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https://www.readbyqxmd.com/read/29790694/advances-in-antibody-therapeutics-targeting-small-cell-lung-cancer
#1
REVIEW
Hongyang Lu, Zhiming Jiang
The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials...
May 16, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29784651/immune-recognition-of-%C3%AE-cells-neoepitopes-as-key-players-in-the-loss-of-tolerance
#2
Eddie A James, Massimo Pietropaolo, Mark J Mamula
Prior to the onset of type 1 diabetes, there is progressive loss of immune self-tolerance, evidenced by the accumulation of islet autoantibodies and emergence of autoreactive T cells. Continued autoimmune activity leads to the destruction of pancreatic β-cells and loss of insulin secretion. Studies of samples from patients with type 1 diabetes and of murine disease models have generated important insights about genetic and environmental factors that contribute to susceptibility and immune pathways that are important for pathogenesis...
June 2018: Diabetes
https://www.readbyqxmd.com/read/29774544/functional-molecules-in-mesothelial-to-mesenchymal-transition-revealed-by-transcriptome-analyses
#3
Sara Namvar, Adrian S Woolf, Leo A H Zeef, Thomas Wilm, Bettina Wilm, Sarah E Herrick
Peritoneal fibrosis is a common complication of abdominal and pelvic surgery, and can also be triggered by peritoneal dialysis, resulting in treatment failure. In these settings, fibrosis is driven by activated myofibroblasts that are considered to be partly derived by mesothelial-to-mesenchymal transition (MMT). We hypothesised that if the molecular signature of MMT could be better defined, these insights could be exploited to block this pathological cellular transition. Rat peritoneal mesothelial cells were purified, using an antibody to HBME1, a protein present on mesothelial cell microvilli, and streptavidin nanobead technology...
May 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29770221/risperidone-induced-type-2-diabetes-presenting-with-diabetic-ketoacidosis
#4
Clarissa Ern Hui Fang, Mohammed Faraz Rafey, Aine Cunningham, Sean F Dinneen, Francis M Finucane
A 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM). On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS) of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2 ). Dipstick urinalysis showed ketonuria and glycosuria...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29769329/isolation-of-state-dependent-monoclonal-antibodies-against-the-12-transmembrane-domain-glucose-transporter-4-using-virus-like-particles
#5
David F Tucker, Jonathan T Sullivan, Kimberly-Anne Mattia, Christine R Fisher, Trevor Barnes, Manu N Mabila, Rona Wilf, Chidananda Sulli, Meghan Pitts, Riley J Payne, Moniquetta Hall, Duncan Huston-Paterson, Xiaoxiang Deng, Edgar Davidson, Sharon H Willis, Benjamin J Doranz, Ross Chambers, Joseph B Rucker
The insulin-responsive 12-transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational mAbs against complex and highly conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking, or detect the conformational state of the protein. Here we report the isolation and characterization of conformational mAbs that recognize the extracellular and intracellular domains of GLUT4, including mAbs that are specific for the inward-open and outward-open states of GLUT4...
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29766635/efficacy-and-safety-of-mk-1293-insulin-glargine-compared-with-originator-insulin-glargine-lantus-in-type-1-diabetes-a-randomized-open-label-clinical-trial
#6
Philip D Home, Raymond L H Lam, Wendy L Carofano, Gregory T Golm, Roy Eldor, Michael F Crutchlow, Michael C Marcos, Julio Rosenstock, Priscilla A Hollander, Baptist Gallwitz
AIMS: Comparison of the efficacy and safety of MK-1293 insulin glargine (Mk-Gla; 100 U/ml) with originator insulin glargine, Lantus (Sa-Gla) in people with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This phase 3, randomized, active-controlled, open-label, 52-week study enrolled 508 people with T1DM (HbA1c ≤ 11.0%; 97 mmol/mol) taking basal and prandial insulin. Participants were randomized 1:1 to once-daily Mk-Gla (n=245) or Sa-Gla (n=263). Dose titration of basal insulin was by a pre-breakfast plasma glucose dosing algorithm...
May 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29761615/efficacy-and-safety-of-mk-1293-insulin-glargine-compared-with-originator-insulin-glargine-lantus-in-type-2-diabetes-a-randomized-open-label-clinical-trial
#7
Priscilla A Hollander, Wendy L Carofano, Raymond L H Lam, Gregory T Golm, Roy Eldor, Michael F Crutchlow, Michael C Marcos, Marc S Rendell, Philip D Home, Baptist Gallwitz, Julio Rosenstock
AIMS: To compare the efficacy and safety of MK-1293 insulin glargine (Mk-Gla) and Lantus (Sa-Gla) in people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This Phase 3, randomized, active-controlled, open-label, 24-week clinical trial enrolled 531 participants with T2DM (HbA1c ≤11.0%) eligible for or currently taking basal insulin (≥10 U/day). Participants were randomized 1:1 to once-daily Mk-Gla (n=263) or Sa-Gla (n=263). Titration of insulin was guided by a fasting plasma glucose (FPG)-based dosing algorithm...
May 14, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29750260/identification-of-mitochondrial-hormone-receptors-in-avian-muscle-cells
#8
K Lassiter, S Dridi, E Greene, B Kong, W G Bottje
The major objective of this study was to assess the expression of mitochondrial hormone receptors for progesterone (PR), estrogen (ER), glucocorticoid (GR), thyroid (TR), and insulin (IR) in avian muscle cells (quail muscle 7, QM7) and in breast muscle of quail and broilers. Visualization of receptor location in QM7 cells was accomplished by immunofluorescence. QM7 cells were stained with Mito Tracker Deep Red CMX, fixed in methanol, immune stained with anti-PR, -GR, -TR, -IR, and -ER primary antibodies overnight at 4°C, and visualized with Alexa Fluor 488-conjugated secondary antibody...
May 10, 2018: Poultry Science
https://www.readbyqxmd.com/read/29749030/a-new-therapeutic-approach-for-type-1-diabetes-rationale-for-gnbac1-an-anti-herv-w-env-monoclonal-antibody
#9
REVIEW
Francois Curtin, Corinne Bernard, Sandrine Levet, Hervé Perron, Hervé Porchet, Julie Médina, Sam Malpass, David Lloyd, Richard Simpson
We describe a newly identified therapeutic target for type 1 diabetes: an envelope protein of endogenous retroviral origin called Human Endogenous Retrovirus W Envelope (HERV-W-Env). HERV-W-Env was found to be detected in the blood of around 60% of type 1 diabetes (T1D) patients and is expressed in acinar pancreatic cells of 75% of T1D patients at post-mortem examination. Preclinical experiments showed that this protein displays direct cytotoxicity on human β-islet cells. In vivo HERV-W-Env impairs the insulin and glucose metabolism in transgenic mice expressing HERV-W-Env...
May 10, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29745910/misdiagnosed-patient-with-latent-autoimmune-diabetes-in-adults-case-report
#10
H Petreski
Latent Autoimmune Diabetes in Adults (LADA) is often misdiagnosed because it lacks both awareness and standardized diagnostic criteria. A 30-year-old patient with high blood glucose, HbA1c level 10.1% and positive GAD antibodies was diagnosed with type 1 diabetes but LADA was not ruled out. Patient refused to receive insulin therapy. He chose to follow the dietary restrictions and therapy with sulfonylurea, initiated by another physician. Following 7 months the patient's HbA1c values decreased, but never achieved the goal...
April 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29744034/new-advances-in-understanding-thyroid-associated-ophthalmopathy-and-the-potential-role-for-insulin-like-growth-factor-i-receptor
#11
REVIEW
Terry J Smith
Thyroid-associated ophthalmopathy (TAO), a localized periocular manifestation of the autoimmune syndrome known as Graves' disease, remains incompletely understood. Discussions of its pathogenesis are generally focused on the thyrotropin receptor, the proposed role for which is supported by substantial evidence. Considerations of any involvement of the insulin-like growth factor-I receptor (IGF-IR) in the disease are frequently contentious. In this brief, topically focused review, I have attempted to provide a balanced perspective based entirely on experimental results that either favor or refute involvement of IGF-IR in TAO...
2018: F1000Research
https://www.readbyqxmd.com/read/29738684/interleukin-4-restores-insulin-sensitivity-in-lipid-induced-insulin-resistant-adipocytes
#12
I S Stafeev, S S Michurina, N V Podkuychenko, A V Vorotnikov, M Yu Menshikov, Ye V Parfyonova
Obesity and latent inflammation in adipose tissue significantly contribute to the development of insulin resistance (IR) and type 2 diabetes. Here we studied whether the antiinflammatory interleukin-4 (IL-4) can restore insulin sensitivity in cultured 3T3-L1 adipocytes. The activity of key components of the insulin signaling cascade was assessed by immunoblotting using phospho-specific antibodies to insulin receptor substrate IRS1 (Tyr612), Akt (Thr308 and Ser473), and AS160 (Ser318) protein that regulates translocation of the GLUT4 glucose transporter to the plasma membrane...
May 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29734859/evaluation-of-serum-anti-nuclear-antibody-among-women-with-pcos-a-hospital-based-single-center-cross-sectional-study
#13
Aafia Rashid, Javaid Ahmad Bhat, Mohd Ashraf Ganie, Imtiyaz Ahmad Wani, Moomin Hussain Bhat, Zaffar Amin Shah, Shariq R Masoodi, R K Marwaha
Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation...
May 7, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29734035/magnetic-multiwalled-carbon-nanotubes-as-nanocarrier-tags-for-sensitive-determination-of-fetuin-in-saliva
#14
Esther Sánchez-Tirado, Araceli González-Cortés, Paloma Yáñez-Sedeño, José M Pingarrón
This paper reports the development and performance of an electrochemical immunosensor using magnetic multiwalled carbon nanotubes (m-MWCNTs) as nanocarrier tags for the determination of human fetuin A (HFA), a relevant biomarker of obesity, insulin resistance, and type-2 diabetes as well as for pancreatic and liver cancers and inflammatory processes. Screen-printed carbon electrodes were grafted with p-aminobezoic acid and streptavidin was covalently immobilized on the electrode surface. A biotinylated capture antibody was immobilized through streptavidin-biotin interaction and a sandwich assay configuration was implemented using m-MWCNTs conjugated with HRP and anti-HFA antibodies as the detection label...
April 30, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29732161/rapid-onset-diabetic-ketoacidosis-secondary-to-nivolumab-therapy
#15
Senhong Lee, Aparna Morgan, Sonali Shah, Peter R Ebeling
We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non-small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29728363/increased-hepatic-pdgf-aa-signaling-mediates-liver-insulin-resistance-in-obesity-associated-type-2-diabetes
#16
Amar Abderrahmani, Loïc Yengo, Robert Caiazzo, Mickaël Canouil, Stéphane Cauchi, Violeta Raverdy, Valérie Plaisance, Valérie Pawlowski, Stéphane Lobbens, Julie Maillet, Laure Rolland, Raphael Boutry, Gurvan Queniat, Maxime Kwapich, Mathie Tenenbaum, Julien Bricambert, Sophie Saussenthaler, Elodie Anthony, Pooja Jha, Julien Derop, Olivier Sand, Iandry Rabearivelo, Audrey Leloire, Marie Pigeyre, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin, Tasnim Dayeh, Guillaume Lassailly, Philippe Mathurin, Bart Staels, Johan Auwerx, Annette Schürmann, Catherine Postic, Clemens Schafmayer, Jochen Hampe, Amélie Bonnefond, François Pattou, Philippe Froguel
In type 2 diabetes (T2D), hepatic insulin resistance is strongly associated with non-alcoholic fatty liver disease (NAFLD). In this study, we hypothesized that DNA methylome of livers from patients with T2D, when compared to livers of individuals with normal plasma glucose levels, can unveil some mechanism of hepatic insulin resistance that could link to NAFLD. Using DNA methylome and transcriptome analyses of livers from obese individuals, we found that both hypomethylation at a CpG site in PDGFA (encoding platelet derived growth factor alpha) and PDGFA overexpression are associated with increased T2D risk, hyperinsulinemia, increased insulin resistance and increased steatohepatitis risk...
May 4, 2018: Diabetes
https://www.readbyqxmd.com/read/29727614/3d-super-resolution-microscopy-reflects-mitochondrial-cristae-alternations-and-mtdna-nucleoid-size-and-distribution
#17
Andrea Dlasková, Hana Engstová, Tomáš Špaček, Anežka Kahancová, Vojtěch Pavluch, Katarína Smolková, Jitka Špačková, Martin Bartoš, Lydie Plecitá Hlavatá, Petr Ježek
3D super-resolution microscopy based on the direct stochastic optical reconstruction microscopy (dSTORM) with primary Alexa-Fluor-647-conjugated antibodies is a powerful method for accessing changes of objects that could be normally resolved only by electron microscopy. Despite the fact that mitochondrial cristae yet to become resolved, we have indicated changes in cristae width and/or morphology by dSTORM of ATP-synthase F1 subunit α (F1 α). Obtained 3D images were analyzed with the help of Ripley's K-function modeling spatial patterns or transferring them into distance distribution function...
May 1, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29718759/increased-insulin-like-growth-factor-binding-protein-1-phosphorylation-in-decidualized-stromal-mesenchymal-cells-in-human-intrauterine-growth-restriction-placentas
#18
Sahil S Singal, Karen Nygard, Robert Gratton, Thomas Jansson, Madhulika B Gupta
Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each)...
May 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29707905/human-herpes-virus-type-8-infection-dna-positivity-is-associated-with-low-insulin-secretion-a-case-control-study-in-a-sub-saharan-african-population-with-diabetes
#19
Eric Lontchi-Yimagou, Jérôme Legoff, Jean-Louis Nguewa, Philippe Boudou, Eric V Balti, Jean Jacques Noubiap, Vicky Kamwa, Barbara Atogho-Tiedeu, Marcel Azabji-Kenfack, Eric N Djahmeni, Martine Etoa, Gaelle Lemdjo, Vanessa Balla, Mesmin Y Dehayem, Fabienne Foufelle, Jean-Claude Mbanya, Jean-Francois Gautier, Eugene Sobngwi
BACKGROUND: Viruses have been considered as potential triggers for diabetes development. This study sought to assess insulin secretion and insulin sensitivity in Human Herpes Virus type 8 (HHV8) infected and non-infected sub-Saharan African people with diabetes. METHODS: We consecutively enrolled 173 people with non-autoimmune diabetes: 124 with type 2 diabetes (T2D), and 49 with ketosis-prone diabetes (KPD) admitted in hyperglycaemic crisis. KPD was further sub-classified as new-onset ketotic phase KPD (n=34) or non-ketotic phase KPD (n=15)...
April 29, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29702025/depp-depp1-c10orf10-regulates-hepatic-glucose-and-fat-metabolism-partly-via-ros-induced-fgf21
#20
Wenli Li, Meiling Ji, Yandie Lin, Yi Miao, Simin Chen, Hao Li
Decidual protein induced by progesterone (DEPP/DEPP1/C10ORF10) is induced by denying access to food and reduced by refeeding in insulin-sensitive organs in vivo. The negative regulation of DEPP by insulin is also proven in several cell lines. However, the functions of DEPP in insulin-sensitive organs remain unknown. In the present study, we investigated the impact of DEPP on hepatic energy metabolism and addressed the underlying mechanisms. The metabolic effects of DEPP were investigated in mice with adenovirus-mediated hepatic overexpression...
April 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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