tbuckley/cabot-search huggingface dataset:
Abstract P175: Selective Regional Injections of Alginate Hydrogel into Cardiac Veins Improve Left Ventricular Function and Reverse Chamber Remodeling in Dogs with Chronic Heart Failure
Authors: Hani N Sabbah, Mengjun Wang, Michael S Sabbah, Sharad Rastogi, Ramesh C Gupta, Sam Helgerson
Journal: Circulation Research (2011)

Background: Progressive LV enlargement and dysfunction are characteristics of heart failure (HF) and are associated with increased mortality and morbidity. We tested the hypothesis that selective regional injections of alginate hydrogel implants (AHI, Algisyl-LVR, Lonestar Heart, Inc.) into isolated segments of epicardial veins of the failing LV will increase LV wall thickness and lead to reduced LV size, lower LV wall stress and improved LV systolic and diastolic function. Methods: 12 dogs with coronary microembolization-induced HF (LV ejection fraction, EF&lt;30%) were studied. During an open-chest procedure, 1.5 to 2.0 cm segments of the 2 nd diagonal branch and the 2 nd marginal branch of the cardiac epicardial veins were isolated by ligation with silk sutures. In 6 dogs, the isolated segments were each injected with 1.0 ml of AHI and in 6 dogs with normal saline (controls). LV ED volume (EDV), ES volume (ESV), EF, stroke volume (SV), ED wall stress (EDWS), deceleration time of early mitral inflow velocity (DT), and severity of functional mitral regurgitation (MR) were measured before therapy (Pre) and at 6 months after AHI or saline delivery (Post). The treatment effect (Δ) was calculated as the difference between Pre and Post. Results: In preliminary we showed that an intravenous injection of 1.0 ml AHI increased regional LV end-diastolic (ED) and end-systolic (ES) wall thickness by 5.8 ± 0.7 % and 9.0 ± 1.0 %, respectively. Compared to saline controls, treatment of HF dogs with AHI prevented the increase in EDV and significantly decreased ESV, EDWS and severity of functional MR (Table). In addition, AHI significantly increased LV EF, SV and DT indicating improved LV systolic and diastolic function (Table). Treatment with Alginate implants also showed a safe and non-arrhythmogenic chronic profile. Conclusion: LV reconstruction using selective regional injections of AHI into epicardial cardiac veins represents a safe novel approach for the treatment of advanced chronic HF. Table 1. Hemodynamic and Ventriculographic Results Control (n=6) AHI (n=6) P-Value ΔEDV (ml) 2.5 ± 1.0 −1.1 ± 0.4 0.114 ΔESV (ml) 4.3 ± 1.7 −3.9 ± 0.4 0.001 ΔEF (%) −3.8 ± 1.5 5.0 ± 0.4 0.001 ΔSV (ml) −1.8 ± 0.8 0.11 ± 0.04 0.001 ΔEDWS (gm/cm²) 9.4 ± 6.5 −23.1 ± 4.6 0.006 ΔDT (msec) −4.7 ± 0.4 27.0 ± 4.4 0.001 ΔMR (%) 1.7 ± 0.8 −3.6 ±1.3 0.004
Surveillance of drug treatments in cancer patients by database linkage.
Authors: Birgitta Lilja, Jamilette Miranda, Gunnar Ljunggren, Sven-Ake Loov, Bjorn Wettermark, Roger Henriksson
Journal: Journal of Clinical Oncology (2014)

e17666 Background: The knowledge about safety and effectiveness of new medicines in clinical practice is limited. To meet the need of evaluating the performance of new drugs, a model for surveillance of cancer treatment has been developed in a Swedish region (2.2 million inhabitants). This study aimed to obtain an overview of available information on cancer patients by linking data from different sources Methods: This is a retrospective registry-based study on 20,759 patients diagnosed with incident malignant C-tumors (ICD-O-2 codes) during 2009-2010 in Stockholm and Gotland, Sweden. Data from national and regional registries including diagnoses (tumor and other), drugs (prescriptions and parenteral preparations), mortality, and socioeconomics was linked using unique patient id. The study was approved by the Regional Ethical Review Board . Results: During the study period 3,493 died. Drug treatment and comorbidity for three major groups of cancer diseases accounting for 8,226 patients (47.6% of all patients alive with malignant C-diagnoses) are shown in the Table. Conclusions: Patient record-linkage allows surveillance of new medicines in healthcare. Cardiovascular disease was the most frequent comorbidity in the prostate cancer group as in the general population. The drug treatments agreed with indications, but unexpected findings require further analysis. Prostate cancer (C61.9) Breast cancer (C50) Skin cancer, excl. melanoma (C44) N 3,298 2,556 885 (51.9% men) Age, mean (SD) 67.7 (8.7) 61.1 (13.8) 75.7 (12.8) Other disease groups N (%) cardiovascular 941 (28.5) urogenital 811 (31.7) skin 271 (30.6) urogenital 897 (27.2) cardiovascular 717 (28.1) cardiovascular 161 (18.2) musculoskeletal 516 (15.6) musculoskeletal 532 (20.8) musculoskeletal 137 (15.5) digestive 409 (12.4) endocrine 330 (12.9) eye 123 (13.9) endocrine 400 (12.1) respiratory 292 (11.4) urogenital 114 (12.9) Drugs N (%) bicalutamide 979 (29.6) tamoxifen 1052 (41.2) fluorouracil 7 (0.8) leuprorelin 616 (18.7) cyclophosphamide 859 (33.6) leuprorelin 6 (0.7) goserelin 132 (4.0) epirubicin 801 (33.3) bicalutamide 6 (0.7) triptorelin 116 (3.5) fluorouracil 663 (25.9) hydroxycarbamide 3 (0.3) tamoxifen 38 (1.2) anastrozole 626 (24.5) cytarabine 2 (0.2)
Hypoxia-inducible factor 1α: A screening tool for predicting development of castrate resistant prostate cancer.
Authors: Weranja Kalana Bodhisiri Ranasinghe, Lin Xiao, Suzana Kovac, Mike Chang, Arthur Shulkes, Damien M Bolton, Graham Baldwin, Oneel Patel
Journal: Journal of Clinical Oncology (2012)

e15117 Background: Currently there is no method to determine which patients starting androgen deprivation therapy (ADT) for prostate cancer (PC) will progress to castrate resistant prostate cancer (CRPC) while the reasons for early metastases and chemoresistance in CRPCs are unknown. We aimed to investigate the potential role of hypoxia inducible factor 1α (HIF1α), a key transcription factor in the cell mediated adaptive response to changes in tissue oxygenation, in predicting the development of CRPC. Methods: 100 prostate tumour samples were divided into Gleason ≤7 (38) and Gleason &gt;7 (62) and stained for HIF1α using immunohistochemistry, blinded to the outcomes. The outcomes of CRPC, metastases and PC specific death were measured and correlated with HIF1α expression. In vitro, the effects of HIF1α on proliferation, survival and migration of PC cells were assessed by cell count and Boyden chamber assays. Results: HIF1α expression in PC was independent of Gleason grade and tumour stage. HIF1α was an independent risk factor for development of CRPC (Hazard Ratio (HR) 10.4), progression to metastases (HR 9.8) and PC specific death (HR 13.4) at median times of 23, 24 and 25 months respectively, from the start of ADT on a multivariate Cox regression analysis (all p&lt;0.05) adjusted for Gleason score, PSA and age. CRPC free survival, metastases free survival and PC specific survival were all significantly decreased in patients with HIF1α on Kaplan Meier analyses. The presence of HIF1α was highly sensitive (all 100%) with excellent negative predictive values (all 100%) for all 3 outcomes, but had poor specificity. HIF1α over-expressing PC3 cells (CRPC) were compared with androgen sensitive LNCaP cells in vitro. PC3 cells were resistant to cytotoxic agents including H 2 O 2 (oxidative stress) and 5-fluorouracil (chemotherapy agent) and had higher rates of migration compared to LNCaP cells. HIF1α knockdown in PC3 cells reversed these effects. Protein translation efficiency in PC3 cells was significantly higher than LNCaP cells. Conclusions: HIF1α is a good screening tool for CRPC. HIF1α expression is likely to contribute to metastases and chemoresistance of CRPCs and is likely upregulated at protein translation in PC cells.
Comparison of three stool antigen assays with the urea breath test for the primary diagnosis of Helicobacter pylori infection and monitoring treatment outcome
Authors: C Hooton, J Keohane, J Clair, S O'Mahony, M Azam, O Crosbie, B Lucey
Journal: Endoscopy (2005)

Aim: To compare three stool antigen assays: Premier platinum HpSA (Meridan Diagnostics); IDEIA-HpStAR (Daykocytomation); and the ImmunoCardSTAT (Meridian Diagnostics), against the urea breath test, and to assess their acceptability as an alternative to the UBT for the primary diagnosis of H. pylori infection and for monitoring treatment outcome.
Distinct immune microenvironments stratify triple-negative breast cancer and predict outcome
Authors: T. Gruosso, M. Gigoux, N. Bertos, V.S.K. Manem, M.-C. Guiot, L. Buisseret, R. Salgado, G. Van den Eyden, B. Haibe-Kains, M. Park
Journal: Annals of Oncology (2017)
T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model
Authors: Xiuxiu Sang, Ruilin Wang, Yanzhong Han, Cong'en Zhang, Honghui Shen, Zhirui Yang, Yin Xiong, Huimin Liu, Shijing Liu, Ruisheng Li, Ruichuang Yang, Jiabo Wang, Xuejun Wang, Zhaofang Bai, Xiaohe Xiao
Journal: Acta Pharmaceutica Sinica B (2017)

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-γ (IFN-γ) in a dose-dependent manner in CD4+ T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.
West Nile virus outbreak in Israel in 2015: phylogenetic and geographic characterization in humans and mosquitoes
Authors: Y. Lustig, Z. Kaufman, B. Mannasse, R. Koren, S. Katz-Likvornik, L. Orshan, A. Glatman-Freedman, E. Mendelson
Journal: Clinical Microbiology and Infection (2017)
Baby thought to have been shaken has rare syndrome, family court finds
Authors: Clare Dyer
Journal: BMJ (2017)

A baby who was thought to have been shaken by one of her parents actually has a rare syndrome that affects her blood vessels, Ehlers-Danlos syndrome type IV, a family court has heard.

Effie Stillwell was taken from her parents and placed with foster carers last September, after she collapsed, at nearly 3 months old, and was taken to hospital unresponsive and with difficulty breathing. Retinal haemorrhages and bleeding on the brain were identified, and police began a criminal investigation. But the medical evidence that emerged during the family court hearing persuaded Buckinghamshire County Council to drop its application for a care order.

The baby was “the first child with a …
Extra corporeal membrane oxygenation in the therapy of cardiogenic shock (<scp>ECMO‐CS</scp>): rationale and design of the multicenter randomized trial
Authors: Petr Ostadal, Richard Rokyta, Andreas Kruger, Dagmar Vondrakova, Marek Janotka, Ondrej Smíd, Jana Smalcova, Milan Hromadka, Ales Linhart, Jan Bělohlávek
Journal: European Journal of Heart Failure (2017)
Clinical and radiological predictive factors of chemosensitivity in pediatric low-grade gliomas: a single center study
Authors: Guillaume Bergthold, Caroline Piette, MA Raquin, Christelle Dufour, Pascale Varlet, Frédéric Dhermain, Stéphanie Puget, Christian Sainte-Rose, M Abely, S Canale, Jacques Grill
Journal: Neuro-Oncology (2012)
Early Post-Transplantation Tacrolimus Levels Correlate with Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation from Related and Unrelated Donors
Authors: Patrick A Hagen, Daniel Kobrinski, Zeina Al-Mansour, Stephanie B. Tsai, Mala Parthasarathy, Stephanie Kliethermes, Tulio E. Rodriguez, Scott E. Smith, Patrick J. Stiff
Journal: Blood (2016)
European Perspectives
Journal: Circulation (2009)

attended a science-oriented high school in Naples but showed no special talents or aptitudes in this area.By the late 1960s, he was playing drums professionally in a rock group.However, under the influence and with the encouragement of a band mate who had ambitions to become a doctor, Volpe enrolled as a medical student at the University of Naples, Federico II.He took to medicine and completed his studies in Naples, graduating with a med-
Phase II Trial of R-CVP Followed By Rituximab Maintenance Therapy for Patients with Advanced Stage Marginal Zone Lymphoma- Consortium for Improving Survival of Lymphoma (CISL) Study
Authors: Sung Yong Oh, Won Seog Kim, Jin Seok Kim, Seok Jin Kim, Suee Lee, Dok Hyun Yoon, Deok-Hwan Yang, Won Sik Lee, Hyo Jung Kim, Ho-Young Yhim, Seong Hyun Jeong, Jong Ho Won, Jee Hyun Kong, Sung-Nam Lim, Jun Ho Ji, Kyung A Kwon, Gyeong-Won Lee, Jae Hoon Lee, Ho Sup Lee, Ho-Jin Shin, Cheolwon Suh
Journal: Blood (2016)
Gene expression and mutation-guided synthetic lethality eradicates proliferating and quiescent leukemia cells
Authors: Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Grazyna Hoser, Silvia Maifrede, Esteban Martinez, Daniela Di Marcantonio, Elisabeth Bolton-Gillespie, Kimberly Cramer-Morales, Jaewong Lee, Min Li, Artur Slupianek, Daniel Gritsyuk, Sabine Cerny-Reiterer, Ilona Seferynska, Tomasz Stoklosa, Lars Bullinger, Huaqing Zhao, Vera Gorbunova, Katarzyna Piwocka, Peter Valent, Curt I. Civin, Markus Muschen, John E. Dick, Jean C.Y. Wang, Smita Bhatia, Ravi Bhatia, Kolja Eppert, Mark D. Minden, Stephen M. Sykes, Tomasz Skorski
Journal: Journal of Clinical Investigation (2017)

Quiescent and proliferating leukemia cells accumulate highly lethal DNA double-strand breaks that are repaired by 2 major mechanisms: BRCA-dependent homologous recombination and DNA-dependent protein kinase-mediated (DNA-PK-mediated) nonhomologous end-joining, whereas DNA repair pathways mediated by poly(ADP)ribose polymerase 1 (PARP1) serve as backups. Here we have designed a personalized medicine approach called gene expression and mutation analysis (GEMA) to identify BRCA- and DNA-PK-deficient leukemias either directly, using reverse transcription-quantitative PCR, microarrays, and flow cytometry, or indirectly, by the presence of oncogenes such as BCR-ABL1. DNA-PK-deficient quiescent leukemia cells and BRCA/DNA-PK-deficient proliferating leukemia cells were sensitive to PARP1 inhibitors that were administered alone or in combination with current antileukemic drugs. In conclusion, GEMA-guided targeting of PARP1 resulted in dual cellular synthetic lethality in quiescent and proliferating immature leukemia cells, and is thus a potential approach to eradicate leukemia stem and progenitor cells that are responsible for initiation and manifestation of the disease. Further, an analysis of The Cancer Genome Atlas database indicated that this personalized medicine approach could also be applied to treat numerous solid tumors from individual patients.
Life-sustaining treatment and palliative care in patients with liver cirrhosis - legal, ethical, and practical issues
Authors: Dong Joon Kim, Moon Seok Choi
Journal: Clinical and Molecular Hepatology (2017)

With the enactment of the 'Act on Decisions on Life-Sustaining Treatment for Patients in Hospice and Palliative Care or at the End of Life' (Act No. 14013) in Korea, there is growing concern about the practicality of this law. In this review, we discuss definitions, ethics, and practical issues related to this law.
Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer
Authors: John D. Norris, Stephanie J. Ellison, Jennifer G. Baker, David B. Stagg, Suzanne E. Wardell, Sunghee Park, Holly M. Alley, Robert M. Baldi, Alexander Yllanes, Kaitlyn J. Andreano, James P. Stice, Scott A. Lawrence, Joel R. Eisner, Douglas K. Price, William R. Moore, William D. Figg, Donald P. McDonnell
Journal: Journal of Clinical Investigation (2017)

The clinical utility of inhibiting cytochrome P450 17A1 (CYP17), a cytochrome p450 enzyme that is required for the production of androgens, has been exemplified by the approval of abiraterone for the treatment of castration-resistant prostate cancer (CRPC). Recently, however, it has been reported that CYP17 inhibitors can interact directly with the androgen receptor (AR). A phase I study recently reported that seviteronel, a CYP17 lyase–selective inhibitor, ædemonstrated a sustained reduction in prostate-specific antigen in a patient with CRPC, and another study showed seviteronel’s direct effects on AR function. This suggested that seviteronel may have therapeutically relevant activities in addition to its ability to inhibit androgen production. Here, we have demonstrated that CYP17 inhibitors, with the exception of orteronel, can function as competitive AR antagonists. Conformational profiling revealed that the CYP17 inhibitor–bound AR adopted a conformation that resembled the unliganded AR (apo-AR), precluding nuclear localization and DNA binding. Further, we observed that seviteronel and abiraterone inhibited the growth of tumor xenografts expressing the clinically relevant mutation AR-F876L and that this activity could be attributed entirely to competitive AR antagonism. The results of this study suggest that the ability of CYP17 inhibitors to directly antagonize the AR may contribute to their clinical efficacy in CRPC.
Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity
Authors: David Olagnier, Rassin R. Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V. Knatko, Albena T. Dinkova-Kostova, John Hiscott, Rongtuan Lin
Journal: Molecular Therapy (2017)
Unravelling mechanisms of resistance to CDK4/6 inhibitors using triple negative breast cancer (TNBC)
Authors: U. Asghar, A. Barr, R. Cutts, M. Beaney, D. Sampath, J. Giltnane, J. Arca Lacap, M. Herrera-Abreu, C. Bakal, N. Turner
Journal: Annals of Oncology (2017)
Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma Harboring a 8q24/MYC Rearrangement: A Retrospective Registry Study from the Japan Society for Hematopoietic Cell Transplantation
Authors: Tsutomu Takahashi, Ritsuro Suzuki, Koji Izutsu, Hideyuki Nakazawa, Sachiko Suzuki, Junya Kuroda, Katsuji Kaida, Hitoshi Ohno, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Junji Suzumiya
Journal: Blood (2016)
Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma
Authors: Ashraf Badros, Elizabeth Hyjek, Ning Ma, Alexander Lesokhin, Ahmet Dogan, Aaron P. Rapoport, Mehmet Kocoglu, Emily Lederer, Sunita Philip, Todd Milliron, Cameron Dell, Olga Goloubeva, Zeba Singh
Journal: Blood (2017)
Genome-Wide shRNA Screen Identifies WEE1 As a Critical Mediator of Cell Fate and Novel Therapeutic Target in AML,
Authors: Christopher C. Porter, Jihye Kim, Susan Fosmire, Christy M. Gearheart, Annemie van Linden, Vadym Zaberezhnyy, Dexiang Gao, Aik Choon Tan, James DeGregori
Journal: Blood (2011)
4-Hydroxynonenal elicits in human hepatic stellate cells a c-jun/JNK2/AP-1 signalling pathway preceeded by early generation of nuclear adducts.
Authors: M Parola, M Pinzani, F Marra, G Robino, G Leonarduzzi, S Camandola, G Poli, G Bellomo, E Albano, M.U. Dianzani
Journal: Journal of Hepatology (1997)
Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction
Authors: Christa F. Gaskill, Erica J. Carrier, Jonathan A. Kropski, Nathaniel C. Bloodworth, Swapna Menon, Robert F. Foronjy, M. Mark Taketo, Charles C. Hong, Eric D. Austin, James D. West, Anna L. Means, James E. Loyd, W. David Merryman, Anna R. Hemnes, Stijn De Langhe, Timothy S. Blackwell, Dwight J. Klemm, Susan M. Majka
Journal: Journal of Clinical Investigation (2017)

Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages. Here, we have shown that lineage-labeled lung MPCs expressing the ATP-binding cassette protein ABCG2 (ABCG2+) are pericyte progenitors that participate in microvascular homeostasis as well as adaptive angiogenesis. Activation of Wnt/β-catenin signaling, either autonomously or downstream of decreased BMP receptor signaling, enhanced ABCG2+ MPC proliferation but suppressed MPC differentiation into a functional pericyte lineage. Thus, enhanced Wnt/β-catenin signaling in ABCG2+ MPCs drives a phenotype of persistent microvascular dysfunction, abnormal angiogenesis, and subsequent exacerbation of bleomycin-induced fibrosis. ABCG2+ MPCs may, therefore, account in part for the aberrant microvessel function and remodeling that are associated with chronic lung diseases.
PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism
Authors: Laurent Calvier, Philippe Chouvarine, Ekaterina Legchenko, Nadine Hoffmann, Jonas Geldner, Paul Borchert, Danny Jonigk, Miklos M. Mozes, Georg Hansmann
Journal: Cell Metabolism (2017)