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Cellular Therapy

Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
Fara Brasó-Maristany, Simone Filosto, Steven Catchpole, Rebecca Marlow, Jelmar Quist, Erika Francesch-Domenech, Darren A Plumb, Leila Zakka, Patrycja Gazinska, Gianmaria Liccardi, Pascal Meier, Albert Gris-Oliver, Maggie Chon U Cheang, Anna Perdrix-Rosell, Manar Shafat, Elodie Noël, Nirmesh Patel, Kristen McEachern, Maurizio Scaltriti, Pau Castel, Farzana Noor, Richard Buus, Sumi Mathew, Johnathan Watkins, Violeta Serra, Pierfrancesco Marra, Anita Grigoriadis, Andrew N Tutt
Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents mitochondrial-mediated apoptosis in TNBC cell lines...
October 24, 2016: Nature Medicine
Aldo Isaac Martínez-Banderas, Antonio Aires, Francisco J Teran, Jose Efrain Perez, Jael F Cadenas, Nouf Alsharif, Timothy Ravasi, Aitziber L Cortajarena, Jürgen Kosel
Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX...
October 24, 2016: Scientific Reports
A Dokala, S S Thakur
The epidermal growth factor receptor (EGFR) is a transmembrane receptor with tyrosine kinase activity involved in regulation of cellular multiplication, survival, differentiation and metastasis. Our knowledge about function and complex management of these receptors has driving the development of specific and targeted treatment modalities for human cancers in the last 20 years. EGFR is the first receptor target against which monoclonal antibodies (mAb) have been evolved for cancer treatment. Here we review the biology of ErbB receptors, including their architecture, signaling, regulation and therapeutic strategies and the mechanisms of resistances offered by the receptors against small-molecule tyrosine kinases and resistance overcome implications of mAbs...
October 24, 2016: Oncogene
Anita Schlierf, Eva Altmann, Jean Quancard, Anne B Jefferson, René Assenberg, Martin Renatus, Matthew Jones, Ulrich Hassiepen, Michael Schaefer, Michael Kiffe, Andreas Weiss, Christian Wiesmann, Richard Sedrani, Jörg Eder, Bruno Martoglio
The COP9 signalosome (CSN) is a central component of the activation and remodelling cycle of cullin-RING E3 ubiquitin ligases (CRLs), the largest enzyme family of the ubiquitin-proteasome system in humans. CRLs are implicated in the regulation of numerous cellular processes, including cell cycle progression and apoptosis, and aberrant CRL activity is frequently associated with cancer. Remodelling of CRLs is initiated by CSN-catalysed cleavage of the ubiquitin-like activator NEDD8 from CRLs. Here we describe CSN5i-3, a potent, selective and orally available inhibitor of CSN5, the proteolytic subunit of CSN...
October 24, 2016: Nature Communications
Hao Wu, Fang Zeng, Hang Zhang, Jiangsheng Xu, Jianrong Qiu, Shuizhu Wu
The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half-life. Herein, a mitochondria-targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio-precursor of photosensitizer under two-photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5-aminolevulinic acid (5-ALA, the bio-precursor) to coumarin; and the nanosystem (CD-ALA-TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria-targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs)...
February 2016: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Jean-Pierre Routy, Bertrand Routy, Gina M Graziani, Vikram Mehraj
The term "immune privilege" was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege...
2016: International Journal of Tryptophan Research: IJTR
Yaarit Adamovich, Benjamin Ladeuix, Marina Golik, Maarten P Koeners, Gad Asher
The mammalian circadian system consists of a master clock in the brain that synchronizes subsidiary oscillators in peripheral tissues. The master clock maintains phase coherence in peripheral cells through systemic cues such as feeding-fasting and temperature cycles. Here, we examined the role of oxygen as a resetting cue for circadian clocks. We continuously measured oxygen levels in living animals and detected daily rhythms in tissue oxygenation. Oxygen cycles, within the physiological range, were sufficient to synchronize cellular clocks in a HIF1α-dependent manner...
October 19, 2016: Cell Metabolism
Ran Xu, Zhen-Zhou Zhang, Lai-Jiang Chen, Hui-Min Yu, Shu-Jie Guo, Ying-Le Xu, Gavin Y Oudit, Yan Zhang, Qing Chang, Bei Song, Dong-Rui Chen, Ding-Liang Zhu, Jiu-Chang Zhong
Apelin has been proved to be a critical mediator of vascular function and homeostasis. Here, we investigated roles of Apelin in aortic remodeling and fibrosis in rats with transverse aortic constriction (TAC). Male Sprague-Dawley rats were subjected to TAC and then randomized to daily deliver Apelin-13 (50μg/kg) or angiotensin type 1 receptor (AT1) blocker Irbesartan (50mg/kg) for 4 weeks. Pressure overload resulted in myocardial hypertrophy, systolic dysfunction, aortic remodeling and adventitial fibrosis with reduced levels of Apelin in ascending aortas of rat after TAC compared with sham-operated group...
October 20, 2016: Peptides
Jonathan C Simmonds, Elie E Rebeiz
Hemangiopericytomas are soft tissue tumors composed of pericytic cells that are characterized by their "staghorn" vascular branching and their variable clinical presentation. Fifteen to 25% of all HPC occur in the head and neck, with only 5% found in the nose or paranasal sinuses. Sinonasal hemangiopericytoma (SNHPC) is considered distinct from its soft tissue counterpart - the former showing a more uniform cellular organization, has convincing pericytic differentiation and is associated with a far better prognosis...
September 28, 2016: American Journal of Otolaryngology
Li Yu, Ling Li, L Jeffrey Medeiros, Ken H Young
The NF-κB pathway, a critical regulator of apoptosis, plays a key role in many normal cellular functions. Genetic alterations and other mechanisms leading to constitutive activation of the NF-κB pathway contribute to cancer development, progression and therapy resistance by activation of downstream anti-apoptotic pathways, unfavorable microenvironment interactions, and gene dysregulation. Not surprisingly, given its importance to normal and cancer cell function, the NF-κB pathway has emerged as a target for therapy...
October 13, 2016: Blood Reviews
Taofeek K Owonikoko, Mukesh Kumar, Shu Yang, Alice O Kamphorst, Rathi N Pillai, Rama Akondy, Vivek Nautiyal, Monica S Chatwal, Wendy M Book, Anurag Sahu, Gabriel L Sica, Rafi Ahmed, Suresh S Ramalingam
INTRODUCTION: The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities. MATERIALS AND METHODS: The mechanism of cardiac allograft rejection in the context of PD-1 antibody therapy was explored in a patient with cutaneous squamous cell cancer complicating long-standing cardiac allograft. Immune cell infiltrate in the myocardium and peripheral blood lymphocyte repertoire were assessed using myocardial biopsy and temporal analysis of peripheral blood samples...
October 22, 2016: Cancer Immunology, Immunotherapy: CII
Dulce Alfaiate, Julie Lucifora, Natali Abeywickrama-Samarakoon, Maud Michelet, Barbara Testoni, Jean-Claude Cortay, Camille Sureau, Fabien Zoulim, Paul Dény, David Durantel
Hepatitis D virus (HDV) super-infection of Hepatitis B virus (HBV)-infected patients is the most aggressive form of viral hepatitis. HDV infection is not susceptible to direct anti-HBV drugs, and only suboptimal antiviral responses are obtained with interferon (IFN)-alpha-based therapy. To get insights on HDV replication and interplay with HBV in physiologically relevant hepatocytes, differentiated HepaRG (dHepaRG) cells, previously infected or not with HBV, were infected with HDV, and viral markers were extensively analyzed...
October 19, 2016: Antiviral Research
Loan Bui, Adham Aleid, Ahmad Alassaf, Otto C Wilson, Christopher B Raub, Victor Frenkel
In vitro investigations of ultrasound mediated, intracellular drug and gene delivery (i.e. sonoporation) are typically carried out in cells cultured in standard plastic well plates. This creates conditions that poorly resemble in vivo conditions, as well as generating unwanted ultrasound phenomena that may confound the interpretation of results. Here, we present our results in the development of a biological scaffold for sonoporation studies. The scaffolds were comprised of cellulose fibers coated with chitosan and gelatin...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Rongfeng Shi, Yinpeng Jin, Chuanwu Cao, Shilong Han, Xiaowen Shao, Lingyu Meng, Jie Cheng, Meiling Zhang, Jiayi Zheng, Jun Xu, Maoquan Li
BACKGROUND: Diabetic foot ulcer (DFU) is an intractable diabetic complication. Patients suffering from diabetes mellitus (DM) frequently present with infected DFUs. In this study, a wound healing model on diabetic rat foot was established to mimic the pathophysiology of clinical patients who suffer from DFUs. Our study aimed to explore the localization of human adipose-derived stem cells (hADSCs) and the role of these cells in the repair of foot ulcerated tissue in diabetic rats, and thus to estimate the possibilities of adipose-derived stem cells for diabetic wound therapy...
October 22, 2016: Stem Cell Research & Therapy
Rory J McCrimmon
Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Simone A A Romariz, Daisyléa S Paiva, Layla T Galindo, Gabriela F Barnabé, Vivian A Guedes, Cesario V Borlongan, Beatriz M Longo
AIMS: Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells...
October 21, 2016: CNS Neuroscience & Therapeutics
Hongyu Sun, Jiajia Tang, Yongchao Mou, Jing Zhou, Linlin Qu, Kayla Duval, Zhu Huang, Ning Lin, Ruiwu Dai, Chengxiao Liang, Zi Chen, Lijun Tang, Fuzhou Tian
: Carbon nanotube (CNT)-based hydrogels have been shown to support cardiomyocyte growth and function. However, their role in cellular integrity among cardiomyocytes has not been studied in detail and the mechanisms underlying this process remain unclear. Here, single walled CNTs incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels were utilized to construct cardiac tissues, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, transmission electron microscopy and intracellular calcium transient measurement, the incorporation of CNTs into the scaffolds was observed to markedly enhance the assembly and formation in the cardiac constructs...
October 18, 2016: Acta Biomaterialia
Virve Sihvola, Anna-Liisa Levonen
Reactive oxygen species (ROS) and products of their reactions with cellular macromolecules such as unsaturated fatty acids have been implicated to be important regulators of signalling processes via oxidation or alkylation of redox active thiol residues in target proteins. One of key redox-sensitive signalling proteins mediating the response to oxidant stress is Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1), which is a negative regulator of transcription factor Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and the central hub for sensing endogenous and environmental oxidative and electrophilic stress...
October 18, 2016: Archives of Biochemistry and Biophysics
Chao Ding, Shaopeng Chen, Cunlong Zhang, Guangnan Hu, Wei Zhang, Lulu Li, Yu Zong Chen, Chunyan Tan, Yuyang Jiang
By merging the critical pharmacophore of EGFR/HER2 and HDAC inhibitors into one compound, a novel series of EGFR, HER-2, and HDAC multitarget inhibitors were synthesized. Compounds 9a-l contained 4-anilinoquinazolines with C-6 triazole-linked long alkyl chains of hydroxamic acid and displayed excellent inhibition against these enzymes (compound 9d exhibited the best inhibitory potency on wild-type EGFR, HDAC1, and HDAC6 with IC50 values 0.12nM, 0.72nM and 3.2nM individually). Furthermore, compounds 9b and 9d potently inhibited proliferation of five human cancer cell lines (with IC50 values between 0...
October 10, 2016: Bioorganic & Medicinal Chemistry
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