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First-in-human clinical studies

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https://www.readbyqxmd.com/read/29140823/single-center-retrospective-study-on-meibomian-gland-loss-in-patients-with-ocular-chronic-graft-versus-host-disease
#1
Lijuan Que, Xiaofeng Zhang, Mengmeng Li
OBJECTIVES: This study aimed to analyze the influencing factors of meibomian gland loss in patients with ocular chronic graft-versus-host disease (GVHD) and its correlation with other clinical ocular surface assessment indexes. METHODS: The clinical data of patients with ocular chronic GVHD from the ocular surface and corneal outpatient clinic of the First Affiliated Hospital of Soochow University were reviewed from June 2012 to June 2016. The relationship between the percentage of meibomian gland acinar area and the influencing factors, such as patient's sex, age, transplantation method, human leukocyte antigen (HLA) matching, the time when eye discomfort appeared after transplantation (month), and the severity of ocular chronic GVHD, was investigated...
November 14, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/29140689/tissue-inhibitor-of-metalloprotease-2-timp-2-bioprocess-development-physicochemical-biochemical-and-biological-characterization-of-highly-expressed-recombinant-protein
#2
Ananda Chowdhury, Robert G Brinson, Beiyang Wei, William G Stetler-Stevenson
Tissue Inhibitor of Metalloprotease -2 (TIMP-2) is a secreted 21 kDa multifunctional protein first described as an endogenous inhibitor of matrix metalloproteinases (MMPs) that prevents breakdown of the extracellular matrix often observed in chronic diseases. TIMP-2 diminishes growth factor-mediated cell proliferation in vitro, as well as neoangiogenesis and tumor growth in vivo independent of its MMP-inhibitory activity, . These physiological properties make TIMP-2 an excellent candidate for further pre-clinical development as a biologic therapy of cancer...
November 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29140435/hmdb-4-0-the-human-metabolome-database-for-2018
#3
David S Wishart, Yannick Djoumbou Feunang, Ana Marcu, An Chi Guo, Kevin Liang, Rosa Vázquez-Fresno, Tanvir Sajed, Daniel Johnson, Carin Li, Naama Karu, Zinat Sayeeda, Elvis Lo, Nazanin Assempour, Mark Berjanskii, Sandeep Singhal, David Arndt, Yonjie Liang, Hasan Badran, Jason Grant, Arnau Serra-Cayuela, Yifeng Liu, Rupa Mandal, Vanessa Neveu, Allison Pon, Craig Knox, Michael Wilson, Claudine Manach, Augustin Scalbert
The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards...
November 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29140074/facile-and-versatile-strategy-for-construction-of-anti-inflammatory-and-antibacterial-surfaces-with-polydopamine-mediated-liposomes-releasing-dexamethasone-and-minocycline-for-potential-implants-applications
#4
Xiao Xu, Lixin Wang, Zuyuan Luo, Yaofeng Ni, Haitao Sun, Xiang Gao, Yongliang Li, Siqi Zhang, Yan Li, Shicheng Wei
Reducing early nonbacterial inflammation induced by implanted materials and infection resulting from bacterial contamination around the implant-abutment interface could greatly accelerate implant osseointegration and reduce implant failure, which would be of clinical significance. In this study, we developed a facile and versatile strategy for the construction of anti-inflammatory and antibacterial surfaces on implants, such as orthopedic/dental implants. Briefly, the surfaces of polystyrene (PS) culture plates were first coated with polydopamine and then decorated with dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes), which was confirmed by contact angle goniometry, X-ray photoelectron spectroscopy, and fluorescence microscopy...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29139305/development-of-optimized-self-nanoemulsifying-lyophilized-tablets-snelts-to-improve-finasteride-clinical-pharmacokinetic-behavior
#5
Tarek A Ahmed, Khalid M El-Say, Khaled M Hosny, Bader M Aljaeid
OBJECTIVE: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS). SIGNIFICANCE: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia. METHODS: Two-step optimization was implemented to achieve the study goals. First; mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested...
November 15, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29139226/cortical-nociceptive-processes-are-reduced-by-visual-alpha-band-entrainment-in-the-human-brain
#6
K Ecsy, C A Brown, A K P Jones
BACKGROUND: Acute noxious stimuli induce a suppression of cortical alpha activity, yet little is known about whether increasing alpha activity affects the processing of noxious stimuli. We have previously shown that visual alpha stimulation reduces experimental pain. Here, we demonstrate that increasing alpha power causes a reciprocal suppression of acute nociceptive processing. METHODS: We attempted to increase cortical alpha activity through visual entrainment at 8 Hz, 10 Hz and 12 Hz to investigate the influence on the electrophysiological pain response...
November 14, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29138811/high-expression-of-mage-a9-contributes-to-stemness-and-malignancy-of-human-hepatocellular-carcinoma
#7
Youping Wei, Yanqin Wang, Jing Gong, Lihua Rao, Zhiwei Wu, Teng Nie, Dongling Shi, Liming Zhang
MAGE-A9, a well-characterized cancer testis antigen (CTA), belongs to a member of melanoma antigen gene (MAGE) family. In human malignancies, aberrant expression of MAGE genes correlated with poor clinical prognosis, increased tumor growth, metastases, and enrichment in stem cell populations of certain cancers. Cancer stem cells (CSCs) have been proposed to contribute to the major malignant phenotypes of liver cancer, including recurrence, metastasis and chemoresistance. However, expression and potential role of MAGE-A9 in liver cancer stem cells (LCSCs) still remain unclear...
November 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29137329/development-of-a-radiolabeled-caninized-anti-egfr-antibody-for-comparative-oncology-trials
#8
Judit Fazekas-Singer, Neydher Berroterán-Infante, Christina Rami-Mark, Monika Dumanic, Miroslawa Matz, Michael Willmann, Fritz Andreae, Josef Singer, Wolfgang Wadsak, Markus Mitterhauser, Erika Jensen-Jarolim
Due to large homology of human and canine EGFR, dogs suffering from spontaneous EGFR+ cancer can be considered as ideal translational models. Thereby, novel immunotherapeutic compounds can be developed for both human and veterinary patients. This study describes the radiolabeling of a canine anti-EGFR IgG antibody (can225IgG) with potential diagnostic and therapeutic value in comparative clinical settings. Can225IgG was functionalized with DTPA for subsequent chelation with the radionuclide (99m)Tc. Successful coupling of 10 DTPA molecules per antibody on average was proven by significant mass increase in MALDI-TOF spectroscopy, gel electrophoresis and immunoblots...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136943/adam12-induces-emt-and-promotes-cell-migration-invasion-and-proliferation-in-pituitary-adenomas-via-egfr-erk-signaling-pathway
#9
Junwen Wang, Zhuo Zhang, Ran Li, Feng Mao, Wei Sun, Juan Chen, Huaqiu Zhang, Jörg-W Bartsch, Kai Shu, Ting Lei
Pituitary adenomas are the second most common primary brain tumor with invasive properties. We have previously identified that ADAM12 (a disintegrin and metalloprotease 12) overexpression is associated with the tumor invasion of pituitary adenomas, however, the underlying mechanism remains unknown. This study aims to elucidate the mechanistic role of ADAM12 in regulating the tumor invasion of pituitary adenomas. In this study, we first showed that ADAM12 expression was concomitant with epithelial to mesenchymal transition (EMT) process in clinical specimens of human pituitary adenomas...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#10
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29136041/profiling-analysis-of-circulating-microrna-in-peripheral-blood-of-patients-with-class-iv-lupus-nephritis
#11
Elkin Navarro-Quiroz, Lisandro Pacheco-Lugo, Roberto Navarro-Quiroz, Hernan Lorenzi, Pierine España-Puccini, Yirys Díaz-Olmos, Lisneth Almendrales, Valeria Olave, Henry Gonzalez-Torres, Anderson Diaz-Perez, Alex Dominguez, Antonio Iglesias, Raul García, Gustavo Aroca-Martinez
Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals...
2017: PloS One
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#12
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135117/what-is-the-connection-between-serum-phosphorus-cancer-and-heroin-a-medical-hypothesis-based-on-observational-studies
#13
Vassilis Kouloulias, Christos-David Papaloucas, Aristofanis Papaloucas
Considering the results of a previous study in which 2321 regular heroin addicts who died without having stopped taking the drug since they had started - from various causes but none from cancer, may mean something. Our first thought was: Can't we hypothesize, reinforcing our previous view that heroin is a "barrier" against cancer and as the user gets in the methadone program he/she lacks the "barrier" and therefore is liable to develop cancer? We have already reported that the amount of blood phosphorus in heroin addicted is significantly lower than in healthy ones...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29134633/first-in-human-study-with-the-inhaled-tlr9-oligonucleotide-agonist-azd1419-results-in-interferon-responses-in-the-lung-and-is-safe-and-well-tolerated
#14
Sam Jackson, Albert F Candia, Stephen Delaney, Simone Floettmann, Clifford Wong, John D Campbell, Sariah Kell, Jeremy Lum, Edith Hessel, Paula Traquina, Mark McHale, Ian Robinson, John Bell, Rainard Fuhr, David Keeling, Robert L Coffman
Current asthma treatments address symptoms rather than the underlying disease pathophysiology, a better understanding of which has led to the identification of the Th2 high endotype. The activation of Toll-like receptors to induce Type I interferons directly in the lungs represents a novel therapeutic approach to reset this underlying Th2 pathophysiology with the potential to provide long-term disease modification. We present the nonclinical data and phase 1 clinical profile of an inhaled TLR9 agonist, AZD1419, a C-type CpG designed to induce interferon in the lung...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29133950/treating-a-novel-plasticity-defect-rescues-episodic-memory-in-fragile-x-model-mice
#15
W Wang, B M Cox, Y Jia, A A Le, C D Cox, K M Jung, B Hou, D Piomelli, C M Gall, Gary Lynch
Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and use of episodes, with semantic (cue identity) information relayed to the structure via the lateral perforant path (LPP). The unusual form of synaptic plasticity expressed by the LPP (lppLTP) was profoundly impaired in Fmr1-KOs relative to wild-type mice...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133838/fungal-networks-serve-as-novel-ecological-routes-for-enrichment-and-dissemination-of-antibiotic-resistance-genes-as-exhibited-by-microcosm-experiments
#16
Rashid Nazir, Ju-Pei Shen, Jun-Tao Wang, Hang-Wei Hu, Ji-Zheng He
Antibiotic resistance genes (ARGs) in the environment and their subsequent acquisition by clinically important microorganisms are a serious concern. However, the spread of environmental ARGs remain largely unknown. We report, for the first time, the involvement of soil fungi in the distribution of bacteria with ARGs via soil microcosms. qPCR assay detected unique ARGs specifically found in the mycosphere of different fungi. Interestingly, the taxonomically and ecologically different fungi exerted different selection pressures on ARGs originating from the same source...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133514/first-prospective-multicenter-italian-study-on-the-impact-of-the-21-gene-recurrence-score-in-adjuvant-clinical-decisions-for-patients-with-er-positive-her2-negative-breast-cancer
#17
Maria Vittoria Dieci, Valentina Guarneri, Tommaso Giarratano, Marta Mion, Giampaolo Tortora, Costanza De Rossi, Stefania Gori, Cristina Oliani, Laura Merlini, Felice Pasini, Giorgio Bonciarelli, Gaia Griguolo, Enrico Orvieto, Silvia Michieletto, Tania Saibene, Paola Del Bianco, Gian Luca De Salvo, PierFranco Conte
BACKGROUND: The Breast DX Italy prospective study evaluated the impact of the 21-gene recurrence score (RS) result on adjuvant treatment decisions for patients with early breast cancer. MATERIALS AND METHODS: Nine centers (two Hub and seven Spoke centers of the Veneto Oncology Network) participated. Consecutive patients with estrogen receptor positive, human epidermal growth receptor negative, T1-T3, N0-N1 early breast cancer were prospectively registered; only those meeting protocol-defined clinicopathological "intermediate risk" criteria were eligible for the RS test...
November 13, 2017: Oncologist
https://www.readbyqxmd.com/read/29133081/-medical-treatment-of-endometriosis-hormonal-treatment-of-pain-impact-on-evolution-and-future-perspectives
#18
Sophie Geoffron, Guillaume Legendre, Emile Daraï, Nathalie Chabbert-Buffet
CONTEXT: Endometriosis is a chronic painful disease, for which hormone therapy is usually offered as a first line option to women not willing to conceive. OBJECTIVES: To analyse and synthesize the literature, from 2006 onwards, on pain control, and disease evolution in oemn using combined hormonal contraceptives, progestins and GnRH analogs. Data on other current and future treatment perspectives is included as well. SOURCES: Medline (Pubmed), the Cochrane Library, and endometriosis treatment recommendations published by European Society of Human Reproduction and Embryology (ESHRE), National Institute for health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), Royal College of Obstetricians and Gynaecologists (RCOG) and Société des Obstétriciens et Gynécologues du Canada (SOGC)...
November 10, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29131675/dedifferentiated-chondrosarcoma-in-the-dog-and-cat-a-case-series-and-review-of-the-literature
#19
Arathi Vinayak, Deanna R Worley, Stephen J Withrow, Dustin S Adams, Barbara E Powers
This retrospective case series describes seven dogs and one cat diagnosed with dedifferentiated chondrosarcoma, an uncommon, aggressive variant of chondrosarcoma. The purpose of the study is to describe clinical, imaging, and histopathological findings of this tumor. Medical records and the diagnostic laboratory database at Colorado State University from 2000 to 2015 were reviewed and complete medical records were available for the eight animals in this report. Similar to what has been reported in people, poor long-term survival and high metastatic rate, particularly to the lungs, was observed in our case series...
November 13, 2017: Journal of the American Animal Hospital Association
https://www.readbyqxmd.com/read/29130960/piwi-proteins-and-piwi-interacting-rna-emerging-roles-in-cancer
#20
Yi-Neng Han, Yuan Li, Sheng-Qiang Xia, Yuan-Yuan Zhang, Jun-Hua Zheng, Wei Li
P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control...
November 3, 2017: Cellular Physiology and Biochemistry
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