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https://www.readbyqxmd.com/read/28927027/cancer-associated-fibroblasts-an-essential-role-in-the-tumor-microenvironment
#1
Leilei Tao, Guichun Huang, Haizhu Song, Yitian Chen, Longbang Chen
Fibroblasts in the tumor stroma are well recognized as having an indispensable role in carcinogenesis, including in the initiation of epithelial tumor formation. The association between cancer cells and fibroblasts has been highlighted in several previous studies. Regulation factors released from cancer-associated fibroblasts (CAFs) into the tumor microenvironment have essential roles, including the support of tumor growth, angiogenesis, metastasis and therapy resistance. A mutual interaction between tumor-induced fibroblast activation, and fibroblast-induced tumor proliferation and metastasis occurs, thus CAFs act as tumor supporters...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926732/multifunctional-mesoporous-zro2-encapsulated-upconversion-nanoparticles-for-mild-nir-light-activated-synergistic-cancer-therapy
#2
Lili Feng, Shili Gai, Fei He, Yunlu Dai, Chongna Zhong, Piaoping Yang, Jun Lin
Desirable nanosystem that could not only deliver drugs safely and effectively into tumor sites, but also be expected to serve as photosensitizer to realize the photodynamic therapeutic function, would be of great significance in the synergistic cancer therapy. To perform this task, a multifunctional nanosystem has been developed for markedly enhanced cancer therapeutic efficacy by loading chemotherapy agent (doxorubicin hydrochloride, DOX) and photosensitive drug chlorin e6 (Ce6) into the channels of mesoporous zirconium dioxide (ZrO2) layer which coats on Nd(3+)-doped upconversion nanoparticles (UCNPs)...
September 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28925872/abdominal-aorta-aneurysm-aaa-is-there-a-role-for-prevention-and-therapy-using-antioxidants
#3
Joël Pincemail, Jean-Olivier Defraigne, Audrey Courtois, Adelin Albert, Jean-Paul Cheramy-Bien, Natzi Sakalihasan
Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin...
September 18, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28924019/kinetics-and-biomarkers-of-severe-cytokine-release-syndrome-after-cd19-chimeric-antigen-receptor-modified-t-cell-therapy
#4
Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Juliane Gust, W Conrad Liles, Mark M Wurfel, José A López, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Sindhu Cherian, Xueyan Chen, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-specific chimeric antigen receptor-modified T cells (CAR-T) has produced impressive antitumor responses in patients with refractory CD19(+) B cell malignancies, but is often associated with cytokine release syndrome (CRS). Our understanding of CRS continues to evolve, and identification of the kinetics of CRS and predictive clinical and laboratory biomarkers of severity are needed to evaluate strategies to mitigate toxicity. We report the clinical presentation and identify biomarkers of severe CRS in 133 adult patients who received CD19 CAR-T cells...
September 18, 2017: Blood
https://www.readbyqxmd.com/read/28923792/p2y2-nucleotide-receptor-prompts-human-cardiac-progenitor-cell-activation-by-modulating-hippo-signaling
#5
Farid G Khalafalla, Steven R Greene, Hashim Khan, Kelli Ilves, Megan M Monsanto, Roberto Alvarez, Monica Chavarria, Jonathan H Nguyen, Benjamin Norman, Walter P Dembitsky, Mark A Sussman
Rationale: Autologous stem cell therapy using human c-Kit(+) cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged HF patients with genetic predispositions and/or comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impairs overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with pro-regenerative molecules ex vivo is crucial for improving the therapeutic outcome in HF patients...
September 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28923397/the-two-novel-dll4-targeting-antibody-drug-conjugates-mvm03-and-mgd03-show-potent-anti-tumour-activity-in-breast-cancer-xenograft-models
#6
Shijing Wang, Rihong Zhou, Fumou Sun, Renjie Li, Min Wang, Min Wu
The anti-human Delta-like 4 (DLL4) monoclonal antibody MMGZ01 has a high affinity to hrDLL4 and arrests the DLL4-mediated human umbilical vein endothelial cell (HUVEC) phenotype, promotes immature vessels, and effectively reduces breast cancer cell growth in vivo. To develop a much more effective therapy, we conjugated MMGZ01 with two small-molecule cytotoxic agents, i.e., monomethyl auristatin E (MMAE) and doxorubicin (DOX), with different linkers to generate antibody-drug conjugates (ADCs), i.e., MMGZ01-vc-MMAE (named MvM03) and MMGZ01-GMBS-DOX (named MGD03), that are more potent therapeutic agents than naked antibody therapeutic agents...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28922494/magnetic-nanotransducers-in-biomedicine
#7
Agostina Grillone, Gianni Ciofani
Owing to their abilities to identify diseased conditions, to modulate biological process, and to control cellular activities, magnetic nanoparticles have become one of the most popular nanomaterials exploited in the biomedical field. Targeted drug delivery, controlled drug release, hyperthermia treatments, imaging, and stimulation of several biological entities are just some of the several tasks that can be accomplished by taking advantage of magnetic nanoparticles in tandem with magnetic fields. The huge interest towards this class of nanomaterials rises from the possibility to physically drive their spatiotemporal localization inside the body, and to deliver an externally applied stimulation at a target site...
September 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28921447/structure-pharmacology-and-roles-in-physiology-of-the-p2y12-receptor
#8
Ivar von Kügelgen
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel block P2Y12 receptors and, thereby, inhibit ADP-induced platelet aggregation...
September 12, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28920426/methotrexate-camptothecin-prodrug-nanoassemblies-as-a-versatile-nanoplatform-for-biomodal-imaging-guided-self-active-targeted-and-synergistic-chemotherapy
#9
Yang Li, Jinyan Lin, Jinyuan Ma, Liang Song, Huirong Lin, Bowen Tang, Dengyue Chen, Guanghao Su, Shefang Ye, Xuan Zhu, Fang-Hong Luo, Zhenqing Hou
"All-in-one" carrier-free-based nano-multi-drug self-delivery system could combine triple advantages of small molecules, nanoscale characteristics, and synergistic combination therapy together. Researches have showed that dual-acting small molecular methotrexate (MTX) could target and kill the folate receptors-overexpressing cancer cells. Inspired by this mechanism, a novel collaborative "early-phase tumor-selective targeting and late-phase synergistic anticancer" approach was developed for the self-assembly of chemotherapeutic drug-drug conjugate, which showed various advantages of more simplicity, efficiency, and flexibility over the conventional approach that was only based on single or combination cancer chemotherapy...
September 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28918581/concurrent-improvement-in-both-binge-eating-and-depressive-symptoms-with-naltrexone-bupropion-therapy-in-overweight-or-obese-subjects-with-major-depressive-disorder-in-an-open-label-uncontrolled-study
#10
Anna I Guerdjikova, Brandon Walsh, Kevin Shan, Amy E Halseth, Eduardo Dunayevich, Susan L McElroy
INTRODUCTION: Binge eating disorder (BED) is associated with obesity and major depressive disorder (MDD). Naltrexone extended-release (ER)/bupropion ER (NB) is approved as an adjunct to diet and physical activity for chronic weight management. In a prospectively designed 24-week open-label, single-arm, single-site trial of 25 women with MDD and overweight/obesity, NB reduced weight and depressive symptoms. METHODS: This post hoc analysis investigated the relationship between change in self-reported binge eating behavior (evaluated with the Binge Eating Scale [BES]) and changes in weight, control of eating, and depressive symptoms...
September 16, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28918253/deep-brain-stimulation-of-the-medial-forebrain-bundle-elevates-striatal-dopamine-concentration-without-affecting-spontaneous-or-reward-induced-phasic-release
#11
Marianne Klanker, Matthijs Feenstra, Ingo Willuhn, Damiaan Denys
Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) induces rapid improvement of depressive symptoms in patients suffering from treatment-refractory major depressive disorder. It has been hypothesized that activation of the dopamine (DA) system contributes to this effect. To investigate whether DBS in the MFB affects DA release in the striatum, we combined DBS with fast-scan cyclic voltammetry (FSCV) in freely moving rats. Animals were implanted with a stimulating electrode at the border of the MFB and the ventral tegmental area, and a FSCV microelectrode in the ventromedial striatum to monitor extracellular DA during the acute onset of DBS and subsequent continued stimulation...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28918023/repression-of-coup-tfi-improves-bone-marrow-derived-mesenchymal-stem-cell-differentiation-into-insulin-producing-cells
#12
Tao Zhang, Xiao-Hang Li, Dian-Bao Zhang, Xiao-Yu Liu, Feng Zhao, Xue-Wen Lin, Rui Wang, Hong-Xin Lang, Xi-Ning Pang
Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI)...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917273/mechanisms-and-risk-factors-of-thrombosis-in-cancer
#13
REVIEW
Anna Falanga, Laura Russo, Viola Milesi, Alfonso Vignoli
The close relationship between cancer and thrombosis is known since more than a century. Venous thromboembolism (VTE) may be the first manifestation of an occult malignancy in an otherwise healthy individual. Cancer patients commonly present with abnormalities of laboratory coagulation tests, indicating an ongoing subclinical hypercoagulable condition. The results of laboratory tests demonstrate that a process of fibrin formation and removal parallels the development of malignancy, which is of particular interest since fibrin and other clotting products are important for both thrombogenesis and tumor progression...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916497/two-step-polymer-and-liposome-enzyme-prodrug-therapies-for-cancer-pdept-and-pelt-concepts-and-future-perspectives
#14
Anna Scomparin, Helena F Florindo, Galia Tiram, Elaine L Ferguson, Ronit Satchi-Fainaro
Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916300/distinct-neuronal-populations-in-the-basolateral-and-central-amygdala-are-activated-with-acute-pain-conditioned-fear-and-fear-conditioned-analgesia
#15
Ryan K Butler, Sarah Ehling, Megan Barbar, Jess Thomas, Mary A Hughes, Charles E Smith, Vladimir M Pogorelov, Dipendra K Aryal, William C Wetsel, B Duncan X Lascelles
Fear-conditioned analgesia (FCA) is modulated by brain areas involved in the descending inhibitory pain pathway such as the basolateral (BLA) and central amygdala (CEA). The BLA contains Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and parvalbumin (PV) neurons. CEA neurons are primarily inhibitory (GABAergic) that comprise enkephalin (ENK) interneurons and corticotropin-releasing factor (CRF) - neurons that project to the periaqueductal grey. The purpose of our experiment was to determine the pattern of activation of CaMKII/PV and ENK/CRF neurons following the expression of acute pain, conditioned fear, and FCA...
September 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28912890/glioma-dual-targeting-nanohybrid-protein-toxin-constructed-by-intein-mediated-site-specific-ligation-for-multistage-booster-delivery
#16
Yingzhi Chen, Meng Zhang, Hongyue Jin, Dongdong Li, Fan Xu, Aihua Wu, Jinyu Wang, Yongzhuo Huang
Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences...
2017: Theranostics
https://www.readbyqxmd.com/read/28912423/the-chinese-herbal-formula-free-and-easy-wanderer-ameliorates-oxidative-stress-through-keap1-nrf2-ho-1-pathway
#17
Chunlan Hong, Jingming Cao, Ching-Fen Wu, Onat Kadioglu, Anja Schüffler, Ulrich Kauhl, Sabine M Klauck, Till Opatz, Eckhard Thines, Norbert W Paul, Thomas Efferth
Posttraumatic stress disorder (PTSD) gains a lot of attention due to high prevalence and strong psychological upset, but the etiology remains undefined and effective treatment is quite limited. Growing studies demonstrated the involvement of oxidative stress in various psychiatry diseases, suggesting anti-oxidation therapy might be a strategy for PTSD treatment. Free and Easy Wanderer (FAEW) is a poly-herbal drug clinically used in China for hundreds of years in the treatment of psychiatric disorder. We hypothesized that FAEW exerts clinical effects through the activity against oxidative stress with fluoxetine as antidepressant control drug...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911823/towards-antibody-drug-conjugates-and-prodrug-strategies-with-extracellular-stimuli-responsive-drug-delivery-in-the-tumor-microenvironment-for-cancer-therapy
#18
REVIEW
Nicolas Joubert, Caroline Denevault-Sabourin, Francesca Bryden, Marie-Claude Viaud-Massuard
The design of innovative anticancer chemotherapies with superior antitumor efficacy and reduced toxicity continues to be a challenging endeavor. Recently, the success of Adcetris(®) and Kadcyla(®) made antibody-drug conjugates (ADCs) serious contenders to reach the envied status of Paul Ehrlich's "magic bullet". However, ADCs classically target overexpressed and internalizing antigens at the surface of cancer cells, and in solid tumors are associated with poor tumor penetration, insufficient targeting in heterogeneous tumors, and appearance of several resistance mechanisms...
August 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28910156/antiproliferative-effects-of-bacillus-coagulans-unique-is2-in-colon-cancer-cells
#19
Ratna Sudha Madempudi, Arunasree M Kalle
In the present study, the in vitro anticancer (antiproliferative) effects of Bacillus coagulans Unique IS2 were evaluated on human colon cancer (COLO 205), cervical cancer (HeLa), and chronic myeloid leukemia (K562) cell lines with a human embryonic kidney cell line (HEK 293T) as noncancerous control cells. The Cytotoxicity assay (MTT) clearly demonstrated a 22%, 31.7%, and 19.5% decrease in cell proliferation of COLO 205, HeLa, and K562 cells, respectively, when compared to the noncancerous HEK 293T cells...
September 14, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28906427/biological-pathways-involved-in-tumor-angiogenesis-and-bevacizumab-based-anti-angiogenic-therapy-with-special-references-to-ovarian-cancer
#20
REVIEW
Vera Loizzi, Vittoria Del Vecchio, Giulio Gargano, Maria De Liso, Anila Kardashi, Emanuele Naglieri, Leonardo Resta, Ettore Cicinelli, Gennaro Cormio
The creation of new blood vessels from existing ones, which is a mechanism called "angiogenesis", is essential in cancer to supply cancerous growth. Moreover, the development and the progression of the tumor and its metastases are the result of an efficient vascular response. Cancer cells release and activate different angiogenic growth factors and their receptors in the tumor microenvironment to promote the angiogenic process. The most important pro-angiogenic factor is the "Vascular Endothelial Growth Factor" (VEGF) because of its mitogen activity on vascular endothelium...
September 14, 2017: International Journal of Molecular Sciences
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