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https://www.readbyqxmd.com/read/28526922/advances-in-systemic-therapy-for-metastatic-breast-cancer-future-perspectives
#1
REVIEW
S P Corona, N Sobhani, A Ianza, G Roviello, G Mustacchi, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28526745/identification-and-characterisation-of-nanobodies-targeting-the-epha4-receptor
#2
Lies Schoonaert, Laura Ru Eacute, Bart Roucourt, Mieke Timmers, Susan Little, Luc Iacutea Ch Aacutevez Guti Eacuterrez, Maarten Dewilde, Peter Joyce, Adam Curnock, Peter Weber, Jurgen Haustraete, Gholamreza Hassanzadeh-Ghassabeh, Bart De Strooper, Ludo Van Den Bosch, Philip Van Damme, Robin Lemmens, Wim Robberecht
The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526600/preparation-and-nanoformulation-of-new-quinolone-scaffold-based-anticancer-agents-enhancing-solubility-for-better-cellular-delivery
#3
Nehal H Elghazawy, Amr Hefnawy, Nada K Sedky, Ibrahim M El-Sherbiny, Reem K Arafa
A new series of 5,7-dibromoquinoline scaffold-based derivatives with varied flexibility substituents at position 8 of the ring system has been synthesized as potential anticancer agents. The new compounds were evaluated for their in vitro antiproliferative activity versus the human breast cancer cell lines MCF-7 and MDA-MB231. Generally, both cell lines were responsive to the cytotoxic effect of the synthesized analogues. Compounds 4a, 5c and 7b were chosen for nanoformulation studies to assess the effect of enhancing their solubility profile on their cytotoxic ability...
May 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#4
REVIEW
Jörg Reichrath, Roman Saternus, Thomas Vogt
The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)2D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2D3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)2D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
May 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28525976/the-adaptation-of-colorectal-cancer-cells-when-forming-metastases-in-the-liver-expression-of-associated-genes-and-pathways-in-a-mouse-model
#5
Derya Bocuk, Alexander Wolff, Petra Krause, Gabriela Salinas, Annalen Bleckmann, Christina Hackl, Tim Beissbarth, Sarah Koenig
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver. METHODS: The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28524181/common-pitfalls-in-preclinical-cancer-target-validation
#6
REVIEW
William G Kaelin
An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a 'down' readout (such as decreased proliferation, decreased viability or decreased tumour growth) that could simply reflect a nonspecific loss of cellular fitness...
May 19, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28521686/prothymosin-alpha-an-alarmin-and-more
#7
Pinelopi Samara, Chrysoula-Evangelia Karachaliou, Kyriaki Ioannou, Nikos E Papaioannou, Ioannis F Voutsas, Christos Zikos, Ioannis Pirmettis, Minas Papadopoulos, Hubert Kalbacher, Evangelia Livaniou, Ourania E Tsitsilonis, Wolfgang Voelter
BACKGROUND/OBJECTIVE: Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similarly to molecules termed "alarmins". Our research team pioneered the elucidation of the mechanisms underlying the observed activities of proTα. RESULTS: We were the first to demonstrate that proTα levels increase during normal and abnormal cell proliferation...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28517363/cleave-but-not-leave-astrotactin-proteins-in-development-and-disease
#8
REVIEW
Hao Chang
Over the years, animal studies have identified astrotactins as important membrane proteins for glial-guided neuronal migration during central nervous system development and hair follicle polarity control during skin development. Biochemical studies have revealed intramembrane proteolysis as an important feature of astrotactins. The two fragments of astrotactins remain linked together by a disulfide bond after the proteolytic cleavage. In humans, mutations in astrotactin genes have also been linked to a wide range of diseases, including several developmental brain disorders, neurodegenerative diseases and cancer...
May 18, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28517004/exploitation-of-new-structurally-diverse-d-glucuronamide-containing-n-glycosyl-compounds-synthesis-and-anticancer-potential
#9
Nuno M Xavier, Alexandre Porcheron, Daniela Batista, Radek Jorda, Eva Řezníčková, Vladimír Kryštof, M Conceição Oliveira
The synthesis and anticancer evaluation of novel N-glycosyl derivatives containing N-substituted glucuronamide moieties, as nucleoside analogs or as prospective mimetics of glycosyl phosphates or of nucleotides, is reported. These compounds comprise N-anomerically-linked nucleobases or motifs that are surrogates of a phosphate group, such as sulfonamide or phosphoramidate moieties. 1-Sulfonamido glucuronamides containing N-benzyl, N-propargyl or N-dodecyl carboxamide units were synthesized through glycosylation of methanesulfonamide with tetra-O-acetyl glucuronamides...
May 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28515914/analysis-of-the-function-of-microrna-375-in-humans-using-bioinformatics
#10
Xiaohua Chen, Baoxia Li, Rongcheng Luo, Sina Cai, Cao Zhang, Xiaolong Cao
MicroRNA-375 (miR-375) is expressed at low levels in many types of solid tumor, particularly in gastrointestinal tumors. It is considered to be important in the development of cancer and certain diseases. Thus, more detailed knowledge is required on the particular functions of miR-375. miRs function by regulating target genes. Therefore, in the current study, miRWalk (which includes the data from 10 prediction software programs) was used to predict the target genes of miR-375. The genes, which were co-predicted using five different software programs were further analyzed using Database for Annotation, Visualization and Integrated Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis]...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28515248/systemic-management-of-colorectal-cancer
#11
Wells A Messersmith
Advances have been made in the systemic treatment of colorectal cancer, with approximately 12 chemotherapy or biologic agents approved for use as a single agent or in a combination. However, numerous gaps in our understanding of the disease remain, such as the lack of benefit with biologics in the adjuvant setting, the absence of biomarkers for most systemic therapies, and the reason why left-sided and right-sided tumors behave differently. At the 22nd NCCN Annual Conference, Dr. Wells A. Messersmith presented several impactful updates to the 2017 NCCN Clinical Practice Guidelines in Oncology for Colon Cancer and reviewed the outcomes with a host of therapies used for both early-stage and metastatic disease...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28514874/oncolytic-recombinant-vesicular-stomatitis-virus-vsv-is-nonpathogenic-and-non-transmissible-in-pigs-a-natural-host-of-vsv
#12
Lauro Velazquez-Salinas, Shruthi Naik, Steven Pauszek, Kah-Whye Peng, Stephen J Russell, Luis Rodriguez
Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally causes disease in livestock including horses, cattle and pigs. The two main identified VSV strains are the New Jersey (VSNJV) and Indiana (VSIV) strains. VSV is a rapidly replicating, potently immunogenic virus that has been engineered to develop novel oncolytic therapies for cancer treatment. Swine are a natural host for VSV and provide a relevant and well-established model, amenable to biological sampling to monitor virus shedding and neutralizing antibodies...
May 17, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28513140/hybrid-prodrug-nanoparticles-with-tumor-penetration-and-programmed-drug-activation-for-enhanced-chemo-resistant-cancer-therapy
#13
Caiyan Zhao, Leihou Shao, Jianqing Lu, Xiongwei Deng, Yujia Tong, Yan Wu
Despite nanomedicine has shown great potential for reverse cancer cells resistance, the suboptimal transport across multiple biological obstacles seriously impedes its reaching targets at an efficacious level, which remains the challenging hurdle for clinical success in resistant cancer therapy. Here, a lipid-based hybrid nanoparticle was designed to efficiently deliver the therapeutics to resistant cells and treat resistant cancer in vivo. The hybrid nanoparticles (D-NPs/TET) are composed of a pH-responsive prodrug 1,2-distearoyl-snglycero-3-phosphoethanolamine (DSPE)-doxorubicin (DOX), a efflux inhibitor tetrandrine (TET) and a surfactant 1,2-distearoyl-snglycero-3-phosphoethanolamine-[methoxy (polyethylene glycol)-2000] (DSPE-mPEG2000), which hierarchically combatted the sequential physiological and pathological barriers of drug resistance, exhibited prolonged blood circulation, high tumor accumulation, and deep tumor parenchyma penetration...
May 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28512646/mri-in-glioma-immunotherapy-evidence-pitfalls-and-perspectives
#14
REVIEW
Domenico Aquino, Andrea Gioppo, Gaetano Finocchiaro, Maria Grazia Bruzzone, Valeria Cuccarini
Pseudophenomena, that is, imaging alterations due to therapy rather than tumor evolution, have an important impact on the management of glioma patients and the results of clinical trials. RANO (response assessment in neurooncology) criteria, including conventional MRI (cMRI), addressed the issues of pseudoprogression after radiotherapy and concomitant chemotherapy and pseudoresponse during antiangiogenic therapy of glioblastomas (GBM) and other gliomas. The development of cancer immunotherapy forced the identification of further relevant response criteria, summarized by the iRANO working group in 2015...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28508858/onset-of-meso-scale-turbulence-in-active-nematics
#15
Amin Doostmohammadi, Tyler N Shendruk, Kristian Thijssen, Julia M Yeomans
Meso-scale turbulence is an innate phenomenon, distinct from inertial turbulence, that spontaneously occurs at low Reynolds number in fluidized biological systems. This spatiotemporal disordered flow radically changes nutrient and molecular transport in living fluids and can strongly affect the collective behaviour in prominent biological processes, including biofilm formation, morphogenesis and cancer invasion. Despite its crucial role in such physiological processes, understanding meso-scale turbulence and any relation to classical inertial turbulence remains obscure...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28508845/dosimetric-comparison-of-head-and-neck-cancer-patients-planned-with-multivendor-volumetric-modulated-arc-therapy-technology
#16
Murugesan Kathirvel, Vellaiyan Subramani, V S Subramanian, Shanmugam Thirumalai Swamy, Gandhi Arun, Subramanian Kala
AIM: Purpose of this study is to dosimetrically compare head and neck (H and N) cancer patients planned with multivendor volumetric modulated arc therapy (VMAT) technology. VMAT treatment planning can be done using biological (treatment planning system [TPSB]: Monaco) or physical (TPSP: Eclipse)-based cost function optimization techniques. Planning and dosimetric comparisons were done in both techniques for H and N cases. MATERIALS AND METHODS: Twenty H and N patients were retrospectively selected for this study...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28508372/effect-of-second-hand-tobacco-smoke-on-the-nitration-of-brain-proteins-a-systems-biology-and-bioinformatics-approach
#17
Firas H Kobeissy, Joy Guingab-Cagmat, Adriaan W Bruijnzeel, Mark S Gold, Kevin Wang
Second-hand smoke (SHS) exposure leads to the death of approximately 48,000 nonsmokers per year in the United States alone. SHS exposure has been associated with cardiovascular, respiratory, and neurodegenerative diseases. While cardiac function abnormalities and lung cancer due to SHS have been well characterized, brain injury due to SHS has not undergone a full systematic evaluation. Oxidative stress and nitration have been associated with smoking and SHS exposure. Animal studies suggest that exposure to tobacco smoke increases oxidative stress...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28508298/stability-of-control-networks-in-autonomous-homeostatic-regulation-of-stem-cell-lineages
#18
Natalia L Komarova, P van den Driessche
Design principles of biological networks have been studied extensively in the context of protein-protein interaction networks, metabolic networks, and regulatory (transcriptional) networks. Here we consider regulation networks that occur on larger scales, namely the cell-to-cell signaling networks that connect groups of cells in multicellular organisms. These are the feedback loops that orchestrate the complex dynamics of cell fate decisions and are necessary for the maintenance of homeostasis in stem cell lineages...
May 15, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28508129/development-and-characterization-of-magnetite-poly-butylcyanoacrylate-nanoparticles-for-magnetic-targeted-delivery-of-cancer-drugs
#19
Margarita López-Viota, Mazen M El-Hammadi, Laura Cabeza, José Prados, Consolación Melguizo, M Adolfina Ruiz Martinez, José L Arias, Ángel V Delgado
A great attention is presently paid to the design of drug delivery vehicles based on surface-modified magnetic nanoparticles. They can, in principle, be directed to a desired target area for releasing their drug payload, a process triggered by pH, temperature, radiation, or even magnetic field. To this, the possibility of forming part of diagnostic tools by enhanced magnetic resonance imaging or that of further treatment by magnetic hyperthermia can be added. Bare particles are rapidly eliminated from the bloodstream by the phagocyte mononuclear system, leading to short biological half-life...
May 15, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28507330/flatbed-epi-relief-contrast-cellular-monitoring-system-for-stable-cell-culture
#20
Tatsuya Osaki, Tatsuto Kageyama, Yuka Shimazu, Dina Mysnikova, Shintaro Takahashi, Shinichi Takimoto, Junji Fukuda
Consistent cell preparation is a fundamental preliminary step for understanding complex cellular mechanisms in various cell-based research fields, including basic cell biology, cancer research, and tissue engineering. However, certain elusive factors, such as cellular de-differentiation and contamination with mycoplasma or other types of cells, have compromised the reproducibility and reliability of cell-based approaches. Here, we propose an epi relief-contrast cellular monitoring system (eRC-CMS) that allows images of cells in a typical culture plate to be acquired, stored, and analysed for daily cell quality control...
May 15, 2017: Scientific Reports
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