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Hendrik Göddeke, M Hadi Timachi, Cedric A Hutter, Laura Galazzo, Markus A Seeger, Mikko Karttunen, Enrica Bordignon, Lars V Schäfer
ATP-binding cassette (ABC) transporters are ATP-driven molecular machines, in which ATP binding and hydrolysis in the nucleotide-binding domains (NBDs) is chemo-mechanically coupled to large-scale, alternating access conformational changes in the transmembrane domains (TMDs), ultimately leading to the translocation of substrates across biological membranes. The precise nature of the structural dynamics behind the large-scale conformational transition as well as the coupling of NBD and TMD motions is still unresolved...
March 16, 2018: Journal of the American Chemical Society
Radosław Mrówczyński, Artur Jędrzak, Kosma Szutkowski, Bartosz F Grześkowiak, Emerson Coy, Roksana Markiewicz, Teofil Jesionowski, Stefan Jurga
Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-β-cyclodextrin (SH-βCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro...
March 16, 2018: Nanomaterials
Yushu Jin, Yusuke Makida, Tatsuya Uchida, Ryoichi Kuwano
A chemoselective hydrogenation of isoquinoline carbocycles was achieved by using the catalyst prepared from Ru(methallyl)2(cod) and trans-chelate chiral ligand PhTRAP. The unique chemoselectivity achieved in this hydrogenation could be ascribed to the trans-chelation of the chiral ligand. The procedure for preparing the catalyst strongly affects the reproducibility of the carbocycle hydrogenation. Various 5-, 6-, 7-, and 8-substituted isoquinolines were selectively hydrogenated at their carbocycles to afford 5,6,7,8-tetrahydroisoquinolines as major products in high yields with moderate or good enantioselectivities...
March 16, 2018: Journal of Organic Chemistry
Hai-Jun Zhang, Alexander W Schuppe, Shi-Tao Pan, Jin-Xiang Chen, Bo-Ran Wang, Timothy R Newhouse, Liang Yin
A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of ,- and ,-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity and good functional group tolerance. This method is additionally capable of oxidizing ,- and ,-unsaturated aldehydes, ketones, amides, nitriles and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. TMG was found to be crucial in its role as a base, but we also speculate it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst...
March 16, 2018: Journal of the American Chemical Society
Enxiang Zhang, Shutao Yin, Xiaotong Lu, Linhu Ye, Lihong Fan, Hongbo Hu
Glycycoumarin (GCM) is a representative of bioactive coumarin compounds isolated from licorice, an edible and medicinal plant widely used for treating various diseases including liver diseases. The purpose of the present study is to examine the possibility of GCM as a sensitizer to improve the efficacy of BH3 mimetic ABT-737 against liver cancer. Three liver cancer cell lines (HepG2, Huh-7 and SMMC-7721) were used to evaluate the in vitro combinatory effect of ABT-737/GCM. HepG2 xenograft model was employed to assess the in vivo efficacy of ABT-737/GCM combination...
March 15, 2018: Nutrients
Juliane Kupsch, Thomas Jackisch, Klaus E Matzel, Joerg Zimmer, Andreas Schreiber, Anja Sims, Helmut Witzigmann, Sigmar Stelzner
PURPOSE: Severity of anorectal dysfunction after low anterior resection is associated with various patient- and treatment-related factors. We aimed to quantify anorectal dysfunction after treatment for rectal cancer using the low anterior resection syndrome (LARS) score. METHODS: We retrieved from a prospective database 331 eligible patients on whom anterior resection for rectal cancer had been performed from 2000 to 2014. All patients were sent a LARS score accompanied by a supplementary questionnaire...
March 15, 2018: International Journal of Colorectal Disease
Justin Stebbing, Kalpit Shah, Lei Cheng Lit, Teresa Gagliano, Angeliki Ditsiou, Tingting Wang, Franz Wendler, Thomas Simon, Krisztina Sára Szabó, Timothy O'Hanlon, Michael Dean, April Camilla Roslani, Swee Hung Cheah, Soo-Chin Lee, Georgios Giamas
Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment...
March 15, 2018: Oncogene
Jutaek Nam, Sejin Son, Lukasz J Ochyl, Rui Kuai, Anna Schwendeman, James J Moon
Photothermal therapy (PTT) is a promising cancer treatment modality, but PTT generally requires direct access to the source of light irradiation, thus precluding its utility against disseminated, metastatic tumors. Here, we demonstrate that PTT combined with chemotherapy can trigger potent anti-tumor immunity against disseminated tumors. Specifically, we have developed polydopamine-coated spiky gold nanoparticles as a new photothermal agent with extensive photothermal stability and efficiency. Strikingly, a single round of PTT combined with a sub-therapeutic dose of doxorubicin can elicit robust anti-tumor immune responses and eliminate local as well as untreated, distant tumors in >85% of animals bearing CT26 colon carcinoma...
March 14, 2018: Nature Communications
Chia-Yang Hsu, Po-Hong Liu, Shu-Yein Ho, Cheng-Yuan Hsia, Praneeth Kudaravalli, Yun-Hsuan Lee, Yi-You Chiou, Ya-Ju Tsai, Yi-Hsiang Huang, Teh-Ia Huo
BACKGROUND: The nomogram of the Barcelona Clinic Liver Cancer (BCLC) for hepatocellular carcinoma (HCC) has been used for outcome prediction. Patients with BCLC stage C HCC often undergo anti-cancer therapy against current treatment guidelines in real world practice. We aimed to use the nomogram to provide guidance on treatment selection for BCLC stage C patients. METHODS: A total of 1317 patients with stage C HCC were retrospectively analyzed and divided into four groups by nomogram points...
March 14, 2018: BMC Cancer
Jeffrey Bruffaerts, Alexandre Vasseur, Sukhdev Singh, Ahmad Masarwa, Dorian Didier, Liron Oskar, Lionel Perrin, Odile Eisenstein, Ilan Marek
Several approaches using organozirconocene species for the remote cleavage of strained three-membered ring carbocycles are de-scribed. omega-Ene polysubstituted cyclopropanes, alkylidenecyclopropanes, omega-ene spiro[2.2]pentanes and omega-ene cyclopropyl methyl ethers were successfully transformed into stereodefined organometallic intermediates allowing an easy access to highly stereoen-riched acyclic scaffolds in good yields and in most cases excellent selectivities. DFT calculations and isotopic labeling experi-ments were performed to delineate the origin of the obtained chemo- and stereoselectivities, demonstrating the importance of microreversibility...
March 14, 2018: Journal of Organic Chemistry
Luca Malfatti, Plinio Innocenzi
Carbon dots are an emerging class of carbon-based nanostructures produced by low-cost raw materials which exhibit a widely-tunable photoluminescence and a high quantum yield. The potential of these nanomaterials as a substitute of semiconductor quantum dots in optoelectronics and biomedicine is very high, however they need a customized chemistry to be integrated in host-guest systems or functionalized in core-shell structures. This review is focused on recent advances of the sol-gel chemistry applied to the C-dots technology...
March 14, 2018: Chemical Record: An Official Publication of the Chemical Society of Japan ... [et Al.]
Sun-Young Jun, Seung-Mo Hong, Young Kyung Bae, Hee Kyung Kim, Kyu Yun Jang, Dae Woon Eom
Heme oxygenase-1 (HO-1), a stress-response protein, is highly induced in various carcinomas. It is implicated in carcinogenesis and tumor progression. High HO-1 expression is associated with better prognosis of patients with colorectal and gastric cancers. Induction or inhibition of HO-1 can mediate chemo-sensitivity, therefore it might be a therapeutic target to develop anticancer agents. To define the clinicopathological and prognostic significance of HO-1 expression in small-intestinal adenocarcinomas (SIACs), immunohistochemical microarray analysis of HO-1 expression was performed for 191 surgically resected SIAC cases and results were compared with various clinicopathologic variables, including survival...
March 14, 2018: Pathology International
Yaqin Zhang, Yi Yuan, Heming Wu, Zhuoying Xie, Yunong Wu, Xiaomeng Song, Jingjing Wang, Wei Shu, Junyong Xu, Bin Liu, Linzhong Wan, Yanan Yan, Xu Ding, Xinghui Shi, Yongchu Pan, Xiaokang Li, Jianrong Yang, Xiaohui Zhao, Lin Wang
Despite significant advances in therapy, the five-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory, and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear...
March 14, 2018: International Journal of Cancer. Journal International du Cancer
M Stanik, A Poprach, D Macik, I Capak, D Maluskova, N Mareckova, R Lakomy, J Jarkovsky, J Dolezel
Patients with clinically node-positive bladder cancer have a poor prognosis, with many receiving only palliative chemo- therapy. We evaluated oncological results in bladder cancer patients with clinically regional and supraregional lymph- adenopathy treated with induction chemotherapy (IC) and consolidative cystectomy. Twenty-five patients with clinically node-positive bladder cancer (including pelvic and retroperitoneal nodes) were treated with 2-4 cycles of IC followed by consolidative cystectomy between 2010 and 2016...
2018: Neoplasma
Shu-Qi Li, Yu-Huan Jiang, Jin Lin, Jing Zhang, Fan Sun, Qiu-Fang Gao, Lei Zhang, Qing-Gen Chen, Xiao-Zhong Wang, Hou-Qun Ying
Chronic inflammation is one of the critical causes to promote the initiation and metastasis of solid malignancies including lung cancer (LC). Here, we aimed to investigate the prognostic roles of albumin (Alb)-to-fibrinogen (Fib) ratio (AFR), Fib and Alb in LC and to establish a novel effective nomogram combined with AFR. Four hundred twelve LC patients diagnosed between February 2005 and December 2014 were recruited in this prospective study. The prognostic roles of AFR, Fib, Alb, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) were identified by X-tile software, Kaplan-Meier curve, Cox regression model, and time-dependent ROC...
March 13, 2018: Cancer Medicine
Brian Z Ring, Rajmohan Murali, Robert A Soslow, David D L Bowtell, Sian Fereday, Anna DeFazio, Nadia Traficante, Catherine J Kennedy, Alison Brand, Raghwa Sharma, Paul Harnett, Goli Samimi
BACKGROUND: Chemo-resistance is a major challenge in ovarian cancer treatment, resulting in poor survival rates. Identifying markers of treatment response is imperative for improving outcome while minimizing unnecessary side effects. We have previously demonstrated that expression of transducin-like enhancer of split 3 (TLE3) is associated with favorable progression-free survival in taxane-treated ovarian cancer patients with non-serous histology. The purpose of this study was to perform an independent evaluation of the association of TLE3 expression with response to taxane-based chemotherapy in non-serous ovarian cancer, to validate its role as a potential therapeutic response marker for taxane-based chemotherapy...
March 12, 2018: Cancer Epidemiology, Biomarkers & Prevention
Lalit Kumar, P Harish, Prabhat S Malik, S Khurana
Management of cervical cancer has undergone refinement in the past two decades; concurrent chemo-radiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach for patients with locally advanced disease (FIGO stage IIB-IVA). About 30%-40% of such patients fail to achieve complete response; alternative approaches are needed to improve outcome for them. Treatment with bevacizumab (an inhibitor of vascular endothelial growth factor) along with chemotherapy is associated with improved survival in patients with recurrent or metastatic cervical cancer...
February 3, 2018: Current Problems in Cancer
M Koëter, M van Putten, R H A Verhoeven, V E P P Lemmens, G A P Nieuwenhuijzen
BACKGROUND: The aim of our study was to describe treatment patterns and the impact on overall survival among elderly patients (75 years and older) with potentially curable esophageal cancer. MATERIAL AND METHODS: Between 2003 and 2013, 13,244 patients from the nationwide population-based Netherlands Cancer Registry (NCR) were diagnosed with potentially curable esophageal cancer (cT2-3, X, any cN, cM0, X) of which 34% were elderly patients (n = 4501). RESULTS: Surgical treatment with or without neoadjuvant treatment remained stable among elderly patients (around the 16% between 2003 and 2013)...
March 12, 2018: Acta Oncologica
Luisa Bonilla, Amit Oza, Stephanie Lheureux
Epithelial Ovarian Cancer (EOC) is the most lethal gynecological malignancy. EOC outcomes remain unsatisfactory despite aggressive surgical approach, disease chemo-sensitivity and recent introduction of agents targeting angiogenesis and tumour genome instability. Advances in EOC research have allowed for a tailored treatment approach and accelerated development of novel treatments strategies from bench to bed side, anticipated to improve patient outcomes. Areas covered: Comprehensive review of growth factor receptor antagonists for EOC treatment currently in different stages of development was performed...
March 2018: Expert Opinion on Emerging Drugs
Ge Zhang, Aijie Cang, Ying Wang, Yanfei Li, Guoxing Xu, Qian Zhang, Tao Xiong, Qian Zhang
The development of an efficient, straightforward approach for access to a wide range of enantioenriched boron-containing 2,3-disubstituted indolines via highly chemo-, diastereo-, and enantioselective copper-catalyzed intramolecular boraylative cyclization of readily available 2-styrylimines is reported. This reaction proceeds under very mild conditions and displays a high degree of functional group compatibility. The practicability of this approach is demonstrated by a gram-scale reaction and further transformations of the chiral borylated indolines...
March 12, 2018: Organic Letters
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