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https://www.readbyqxmd.com/read/28734664/ph-responsive-biodegradable-nanogels-for-sustained-release-of-bleomycin
#1
Prashant Sahu, Sushil K Kashaw, Varun Kushwah, Samaresh Sau, Sanyog Jain, Arun K Iyer
Site specific drug delivery with desired therapeutic effect still remains challenging task due to suboptimal release, tissue toxicity, low selectivity and meager therapeutic efficacy in skin cancers. The aim of the current study was to fabricate pH responsive, self-assembled, chemically cross-linked biodegradable chitosan nanogel loaded with bleomycin to target the dermal area of the skin. The nanogel synthesized by ion gelation technique and was characterized for drug loading, swelling and thermal stability followed by in vitro analysis...
June 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28732357/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#2
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731719/discovery-structure-activity-relationship-and-binding-mode-of-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#3
Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen Van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases and inflammation among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high throughput screening (HTS). A co-crystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28731690/the-metal-drives-the-chemistry-dual-functions-of-acireductone-dioxygenase
#4
Aditi R Deshpande, Thomas C Pochapsky, Dagmar Ringe
Acireductone dioxygenase (ARD) from the methionine salvage pathway (MSP) is a unique enzyme that exhibits dual chemistry determined solely by the identity of the divalent transition-metal ion (Fe(2+) or Ni(2+)) in the active site. The Fe(2+)-containing isozyme catalyzes the on-pathway reaction using substrates 1,2-dihydroxy-3-keto-5-methylthiopent-1-ene (acireductone) and dioxygen to generate formate and the ketoacid precursor of methionine, 2-keto-4-methylthiobutyrate, whereas the Ni(2+)-containing isozyme catalyzes an off-pathway shunt with the same substrates, generating methylthiopropionate, carbon monoxide, and formate...
July 21, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28731050/genomic-abnormalities-in-invasive-endocervical-adenocarcinoma-correlate-with-pattern-of-invasion-biologic-and-clinical-implications
#5
Anjelica Hodgson, Yutaka Amemiya, Arun Seth, Matthew Cesari, Bojana Djordjevic, Carlos Parra-Herran
The pattern-based classification system for HPV-related endocervical adenocarcinoma, which classifies tumors based on the destructiveness of stromal invasion, is predictive of the risk of nodal metastases and adverse outcome. Previous studies have demonstrated clinically important molecular alterations in endocervical adenocarcinoma, including KRAS and PIK3CA mutations; however, correlation between the molecular landscape and pathological variables including pattern of invasion has not been thoroughly explored...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730494/deconstructing-the-metabolic-networks-of-oncogenic-signaling-using-targeted-liquid-chromatography-tandem-mass-spectrometry-lc-ms-ms
#6
George Poulogiannis
Metabolic reprogramming is recognized as an emerging hallmark of oncogenic signaling and cancer development. Hence the need to identify novel quantitative analytical platforms for studying metabolism in vitro and in vivo has dramatically increased. Here, we describe the experimental workflow for a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach involving positive/negative ion switching to analyze >250 metabolites of central carbon metabolism, nucleotides, and amino acids.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730303/exhaled-breath-online-measurement-for-cervical-cancer-patients-and-healthy-subjects-by-proton-transfer-reaction-mass-spectrometry
#7
Wenzhao Zhou, Chaoqun Huang, Xue Zou, Yan Lu, Chengyin Shen, Xiping Ding, Hongzhi Wang, Haihe Jiang, Yannan Chu
Cervical cancer is a common cancer among women and has a high morbidity and mortality. The traditional clinical methods for cervical cancer screening are invasive and limited in terms of cost and time. There is an unmet clinical need for new methods to aid clinicians in the rapid screening and auxiliary diagnosis of cervical precancer. Recently, breath analysis has become an attractive approach for investigation of cancer biomarkers and shows great potential in cancer screening owing to its high sensitivity, quickness, and non-invasive nature...
July 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28730229/molecular-analysis-of-brca1-and-brca2-genes-by-next-generation-sequencing-and-ultrastructural-aspects-of-breast-tumor-tissue
#8
Corina Elena Mihalcea, Ana Maria Moroşanu, Daniela Murăraşu, Liliana Puiu, Sabin Aurel Cinca, Silviu Cristian Voinea, Nicolae Mirancea
In this paper, we focus our interest on the dynamics alterations of the tumor-stroma interface at the ultrastructural level and to detect BRCA1 and BRCA2 mutations using next generation sequencing (NGS) of breast tumor tissue. Electron microscopic investigation revealed some peculiar infrastructural alterations of the tumor cells per se as well as of the tumor-stroma interface: invadopodia, shedding microvesicles, altered morphology and reduced number of telocytes, different abnormalities of the microvasculature...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28727901/carbon-ion-radiotherapy-for-isolated-para-aortic-lymph-node-recurrence-from-colorectal-cancer
#9
Yuka Isozaki, Shigeru Yamada, Shohei Kawashiro, Shigeo Yasuda, Naomi Okada, Daniel Ebner, Hiroshi Tsuji, Tadashi Kamada, Hisahiro Matsubara
BACKGROUND: The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively. METHODS: CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)). RESULTS: The median follow-up duration for all patients was 24...
July 20, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28727412/a-novel-host-guest-recognition-assisted-electrochemical-release-its-reusable-sensing-application-based-on-dna-cross-configuration-fueled-target-cycling-and-sdr-amplification
#10
Yuanyuan Chang, Ying Zhuo, Yaqin Chai, Ruo Yuan
In this work, an elegantly designed host-guest recognition-assisted electrochemical release was established and applied in a reusable electrochemical biosensor for the detection of microRNA-182-5p (miRNA-182-5p), a prostate cancer biomarker in prostate cancer, based on the DNA cross configuration-fueled target cycling and strand displacement reaction (SDR) amplification. With such design, the single target miRNA input could be converted to large numbers of single-stranded DNA (S1-Trp and S2-Trp) output which could be trapped by cucurbit[8]uril-methyl viologen (CB-8-MV2+) based on the host-guest recognition, significantly enhancing the sensitivity for miRNA detection...
July 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28726673/off-on-fluorescence-monitoring-of-intracellular-ag-in-single-living-cells-using-an-ag-responsive-probe
#11
Jian Lv, Li-Jun Zhao, Ruo-Can Qian, Yi-Tao Long
Detection of silver ions (Ag+) in living cells has becoming more and more attractive due to the important biological impact of Ag+ on cellular functions. Here, we put forward a new approach to realize the in situ fluorescence imaging and detection of Ag+ in single cells via an ultrasensitive Ag+-responsive probe, 3', 6'-bis (diethylamino)-2-(2-iodoethyl) spiro[isoindoline-1, 9'-xanthen]-3-one (BDISIX). In the presence of Ag+, the fluorescence of the probe can be turned "on", generating strong red fluorescence...
July 20, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#12
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28723646/collagen-type-1-promotes-survival-of-human-breast-cancer-cells-by-overexpressing-kv10-1-potassium-and-orai1-calcium-channels-through-ddr1-dependent-pathway
#13
Mehdi Badaoui, Cloé Mimsy-Julienne, Charles Saby, Laurence Van Gulick, Marta Peretti, Pierre Jeannesson, Hamid Morjani, Halima Ouadid-Ahidouch
Collagen type 1 is among the tumor microenvironment (TM) factors, that regulates proliferation, survival, migration and invasion. Ion channels are key players in interactions between tumor cells and TM. Kv10.1 has been shown to play an essential role in breast cancer cell proliferation and migration by permitting Ca2+ influx notably via Orai1. Here, we show that human breast cancer (BC) cells growing, in culture media completely devoid of the serum and seeded on collagen 1 coating, exhibited less apoptotic rate and a decrease in Bax expression when compared to those grown on plastic...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720769/concentration-dependent-binding-of-small-ligands-to-multiple-saturable-sites-in-membrane-proteins
#14
Letícia Stock, Juliana Hosoume, Werner Treptow
Membrane proteins are primary targets for most therapeutic indications in cancer and neurological diseases, binding over 50% of all known small molecule drugs. Understanding how such ligands impact membrane proteins requires knowledge on the molecular structure of ligand binding, a reasoning that has driven relentless efforts in drug discovery and translational research. Binding of small ligands appears however highly complex involving interaction to multiple transmembrane protein sites featuring single or multiple occupancy states...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718972/enhancement-of-mtor-signaling-contributes-to-acquired-x-ray-and-c-ion-resistance-in-mouse-squamous-carcinoma-cell-line
#15
Katsutoshi Sato, Rikako Azuma, Takashi Imai, Takashi Shimokawa
Our aim was to evaluate whether repetition of C-ion (carbon ion beam) irradiation induces radioresistance as well as repeated X-ray irradiation in cancer cell lines, and to find the key molecular pathway for radioresistance by comparing radioresistant cancer cells with their parental cells. A mouse squamous cell carcinoma cell line, NR-S1, and radioresistant cancer cells, NR-S1-C30 (C30) and NR-S1-X60 (X60) established by repetition of C-ion and X-ray irradiation respectively, were used. X-ray and C-ion sensitivity, changes in lysosome, mitochondria, intracellular ATP and ROS (reactive oxygen species) level, and mTOR (mechanistic target of rapamycin) signaling were evaluated...
July 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28717896/optimization-of-lipid-extraction-and-analytical-protocols-for-uhplc-esi-hrms-based-lipidomic-analysis-of-adherent-mammalian-cancer-cells
#16
Huizhen Zhang, Yue Gao, Jiahong Sun, Shicheng Fan, Xinpeng Yao, Xiaorong Ran, Chuanqi Zheng, Min Huang, Huichang Bi
Lipidomics, which reveals comprehensive characterization of molecular lipids, is a rapidly growing technology used in biomedical research. Lipid extraction is a critical step in lipidomic analysis. However, the effectiveness of different lipid extract solvent systems from cellular samples still remains unclear. In the current study, the protocol of reverse-phase liquid chromatography mass spectrometry (LC/MS)-based lipidomics was optimized for extraction and detection of lipids from human pancreatic cancer cell line PANC-1...
July 17, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28713289/mitochondrial-vdac1-a-key-gatekeeper-as-potential-therapeutic-target
#17
REVIEW
Amadou K S Camara, YiFan Zhou, Po-Chao Wen, Emad Tajkhorshid, Wai-Meng Kwok
Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713156/discovery-of-a-novel-calcium-sensitive-fluorescent-probe-for-%C3%AE-ketoglutarate
#18
Lin-Lin Gan, Lin-Hai Chen, Fa-Jun Nan
α-Ketoglutarate (α-KG), a pivotal metabolite in energy metabolism, has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers. It is recently proposed that plasma α-KG is a surrogate biomarker of NAFLD. Here, we report the development of a novel "turn-on" chemosensor for α-KG that contains a coumarin moiety as a fluorophore. Using benzothiazole-coumarin (BTC) as inspiration, we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for α-KG measurement...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28711857/methotrexate-f127-conjugated-mesoporous-zinc-hydroxyapatite-as-an-efficient-drug-delivery-system-for-overcoming-chemotherapy-resistance-in-osteosarcoma-cells
#19
Azadeh Meshkini, Hamid Oveisi
The resistance of cancer cells to chemotherapeutic agents and the poor selectivity of drugs toward tumor cells are regarded as the main impediments in successful cancer therapy. Currently, the design and fabrication of stimulus-responsive drug delivery systems with high specificity toward cancer cells are gaining increasing attention and they show a promising potential for clinical applications. In this study, mesoporous zinc-substituted hydroxyapatite has been synthesized and served as a drug delivery vehicle owing to its biocompatibility and high drug loading capacity...
July 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28711020/synthesis-structures-nuclease-activity-cytotoxicity-dft-and-molecular-docking-studies-of-two-nitrato-bridged-homodinuclear-cu-cu-zn-zn-complexes-containing-2-2-bipyridine-and-a-chalcone-derivative
#20
Ruchi Gaur, Diksha Kumari Choubey, Mohammad Usman, Benzamin D Ward, Jagat Kumar Roy, Lallan Mishra
Nitrato briged dinuclear complexes of type [Cu2(L)2(bpy)2(NO3)](NO3)·4H2O, 1 and [Zn2(L)2(bpy)2(NO3)](NO3)·4H2O, 2 (L=deprotonated form of free ligand LH, [1-(2-hydroxyphenyl)-3-(9-anthracenyl) propenone; bpy=2,2'bipyridine] are synthesized and characterized using a battery of physicochemical techniques and X-ray crystallography. A distorted square pyramidal geometry is assigned to them with N2O3 coordination core around the metal ion. The co-ligand L binds the metal ions through its O,O' atoms in anti-syn mode...
July 8, 2017: Journal of Photochemistry and Photobiology. B, Biology
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