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Endosomal cancer

Soumyalekshmi Nair, Kai Dun Tang, Liz Kenny, Chamindie Punyadeera
Over the past decade, there has been emerging research in the field of extracellular vesicles, especially those originating from endosomes, referred to as 'exosomes. Exosomes are membrane-bound nanovesicles secreted by most cell types upon fusion of multivesicular bodies (MVBs) to the cell plasma membrane. These vesicles are present in almost all body fluids such as blood, urine, saliva, breast milk, cerebrospinal and peritoneal fluids. Exosomes participate in intercellular communication by transferring the biologically active molecules like proteins, nucleic acids, and lipids to neighboring cells...
September 2018: Oral Oncology
Vasiliki Panou, Meghana Gadiraju, Arthur Wolin, Caroline M Weipert, Emily Skarda, Aliya N Husain, Jyoti D Patel, Buerkley Rose, Shannon R Zhang, Madison Weatherly, Viswateja Nelakuditi, Amy Knight Johnson, Maria Helgeson, David Fischer, Arpita Desai, Nanna Sulai, Lauren Ritterhouse, Oluf D Røe, Kiran K Turaga, Dezheng Huo, Jeremy Segal, Sabah Kadri, Zejuan Li, Hedy L Kindler, Jane E Churpek
Purpose The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM). Methods We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM. Results Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%)...
August 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
John R Veloria, Luxi Chen, Lin Li, Gail A M Breen, Jiyong Lee, Warren J Goux
The goal of this study was to develop a peptide which could use the toxic effects of amyloid, a substance which is the hallmark of over 25 known human diseases, to selectively kill cancer cells. Here we demonstrate that two separate amyloid-forming hexapeptides, one from the microtubule associated protein Tau involved in formation of paired helical filaments of Alzheimer's disease, and the other an amyloid forming sequence from apolipoprotein A1 , when conjugated to a cell penetrating peptide (CPP) sequence, form toxic oligomers which are stable for up to 14 h and able to enter cells by a combination of endocytosis and transduction...
January 1, 2018: MedChemComm
Feng Qiu, Kyle W Becker, Frances C Knight, Jessalyn J Baljon, Sema Sevimli, Daniel Shae, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Cancer vaccines targeting patient-specific tumor neoantigens have recently emerged as a promising component of the rapidly expanding immunotherapeutic armamentarium. However, neoantigenic peptides typically elicit weak CD8+ T cell responses, and so there is a need for universally applicable vaccine delivery strategies to enhance the immunogenicity of these peptides. Ideally, such vaccines could also be rapidly fabricated using chemically synthesized peptide antigens customized to an individual patient. Here, we describe a strategy for simple and rapid packaging of peptide antigens into pH-responsive nanoparticles with endosomal escape activity...
July 30, 2018: Biomaterials
Sungjin Kim, Anuj K Sharma, Olena K Vatamaniuk
The chronic exposure of humans to toxic metals such as cadmium from food and air causes dysfunction of vital organs, neurodegenerative conditions, and cancer. In this regard, members of the ABCB sub-family of the ATP-binding cassette (ABC) transporter superfamily, ABCB6/HMT-1, are acutely required for the detoxification of heavy metals and are present in genomes of many organisms including the nematode worm, Caenorhabditis elegans and humans. We showed previously that C. elegans ABCB6/HMT-1 detoxifies cadmium, copper, and arsenic, and is expressed in liver-like cells, the coelomocytes, head neurons and intestinal cells, which are the cell types that are affected by heavy metal poisoning in humans...
2018: Frontiers in Physiology
Giusi Caldieri, Maria Grazia Malabarba, Pier Paolo Di Fiore, Sara Sigismund
Signaling from the epidermal growth factor receptor (EGFR) elicits multiple biological responses, including cell proliferation, migration, and survival. Receptor endocytosis and trafficking are critical physiological processes that control the strength, duration, diversification, and spatial restriction of EGFR signaling through multiple mechanisms, which we review in this chapter. These mechanisms include: (i) regulation of receptor density and activation at the cell surface; (ii) concentration of receptors into distinct nascent endocytic structures; (iii) commitment of the receptor to different endocytic routes; (iv) endosomal sorting and postendocytic trafficking of the receptor through distinct pathways, and (v) recycling to restricted regions of the cell surface...
2018: Progress in Molecular and Subcellular Biology
Maria Podinovskaia, Anne Spang
Endocytosis is a means for the cell to sample its environment for nutrients and regulate plasma membrane (PM) composition and area. Whereas the majority of internalized cargo is recycled back to the cell surface, select material is sent to the lysosome for degradation. Endosomes further play major roles in central cell activities as diverse as establishment of cell polarity and signaling, lysosomal storage and immunity. The complexity of endosomal functions is reflected by the extensive changes to endosome properties as they mature...
2018: Progress in Molecular and Subcellular Biology
Sonal Deshpande, Smita Patil, Neetu Singh
Polo-like-kinase 1 (PLK1), which is a serine-threonine protein kinase overexpressed in cancer cells, is known to regulate tumor growth and have recently gathered attention as a target gene for RNA interference because of the poor bioavailability and nonspecificity of the available inhibitors. However, the lower transfection efficiency of siRNA and its poor stability in biological mileu necessitate the need of efficient siRNA delivery systems. Here, we report efficacious polymeric nanoparticles for the delivery of PLK1 siRNA in mammalian cancer cells...
July 31, 2018: ACS Omega
Xi Yang, Bo Fan, Wei Gao, Liping Li, Tingting Li, Jinghua Sun, Xiaoyang Peng, Xiaoyan Li, Zhenjun Wang, Binquan Wang, Ruiping Zhang, Jun Xie
Background: Effective endosomal escape is still a critical bottleneck for intracellular delivery of small interfering RNAs (siRNAs) to maximize their therapeutic efficacy. To overcome this obstacle, we have developed a photothermally triggered system by using the near-infrared (NIR) irradiation to achieve "on-demand" endosomal escape and subsequent siRNA release into cytoplasm. Materials and methods: Herein, the poly-L-lysine (PLL) was successfully conjugated with melanin to obtain melanin-poly-L-lysine (M-PLL) polymer as a siRNA vehicle...
2018: International Journal of Nanomedicine
Yang Song, Xu Yan, Grayson Ostermeyer, Suiqiong Li, Ling-Bo Qu, Dan Du, Zhaohui Li, Yuehe Lin
Intracellular miRNA detection is vital important for diagnosing severe diseases like cancer and for resolving the ensemble of gene products that orchestrate the living state of cells. Recent advances in the design, synthesis and application of biocompatible nanomaterials as platforms for probing miRNAs have enabled widespread efforts to mobilize new compounds in biomedical research. 2D graphene-like nanomaterials exhibit desirable physical properties such as convenient quantum size and dynamic interface functionality...
August 6, 2018: Analytical Chemistry
Jing Xu, Robert Camfield, Sharon M Gorski
The eukaryotic endomembrane system is a complex series of interconnected membranous organelles that play important roles in responding to stress and maintaining cell homeostasis during health and disease. Two components of this system, exosome biogenesis and autophagy, are linked by the endolysosomal pathway. Exosomes are cargo-laden extracellular vesicles that arise from endosome-derived multivesicular bodies, and autophagy is a lysosomal-dependent degradation and recycling pathway. Recent studies have revealed shared molecular machinery between exosome biogenesis and autophagy, as well as substantial crosstalk between these two processes...
August 3, 2018: Journal of Cell Science
Wayne Stallaert, Yannick Brüggemann, Ola Sabet, Lisa Baak, Marina Gattiglio, Philippe I H Bastiaens
The ability of cells to adapt their response to growth factors in relation to their environment is an essential aspect of tissue development and homeostasis. We found that signaling mediated by the Eph family of receptor tyrosine kinases from cell-cell contacts changed the cellular response to the growth factor EGF by modulating the vesicular trafficking of its receptor, EGFR. Eph receptor activation trapped EGFR in Rab5-positive early endosomes by inhibiting Akt-dependent vesicular recycling. By altering the spatial distribution of EGFR activity, EGF-promoted Akt signaling from the plasma membrane was suppressed, thereby inhibiting cell migration...
July 31, 2018: Science Signaling
Sanaa Ben Djemaa, Stephanie David, Katel Hervé-Aubert, Annarita Falanga, Stefania Galdiero, Emilie Allard-Vannier, Igor Chourpa, Emilie Munnier
The development of an efficient small interfering RNA (siRNA) delivery system has held scientists interest since the discovery of the RNA interference mechanism (RNAi). This strategy gives hope for the treatment of many severe diseases. Herein, we developed hybrid nanovectors able to deliver siRNA to triple negative breast cancer cells. The nanovectors are based on PEGylated superparamagnetic iron oxide nanoparticles (SPION) functionalized with gH625 peptide, chitosan and poly-L-arginine. Every component has a key role and specific function: SPION is the core scaffolding the nanovector; PEG participates in the colloidal stability and the immune stealthiness; gH625 peptide promotes the nanovector internalization into cancer cells; cationic polymers provide the siRNA protection and favor siRNA endosomal escape and delivery to cytosol...
July 28, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Thipapun Plyduang, Ana Armiñán, Julie Movellan, Richard M England, Ruedeekorn Wiwattanapatapee, María J Vicent
The high incidence of prostate carcinogenesis has prompted the search for novel effective treatment approaches. We have employed curcumin (Curc) and diethylstilbestrol (DES) to synthesize a series of polyacetal (PA)-based combination conjugates for prostate cancer (PCa) treatment. Given their bihydroxyl functionalities, Curc and DES molecules were incorporated into a PA mainchain using a one-pot reaction between diols and divinyl ethers. The PA-conjugates released both drugs under acidic conditions, such as those found in the tumor microenvironment, endosomes, or lysosomes, while remaining stable at neutral pH 7...
July 30, 2018: Macromolecular Rapid Communications
S Jiang, C Hu, P Liu, M Lu
Exosomes are endosomes secreted from the membrane by exocytosis as multivesicular bodies and are generally defined by their spherical, unilamellar morphology, size and the expression of specific biomarkers used for diagnosis or therapy targets. Recent research has reported a higher relationship between exosome enrichment and tumor disease development. In this review, we discuss exosome intercellular communication and functions in the pathology of disease, especially on the cancer metastasis related with exosome...
July 26, 2018: Clinical & Translational Oncology
Xiaowei Gong, Yuliia Didan, John G Lock, Staffan Strömblad
Membrane blebbing-dependent (blebby) amoeboid migration can be employed by lymphoid and cancer cells to invade 3D-environments. Here, we reveal a mechanism by which the small GTPase RhoB controls membrane blebbing and blebby amoeboid migration. Interestingly, while all three Rho isoforms (RhoA, RhoB and RhoC) regulated amoeboid migration, each controlled motility in a distinct manner. In particular, RhoB depletion blocked membrane blebbing in ALL (acute lymphoblastic leukaemia), melanoma and lung cancer cells as well as ALL cell amoeboid migration in 3D-collagen, while RhoB overexpression enhanced blebbing and 3D-collagen migration in a manner dependent on its plasma membrane localization and down-stream effectors ROCK and Myosin II RhoB localization was controlled by endosomal trafficking, being internalized via Rab5 vesicles and then trafficked either to late endosomes/lysosomes or to Rab11-positive recycling endosomes, as regulated by KIF13A...
July 26, 2018: EMBO Journal
Toshihiko Tashima
Cancer is one of the major causes of death globally. The current treatment options are insufficient, leading to unmet medical needs in cancer treatment. Off-target side effects, multidrug resistance, selective distribution to cancerous tissues, and cell membrane permeation of anti-cancer agents are critical problems to overcome. There is a method to solve these problems by using receptor-mediated endocytosis (RME). It is well known that proteins such as integrin, HER2, EGFR, or other cancer biomarkers are specifically overexpressed on the surface of target cancer cells...
July 11, 2018: Bioorganic & Medicinal Chemistry Letters
Ryou-U Takahashi, Marta Prieto-Vila, Isaku Kohama, Takahiro Ochiya
MicroRNAs(miRNAs)are small non-coding RNAs that function in diverse biological processes and are approximately 20-22 nucleotide RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. A number of studies report that miRNAs are involved in homeostatic maintenance such as cell cycle regulation, cell division and apoptosis, and that aberrant expression of miRNAs is often detected in various types of diseases, including cancer. In cancer biology, miRNAs play functional roles in tumor seeding, drug sensitivity, and metastasis...
June 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Beatrix Peter, Istvan Lagzi, Satoshi Teraji, Hideyuki Nakanishi, Laszlo Cervenak, Dániel Zámbó, András Deák, Kinga Molnár, Monika Truszka, Inna Szekacs, Robert Horvath
Functionalized nanoparticles (NPs) can penetrate into living cells and vesicles, opening up an extensive range of novel directions. For example, NPs are intensively employed in targeted drug delivery and biomedical imaging. However, the real-time kinetics and dynamics of NP-living cell interactions remained uncovered. In this study, we in situ monitored the cellular uptake of gold NPs-functionalized with positively charged alkaline thiol-into surface-adhered cancer cells, by using a high-throughput label-free optical biosensor employing resonant waveguide gratings...
July 31, 2018: ACS Applied Materials & Interfaces
Scott Shaw, Wenqi Liu, César Fernando Azael Gómez Durán, Cynthia Schreiber, María de Lourdes Betancourt Mendiola, Canjia Zhai, Felicia Roland, Simon Padanilam, Bradley D Smith
Fluorescent molecular probes were prepared by a programmed non-covalent pre-assembly process that used a near-infrared fluorescent squaraine dye to thread a macrocycle bearing a cancer targeting unit. Cell microscopy studies using OVCAR-4 (ovarian cancer) and A549 (lung cancer) cells that express high levels of the integrin αvβ3 or αvβ5 receptors, respectively, revealed a multivalent cell targeting effect. That is, there was comparatively more cell uptake of a pre-assembled probe equipped with two copies of the cRGDfK antagonist than a pre-assembled probe with only one appended cRGDfK antagonist...
July 18, 2018: Chemistry: a European Journal
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