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https://www.readbyqxmd.com/read/27913543/hemophilia-and-inhibitors-current-treatment-options-and-potential-new-therapeutic-approaches
#1
Shannon L Meeks, Glaivy Batsuli
The immune response to infused factor concentrates remains a major source of morbidity and mortality in the treatment of patients with hemophilia A and B. This review focuses on current treatment options and novel therapies currently in clinical trials. After a brief review of immune tolerance regimens, the focus of the discussion is on preventing bleeding in patients with hemophilia and inhibitors. Recombinant factor VIIa and activated prothrombin complex concentrates are the mainstays in treating bleeds in patients with inhibitors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#2
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27910951/molecular-imaging-with-engineered-physiology
#3
Mitul Desai, Adrian L Slusarczyk, Ashley Chapin, Mariya Barch, Alan Jasanoff
In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27910055/selective-pressure-regulated-retroinfusion-for-gene-therapy-application-in-ischemic-heart-disease
#4
Rabea Hinkel, Christian Kupatt
Coronary heart disease is still the leading cause of death in industrialized nations. Even though revascularization strategies such as coronary artery bypass graft surgery, percutaneous coronary intervention and enhanced drug therapy significantly improved the outcome, about 30 % of patients develop chronic heart failure. Ischemic heart disease and heart failure are characterized by an adverse remodeling of the heart, featuring cardiomyocyte hypertrophy, increased fibrosis and capillary rarefaction. Therefore, gene therapeutic approaches for the treatment of heart failure, such as the modulating contractile function or therapeutic neovascularization, seem to be promising...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27904766/the-role-of-pim1-in-the-ibrutinib-resistant-abc-subtype-of-diffuse-large-b-cell-lymphoma
#5
Hsu-Ping Kuo, Scott A Ezell, Sidney Hsieh, Karl J Schweighofer, Leo Wk Cheung, Shiquan Wu, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Yu Liang, Jeff Hsu, Chun-Te Chen, Darrin Beaupre, Betty Y Chang
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma and the most common subtype of non-Hodgkin lymphoma, accounting for roughly 30% of newly diagnosed cases in the United States. DLBCL can be separated into the activated B cell-like (ABC) and germinal center B cell-like (GCB) subtypes, with distinct gene expression profiles, oncogenic aberrations, and clinical outcomes. ABC-DLBCL is characterized by chronically active B-cell receptor (BCR) signaling that can be modulated by Bruton's tyrosine kinase (BTK) activity...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27898390/novel-concentrated-insulin-delivery-devices-developments-for-safe-and-simple-dose-conversions
#6
REVIEW
Jeremy L Johnson, Jessica M Downes, Cassandra K Obi, Nana B Asante
To aid the burden of large dosing volumes, concentrated insulin products have been available in some form since the 1950s, albeit requiring significant and cumbersome detail in prescribing, converting doses from other products, and educating patients on how to administer. In 2015 and 2016, new concentrated products have been introduced that are available exclusively in pen devices that perform the conversion automatically, and thus, help to bypass the necessity for confusing calculations or administration. Providers and patients accustomed to traditional methods must recognize the differences and utility of these products to avoid dosing errors, as there are major differences in dosing procedures as well as their role in clinical practice...
November 27, 2016: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/27893176/desmopressin-for-treatment-of-platelet-dysfunction-and-reversal-of-antiplatelet-agents-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#7
M J R Desborough, K A Oakland, G Landoni, M Crivellari, C Doree, L J Estcourt, S J Stanworth
BACKGROUND: Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear. OBJECTIVES: To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding for patients with platelet dysfunction. PATIENTS/METHODS: We searched for randomised controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and ISI Web of Science to 7(th) July 2016...
November 28, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27889209/structural-basis-for-the-subversion-of-map-kinase-signaling-by-an-intrinsically-disordered-parasite-secreted-agonist
#8
Erika Pellegrini, Andrés Palencia, Laurence Braun, Ulrike Kapp, Alexandre Bougdour, Hassan Belrhali, Matthew W Bowler, Mohamed-Ali Hakimi
The causative agent of toxoplasmosis, the intracellular parasite Toxoplasma gondii, delivers a protein, GRA24, into the cells it infects that interacts with the mitogen-activated protein (MAP) kinase p38α (MAPK14), leading to activation and nuclear translocation of the host kinase and a subsequent inflammatory response that controls the progress of the parasite. The purification of a recombinant complex of GRA24 and human p38α has allowed the molecular basis of this activation to be determined. GRA24 is shown to be intrinsically disordered, binding two kinases that act independently, and is the only factor required to bypass the canonical mitogen-activated protein kinase activation pathway...
November 14, 2016: Structure
https://www.readbyqxmd.com/read/27885231/two-elderly-patients-with-difficult-to-treat-acquired-hemophilia-a
#9
Makoto Saito, Masanobu Morioka
We herein report the cases of two elderly patients with acquired hemophilia A (AHA) for whom treatment was difficult.An 89-year-old woman (Case 1) was admitted to our department with subcutaneous hemorrhage and melena. Her activated partial thromboplastin time (APTT), factor VIII activity, and factor VIII inhibitor level were 127.7 seconds, 1.0%, and 48 BU/mL, respectively, which was suggestive of AHA. The administration of prednisolone (PSL 0.5 mg/kg) was initiated. After 3 weeks, PSL was combined with cyclophosphamide (CPA 50 mg)...
2016: Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
https://www.readbyqxmd.com/read/27873490/egf-induced-ret-inhibitor-resistance-in-ccdc6-ret-lung-cancer-cells
#10
Hyun Chang, Ji Hea Sung, Sung Ung Moon, Han Soo Kim, Jin Won Kim, Jong Seok Lee
PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27872957/utility-of-18-f-fluoroestradiol-18-f-fes-pet-ct-imaging-as-a-pharmacodynamic-marker-in-patients-with-refractory-estrogen-receptor-positive-solid-tumors-receiving-z-endoxifen-therapy
#11
Frank I Lin, E M Gonzalez, S Kummar, K Do, J Shih, S Adler, K A Kurdziel, A Ton, B Turkbey, P M Jacobs, S Bhattacharyya, A P Chen, J M Collins, J H Doroshow, P L Choyke, M L Lindenberg
BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. (18)F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes (18)F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen...
November 21, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27847780/recurrent-carotid-cavernous-fistula-originating-from-a-giant-cerebral-aneurysm-after-placement-of-a-covered-stent
#12
Jung Wook Baek, Sung Tae Kim, Young Seo Lee, Young-Gyun Jeong, Hae Woong Jeong, Jin Wook Baek, Jung Hwa Seo
We report the case of a recurrent carotid cavernous fistula (CCF) originating from a giant cerebral aneurysm (GCA) after placement of a covered stent. A 47-year-old woman presented with sudden onset of severe headache, and left-sided exophthalmos and ptosis. Cerebral angiography revealed a CCF caused by rupture of a GCA in the cavernous segment of the left internal carotid artery. Two covered stents were placed at the neck of the aneurysm. The neurological symptoms improved at first, but were aggravated in the 6 months following the treatment...
September 2016: Journal of Cerebrovascular and Endovascular Neurosurgery
https://www.readbyqxmd.com/read/27843336/treatment-of-bleeding-in-acquired-hemophilia-a-with-the-proper-administration-of-recombinant-activated-factor-vii-single-center-study-of-7-cases
#13
Makoto Saito, Minoru Kanaya, Koh Izumiyama, Akio Mori, Tatsuro Irie, Masanori Tanaka, Masanobu Morioka, Masahiro Ieko
Recombinant activated factor VII (rFVIIa) is the bypassing agent used in the first-line hemostatic therapy for acquired hemophilia A (AHA); however, the occurrence of thrombotic complications in rFVIIa-treated AHA patients was recently reported to be 2.9-6.5%. Therefore, the investigation of the proper administration of rFVIIa for AHA is needed. In the present study, we retrospectively investigated the clinical features of AHA with regards to the use of rFVIIa (presence or absence of use and total amount) in 7 AHA patients encountered in our department for 7 years between January 2008 and December 2014...
2016: International Journal of General Medicine
https://www.readbyqxmd.com/read/27837525/a-case-report-of-curative-distal-gastrectomy-for-stage-iv-gastric-cancer-after-chemoradiotherapy-in-a-patient-with-a-gastrojejunal-gastric-bypass
#14
Masataka Shimonosono, Sumiya Ishigami, Takaaki Arigami, Yoshikazu Uenosono, Yasuto Uchikado, Yoshiaki Kita, Yuko Kijima, Hiroshi Kurahara, Yuko Mataki, Kosei Maemura, Shoji Natsugoe
BACKGROUND: Advanced gastric cancer in the lower third of the stomach often results in stricture of the gastric cavity and digestive symptoms. Gastrojejunostomy has been suggested to improve such symptoms, and the advent of new anticancer agents for gastric cancer has improved the response rate of the disease, which makes it possible to perform R0 gastrectomy in part of patients with stage IV gastric cancer. We experienced a rare case in which a patient with stage IV gastric cancer and cancerous pyloric stenosis was treated with R0 surgery after undergoing a gastrojejunal bypass procedure and multidisciplinary treatment...
December 2016: Surgical Case Reports
https://www.readbyqxmd.com/read/27835985/hypoxia-response-in-arabidopsis-roots-infected-by-plasmodiophora-brassicae-supports-the-development-of-clubroot
#15
Antoine Gravot, Gautier Richard, Tanguy Lime, Séverine Lemarié, Mélanie Jubault, Christine Lariagon, Jocelyne Lemoine, Jorge Vicente, Alexandre Robert-Seilaniantz, Michael J Holdsworth, Maria J Manzanares-Dauleux
BACKGROUND: The induction of alcohol fermentation in roots is a plant adaptive response to flooding stress and oxygen deprivation. Available transcriptomic data suggest that fermentation-related genes are also frequently induced in roots infected with gall forming pathogens, but the biological significance of this induction is unclear. In this study, we addressed the role of hypoxia responses in Arabidopsis roots during infection by the clubroot agent Plasmodiophora brassicae. RESULTS: The hypoxia-related gene markers PYRUVATE DECARBOXYLASE 1 (PDC1), PYRUVATE DECARBOXYLASE 2 (PDC2) and ALCOHOL DEHYDROGENASE 1 (ADH1) were induced during secondary infection by two isolates of P...
November 11, 2016: BMC Plant Biology
https://www.readbyqxmd.com/read/27835596/cd99-triggering-induces-methuosis-of-ewing-sarcoma-cells-through-igf-1r-ras-rac1-signaling
#16
Maria Cristina Manara, Mario Terracciano, Caterina Mancarella, Marika Sciandra, Clara Guerzoni, Michela Pasello, Andrea Grilli, Nicoletta Zini, Piero Picci, Mario P Colombo, Andrea Morrione, Katia Scotlandi
CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834982/telmisartan-decreases-microalbuminuria-in-patients-with-type-2-diabetes-mellitus-following-coronary-artery-bypass-grafting
#17
Cevdet Furat, Riza Dogan, Gokhan Ilhan, Ekrem Bayar, Berkan Ozpak, Hakan Kara, Şahin Bozok
OBJECTIVE: This prospective study aimed to investigate the effects of the selective angiotensin receptor antagonist, telmisartan, on microalbuminuria after coronary artery bypass surgery in patients with diabetes mellitus. METHODS: Patients were divided into two groups with block randomisation, using the sealed envelope technique: group T (telmisartan group) consisted of patients who received the angiotensin receptor blocking agent telmisartan 80 mg daily for at least six months in the pre-operative period; group N-T (non-telmisartan group) consisted of patients who received no telmisartan treatment...
November 10, 2016: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/27818111/protides-of-bvdu-as-potential-anticancer-agents-upon-efficient-intracellular-delivery-of-their-activated-metabolites
#18
Sahar Kandil, Jan Balzarini, Stephanie Rat, Andrea Brancale, Andrew D Westwell, Christopher McGuigan
Nucleosides represent a major chemotherapeutic class for treating cancer, however their limitations in terms of cellular uptake, nucleoside kinase-mediated activation and catabolism are well-documented. The monophosphate pro-nucleotides known as ProTides represents a powerful strategy for bypassing the dependence on active transport and nucleoside kinase-mediated activation. Herein, we report the structural tuning of BVdU ProTides. Forty six phosphoramidates were prepared and biologically evaluated against three different cancer cell lines; murine leukemia (L1210), human CD4(+) T-lymphocyte (CEM) and human cervical carcinoma (HeLa)...
October 27, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27810409/a-novel-anti-pollution-filter-for-volatile-agents-during-cardiopulmonary-bypass-preliminary-tests
#19
Caetano Nigro Neto, Giovanni Landoni, Maria Angela Tardelli
OBJECTIVE: Concerns regarding pollution of the operating room by volatile anesthetics and effects on atmospheric ozone depletion exist. Volatile agents commonly are used during cardiopulmonary bypass to provide anesthesia independent of any supposed myocardial protective effects. The authors' aim was to create and to assess the performance of a prototype filter for volatile agents to be connected to the cardiopulmonary bypass circuit to avoid the emission of volatile agents to the operating room, and also to the environment without causing damage to the membrane oxygenator...
August 10, 2016: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/27806517/current-trends-in-knee-arthroplasty
#20
Mohammadjavad Zehtab, Mohammadhassan Kaseb, Mohammadnaghi Tahmasebi, Mohammad Ayati Firoozabadi
Total knee arthroplasty (TKA) is a commonly performed surgical procedure designed to alleviate knee pain and improve function in individuals with knee osteoarthritis the purpose of collecting the latest information and updating the reports is to summarize the published articles and inform the colleagues. In so doing, the articles published in American journals of arthroplasty and joint surgery and the proceedings of the conferences that were mostly held in 2004 have been utilized so that delicate and precise spotlights retrieved from scholars' breakthroughs can be applied in daily medical practices...
July 25, 2016: Global Journal of Health Science
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