objective tumor response was captured by protocol-defined tumor imaging according to RECIST. Target lesions were followed for TS. eTS was assessed at first post-baseline scan and analyzed for sensitivity and specifity by receiver-operating characteristic (ROC) analyses to predict response measured by median progression free survival (PFS) or overall survival (OS). Patients were classified as responders if PFS (7 mo.) or OS (20 mo.) were above the median. Results: 4736 pts (71% male) with median age 59 years were identified within the database. Most patients were treatment naïve (67%), had clear cell histology (89%), and favorable performance status (ECOG 0/1: 53/47%). Overall, an eTS of 7% or 8% was identified as the optimal cut-off for prediction of PFS or OS, respectively. Subgroups were analyzed and are depicted in table. Conclusions: Using a large clinical trials database in mRCC, we explored the predictive value of eTS in mRCC. Our analyses showed that the conventional 30% tumor shrinkage threshold is too high and that a cut-off at approximately 10% early TS predicts PFS and OS in mRCC. This finding is confirmed by a recent report on observer variability of eTS in mRCC. eTS should be further explored as a novel endpoint for clinical studies in mRCC. eTS as predictor in mRCC. PFS sensitivity/specifity OS sensitivity/specifity all 7% 0.611/0.674 8% 0.603/0.632 1st line 11% 0.632/0.684 8% 0.596/0.621 2nd line 4% 0.530/0.724 5% 0.673/0.704 axitinib, sorafenib, sunitinib 10% 0.647/0.598 10% 0.653/0.659 temsirolimus 11% 0.652/0.631 12% 0.616/0.621 IFN 1% 0.728/0.621 1% 0.712/0.508
Low Expression of CXCR4 in Bortezomib-Resistant Multiple Myeloma Correlates with Extramedullary Disease in a Murine Mouse Model
Authors: Holly A. F. Stessman, Aatif Mansoor, Fenghuang Zhan, Guido J. Tricot, John Sunderland, Susan A. Walsh, Siegfried Janz, Brian Van Ness, Linda B. Baughn
Journal: Blood (2012)
PTH-037 Magnitude of the physiological response to CCK does not predict changes in hunger or fullness in response to a test meal
Authors: R B Jones, G J Dockray, D G Thompson
Journal: Gut (2010)

<h3>Introduction</h3> Cholecystokinin (CCK) and the CCK1 receptor play an important role in both gastric emptying1 and the control of food intake in man.2 Accordingly CCK antagonism increases feeling of hunger, decreases feelings of fullness2 and leads to accelerated gastric emptying.1 It is not known if the magnitude of physiological response to CCK antagonism relates to the magnitude of changes in reported hunger and fullness elicited by a test meal. <h3>Objectives</h3> To determine if the magnitude of changes in gastric emptying relate to the magnitude of changes in feelings of hunger and fullness, in response to a test meal, after CCK1 receptor antagonism. <h3>Methods</h3> 25 healthy subjects (12 female, mean age 23, mean BMI 23.7) underwent six gastric emptying studies of a nutrient test meal (milk) using the <sup>13</sup>C acetate breath test. On three occasions they were pre-treated with the CCK1 receptor antagonist, dexloxiglumide 600 mg. Subjects rated feelings if hunger and fullness in a visual analogue scale at 5-min intervals throughout the duration of the study (45 min). Average area under curve (AUC) for hunger and fullness were recorded and scores for the upper quartile (UQ, with the biggest response to dexloxiglumide) were compared to those in the lowest quartile (LQ, with the least response to dexloxiglumide). <h3>Results</h3> After dexloxiglumide, the mean per cent change in gastric emptying for the six greatest responders was 64±10 and for the six smallest responders 10±10. When the two groups were compared, no difference in per cent change in AUC was seen for reported hunger (UQ: 170±318 vs LQ: −33±232, p=0.31) or fullness (UQ: 167±137 vs LQ: 168±274). <h3>Conclusion</h3> The magnitude of response to CCK1 receptor antagonism, as measured by change in gastric emptying rate, does not relate to changes in reported feelings of fullness or hunger after a test meal. This calls into question the physiological role of CCK in appetite control.
Zanolimumab (HuMax-CD4™), a Fully Human Monoclonal Antibody: Efficacy and Safety in Patients with Relapsed or Treatment-Refractory Non-Cutaneous CD4+ T-Cell Lymphoma.
Authors: Francesco d’Amore, John Radford, Mats Jerkeman, Thomas Relander, Herve Tilly, Anders Osterborg, Franck Morschhauser, Martin Gramatzki, Martin Dreyling, Bo Bang, Ole Baadsgaard, Hans Hagberg
Journal: Blood (2007)
Abstract 4990: The RET receptor Y791F variant activates the kinase but diminishes ligand responsiveness
Authors: Andrew Fetz, Mathieu J.F. Crupi, Eric Lian, Brandy D. Hyndman, Lois M. Mulligan
Journal: Cancer Research (2015)

Abstract The RET receptor tyrosine kinase is essential for normal development of the kidneys and enteric nervous system, and is also implicated in several human pathologies. Gain-of-function mutations in RET are associated with the familial cancer syndrome multiple endocrine neoplasia type 2 (MEN 2), where single amino acid substitutions lead to constitutive RET activation in the absence of its ligands of the glial cell line-derived neurotrophic factor (GDNF) family. Conversely, loss-of-function RET mutations are associated with Hirschsprung disease, a congenital abnormality of the enteric nervous system. Previous studies have identified a specific substitution variant of a phenylalanine for tyrosine at amino acid 791 in the RET kinase domain in both cancer and Hirschsprung disease patients. Thus, the functional implications of this variant and its contributions to these diverse phenotypes are not clear. Here, we have explored the role of MEN 2-associated RET mutations in RET-mediated cell invasion and migration. We showed that GDNF-stimulation promotes RET-mediated cell migration and that a GDNF-chemotactic gradient significantly increased invasion of cells expressing wild type RET or a MEN2B (M918T) mutant RET form. However, we found that a GDNF gradient did not enhance invasion of cells expressing RET-Y791F. Consistent with this, we showed that MEN 2-associated RET mutants M918T and Y791F were phosphorylated in the absence of GDNF and stimulated downstream signaling pathways. GDNF treatment further increased phosphorylation of the RET-M918T but not RET-Y791F proteins, suggesting that RET-Y791F has reduced responsiveness to GDNF ligand. Our results suggest that despite constitutive activation of RET signaling, cells expressing the Y791F variant may possess a diminished capacity to recognize and respond to GDNF in the cell microenvironment. This may be linked to a disturbance in the directional migration of cells expressing the mutant receptor thus contributing to the phenotypic variability observed. Citation Format: Andrew Fetz, Mathieu J.F. Crupi, Eric Lian, Brandy D. Hyndman, Lois M. Mulligan. The RET receptor Y791F variant activates the kinase but diminishes ligand responsiveness. [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 4990. doi:10.1158/1538-7445.AM2015-4990
Prognostic Relevance of Gene Expression Using RT-PCR in Diffuse Large B-Cell Lymphoma.
Authors: Hee-Nam Kim, Je-Jung Lee, Deok-Hwan Yang, Yeo-Kyeoung Kim, Nan Young Kim, Kyeong-Soo Park, Hyo-Jung Kim, Dae-Young Jang, Jin-Seok Ahn, Sung-Hwa Bae, Hun-Mo Ryoo, Hyeoung-Joon Kim
Journal: Blood (2004)