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https://www.readbyqxmd.com/read/28319295/cytosine-radical-cation-a-gas-phase-study-combining-irmpd-spectroscopy-uv-pd-spectroscopy-ion-molecule-reactions-and-theoretical-calculations
#1
Michael Lesslie, John T Lawler, Andy Dang, Joseph A Korn, Daniel Bim, Vincent Steinmetz, Philippe Maitre, Frantisek Turecek, Victor Ryzhov
The radical cation of cytosine (Cyt*+) was generated via dissociative oxidation from a ternary Cu(II) complex in the gas phase. The radical cation was characterized by infrared multiple photon dissociation (IRMPD) spectroscopy in the fingerprint region, UV-VIS photodissociation (UV-PD), ion-molecule reactions, and theoretical calculations (density functional theory and ab initio). The IRMPD experimental spectrum has diagnostic bands for two enol/amino and two keto/amino tautomers of Cyt*+, that were calculated to be among the lowest-energy isomers in concert with a previous work (J...
March 20, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28318943/synthesis-and-antitumor-evaluation-of-2-3-diarylbenzofuran-derivatives-on-hela-cells
#2
Guo-Xue He, Jing-Mei Yuan, Hai-Miao Zhu, Kai Wei, Ling-Yun Wang, Shi-Lin Kong, Dong-Liang Mo, Cheng-Xue Pan, Gui-Fa Su
2,2-Dihydroxyarylethanones, readily prepared from the commercially available aromatic ethyl ketones, were reacted with resorcinol, 3-methoxyphenol or 2-methoxyphenol in multi steps one-pot manner promoted by trifluoroacetic acid to furnish the 2,3-diarylbenzofuran derivatives in 22-95% yield. Sixteen targeted compounds were synthesized and characterized by (1)H NMR, (13)C NMR and HRMS. MTT assay indicated that most compounds possessed effectively inhibitory activities against the proliferation of HeLa cell...
March 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28301600/the-hdac-inhibitor-sb939-overcomes-resistance-to-bcr-abl-kinase-inhibitors-conferred-by-the-bim-deletion-polymorphism-in-chronic-myeloid-leukemia
#3
Muhammad Rauzan, Charles T H Chuah, Tun Kiat Ko, S Tiong Ong
Chronic myeloid leukemia (CML) treatment has been improved by tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) but various factors can cause TKI resistance in patients with CML. One factor which contributes to TKI resistance is a germline intronic deletion polymorphism in the BCL2-like 11 (BIM) gene which impairs the expression of pro-apoptotic splice isoforms of BIM. SB939 (pracinostat) is a hydroxamic acid based HDAC inhibitor with favorable pharmacokinetic, physicochemical and pharmaceutical properties, and we investigated if this drug could overcome BIM deletion polymorphism-induced TKI resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28300825/cysteine-linked-dimerization-of-bst-2-confers-anoikis-resistance-to-breast-cancer-cells-by-negating-proapoptotic-activities-to-promote-tumor-cell-survival-and-growth
#4
Wadie D Mahauad-Fernandez, Chioma M Okeoma
Almost all breast tumors express the antiviral protein BST-2 with 67%, 25% and 8.2% containing high, medium or low levels of BST-2, respectively. Breast tumor cells and tissues that contain elevated levels of BST-2 are highly aggressive. Suppression of BST-2 expression reprograms tumorigenic properties of cancer cells and diminishes cancer cell aggressiveness. Using structure/function studies, we report that dimerization of BST-2 through cysteine residues located in the BST-2 extracellular domain (ECD), leads to anoikis resistance and cell survival through proteasome-mediated degradation of BIM-a key proapoptotic factor...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28300345/benzimidazole-pyridoimidazole-cored-organic-sensitizers-for-high-performance-dye-sensitized-solar-cells
#5
Sumit Chaurasia, Chun Ting Li, Mulu Berhe Desta, Jen Shyang Ni, Jiann T Lin
A new series of benzimidazole (BIm) based dyes (SC32 and SC33) and pyridoimidazole (PIm) based dyes (SC35 and SC36) were synthesized as the sensitizers for dye-sensitized solar cells. The N-substituent and C-substituent at the BIm and PIm cores was found to be the dominating factor in deciding the electronic properties of the dyes and their DSSCs performance. The efficiency of BIm-based dyes (SC35 and SC36) was found higher than the BIm-based dyes (SC32 and SC33) due to better light harvesting. The C-substituent in SC36, 4-hexylloxybenzene, is beneficial to dark current suppression, and hence SC36 achieves the best efficiency of 7...
March 16, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28294596/the-macrolide-toxin-mycolactone-promotes-bim-dependent-apoptosis-in-buruli-ulcer-through-inhibition-of-mtor
#6
Raphael Bieri, Nicole Scherr, Thérèse Ruf, Jean-Pierre Dangy, Philipp Gersbach, Matthias Gehringer, Karl-Heinz Altmann, Gerd Pluschke
Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, is central to the pathogenesis of the chronic necrotizing skin disease Buruli ulcer (BU). Here we show that mycolactone acts as an inhibitor of the mechanistic Target of Rapamycin (mTOR) signaling pathway by interfering with the assembly of the two distinct mTOR protein complexes mTORC1 and mTORC2, which regulate different cellular processes. Inhibition of the assembly of the rictor containing mTORC2 complex by mycolactone prevents phosphorylation of the serine/threonine protein kinase Akt...
March 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28290615/mir-214-regulates-oral-cancer-kb-cell-apoptosis-through-targeting-rassf5
#7
T K Li, K Yin, Z Chen, Y Bao, S X Zhang
Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (pro-apoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood...
March 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28286738/tsc2-rheb-signaling-mediates-erk-dependent-regulation-of-mtorc1-activity-in-c2c12-myoblasts
#8
Mitsunori Miyazaki, Tohru Takemasa
The enhanced rate of protein synthesis in skeletal muscle cells results in a net increase in total protein content that leads to skeletal muscle growth/hypertrophy. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent regulation of the activity of mechanistic target of rapamycin (mTOR) and subsequent protein synthesis has been suggested as a regulatory mechanism; however, the exact molecular processes underlying such a regulation are poorly defined. The purpose of this study was to investigate regulatory mechanisms involved in the MEK/ERK-dependent pathway leading to mTORC1 activation in skeletal muscle cells...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286052/a-systems-biology-approach-to-overcome-trail-resistance-in-cancer-treatment
#9
REVIEW
Kumar Selvarajoo
Over the last decade, our research team has investigated the dynamic responses and global properties of living cells using systems biology approaches. More specifically, we have developed computational models and statistical techniques to interpret instructive cell signaling and high-throughput transcriptome-wide behaviors of immune, cancer, and embryonic development cells. Here, I will focus on our recent works in overcoming cancer resistance. TRAIL (tumor necrosis factor related apoptosis-inducing ligand), a proinflammatory cytokine, has shown promising success in controlling cancer threat due to its ability to induce apoptosis in cancers specifically, while having limited effect on normal cells...
March 9, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28285685/combination-treatment-with-erlotinib-and-ampelopsin-overcomes-erlotinib-resistance-in-nsclc-cells-via-the-nox2-ros-bim-pathway
#10
Seung-Woo Hong, Nam-Sook Park, Min Hye Noh, Ju A Shim, Byul-Nim Ahn, Yeong Seok Kim, Daejin Kim, Hyun-Kyung Lee, Dae Young Hur
OBJECTIVES: Erlotinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), has been shown to have a dramatic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the presence of primary resistance or acquired resistance to EGFR-TKI is the most common reason for switching to other anti-cancer agents. Even though there are newer agents that have activity in the presence of the T790M mutation, identification of potential agents that could overcome resistance to EGFR-TKI is still needed for the treatment of NSCLC patients...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28277671/enzyme-cleavable-polymeric-micelles-for-the-intracellular-de-livery-of-pro-apoptotic-peptides
#11
Hanna B Kern, Selvi Srinivasan, Anthony J Convertine, David Hockenbery, Oliver W Press, Patrick S Stayton
Peptides derived from the third Bcl-2 homology domain (BH3) renormalize apoptotic signaling by antagonizing pro-survival Bcl-2 family members. They serve as a model for potential peptide drugs that possess therapeutic activities but are limited by delivery barriers including short circulation half-lives and poor penetration into cells. A diblock polymeric micelle carrier for the BIM BH3 peptide was recently described that demonstrated anti-tumor activity in a B-cell lymphoma xenograft model [Berguig et al., Mol Ther, 2015]...
March 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28276530/overcoming-sorafenib-evasion-in-hepatocellular-carcinoma-using-cxcr4-targeted-nanoparticles-to-co-deliver-mek-inhibitors
#12
Yunching Chen, Ya-Chi Liu, Yun-Chieh Sung, Rakesh R Ramjiawan, Ts-Ting Lin, Chih-Chun Chang, Kuo-Shyang Jeng, Chiung-Fang Chang, Chun-Hung Liu, Dong-Yu Gao, Fu-Fei Hsu, Annique M Duyverman, Shuji Kitahara, Peigen Huang, Simona Dima, Irinel Popescu, Keith T Flaherty, Andrew X Zhu, Nabeel Bardeesy, Rakesh K Jain, Cyril H Benes, Dan G Duda
Sorafenib is a RAF inhibitor approved for several cancers, including hepatocellular carcinoma (HCC). Inhibition of RAF kinases can induce a dose-dependent "paradoxical" upregulation of the downstream mitogen-activated protein kinase (MAPK) pathway in cancer cells. It is unknown whether "paradoxical" ERK activation occurs after sorafenib therapy in HCC, and if so, if it impacts the therapeutic efficacy. Here, we demonstrate that RAF inhibition by sorafenib rapidly leads to RAF dimerization and ERK activation in HCCs, which contributes to treatment evasion...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271883/catalytic-addition-of-alcohols-into-carbodiimides-promoted-by-organoactinide-complexes
#13
Heng Liu, Maxim Khononov, Natalia Fridman, Matthias Tamm, Moris S Eisen
The insertion of alcohols into carbodiimides mediated by benzimidazolin-2-iminato actinide complexes [(Bim(R1/R2)N)AnN″3] [N″ = N(SiMe3)2] is presented herein. Analysis of single-crystal data revealed that steric hindrance, rather than electronic properties, plays an important role in determining the accessibility for this insertion process. All actinide complexes showed excellent activities under very mild conditions. Stoichiometric reactions in combination with kinetic and thermodynamic studies allow us to propose a plausible active species and a mechanism for the catalytic cycle...
March 8, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28264627/natural-polyphenolic-inhibitors-against-the-antiapoptotic-bcl-2
#14
Sharad Verma, Aditi Singh, Anchala Kumari, Chetna Tyagi, Sukriti Goyal, Salma Jamal, Abhinav Grover
The apoptotic mechanism is regulated by the BCL-2 family of proteins, such as BCL-2 or Bcl-xL, which block apoptosis while Bad, Bak, Bax, Bid, Bim or Hrk induce apoptosis. The overexpression of BCL-2 was found to be related to the progression of cancer and also providing resistance towards chemotherapeutic treatments. In the present study, we found that all polyphenols (apigenin, fisetin, galangin and luteolin) bind to the hydrophobic groove of BCL-2 and the interaction is stable throughout MD simulation run...
March 6, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28262818/phage-host-interactions-in-streptococcus-thermophilus-genome-analysis-of-phages-isolated-in-uruguay-and-ectopic-spacer-acquisition-in-crispr-array
#15
Rodrigo Achigar, Alfonso H Magadán, Denise M Tremblay, María Julia Pianzzola, Sylvain Moineau
Three cos-type virulent Streptococcus thermophilus phages were isolated from failed mozzarella production in Uruguay. Genome analyses showed that these phages are similar to those isolated elsewhere around the world. The CRISPR1 and CRISPR3 arrays of the three S. thermophilus host strains from Uruguay were also characterized and similarities were noted with previously described model strains SMQ-301, LMD-9 and DGCC7710. Spontaneous bacteriophage-insensitive S. thermophilus mutants (BIMs) were obtained after challenging the phage-sensitive wild-type strain Uy02 with the phage 128 and their CRISPR content was analyzed...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260921/six1-overexpression-predicts-poor-prognosis-and-induces-radioresistance-through-akt-signaling-in-esophageal-squamous-cell-carcinoma
#16
Zheng He, Guang Li, Lingrong Tang, Yaming Li
The Sineoculis homeobox homolog 1 (SIX1) protein has been found to be overexpressed in several human cancers. However, its expression pattern and biological roles in esophageal squamous cell carcinoma (ESCC) remain unexplored. This study examined the clinical significance of SIX1 in 119 ESCC tissues. It was found that SIX1 protein was upregulated in 36.9% (44/119) cases. SIX1 overexpression was an independent predictor for short survival of ESCC patients. siRNA knockdown and plasmid transfection were carried out in ESCC cell lines...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28259821/inhibition-of-mapkinase-pathway-sensitizes-thyroid-cancer-cells-to-abt-737-induced-apoptosis
#17
Viswanath Gunda, Kristopher A Sarosiek, Eran Brauner, Yon Seon Kim, Salma Amin, Zhiheng Zhou, Antony Letai, Sareh Parangi
Bcl2 family proteins play an important role in the resistance of thyroid cancer cells to apoptosis induced by chemotherapeutic drugs and targeted therapies. BH3-profiling of seven fresh primary papillary thyroid cancer (PTC) tumors showed dependence for survival on Bcl-xL (2/7), Bcl2 (2/7), and Mcl-1 (2/7), while the majority of thyroid cell lines were mainly dependent on Bcl-xL. Targeting Bcl2 family proteins with the BH3 mimetic, ABT-737, while simultaneously inhibiting ERK pathway proteins with PLX4720 and PD325901 was shown to induce significantly high apoptosis in the majority of cell lines (8505c, SW1736, HTh7, BCPAP) and moderate apoptosis in the TPC-1 cell line...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28254439/the-microrna-423-3p-bim-axis-promotes-cancer-progression-and-activates-oncogenic-autophagy-in-gastric-cancer
#18
Pengfei Kong, Xiaofeng Zhu, Qirong Geng, Liangping Xia, Xiaowei Sun, Yingbo Chen, Wei Li, Zhiwei Zhou, Youqing Zhan, Dazhi Xu
Human serum microRNAs (miRNAs) have been shown to serve as disease fingerprints for predicting survival of cancer patients. However, the roles of specific miRNAs involved in gastric cancer (GC) are largely unknown. In this study, miRNA profiling was performed on sera obtained from six patients in good- and poor-survival groups. Expression of miR-423-3p was validated by quantitative RT-PCR in another 67 GC serum samples and paired normal and cancerous gastric tissues. Luciferase reporter assays were used to identify the target gene Bcl-2-interacting mediator of cell death (Bim)...
February 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28251705/selenium-supplementation-modulates-apoptotic-processes-in-thyroid-follicular-cells
#19
Immacolata C Nettore, Emma De Nisco, Silvio Desiderio, Carmela Passaro, Luigi Maione, Mariarosaria Negri, Luigi Albano, Rosario Pivonello, Claudia Pivonello, Giuseppe Portella, Paola Ungaro, Annamaria Colao, Paolo E Macchia
Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate...
March 2, 2017: BioFactors
https://www.readbyqxmd.com/read/28249906/nr4a3-suppresses-lymphomagenesis-through-induction-of-pro-apoptotic-genes
#20
Alexander Ja Deutsch, Beate Rinner, Martin Pichler, Katharina Troppan, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Margrethe Krogsdam, Heinz Sill, Gerhard G Thallinger, Hildegard T Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared to vector control and uninduced cells which formed massive tumors...
March 1, 2017: Cancer Research
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