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https://www.readbyqxmd.com/read/28228362/development-of-mbri-001-a-deuterium-substituted-plinabulin-derivative-as-a-potent-anti-cancer-agent
#1
Zhongpeng Ding, Hejuan Cheng, Shixiao Wang, Yingwei Hou, Jianchun Zhao, Huashi Guan, Wenbao Li
Plinabulin, a drug targeting microtubule of cancer cells, has been currently tried in its phase III clinical study. However, low efficacy caused by poor pharmacokinetic (PK) properties has been considered to be the main obstacle to approved by the Food and Drug Administration. Herein, we introduced a deuterium atom as an isostere in its structure to become a new compound named (MBRI-001, No. 9 in a series of deuterium-substituted compounds). The structure of MBRI-001 was characterized by HRMS, NMR, IR and a single crystal analysis...
February 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28225628/insights-into-the-diels-alder-reaction-between-3-vinylindoles-and-methyleneindolinone-without-and-with-the-assistance-of-hydrogen-bonding-catalyst-bisthiourea-mechanism-origin-of-stereoselectivity-role-of-catalyst
#2
Chao-Xian Yan, Fan Yang, Xing Yang, Da-Gang Zhou, Pan-Pan Zhou
The Diels-Alder reaction between 3-vinylindoles and methyleneindolinone can proceed both with catalyst-free and bisthiourea catalyst, the reaction with bisthiourea is much faster and yields product with even higher stereoselectivity. The reaction mechanisms, origin of stereoselectivity and role of catalyst were elaborated based on quantum mechanical calculations and theoretical methods of reactivity indexes, NCI, QTAIM and distortion/interaction models. In uncatalyzed reaction, the two C-C bonds formed undergo the conversion from noncovalent to covalent bonding via concerted asynchronous mechanism...
February 22, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28225579/intravoxel-incoherent-motion-mri-assessment-of-chemoradiation-induced-pelvic-bone-marrow-changes-in-cervical-cancer-and-correlation-with-hematological-toxicity
#3
Elaine Yuen Phin Lee, Jose Angelo Udal Perucho, Vince Vardhanabhuti, Jian He, Steven Wai Kwan Siu, Siew Fei Ngu, Nina A Mayr, William T C Yuh, Queenie Chan, Pek-Lan Khong
PURPOSE: To investigate bone marrow changes after chemoradiation (CRT) using intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) and correlate imaging changes with hematological toxicity (HT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: Thirty-nine patients with newly diagnosed cervical cancer were prospectively recruited for two sequential 3.0T IVIM-MRI studies: before treatment (MRI-1) and 3-4 weeks after standardized CRT (MRI-2)...
February 22, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28225208/weak-supramolecular-interactions-governing-parallel-and-antiparallel-dna-quadruplexes-insights-from-large-scale-qm-analysis-of-experimentally-derived-models
#4
Yevgen P Yurenko, Jan Novotný, Radek Marek
The topology and energetics of guanine (G) quadruplexes is governed by supramolecular interactions within their strands. In this work, we performed an extensive QM study of supramolecular interactions shaping the stems of (4+0) parallel (P) and (2+2) antiparallel (AP) systems. The large-scale (~ 400 atoms) models of P and AP were constructed from high-quality experimental structures. The results evidence that each of the P and AP structures is shaped by a distinct network of supramolecular interactions. The analysis of electron topological characteristics of H-bonds in P and AP systems indicates that the P model benefits from the stronger intra-tetrad H-bonding...
February 22, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28223426/resistance-mechanism-against-trastuzumab-in-her2-positive-cancer-cells-and-its-negation-by-src-inhibition
#5
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773)...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223140/reduced-cell-viability-and-apoptosis-induction-in-human-thyroid-carcinoma-and-mesothelioma-cells-exposed-to-cidofovir
#6
Simona Catalani, Francesco Palma, Serafina Battistelli, Barbara Nuvoli, Rossella Galati, Serena Benedetti
Besides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment...
February 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#7
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28218720/time-concentration-and-ph-dependent-transport-and-uptake-of-anthocyanins-in-a-human-gastric-epithelial-nci-n87-cell-line
#8
Allison A Atnip, Gregory T Sigurdson, Joshua Bomser, M Mónica Giusti
Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28214288/an-accelerator-mass-spectrometry-enabled-microtracer-study-to-evaluate-the-first-pass-effect-on-the-absorption-of-yh4808
#9
Anhye Kim, Byung-Yong Yu, Stephen R Dueker, Kwang-Hee Shin, Hwa Suk Kim, Hyungmi Ahn, Joo-Youn Cho, Kyung-Sang Yu, In-Jin Jang, Howard Lee
(14) C-labeled YH4808, a novel potassium-competitive acid blocker, was intravenously administered as a microtracer at 80 μg (11.8 kBq or 320 nCi) concomitantly with the non-radiolabeled oral drug at 200 mg to determine the absolute bioavailability and to assess the effect of pharmacogenomics on the oral absorption of YH4808. The absolute bioavailability was low and highly variable (mean, 10.1%; range, 2.3-19.3%), and M3 and M8, active metabolites of YH4808, were formed 22.6- and 38.5-fold higher after oral administration than intravenous administration, respectively...
February 18, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28212901/the-dissociation-of-the-hsp60-pro-caspase-3-complex-by-bis-pyridyl-oxadiazole-copper-complex-cubipyoxa-leads-to-cell-death-in-nci-h292-cancer-cells
#10
Celeste Caruso Bavisotto, Dragana Nikolic, Antonella Marino Gammazza, Rosario Barone, Filippa Lo Cascio, Emanuele Mocciaro, Giovanni Zummo, Everly Conway de Macario, Alberto Jl Macario, Francesco Cappello, Valentina Giacalone, Andrea Pace, Giampaolo Barone, Antonio Palumbo Piccionello, Claudia Campanella
Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)2(H2O)2](ClO4)2, CubipyOXA, a copper-containing compound with cytotoxic properties...
February 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28209610/the-tumor-microenvironment-at-a-turning-point-knowledge-gained-over-the-last-decade-and-challenges-and-opportunities-ahead-a-white-paper-from-the-nci-tme-network
#11
Yves A DeClerck, Kenneth J Pienta, Elisa C Woodhouse, Dinah S Singer, Suresh Mohla
Over the past 10 years, the Tumor Microenvironment Network (TMEN), supported by the NCI (Bethesda, MD), has promoted collaborative research with the explicit goal of fostering multi-institutional and transdisciplinary groups that are capable of addressing complex issues involving the tumor microenvironment. The main goal of the TMEN was to generate novel information about the dynamic complexity of tumor-host interactions in different organ systems with emphasis on using human tissues and supplemented by experimental models...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209594/adolescents-and-young-adults-with-acute-lymphoblastic-leukemia-and-acute-myeloid-leukemia-impact-of-care-at-specialized-cancer-centers-on-survival-outcome
#12
Julie Wolfson, Can-Lan Sun, Laura Wyatt, Wendy Stock, Smita Bhatia
Background: Adolescents and young adults (AYA; 15-39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied.Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group...
February 16, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28208650/dietary%C3%A2-patterns%C3%A2-of%C3%A2-european%C3%A2-children%C3%A2-and%C3%A2-their%C3%A2-parents%C3%A2-in%C3%A2-association%C3%A2-with%C3%A2-family%C3%A2-food%C3%A2-environment-%C3%A2-results%C3%A2-from%C3%A2-the%C3%A2-i-family%C3%A2-study
#13
Antje Hebestreit, Timm Intemann, Alfonso Siani, Stefaan De Henauw, Gabriele Eiben, Yiannis A Kourides, Eva Kovacs, Luis A Moreno, Toomas Veidebaum, Vittorio Krogh, Valeria Pala, Leonie H Bogl, Monica Hunsberger, Claudia Börnhorst, Iris Pigeot
The aim of this study was to determine whether an association exists between children's  and  parental  dietary  patterns  (DP),  and  whether  the  number  of  shared  meals  or  soft  drink  availability  during  meals  strengthens  this  association.  In  2013/2014  the  I.Family  study  cross-sectionally assessed the dietary intakes of families from eight European countries using 24-h  dietary recalls. Usual energy and food intakes from six- to 16-year-old children and their parents  were estimated based on the NCI Method...
February 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28208014/improved-antitumor-efficacy-of-hyaluronic-acid-complexed-paclitaxel-nanoemulsions-in-treating-non-small-cell-lung-cancer
#14
Joo-Eun Kim, Young-Joon Park
Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than 1 µg/mL, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of DL-α-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28205185/use-of-an-alpha-lipoic-methylsulfonylmethane-and-bromelain-dietary-supplement-opera-%C3%A2-for-chemotherapy-induced-peripheral-neuropathy-management-a-prospective-study
#15
Isacco Desideri, Giulio Francolini, Carlotta Becherini, Francesca Terziani, Camilla Delli Paoli, Emanuela Olmetto, Mauro Loi, Marco Perna, Icro Meattini, Vieri Scotti, Daniela Greto, Pierluigi Bonomo, Susanna Sulprizio, Lorenzo Livi
Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA(®) (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA(®) supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28197874/a-dosimetric-comparison-between-cyberknife-and-tomotherapy-treatment-plans-for-single-brain-metastasis
#16
Daniela Greto, Stefania Pallotta, Laura Masi, Cinzia Talamonti, Livia Marrazzo, Raffaella Doro, Calogero Saieva, Silvia Scoccianti, Isacco Desideri, Lorenzo Livi
PURPOSE: Radiosurgery (RS) is a well-established treatment in selected patients with brain metastasis. The aim of this study is to compare the differences between CyberKnife (CK) and TomoTherapy (HT) treatment plans of RS of single brain metastasis (BM) to define when HT should be used in cases beyond Cyberknife-when both systems are readily available for the radiation oncologist. METHODS AND MATERIALS: Nineteen patients with single brain metastasis treated with CK were re-planned for radiosurgery using TomoTherapy Hi-ART system...
February 15, 2017: La Radiologia Medica
https://www.readbyqxmd.com/read/28194370/peptide-agonists-of-vasopressin-v2-receptor-reduce-expression-of-neuroendocrine-markers-and-tumor-growth-in-human-lung-and-prostate-tumor-cells
#17
Marina Pifano, Juan Garona, Carla S Capobianco, Nazareno Gonzalez, Daniel F Alonso, Giselle V Ripoll
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28194306/a-randomized-exploratory-phase-2-study-in-patients-with-chemotherapy-related-peripheral-neuropathy-evaluating-whole-body-vibration-training-as-adjunct-to-an-integrated-program-including-massage-passive-mobilization-and-physical-exercises
#18
Stefan S Schönsteiner, Heidi Bauder Mißbach, Axel Benner, Silja Mack, Thomas Hamel, Michael Orth, Bernhard Landwehrmeyer, Sigurd D Süßmuth, Carolin Geitner, Regine Mayer-Steinacker, Anneliese Riester, Andrea Prokein, Elfriede Erhardt, Jelena Kunecki, Anna M Eisenschink, Rainer Rawer, Hartmut Döhner, Elisabeth Kirchner, Richard F Schlenk
BACKGROUND: Chemotherapy-induced polyneuropathy (CIPN) is a common toxicity after chemotherapy, immunomodulatory drugs or proteasome inhibitors, which is difficult to treat and may also have impact on quality of life. The objective of the study was to evaluate whole-body vibration (WBV) on the background of an integrated program (IP) including massage, passive mobilization and physical exercises on CIPN. PATIENTS AND METHODS: In an exploratory phase-2 study patients with CIPN (NCI CTC grade 2/3) were randomized for WBV plus IP (experimental) to IP alone (standard)...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28192709/tetrazolylmethyl-quinolines-design-docking-studies-synthesis-anticancer-and-antifungal-analyses
#19
Saba Kauser J Shaikh, Ravindra R Kamble, Shilpa M Somagond, H C Devarajegowda, Sheshagiri R Dixit, Shrinivas D Joshi
A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-[(5-benzyl/benzylthio-2H-tetrazol-2-yl) methyl]-2-chloro-6-substituted quinoline 6h-q and 3-[(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl]-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding...
February 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28192510/downregulation-of-sp1-by-minnelide-leads-to-decrease-in-hsp70-and-decrease-in-tumor-burden-of-gastric-cancer
#20
Nivedita Arora, Osama Alsaied, Patricia Dauer, Kaustav Majumder, Shrey Modi, Bhuwan Giri, Vikas Dudeja, Sulagna Banerjee, Daniel Von Hoff, Ashok Saluja
BACKGROUND: Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11...
2017: PloS One
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