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https://www.readbyqxmd.com/read/28640835/bilateral-blockade-of-mek-and-pi3k-mediated-pathways-downstream-of-mutant-kras-as-a-treatment-approach-for-peritoneal-mucinous-malignancies
#1
Murali R Kuracha, Peter Thomas, Brian W Loggie, Venkatesh Govindarajan
Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28628116/cadherin-composition-and-multicellular-aggregate-invasion-in-organotypic-models-of-epithelial-ovarian-cancer-intraperitoneal-metastasis
#2
Y Klymenko, O Kim, E Loughran, J Yang, R Lombard, M Alber, M S Stack
During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multicellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich submesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior; however, the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28619839/transcranial-duplex-sonography-predicts-outcome-following-an-intracerebral-hemorrhage
#3
P Camps-Renom, J Méndez, E Granell, F Casoni, L Prats-Sánchez, A Martínez-Domeño, D Guisado-Alonso, J Martí-Fàbregas, R Delgado-Mederos
BACKGROUND AND PURPOSE: Several radiologic features such as hematoma volume are related to poor outcome following an intra- cerebral hemorrhage and can be measured with transcranial duplex sonography. We sought to determine the prognostic value of transcranial duplex sonography in patients with intracerebral hemorrhage. MATERIALS AND METHODS: We conducted a prospective study of patients diagnosed with spontaneous intracerebral hemorrhage. Transcranial duplex sonography examinations were performed within 2 hours of baseline CT, and we recorded the following variables: hematoma volume, midline shift, third ventricle and lateral ventricle diameters, and the pulsatility index in both MCAs...
June 15, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28609557/validation-of-international-consensus-equation-for-acute-serum-total-tryptase-in-mast-cell-activation-a-perioperative-perspective
#4
Richard L Baretto, Sarah Beck, Jane Heslegrave, Cathryn Melchior, Omar Mohamed, Anjali Ekbote, Aarnoud P Huissoon, Mamidipudi T Krishna
INTRODUCTION: There is no standardised method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2x baseline tryptase+2mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS). AIM: To validate consensus equation in a setting of perioperative anaphylaxis. METHODS: Analyses of suspected perioperative anaphylaxis during general anaesthesia (GA). Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria...
June 13, 2017: Allergy
https://www.readbyqxmd.com/read/28601643/heterogeneous-cadherin-expression-and-multicellular-aggregate-dynamics-in-ovarian-cancer-dissemination
#5
Yuliya Klymenko, Jeffrey Johnson, Brandi Bos, Rachel Lombard, Leigh Campbell, Elizabeth Loughran, M Sharon Stack
Epithelial ovarian carcinoma spreads via shedding of cells and multicellular aggregates (MCAs) from the primary tumor into peritoneal cavity, with subsequent intraperitoneal tumor cell:mesothelial cell adhesion as a key early event in metastatic seeding. Evaluation of human tumor extracts and tissues confirms that well-differentiated ovarian tumors express abundant E-cadherin (Ecad), whereas advanced lesions exhibit upregulated N-cadherin (Ncad). Two expression patterns are observed: "mixed cadherin," in which distinct cells within the same tumor express either E- or Ncad, and "hybrid cadherin," wherein single tumor cell(s) simultaneously expresses both cadherins...
June 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28596832/mechanical-and-vasomotor-properties-of-piglet-isolated-middle-cerebral-artery
#6
Vibeke R Eriksen, Bahareh Abdolalizadeh, Simon Trautner, Gorm Greisen, Majid Sheykhzade
Piglets are often used as experimental models for studying cerebrovascular responses in newborn infants. However, the mechanical characteristics of piglets' middle cerebral arteries (MCA) are not well characterized. Additionally, the vessels' response to dopamine, the most commonly used vasopressor in newborns, is not characterized in piglets' MCA. Finally, the influence of preterm birth on the dopamine response is not known. The aim of this current was to compare by wire myography the active and passive mechanical characteristics and dopamine concentration-response relations of MCAs isolated from preterm and term newborn piglets...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28588733/differences-in-the-sensitivity-of-ovarian-cancer-to-photodynamic-therapy-and-the-mechanisms-for-those-differences
#7
Yoshihito Yokoyama, Tatsuhiko Shigeto, Rie Miura, Asami Kobayashi, Makito Mizunuma, Aisa Yamauchi, Masayuki Futagami, Hideki Mizunuma
Protoporphyrin IX (PpIX) levels are crucial to the antitumor action of photodynamic therapy (PDT). In the present study, the underling molecular mechanisms for the variation in PpIX levels in ovarian cancer cells were investigated. Five ovarian cancer cell lines were subcutaneously grafted onto the backs of nude mice. Once tumors had developed, 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA) was administered intraperitoneally and the tumor was irradiated twice/week. PpIX levels in the tumor were assayed using high-performance liquid chromatography...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28524378/psychometric-characteristics-of-the-mental-health-crisis-assessment-scale-in-youth-with-autism-spectrum-disorder
#8
Luther G Kalb, Louis P Hagopian, Alden L Gross, Roma A Vasa
BACKGROUND: Youth with autism spectrum disorder (ASD) exhibit high rates of psychopathology. These symptoms can pose a risk of injury to self or others when the child is in crisis. Despite this danger, there are no instruments available to identify those with ASD who are at risk or actively in crisis. This study examined the psychometric properties of the Mental Health Crisis Assessment Scale (MCAS), a 28 item parent report measure. METHODS: The MCAS was administered to the parents of 606 children and young adults (aged 3-25 years, M age = 13 years, SD = 5 years) enrolled in the Interactive Autism Network, an online registry of families raising a child with ASD...
May 19, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28441325/the-effects-of-taekwondo-training-on-peripheral-neuroplasticity-related-growth-factors-cerebral-blood-flow-velocity-and-cognitive-functions-in-healthy-children-a-randomized-controlled-trial
#9
Su-Youn Cho, Wi-Young So, Hee-Tae Roh
Although regular Taekwondo (TKD) training has been reported to be effective for improving cognitive function in children, the mechanism underlying this improvement remains unclear. The purpose of the present study was to observe changes in neuroplasticity-related growth factors in the blood, assess cerebral blood flow velocity, and verify the resulting changes in children's cognitive function after TKD training. Thirty healthy elementary school students were randomly assigned to control (n = 15) and TKD (n = 15) groups...
April 25, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28420596/the-behaviors-and-experiences-of-the-community-pharmacy-team-on-the-provision-of-multi-compartment-compliance-aids
#10
Derek Stewart, Craig McDonald, Joan MacLeod, Katie MacLure, Gwen Gray, Trudi McIntosh
BACKGROUND: Multi-compartment compliance aids (MCAs) are repackaging systems for solid dosage form medicines. Acknowledging the lack of evidence that MCAs improve adherence or clinical outcomes, the Royal Pharmaceutical Society has expressed concern that MCAs have 'become regarded as a panacea for medicines use'. OBJECTIVES: To determine the behaviors and experiences of the community pharmacy team around MCA provision. METHODS: A cross-sectional survey was conducted in 26 community pharmacies in the north east of Scotland...
April 9, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28386644/mutational-profiling-in-the-peripheral-blood-leukocytes-of-patients-with-systemic-mast-cell-activation-syndrome-using-next-generation-sequencing
#11
Janine Altmüller, Britta Haenisch, Amit Kawalia, Markus Menzen, Markus M Nöthen, Heide Fier, Gerhard J Molderings
Mast cell activation syndrome (MCAS) and systemic mastocytosis (SM) are two clinical systemic mast cell activation disease variants. Few studies to date have investigated the genetic basis of MCAS. The present study had two aims. First, to investigate whether peripheral blood leukocytes from MCAS patients also harbor somatic mutations in genes implicated in SM using next-generation sequencing (NGS) technology and a relatively large MCAS cohort. We also addressed the question, whether some of the previously as somatic reported mutations are indeed germline mutations...
June 2017: Immunogenetics
https://www.readbyqxmd.com/read/28382662/successful-targeted-treatment-of-mast-cell-activation-syndrome-with-tofacitinib
#12
Lawrence B Afrin, Roger W Fox, Susan L Zito, Leo Choe, Sarah C Glover
Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile...
April 6, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28292237/gadolinium-iii-based-polymeric-magnetic-resonance-imaging-agents-for-tumor-imaging
#13
Guangyue Zu, Ye Kuang, Jingjin Dong, Tingting Zhang, Yi Cao, Min Liu, Liqiang Luo, Renjun Pei
Contrast agents (CAs) are widely used to improve the signal-noise ratio in the magnetic resonance imaging (MRI) examinations. The majority of MRI CAs used in clinic are gadolinium(III) (Gd(III)) chelates with low molecular weight. Compared with these small-molecule CAs, Gd(III)-based polymeric magnetic resonance imaging agents (i.e. macromolecular contrast agents, mCAs), prepared by conjugating small-molecule Gd(III) chelates onto macromolecules, possess high relaxivity and relative long blood circulation time, which are favorable for MRI examinations...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28280363/discrimination-of-serous-cystadenoma-from-mucinous-cystadenoma-in-the-pancreas-with-contrast-enhanced-ultrasonography-a-prospective-study-in-61-patients
#14
Ya Sun, Fubo Zhou, Fangyi Liu, Yanyan Hu, Shuilian Tan, Ping Liang, Enqiang Linghu, Xiaoling Yu
OBJECTIVES: The preoperative diagnosis between serous cystadenomas (SCAs) and mucinous cystadenomas (MCAs) in pancreas is significant due to their completely different biological behaviors. The purpose of our study was to examine and compare detailed contrast-enhanced ultrasonography (CEUS) images of SCAs and MCAs and to determine whether there are significant findings that can contribute to the discrimination between these two diseases. METHODS: From April 2015 to June 2016, 61 patients (35 patients with SCAs and 26 patients with MCAs) were enrolled in this study...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28262205/characterization-of-mast-cell-activation-syndrome
#15
Lawrence B Afrin, Sally Self, Jeremiah Menk, John Lazarchick
BACKGROUND: Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and thus important. We report the first systematic characterization of a large MCAS population. METHOD: Demographics, comorbidities, symptoms, family histories, physical examination and laboratory findings were reviewed in 298 retrospective and 115 prospective patients with MCAS. Blood samples from prospective subjects were examined by flow cytometry for clonal mast cell disease and tested for cytokines potentially driving the monocytosis frequent in MCAS...
March 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28262030/highly-sensitive-assays-are-mandatory-for-the-differential-diagnosis-of-patients-presenting-with-symptoms-of-mast-cell-activation-diagnostic-work-up-of-38-patients
#16
Bea Van den Poel, Anne-Marie Kochuyt, Elke Del Biondo, Barbara Dewaele, Els Lierman, Thomas Tousseyn, Gert de Hertogh, Peter Vandenberghe, Nancy Boeckx
Mastocytosis is a heterogeneous disease caused by excessive mast cell (MC) proliferation. Diagnosis of systemic mastocytosis (SM) is based on the presence of major and minor criteria defined by the World Health Organization. Symptoms of MC activation can also occur in patients without SM or without allergic or inflammatory disease. These MC activation syndromes (MCAS) can be divided into primary (monoclonal) MCAS (MMAS) vs. secondary and idiopathic MCAS. In this single center study, the diagnostic work-up of 38 patients with a clinical suspicion of SM and/or with elevated basic tryptase levels is presented...
April 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28249552/hypertension-induced-enhanced-myogenic-constriction-of-cerebral-arteries-is-preserved-after-traumatic-brain-injury
#17
Nikolett Szarka, Krisztina Amrein, Peter Horvath, Ivan Ivic, Endre Czeiter, Andras Buki, Akos Koller, Peter Toth
Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue from pressure/volume overload; however, it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels...
April 26, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28239641/macrovascular-and-microvascular-cerebral-blood-flow-in-adults-at-risk-for-alzheimer-s-disease
#18
Lindsay R Clark, Sara E Berman, Leonardo A Rivera-Rivera, Siobhan M Hoscheidt, Burcu F Darst, Corinne D Engelman, Howard A Rowley, Cynthia M Carlsson, Sanjay Asthana, Patrick Turski, Oliver Wieben, Sterling C Johnson
INTRODUCTION: Capillary hypoperfusion is reported in asymptomatic adults at-risk for Alzheimer's disease (AD), but the extent that can be explained by reduced flow in intracranial arteries is unknown. METHODS: One hundred fifty-five asymptomatic adults enriched for AD risk (mean age 61 years) completed arterial spin labeling (pcASL) and 4D-flow MRI sequences. Voxel-wise regression models investigated the relationship between mean flow in bilateral cerebral arteries and capillary perfusion, and tested potential moderators of this relationship...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28229321/cerebral-endothelial-dysfunction-in-reversible-cerebral-vasoconstriction-syndrome-a-case-control-study
#19
Hyun Ah Choi, Mi Ji Lee, Chin-Sang Chung
BACKGROUND: The aim of this study is to investigate cerebral endothelial dysfunction in patients with reversible cerebral vasoconstriction syndrome (RCVS). METHODS: We prospectively recruited patients with RCVS, age-matched controls with episodic migraine, and age-matched healthy controls at Samsung Medical Center from Apr 2015 to Jul 2016. All participants underwent transcranial Doppler evaluation, with a breath-holding maneuver, for the evaluation of bilateral middle cerebral arteries (MCAs), posterior cerebral arteries (PCAs), and the basilar artery (BA)...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28216128/mucinous-cystadenoma-in-children-and-adolescents
#20
Renee A Cowan, Erin N Haber, Fabio R Faucz, Constantine A Stratakis, Veronica Gomez-Lobo
STUDY OBJECTIVE: Mucinous cystadenomas (MCAs) are benign epithelial ovarian tumors that occur rarely in children and adolescents. As children and adolescents typically have their childbearing years ahead of them, conservative therapy is indicated. However, there is concern that ovarian cystectomy may be associated with significant recurrence risk in MCA. Furthermore, GNAS gene mutations are associated with McCune-Albright Syndrome, which is associated with cystic ovaries. We sought to evaluate the outcomes of children and adolescents with MCA treated conservatively...
February 16, 2017: Journal of Pediatric and Adolescent Gynecology
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