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https://www.readbyqxmd.com/read/29454236/stingel-controlled-release-of-a-cyclic-dinucleotide-for-enhanced-cancer-immunotherapy
#1
David G Leach, Neeraja Dharmaraj, Stacey L Piotrowski, Tania L Lopez-Silva, Yu L Lei, Andrew G Sikora, Simon Young, Jeffrey D Hartgerink
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call "STINGel...
February 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29452720/evaluation-of-the-biological-activities-of-the-il-15-superagonist-complex-alt-803-following-intravenous-versus-subcutaneous-administration-in-murine-models
#2
Bai Liu, Monica Jones, Lin Kong, Terra Noel, Emily K Jeng, Sixiang Shi, Christopher G England, Sarah Alter, Jeffrey S Miller, Weibo Cai, Peter R Rhode, Hing C Wong
ALT-803 is a fusion protein complex consisting of an interleukin (IL)-15 superagonist and a dimeric IL-15 receptor alpha sushi domain IgG1 Fc fusion protein. When administered to mice, ALT-803 is capable of inducing natural killer (NK) and CD8 + T cell proliferation and activation, and effectively promoting potent anti-tumor responses. Currently, ALT-803 is in clinical trials for treatment of various solid tumors and hematological malignancies. In the initial phase of these clinical studies, intravenous (iv) injection was used according to the route used in pre-clinical efficacy studies...
February 13, 2018: Cytokine
https://www.readbyqxmd.com/read/29439603/semaglutide-in-type-2-diabetes-is-it-the-best-glucagon-like-peptide-1-receptor-agonist-glp-1r-agonist
#3
Sheila A Doggrell
Glucagon-like peptide-1 (GLP-1) is produced by the gut, and in a glucose-dependent manner stimulates insulin secretion while inhibiting glucagon secretion, reduces appetite and energy intake, and delays gastric emptying. The GLP-1R agonist semaglutide has recently been registered for use in the treatment of type 2 diabetes. Area covered: This review is of semaglutide in type 2 diabetes, and considers which properties of this GLP-1R agonist, may be responsible for its clinical outcome benefits in this condition...
February 13, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29439258/bone-marrow-cell-therapy-on-1-2-dimethylhydrazine-dmh-induced-colon-cancer-in-rats
#4
Manal F El-Khadragy, Heba M Nabil, Basmaa N Hassan, Amany A Tohamy, Hanaa F Waaer, Hany M Yehia, Afra M Alharbi, Ahmed Esmat Abdel Moneim
BACKGROUND/AIMS: Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#5
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29434784/effects-of-intratumoral-injection-of-immunoactivator-after-microwave-ablation-on-antitumor-immunity-in-a-mouse-model-of-hepatocellular-carcinoma
#6
Hao Wu, Bin Chen, Baogang Peng
This study investigated the effects of intratumoral injection of immunoactivator after microwave ablation on antitumor immunity in a mouse model of hepatocellular carcinoma. Hepatocellular carcinoma cell line Hepa1-6 was subcutaneously injected into C57/B6 mice to establish a mouse model of hepatocellular carcinoma. When tumor diameter reached 8 mm, microwave ablation was performed for 3 min with temperature controlled at 55°C. Cytokine sustained-release microspheres (CytoMPS) containing human interleukin-2 (hIL-2) and mouse granulocyte macrophage colony-stimulating factor (mGM-CSF) were injected into the tumor of mice in the experimental group (n=5) at 3, 7 and 14 days after ablation, while sustained-release microspheres containing no cytokine were used in the control group (n=5)...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29425108/neck-adipose-tissue-tying-ties-in-metabolic-disorders
#7
REVIEW
Vlatka Pandzic Jaksic, Danijela Grizelj, Ana Livun, Drago Boscic, Marko Ajduk, Rajko Kusec, Ozren Jaksic
Upper body adipose tissue accumulation has been associated with clustering of metabolic disorders and increased cardiovascular risk. Neck circumference (NC) indicated that subcutaneous adipose tissue (SAT) in that region is an independent pathogenic depot that might account for the additional risk missed by visceral adipose tissue (VAT). Neck adipose tissue (NAT) is not only one more ectopic depot but has several particular features that might modulate its metabolic role. Besides a controversial impact on obstructive apnea syndrome, neck fat encompasses carotid arteries as an important perivascular adipose tissue (PVAT) depot...
February 9, 2018: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/29424439/divergent-response-of-murine-and-porcine-adipocytes-to-stimulation-of-browning-genes-by-18-carbon-polyunsaturated-fatty-acids-and-beta-receptor-agonists
#8
Sunhye Shin, Kolapo M Ajuwon
Long-chain fatty acids (LCFA) are known to activate brown and beige adipocytes. However, very little is known about the effects of the number and the position of double bonds in LCFA with the same length on brown fat-specific gene expression. To determine the specificity of LCFA in the regulation of these genes in different adipocyte models, fully differentiated 10T1/2, 3T3-L1, murine, or porcine primary adipocytes (obtained from the subcutaneous fat pad of C57BL/6 mice or Landrace × Yorkshire × Duroc crossbred piglets) were treated with 50 μM of the following 18-carbon fatty acids: stearic acid (STA; 18:0), oleic acid (OLA; 18:1, Δ9), linoleic acid (LNA; 18:2, Δ9,12), α-linolenic acid (ALA; 18:3, Δ9,12,15), γ-linolenic acid (GLA; 18:3, Δ6,9,12), or pinolenic acid (PLA; 18:3, Δ5,9,12) for 24 h with or without 4-h norepinephrine (NE) treatment...
February 9, 2018: Lipids
https://www.readbyqxmd.com/read/29423373/changes-in-basophil-activation-during-immunotherapy-with-house-dust-mite-and-mugwort-in-patients-with-allergic-rhinitis
#9
Sae-Hoon Kim, Soon-Hee Kim, Soo-Jie Chung, Jung-Hyun Kim, Suh-Young Lee, Byung-Keun Kim, Kyung-Whan Lim, Yoon-Seok Chang
Background: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. Objective: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. Methods: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort...
January 2018: Asia Pacific Allergy
https://www.readbyqxmd.com/read/29421337/role-of-d1-and-d2-like-dopaminergic-receptors-in-the-nucleus-accumbens-in-modulation-of-formalin-induced-orofacial-pain-involvement-of-lateral-hypothalamus
#10
Iman Shafiei, Mahsaneh Vatankhah, Leila Zarepour, Somayeh Ezzatpanah, Abbas Haghparast
The role of dopaminergic system in modulation of formalin-induced orofacial nociception has been established. The present study aims to investigate the role of dopaminergic receptors in the nucleus accumbens (NAc) in modulation of nociceptive responses induced by formalin injection in the orofacial region. One hundred and six male Wistar rats were unilaterally implanted with two cannulae into the lateral hypothalamus (LH) and NAc. Intra-LH microinjection of carbachol, a cholinergic receptor agonist, was done 5min after intra-accumbal administration of different doses of SCH23390 (D1-like receptor antagonist) or sulpiride (D2-like receptor antagonist)...
January 29, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29415817/heterologous-human-rat-her2-specific-exosome-targeted-t-cell-vaccine-stimulates-potent-humoral-and-ctl-responses-leading-to-enhanced-circumvention-of-her2-tolerance-in-double-transgenic-hla-a2-her2-mice
#11
Yufeng Xie, Jie Wu, Aizhang Xu, Shahid Ahmeqd, Amer Sami, Rajni Chibbar, Andrew Freywald, Changyu Zheng, Jim Xiang
DNA vaccines composed of heterologous human HER2 and rat neu sequences induce stronger antibody response and protective antitumor immunity than either HER2 or neu DNA vaccines in transgenic mice. We previously developed HER2-specific exosome-targeted T-cell vaccine HER2-TEXO capable of stimulating HER2-specific CD8+ T-cell responses, but only leading to partial protective immunity in double-transgenic HLA-A2/HER2 mice with self-immune tolerance to HER2. Here, we constructed an adenoviral vector AdVHuRt expressing HuRt fusion protein composed of NH2-HER21-407 (Hu) and COOH-neu408-690 (Rt) fragments, and developed a heterologous human/rat HER2-specific exosome-targeted T-cell vaccine HuRt-TEXO using polyclonal CD4+ T-cells uptaking exosomes released by AdVHuRt-transfected dendritic cells...
February 5, 2018: Vaccine
https://www.readbyqxmd.com/read/29414316/ppar%C3%AE-agonist-rosiglitazone-switches-fuel-preference-to-lipids-in-promoting-thermogenesis-under-cold-exposure-in-c57bl-6-mice
#12
Rong Gao, Wei Chen, Huang Yan, Xinni Xie, Dongqi Liu, Chenxi Wu, Zhaohui Zhu, Haijing Li, Fangting Dong, Lili Wang
Brown and beige adipose tissues play key roles in adaptive thermogenesis, which is essential for homoiotherms to maintain core temperature under cold exposure. PPARγ is a transcriptional regulator critical for brown adipose tissue (BAT) recruitment and white adipose tissue (WAT) browning. Here we evaluated the impact of PPARγ activation on thermogenic activity in C57BL/6 mice under thermo-neutral and 4 °C cold environment, and revealed the regulating mechanism and metabolic basis. Rosiglitazone slowed body temperature loss in cold environment in C57BL/6 mice, suppressed cold-induced decreases in blood glucose, reversed cold-promoted 18F-FDG uptake, and increased lipid consumption in BAT...
January 27, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29414294/multiple-sclerosis-onset-after-granulocyte-macrophage-colony-stimulating-factor-withdrawal
#13
J Chong, M Cohen, E Waubant
A 51-year old woman with stage III melanoma participated in a phase II clinical trial in which she received subcutaneous rhGM-CSF injections for 3 years. She was in remission by the end of the trial. Seven months after discontinuing GM-CSF she had her first MS event. The unique timeline of rh-GM-CSF injections in a melanoma trial, during which yearly MRI scans showed subtle stable demyelination followed by RRMS onset shortly after discontinuation of treatment, may provide some insight on the role of GM-CSF in MS...
February 1, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29412382/thyroid-disorders-in-obese-patients-does-insulin-resistance-make-a-difference
#14
Nicoleta Răcătăianu, Nicoleta Leach, Cosmina Ioana Bondor, Smaranda Mârza, Daniela Moga, Ana Valea, Cristina Ghervan
OBJECTIVE: The aim of this study was to evaluate the association between insulin resistance and thyroid pathology in obese patients, and compare the results between insulin-resistant and noninsulin-resistant patients. SUBJECTS AND METHODS: Obese/nondiabetic patients, aged 18-70 years, attending the outpatient endocrinology service for 2 years were consecutively included. We evaluated the patients' fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), thyroid-stimulating hormone (TSH), free thyroxine (FT4), antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), and thyroid ultrasound...
December 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29412161/comparative-experimental-infection-study-in-mice-with-b-melitensis-and-its-lipopolysaccharide-via-subcutaneous-route-of-inoculation
#15
Abdinasir Yusuf Osman, Abdul Aziz Saharee, Arifah Abdul Kadir
Brucella melitensis is a major zoonotic pathogen in which lipopolysaccharide (LPS) is believed to play a major role in the diseases pathogenesis. To study the immunopathophysiological aspects, we established a mouse model experimentally infected with whole cell of B. melitensis and its lipopolysaccharide via oral route of inoculation. Eighty four mice, BALB/c, both sexes with equal gender distribution and 6-8 weeks-old were randomly assigned into 3 groups. Group 1 (n = 36) were subcutaneoulsy inoculated with 0...
February 2, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29409758/postprandial-regulation-of-natriuretic-peptides-in-vivo-and-of-their-receptors-by-fatty-acids-in-adipocytes-in-vitro
#16
Andreas Schmid, Jens Albrecht, Judith Brock, Maria Koukou, Efthymia Arapogianni, Andreas Schäffler, Thomas Karrasch
BACKGROUND AND AIM: Natriuretic peptides (NPs) and their receptors gain attention regarding adipocyte function. It was the aim to investigate the expression of natriuretic peptide receptors NPR-A, NPR-B, NPR-C during adipocyte differentiation (AD), upon stimulation with fatty acids (FA), and in murine and human adipose tissue depots (AT) of patients undergoing bariatric surgery (n = 44). PATIENTS, MATERIAL AND METHODS: The postprandial regulation of NT-proANP and NT-proBNP levels was measured by ELISA and was studied in two cohorts of healthy individuals undergoing an oral glucose tolerance test (OGTT) (n = 100) and an oral lipid tolerance test (OLTT) (n = 100)...
January 30, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29409019/altered-expression-of-mir-181a-5p-and-mir-23a-3p-is-associated-with-obesity-and-tnf%C3%AE-induced-insulin-resistance
#17
Javier Lozano-Bartolomé, Gemma Llauradó, Manel Portero Otin, Antonio Altuna-Coy, Gemma Rojo-Martínez, Joan Vendrell, Rosa Jorba, Esther Rodríguez-Gallego, Matilde R Chacón
Context: The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). While several miRNAs are believed to be involved in the development of adipose tissue (AT) IR, the role of miRNAs in the association between inflammation and IR is poorly understood. Objective: To investigate the expression profile of miR-181a-5p and miR-23a-3p in obesity and to study their role in TNFα-induced IR in adipocytes. Design: Two separate cohorts were employed...
February 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29407803/comparative-effects-of-bisphenol-s-and-bisphenol-a-on-the-development-of-female-reproductive-system-in-rats-a-neonatal-exposure-study
#18
Nida Ahsan, Hizb Ullah, Waheed Ullah, Sarwat Jahan
Bisphenol A (BPA) has been well documented for its endocrine disrupting potential however, very little is known about endocrine disrupting abilities of bisphenol S (BPS). The present study aimed to compare the endocrine disrupting potentials of BPS with BPA, using female rats as an experimental animal model. On postnatal day 1 (PND 1) female pups born were randomly assigned to seven different treatments. Control group received subcutaneous injection of castor oil (50 μL) from PND 1 to PND 10. Three groups of female pups were injected subcutaneously with different concentrations (0...
January 12, 2018: Chemosphere
https://www.readbyqxmd.com/read/29402721/optimized-administration-of-hetil-15-expands-lymphocytes-and-minimizes-toxicity-in-rhesus-macaques
#19
Cristina Bergamaschi, Dionysios C Watson, Antonio Valentin, Jenifer Bear, Cody J Peer, William D Figg, Barbara K Felber, George N Pavlakis
The common γ-chain cytokine interleukin-15 (IL-15) plays a significant role in regulating innate and adaptive lymphocyte homeostasis and can stimulate anti-tumor activity of leukocytes. We have previously shown that the circulating IL-15 in the plasma is the heterodimeric form (hetIL-15), produced upon co-expression of IL-15 and IL-15 Receptor alpha (IL-15Rα) polypeptides in the same cell, heterodimerization of the two chains and secretion. We investigated the pharmacokinetic and pharmacodynamic profile and toxicity of purified human hetIL-15 cytokine upon injection in rhesus macaques...
February 2, 2018: Cytokine
https://www.readbyqxmd.com/read/29398370/depot-specific-and-gh-dependent-regulation-of-igf-binding-protein-4-pregnancy-associated-plasma-protein-a-and-stanniocalcin-2-in-murine-adipose-tissue
#20
Rikke Hjortebjerg, Darlene E Berryman, Ross Comisford, Edward O List, Claus Oxvig, Mette Bjerre, Jan Frystyk, John J Kopchick
INTRODUCTION: Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF)-I action through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. Most members of the IGF system are expressed in adipose tissue (AT), but there is a relative paucity of information on the distribution of IGFBP-4, PAPP-A, and STC2 in different AT depots. Since IGF-I expression in AT is highly GH-dependent, we used bovine GH transgenic (bGH) and GH receptor knockout (GHR-/-) mice to investigate AT depot-specific expression patterns of IGFBP-4, PAPP-A, and STC2, and whether the regulation is GH-dependent...
February 2, 2018: Growth Hormone & IGF Research
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