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https://www.readbyqxmd.com/read/28817827/role-of-next-generation-sequencing-as-a-diagnostic-tool-for-the-evaluation-of-bone-and-soft-tissue-tumors
#1
Kinga Szurian, Karl Kashofer, Bernadette Liegl-Atzwanger
Bone and soft-tissue tumors are in general rare. Diagnosing these tumors is challenging based on the significant number of different tumor entities, the rareness of these tumors, and the considerable morphological heterogeneity which can be found within a single tumor entity. Considering that more than half of the described soft-tissue tumors and approximately 25% of the bone tumors harbor recurrent genetic alterations, the use of auxiliary molecular examinations should be strongly considered. Molecular analyses are important to confirm the diagnosis, to guide treatment, to provide information about prognosis, and to allow patient recruitment for basket trials based on the molecular signature of a tumor...
August 18, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28815518/organelle-communication-at-membrane-contact-sites-mcs-from-curiosity-to-center-stage-in-cell-biology-and-biomedical-research
#2
Thomas Simmen, Mitsuo Tagaya
Cell biology has long recognized that organelles can communicate with each other. Initially, such communication was thought to occur primarily via vesicular trafficking between biochemically distinct organelles. However, studies starting in the 1970s on lipid metabolism have unearthed another way how organelles can communicate and have spawned the field of membrane contact sites (MCS). While, initially, MCS had been recognized as fluid entities that mediate lipid and ion transport in an ad hoc manner, more recently MCS have been found to depend on protein-protein interactions that control themselves a variety of MCS functions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28811720/endoscopic-occlusion-with-silicone-spigots-for-the-closure-of-refractory-esophago-bronchiole-fistula-after-esophagectomy
#3
Masaya Uesato, Tsuguaki Kono, Yasunori Akutsu, Kentarou Murakami, Akiko Kagaya, Yorihiko Muto, Akira Nakano, Mizuho Aikawa, Tomohide Tamachi, Hiroyuki Amagai, Takahiro Arasawa, Yasuhide Muto, Hisahiro Matsubara
A 65-year-old man with cT1bN0M0 stage I middle thoracic esophageal cancer underwent subtotal esophagectomy and gastric tube reconstruction through the posterior mediastinal route after preoperative carbon-ion radiotherapy and chemotherapy in a clinical trial. Anastomotic leakage occurred, but it spontaneously improved. At six months after the operation, he was rehospitalized with a cough and dysphagia. An esophago-bronchiole fistula and stenosis of the gastric tube were observed. He first underwent stent placement in the gastric tube...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28810912/inhibition-of-trpm7-suppresses-cell-proliferation-of-colon-adenocarcinoma-in-vitro-and-induces-hypomagnesemia-in-vivo-without-affecting-azoxymethane-induced-early-colon-cancer-in-mice
#4
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, F Kelly Galbraith Kawabata, David Horgen, Toshihiko Kawamori, Reinhold Penner, Andrea Fleig
BACKGROUND: Magnesium (Mg(2+)) is an essential cation implicated in carcinogenesis, solid tumor progression and metastatic potential. The Transient Receptor Potential Melastatin Member 7 (TRPM7) is a divalent ion channel involved in cellular and systemic Mg(2+) homeostasis. Abnormal expression of TRPM7 is found in numerous cancers, including colon, implicating TRPM7 in this process. METHODS: To establish a possible link between systemic magnesium (Mg(2+)) status, the Mg(2+) conducting channel TRPM7 in colon epithelial cells, and colon carcinogenesis, in vitro whole-cell patch clamp electrophysiology, qPCR, and pharmacological tools were used probing human colorectal adenocarcinoma HT-29 as well as normal primary mouse colon epithelial cells...
August 15, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28807675/substantial-protection-against-mptp-associated-parkinson-s-neurotoxicity-in-vitro-and-in-vivo-by-anti-cancer-agent-su4312-via-activation-of-mef2d-and-inhibition-of-mao-b
#5
Baojian Guo, Shengquan Hu, Chengyou Zheng, Hongyu Wang, Fangcheng Luo, Haitao Li, Wei Cui, Xifei Yang, Guozhen Cui, Shinghung Mak, Tony Chung-Lit Choi, Edmond Dik-Lung Ma, Yuqiang Wang, Simon Ming Yuen Lee, Zaijun Zhang, Yifan Han
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28806761/transcriptome-analysis-of-pdgfr%C3%AE-cells-identifies-t-type-ca2-channel-cacna1g-as-a-new-pathological-marker-for-pdgfr%C3%AE-cell-hyperplasia
#6
Se Eun Ha, Moon Young Lee, Masaaki Kurahashi, Lai Wei, Brian G Jorgensen, Chanjae Park, Paul J Park, Doug Redelman, Kent C Sasse, Laren S Becker, Kenton M Sanders, Seungil Ro
Platelet-derived growth factor receptor alpha (PDGFRα)+ cells are distributed into distinct morphological groups within the serosal, muscular, and submucosal layers as well as the myenteric and deep muscular plexi. PDGFRα+ cells directly interact with interstitial cells of Cajal (ICC) and smooth muscle cells (SMC) in gastrointestinal smooth muscle tissue. These three cell types, SMC, ICC, and PDGFRα+ cells (SIP cells), form an electrical syncytium, which dynamically regulates gastrointestinal motility. We have previously reported the transcriptomes of SMC and ICC...
2017: PloS One
https://www.readbyqxmd.com/read/28805809/x-ray-structures-of-endothelin-etb-receptor-bound-to-clinical-antagonist-bosentan-and-its-analog
#7
Wataru Shihoya, Tomohiro Nishizawa, Keitaro Yamashita, Asuka Inoue, Kunio Hirata, Francois Marie Ngako Kadji, Akiko Okuta, Kazutoshi Tani, Junken Aoki, Yoshinori Fujiyoshi, Tomoko Doi, Osamu Nureki
Endothelin receptors (ETRs) have crucial roles in vascular control and are targets for drugs designed to treat circulatory-system diseases and cancer progression. The nonpeptide dual-ETR antagonist bosentan is the first oral drug approved to treat pulmonary arterial hypertension. Here we report crystal structures of human endothelin ETB receptor bound to bosentan and to the ETB-selective analog K-8794, at 3.6-Å and 2.2-Å resolution, respectively. The K-8794-bound structure reveals the detailed water-mediated hydrogen-bonding network at the transmembrane core, which could account for the weak negative allosteric modulation of ETB by Na(+) ions...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28805211/all-atom-md-indicates-ion-dependent-behavior-of-therapeutic-dna-polymer
#8
Ryan L Melvin, William H Gmeiner, Freddie R Salsbury
Understanding the efficacy of and creating delivery mechanisms for therapeutic nucleic acids requires understanding structural and kinetic properties which allow these polymers to promote the death of cancerous cells. One molecule of interest is a 10 mer of FdUMP (5-fluoro-2'-deoxyuridine-5'-O-monophosphate) - also called F10. Here we investigate the structural and kinetic behavior of F10 in intracellular and extracellular solvent conditions along with non-biological conditions that may be efficacious in in vitro preparations of F10 delivery systems...
August 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28800931/molecular-signatures-of-longevity-insights-from-cross-species-comparative-studies
#9
REVIEW
Siming Ma, Vadim N Gladyshev
Much of the current research on longevity focuses on the aging process within a single species. Several molecular players (e.g. IGF1 and MTOR), pharmacological compounds (e.g. rapamycin and metformin), and dietary approaches (e.g. calorie restriction and methionine restriction) have been shown to be important in regulating and modestly extending lifespan in model organisms. On the other hand, natural lifespan varies much more significantly across species. Within mammals alone, maximum lifespan differs more than 100 fold, but the underlying regulatory mechanisms remain poorly understood...
August 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28799592/rapid-determination-of-the-tumour-stroma-ratio-in-squamous-cell-carcinomas-with-desorption-electrospray-ionization-mass-spectrometry-desi-ms-a-proof-of-concept-demonstration
#10
Michael Woolman, Alessandra Tata, Delaram Dara, Jalna Meens, Elisa D'Arcangelo, Consuelo J Perez, Shamina Saiyara Prova, Emma Bluemke, Howard J Ginsberg, Demian Ifa, Alison McGuigan, Laurie Ailles, Arash Zarrine-Afsar
Squamous cell carcinomas constitute a major class of head & neck cancers, where the tumour stroma ratio (TSR) carries prognostic information. Patients affected by stroma-rich tumours exhibit a poor prognosis and a higher chance of relapse. As such, there is a need for a technology platform that allows rapid determination of the tumour stroma ratio. In this work, we provide a proof-of-principle demonstration that Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) can be used to determine tumour stroma ratios...
August 11, 2017: Analyst
https://www.readbyqxmd.com/read/28798096/activation-of-tissue-plasminogen-activator-by-metastasis-inducing-s100p-protein
#11
Christopher Clarke, Stephane R Gross, Thamir M Ismail, Philip S Rudland, Morteta Al-Medhtiy, Michael Santangeli, Roger Barraclough
S100P protein in human breast cancer cells is associated with reduced patient survival and, in a model system of metastasis, it confers a metastatic phenotype upon benign mammary tumour cells. S100P protein possesses a C-terminal lysine residue. Using a multiwell in vitro assay, S100P is now shown for the first time to exhibit a strong, C-terminal-lysine-dependent activation of tissue plasminogen activator (tPA), but not of urokinase-catalysed plasminogen activation.  The presence of 10 mM calcium ions stimulates tPA activation of plasminogen 2-fold in an S100P-dependent manner...
August 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28796828/acid-free-glyoxal-as-a-substitute-of-formalin-for-structural-and-molecular-preservation-in-tissue-samples
#12
Gianni Bussolati, Laura Annaratone, Enrico Berrino, Umberto Miglio, Mara Panero, Marco Cupo, Patrizia Gugliotta, Tiziana Venesio, Anna Sapino, Caterina Marchiò
Tissue fixation in phosphate buffered formalin (PBF) remains the standard procedure in histopathology, since it results in an optimal structural, antigenic and molecular preservation that justifies the pivotal role presently played by diagnoses on PBF-fixed tissues in precision medicine. However, toxicity of formaldehyde causes an environmental concern and may demand substitution of this reagent. Having observed that the reported drawbacks of commercially available glyoxal substitutes of PBF (Prefer, Glyo-fix, Histo-Fix, Histo-CHOICE, and Safe-Fix II) are likely related to their acidity, we have devised a neutral fixative, obtained by removing acids from the dialdehyde glyoxal with an ion-exchange resin...
2017: PloS One
https://www.readbyqxmd.com/read/28795251/5-fluorouracil-induced-mitochondrial-oxidative-cytotoxicity-and-apoptosis-are-increased-in-mcf-7-human-breast-cancer-cells-by-trpv1-channel-activation-but-not-hypericum-perforatum-treatment
#13
Haci Ahmet Deveci, Mustafa Nazıroğlu, Gökhan Nur
5-Fluorouracil (5-FU) is a widely used chemotherapy agent for breast cancer, although drug resistance is a critical issue regarding the use of this agent in the disease. Calcium signaling is a well-known main cause of proliferation and apoptosis in breast cancer cells. Although previous studies have implicated TRPV1 inhibitor, anticancer, and apoptotic roles of Hypericum perforatum (HPer) in several cells, the synergistic inhibition effects of HPer and 5-FU in cancer and the stimulation of ongoing apoptosis have not yet been clarified in MCF-7 cells...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28789518/theranostic-iron-oxide-gold-ion-nanoprobes-for-mr-imaging-and-noninvasive-rf-hyperthermia
#14
Sajid Fazal, Bindhu Paul-Prasanth, Shantikumar V Nair, Deepthy Menon
This work focuses on the development of a nanoparticulate system that can be used for magnetic resonance (MR) imaging and E-field noninvasive radiofrequency (RF) hyperthermia. For this purpose, an amine-functional gold ion complex (GIC), [Au(III)(diethylenetriamine)Cl]Cl2, which generates heat upon RF exposure, was conjugated to carboxyl-functional poly(acrylic acid)-capped iron-oxide nanoparticles (IO-PAA NPs) to form IO-GIC NPs of size ∼100 nm. The multimodal superparamagnetic IO-GIC NPs produced T2-contrast on MR imaging and unlike IO-PAA NPs generated heat on RF exposure...
August 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28783501/high-risk-family-colorectal-cancer-screening-service-in-ireland-critical-review-of-clinical-outcomes
#15
Margaret Walshe, Robert Moran, Marie Boyle, Ion Cretu, Zita Galvin, Victoria Swan, Jason Trikovic, Michael P Farrell, Sinéad Foy, Loretta O'Brien, Jan Leyden, Niall Mulligan, Helen Fenlon, David J Gallagher, Padraic MacMathúna
BACKGROUND: We present the 15-year experience of a family colorectal cancer screening service in Ireland with emphasis on real life experience and outcomes. METHODS: Questionnaires were used to assess family cancer history and assign patients to risk categories; 'Moderate Risk', HNPCC, (suspected) genetic syndrome (non-HNPCC), 'Low Risk'. Screening was by full colonoscopy. We report neoplastic yield, examining effect of risk category, age, gender, and index colonoscopy findings...
August 4, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28783331/discovery-and-synthesis-of-caracolamide-a-an-ion-channel-modulating-dichlorovinylidene-containing-phenethylamide-from-a-panamanian-marine-cyanobacterium-cf-symploca-species
#16
C Benjamin Naman, Jehad Almaliti, Lorene Armstrong, Eduardo J Caro-Díaz, Marsha L Pierce, Evgenia Glukhov, Amanda Fenner, Carmenza Spadafora, Hosana M Debonsi, Pieter C Dorrestein, Thomas F Murray, William H Gerwick
A recent untargeted metabolomics investigation into the chemical profile of 10 organic extracts from cf. Symploca spp. revealed several interesting chemical leads for further natural product drug discovery. Subsequent target-directed isolation efforts with one of these, a Panamanian marine cyanobacterium cf. Symploca sp., yielded a phenethylamide metabolite that terminates in a relatively rare gem-dichlorovinylidene moiety, caracolamide A (1), along with a known isotactic polymethoxy-1-alkene (2). Detailed NMR and HRESIMS analyses were used to determine the structures of these molecules, and compound 1 was confirmed by a three-step synthesis...
August 7, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28782419/generation-of-amber-force-field-parameters-for-zinc-centres-of-m1-and-m17-family-aminopeptidases
#17
Wei Yang, Blake T Riley, Xiangyun Lei, Benjamin T Porebski, Itamar Kass, Ashley M Buckle, Sheena McGowan
The M1 and M17 aminopeptidases are metallo-exopeptidases that rely on the presence of divalent cations, usually zinc, in their active site for proteolytic activity. They are from separate protease superfamilies, however, members often have overlapping substrate specificity. Inhibitors of one or both enzymes can be used to modulate hypertension, reduce proliferation of certain types of cancers and control malaria parasites. Current inhibitors act to chelate the zinc ions in the active site, locking the enzymes in an inactive transition state...
August 6, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28781795/transmembrane-channel-like-protein-8-as-a-potential-biomarker-for-poor-prognosis-of-hepatocellular-carcinoma
#18
Panpan Lu, Qiang Ding, Shuping Ding, Yuhui Fan, Xin Li, Dean Tian, Mei Liu
Hepatocellular carcinoma (HCC) is an aggressive malignant tumor and the third leading cause of cancer-related mortality worldwide. Transmembrane channel-like protein 8 (TMC8) is reported to play a major role in several aspects of human pathophysiology, such as ion channel permeability, human papillomavirus infection and skin cancer; however, its role in HCC has not been fully elucidated. The aim of the present study was to investigate the expression levels of TMC8 in 146 pairs of liver cancer samples and adjacent non-tumorous samples using immunohistochemistry...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28780124/antitumour-activity-of-resveratrol-on-human-melanoma-cells-a-possible-mechanism-related-to-its-interaction-with-malignant-cell-telomerase
#19
Chiara Platella, Serena Guida, Laura Bonmassar, Angelo Aquino, Enzo Bonmassar, Giampiero Ravagnan, Daniela Montesarchio, Giovanni N Roviello, Domenica Musumeci, Maria Pia Fuggetta
BACKGROUND: trans-resveratrol (tRES) is a polyphenolic stilbene found in plant products which has attracted great attention because of its antioxidant, anti-inflammatory and anticancer properties. METHODS: The possible correlation between tRES-induced suppression of melanoma cell growth and its influence on telomerase expression has been investigated by biological assays. Moreover, in order to gain new knowledge about possible mechanisms of action of tRES as antineoplastic agent, its interaction with biologically relevant secondary structure-forming DNA sequences, its aggregation properties and copper-binding activity have been studied by CD, UV and fluorescence spectroscopies...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28779947/gadolinium-based-nanoparticles-as-sensitizing-agents-to-carbon-ions-in-head-and-neck-tumor-cells
#20
Anne-Sophie Wozny, Marie-Thérèse Aloy, Gersende Alphonse, Nicolas Magné, Marc Janier, Olivier Tillement, François Lux, Michael Beuve, Claire Rodriguez-Lafrasse
Hadrontherapy presents the major advantage of improving tumor sterilization while sparing surrounding healthy tissues because of the particular ballistic (Bragg peak) of carbon ions. However, its efficacy is still limited in the most resistant cancers, such as grade III-IV head and neck squamous cell carcinoma (HNSCC), in which the association of carbon ions with gadolinium-based nanoparticles (AGuIX®) could be used as a Trojan horse. We report for the first time the radioenhancing effect of AGuIX® when combined with carbon ion irradiation in human tumor cells...
August 2, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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