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Pearl Therapeutics

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https://www.readbyqxmd.com/read/28931755/combination-central-tolerance-and-peripheral-checkpoint-blockade-unleashes-antimelanoma-immunity
#1
Pearl Bakhru, Meng-Lei Zhu, Hsing-Hui Wang, Lee K Hong, Imran Khan, Maria Mouchess, Ajay S Gulati, Joshua Starmer, Yafei Hou, David Sailer, Sandra Lee, Fengmin Zhao, John M Kirkwood, Stergios Moschos, Lawrence Fong, Mark S Anderson, Maureen A Su
Blockade of immune checkpoint proteins (e.g., CTLA-4, PD-1) improves overall survival in advanced melanoma; however, therapeutic benefit is limited to only a subset of patients. Because checkpoint blockade acts by "removing the brakes" on effector T cells, the efficacy of checkpoint blockade may be constrained by the limited pool of melanoma-reactive T cells in the periphery. In the thymus, autoimmune regulator (Aire) promotes deletion of T cells reactive against self-antigens that are also expressed by tumors...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28830645/ictc-drug-resistance-cdr-testing-ex-vivo-for-evaluation-of-available-therapies-to-treat-patients-with-epithelial-ovarian-cancer
#2
Michael L Pearl, Huan Dong, Qiang Zhao, Shaun Tulley, Marlo K Dombroff, Wen-Tien Chen
GOALS: Management of epithelial ovarian cancer (EOC) could use serial measurements of invasive circulating tumor cells (iCTCs) for monitoring therapeutic response and early detection of disease progression/recurrence. Goals of this study are to develop an iCTC drug resistance (CDR) assay and to evaluate clinical significance of patient-derived, cultured iCTCs in selecting available therapies. METHODS: The CDR assay using Taxol-Carboplatin and eight other EOC drugs at the concentration used for patients was performed...
August 19, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28821260/24-h-bronchodilation-and-inspiratory-capacity-improvements-with-glycopyrrolate-formoterol-fumarate-via-co-suspension-delivery-technology-in-copd
#3
Colin Reisner, Gregory Gottschlich, Faisal Fakih, Andras Koser, James Krainson, Luis Delacruz, Samir Arora, Gregory Feldman, Krishna Pudi, Shahid Siddiqui, Chad Orevillo, Andrea Maes, Earl St Rose, Ubaldo Martin
BACKGROUND: Symptoms of chronic obstructive pulmonary disease may vary throughout the day and it is important that therapeutic approaches provide 24-h symptom control. We report the results of two phase IIIb crossover studies, PT003011 and PT003012, investigating the 24-h lung function profile of GFF MDI (glycopyrrolate/formoterol fumarate 18/9.6 μg delivered using innovative co-suspension delivery technology) administered twice daily. METHODS: Patients with moderate-to-very severe chronic obstructive pulmonary disease received 4 weeks' treatment with each of GFF MDI, placebo MDI, and open-label tiotropium (PT003011 only)...
August 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28810268/swallowing-mechanics-associated-with-artificial-airways-bolus-properties-and-penetration-aspiration-status-in-trauma-patients
#4
Angela M Dietsch, Christopher B Rowley, Nancy Pearl Solomon, William G Pearson
Purpose: Artificial airway procedures such as intubation and tracheotomy are common in the treatment of traumatic injuries, and bolus modifications may be implemented to help manage swallowing disorders. This study assessed artificial airway status, bolus properties (volume and viscosity), and the occurrence of laryngeal penetration and/or aspiration in relation to mechanical features of swallowing. Method: Coordinates of anatomical landmarks were extracted at minimum and maximum hyolaryngeal excursion from 228 videofluoroscopic swallowing studies representing 69 traumatically injured U...
September 18, 2017: Journal of Speech, Language, and Hearing Research: JSLHR
https://www.readbyqxmd.com/read/28800286/clinical-pet-imaging-in-prostate-cancer
#5
Kathryn L Wallitt, Sairah R Khan, Suraiya Dubash, Henry H Tam, Sameer Khan, Tara D Barwick
Prostate cancer is the second most common cancer in men worldwide, with a wide spectrum of biologic behavior ranging from indolent low-risk disease to highly aggressive castration-resistant prostate cancer. Conventional imaging with computed tomography, magnetic resonance imaging, and bone scintigraphy is limited for the detection of nodal disease and distant bone metastases. In addition, advances in the available therapeutic options, both localized and systemic, drive the requirement for precise diagnostic and prognostic tools to refine the individual therapeutic approach at various times in the management of patients with prostate cancer...
September 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28770843/corrigendum-modulating-the-therapeutic-response-of-tumours-to-dietary-serine-and-glycine-starvation
#6
Oliver D K Maddocks, Dimitris Athineos, Eric C Cheung, Pearl Lee, Tong Zhang, Niels J F van den Broek, Gillian M Mackay, Christiaan F Labuschagne, David Gay, Flore Kruiswijk, Julianna Blagih, David F Vincent, Kirsteen J Campbell, Fatih Ceteci, Owen J Sansom, Karen Blyth, Karen H Vousden
This corrects the article DOI: 10.1038/nature22056.
August 2, 2017: Nature
https://www.readbyqxmd.com/read/28745570/soft-tissue-tumor-immunohistochemistry-update-illustrative-examples-of-diagnostic-pearls-to-avoid-pitfalls
#7
Shi Wei, Evita Henderson-Jackson, Xiaohua Qian, Marilyn M Bui
CONTEXT: - Current 2013 World Health Organization classification of tumors of soft tissue arranges these tumors into 12 groups according to their histogenesis. Tumor behavior is classified as benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant. In our practice, a general approach to reaching a definitive diagnosis of soft tissue tumors is to first evaluate clinicoradiologic, histomorphologic, and cytomorphologic features of the tumor to generate some pertinent differential diagnoses...
August 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28661116/dental-emergencies-management-strategies-that-improve-outcomes-digest
#8
Whitney K Bryant, Sanjay Shewakramani, Milana Zaurova
Points & Pearls is a digest of Emergency Medicine Practice. Acute dental emergencies are a common chief complaint presenting to emergency departments, and they are increasing substantially in frequency. The diagnosis and management of dental emergencies is a core competency of the emergency clinician, and proper therapeutic strategies can significantly improve cosmetic and functional outcomes for patients. This issue provides a systematic review of the literature on common acute traumatic and atraumatic dental emergencies with a focus on the historical and physical examination findings that must be understood to identify life-threatening infections, relieve pain, salvage natural teeth, and communicate with specialists in the further management of patients after emergency treatment...
June 22, 2017: Emergency Medicine Practice
https://www.readbyqxmd.com/read/28636940/hectd3-mediates-an-hsp90-dependent-degradation-pathway-for-protein-kinase-clients
#9
Zhaobo Li, Lihong Zhou, Chrisostomos Prodromou, Velibor Savic, Laurence H Pearl
Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiquitylation is not understood, and the E3 ubiquitin ligases involved are largely unknown. Using a siRNA screen, we have identified components of two independent degradation pathways for the HSP90 client kinase CRAF...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28631742/kidney-cancer-diving-into-the-genome-of-papillary-rcc-unearths-therapeutic-pearls
#10
Annette Fenner
No abstract text is available yet for this article.
August 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28579828/the-effect-of-quercetin-on-pro-and-anti-inflammatory-cytokines-in-a-prenatally-stressed-rat-model-of-febrile-seizures
#11
Nombuso Valencia Pearl Mkhize, Lihle Qulu, Musa Vuyisile Mabandla
Febrile seizures are childhood convulsions resulting from an infection that leads to an inflammatory response and subsequent convulsions. Prenatal stress has been shown to heighten the progression and intensity of febrile seizures. Current medications are costly and have adverse effects associated with prolonged use. Quercetin flavonoid exhibits anti-inflammatory, anti-convulsant, and anti-stress effects. This study was aimed to investigate the therapeutic effect of quercetin in a prenatally stressed rat model of febrile seizures...
2017: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/28551900/-aortic-dissection-diagnosed-by-the-suprasternal-echocardiographic-view
#12
Shmuel Schwartzenberg, Pearl Herskovitz, Ron Brauner, Natalie Schnieder, Jacob Goerge, Sara Shimoni
Patients with suspected dissection of the thoracic aorta require immediate diagnostic evaluation so that urgent therapeutic interventions can begin. We present a case of aortic dissection with an atypical initial presentation mimicking acute pericarditis, in which the correct diagnosis was made on the basis of the suprasternal view of transthoracic echocardiography.
February 2017: Harefuah
https://www.readbyqxmd.com/read/28503985/diagnostic-and-therapeutic-management-of-a-first-unprovoked-seizure-in-children-and-adolescents-with-a-focus-on-the-revised-diagnostic-criteria-for-epilepsy
#13
Arnold J Sansevere, Jennifer Avalone, Lauren Doyle Strauss, Archana A Patel, Anna Pinto, Maya Ramachandran, Ivan Sanchez Fernandez, Ann M Bergin, Amir Kimia, Phillip L Pearl, Tobias Loddenkemper
By definition, unprovoked seizures are not precipitated by an identifiable factor, such as fever or trauma. A thorough history and physical examination are essential to caring for pediatric patients with a potential first unprovoked seizure. Differential diagnosis, EEG, neuroimaging, laboratory tests, and initiation of treatment will be reviewed. Treatment is typically initiated after 2 unprovoked seizures, or after 1 seizure in select patients with distinct epilepsy syndromes. Recent expansion of the definition of epilepsy by the ILAE allows for the diagnosis of epilepsy to be made after the first seizure if the clinical presentation and supporting diagnostic studies suggest a greater than 60% chance of a second seizure...
July 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28503347/wasting-of-extensor-digitorum-brevis-as-a-decisive-preoperative-clinical-indicator-of-lumbar-canal-stenosis-a-single-center-prospective-cohort-study
#14
S Munakomi, B M Kumar
BACKGROUND: The dilemma in managing patients with low back ache lies in differentiating radiculopathy from lumbar canal stenosis. This has a huge bearing in patients being planned for surgical intervention as underperforming leads to failed back syndrome whereas over-doing leads to instability. There still remains a loophole in clinically diagnosing lumbar canal stenosis. AIM: We opt to utilize a simple bedside clinical examination in routinely assessing patients presenting with low back ache in ruling out underlying canal stenosis...
September 2016: Annals of Medical and Health Sciences Research
https://www.readbyqxmd.com/read/28462602/-big-data-approaches-for-novel-anti-cancer-drug-discovery
#15
REVIEW
Graeme Benstead-Hume, Sarah K Wooller, Frances M G Pearl
The development of improved cancer therapies is frequently cited as an urgent unmet medical need. Recent advances in platform technologies and the increasing availability of biological 'big data' are providing an unparalleled opportunity to systematically identify the key genes and pathways involved in tumorigenesis. The discoveries made using these new technologies may lead to novel therapeutic interventions. Areas covered: The authors discuss the current approaches that use 'big data' to identify cancer drivers...
June 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28457677/research-pearls-the-significance-of-statistics-and-perils-of-pooling-part-3-pearls-and-pitfalls-of-meta-analyses-and-systematic-reviews
#16
Joshua D Harris, Jefferson C Brand, Mark P Cote, Aman Dhawan
Within the health care environment, there has been a recent and appropriate trend towards emphasizing the value of care provision. Reduced cost and higher quality improve the value of care. Quality is a challenging, heterogeneous, variably defined concept. At the core of quality is the patient's outcome, quantified by a vast assortment of subjective and objective outcome measures. There has been a recent evolution towards evidence-based medicine in health care, clearly elucidating the role of high-quality evidence across groups of patients and studies...
August 2017: Arthroscopy: the Journal of Arthroscopic & related Surgery
https://www.readbyqxmd.com/read/28425994/modulating-the-therapeutic-response-of-tumours-to-dietary-serine-and-glycine-starvation
#17
Oliver D K Maddocks, Dimitris Athineos, Eric C Cheung, Pearl Lee, Tong Zhang, Niels J F van den Broek, Gillian M Mackay, Christiaan F Labuschagne, David Gay, Flore Kruiswijk, Julianna Blagih, David F Vincent, Kirsteen J Campbell, Fatih Ceteci, Owen J Sansom, Karen Blyth, Karen H Vousden
The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de novo serine synthesis, many others rely on exogenous serine for optimal growth. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation)...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28411234/phenotype-of-gaba-transaminase-deficiency
#18
REVIEW
Mary Kay Koenig, Ryan Hodgeman, James J Riviello, Wendy Chung, Jennifer Bain, Claudia A Chiriboga, Kazushi Ichikawa, Hitoshi Osaka, Megumi Tsuji, K Michael Gibson, Penelope E Bonnen, Phillip L Pearl
OBJECTIVE: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype. METHODS: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil. RESULTS: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth...
May 16, 2017: Neurology
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#19
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28323755/cyp2b6-genotype-directed-dosing-is-required-for-optimal-efavirenz-exposure-in-children-3-36-months-with-hiv-infection
#20
Carolyn Bolton Moore, Edmund V Capparelli, Pearl Samson, Mutsa Bwakura-Dangarembizi, Patrick Jean-Philippe, Carol Worrell, Barbara Heckman, Lynette Purdue, Stephen A Spector, Alex Benns, William Borkowsky, Amy Loftis, Elizabeth Hawkins, Carole Wallis, Ellen G Chadwick
OBJECTIVES: To determine safety-specific, efficacy-specific and genotypic-specific dose requirements of efavirenz (EFV) in children aged 3 to less than 36 months with HIV infection. DESIGN: IMPAACT P1070 was a 24-week prospective cohort trial of EFV (as open capsules) and two nucleoside reverse transcriptase inhibitors in children with HIV infection 3 to less than 36 months without tuberculosis (Cohort 1). METHODS: CYP2B6 G516T genotype was determined, and intensive pharmacokinetics was performed at week 2...
May 15, 2017: AIDS
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