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https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#1
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29781033/microarray-analysis-of-circular-rna-expression-profiles-associated-with-gemcitabine-resistance-in-pancreatic-cancer-cells
#2
Chao Xu, Yue Yu, Fei Ding
Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29779428/understanding-men-s-elevated-alcohol-use-gender-equity-ideologies-and-intimate-partner-violence-among-married-couples-in-rural-india
#3
Anindita Dasgupta, Jay Silverman, Niranjan Saggurti, Mohan Ghule, Balaiah Donta, Madhusudana Battala, Saritha Nair, Velhal Gajanan, Anita Raj
Qualitative evidence suggests that husbands' inequitable gender equity (GE) ideologies may influence associations between husbands' alcohol use and intimate partner violence (IPV) against wives. However, little quantitative research exists on the subject. To address this gap in the literature, associations of husbands' elevated alcohol use and GE ideologies with wives' reports of IPV victimization among a sample of married couples in Maharashtra, India, were examined. Cross-sectional analyses were conducted using data from the baseline sample of the Counseling Husbands to Achieve Reproductive Health and Marital Equity (CHARM) study...
May 1, 2018: American Journal of Men's Health
https://www.readbyqxmd.com/read/29778928/how-does-binuclear-zinc-amidohydrolase-fwda-work-in-the-initial-step-of-methanogenesis-from-formate-to-formyl-methanofuran
#4
Xue-Wei Zhang, Shi-Lu Chen
The initial step of methanogenesis is the fixation of CO2 to formyl-methanofuran (formyl-MFR) catalyzed by formyl-MFR dehydrogenase, which can be divided into two half reactions. Herein, the second half reaction catalyzed by FwdA (formyl-methanofuran dehydrogenase subunit A), i.e., from formate to formyl-methanofuran, has been investigated using density functional theory and a chemical model based on the X-ray crystal structure. The calculations indicate that, compared with other well-known di-zinc hydrolases, the FwdA reaction employs a reverse mechanism, including the nucleophilic attack of MFR amine on formate carbon leading to a tetrahedral gem-diolate intermediate, two steps of proton transfer from amine to formate moieties assisted by the Asp385, and the CO bond dissociation to form the formyl-MFR product...
May 11, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29775314/qm-mm-simulations-with-the-gaussian-electrostatic-model-a-density-based-polarizable-potential
#5
Hatice Gokcan, Eric Granville Kratz, Thomas A Darden, Jean-Philip Piquemal, Gerardo Andres Cisneros
The use of advanced polarizable potentials in Quantum Mechanical/Molecular Mechanical (QM/MM) simulations have been shown to improve the overall accuracy of the calculation. We have developed a density-based potential called the Gaussian Electrostatic Model (GEM), which has been shown to provide very accurate environments for QM wavefunctions in QM/MM. In this contribution we present a new implementation of QM/GEM that extends our implementation to include all components (Coulomb, exchange-repulsion, polarization, and dispersion) for the total inter-molecular interaction energy in QM/MM calculations, except for the charge-transfer term...
May 18, 2018: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/29775284/multifunctional-tumor-targeting-cathepsin-b-sensitive-gemcitabine-prodrug-covalently-targets-albumin-in-situ-and-improves-cancer-therapy
#6
Huicong Zhang, Zhisu Sun, Kuanglei Wang, Na Li, Hongxiang Chen, Xiao Tan, Lingxiao Li, Zhonggui He, Jin Sun
We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting and site-specific drug release are achieved and such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.
May 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29770981/a-dehydrogenase-dual-hydrogen-abstraction-mechanism-promotes-estrogen-biosynthesis-can-we-expand-the-functional-annotation-of-the-aromatase-enzyme
#7
Angelo Spinello, Matic Pavlin, Lorenzo Casalino, Alessandra Magistrato
Cytochromes P450 (CYP450) are involved in the metabolism of exogenous compounds and in the synthesis of signaling molecules. Among the latter, human aromatase (HA) promotes estrogen biosynthesis, being a key pharmacological target against breast cancers. After decades of debate, the interest in gaining a comprehensive picture of HA catalysis has been renewed by the recent discovery that Compound I (Cpd I) is the reactive species of the peculiar aromatization step. Here, we provide for the first time a complete atomic-level picture of all controversial steps of estrogen biosynthesis...
May 17, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29770847/the-investigation-of-the-survival-time-after-recurrence-in-patients-with-pancreatic-ductal-adenocarcinoma-for-individualization-of-adjuvant-chemotherapy
#8
Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Tadafumi Asaoka, Takehiro Noda, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Masaki Mori, Yuichiro Doki
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease; however, the frequency of recurrence can be reduced if curative surgery following adjuvant chemotherapy is applied. At present, adjuvant chemotherapy is uniformly performed in all patients, as it is unclear which tumor types are controlled best or worst. We investigated patients with recurrence to establish the optimum treatment strategy. METHODS: Of 138 patients who underwent curative surgery for PDAC, 85 developed recurrence...
May 17, 2018: Surgery Today
https://www.readbyqxmd.com/read/29768008/striking-a-balance-between-carbonate-carbamate-linkage-bond-and-reduction-sensitive-disulfide-bond-bearing-linker-for-tailored-controlled-release-in-situ-covalently-albumin-binding-gemcitabine-prodrugs-promote-bioavailability-and-tumor-accumulation
#9
Huicong Zhang, Kuanglei Wang, Kexin Na, Dan Li, Zhenbao Li, Dongyang Zhao, Lu Zhong, Menglin Wang, Longfa Kou, Cong Luo, Haotian Zhang, Qiming Kan, Huaiwei Ding, Zhonggui He, Jin Sun
To address the challenge of rapid enzyme inactivation, poor tumor targeting, acquired drug resistance in gemcitabine (GEM) application, we report two groups of maleimide-functionalised GEM prodrugs conjugating covalently in situ with cys-34 of blood-circulating albumin, resulting in macromolecular prodrugs after intravenous administration. Specially, tailored and accurate controlled release was achieved through different combinations of linkage bonds relatively stable and labile (carbamate and carbonate, respectively) and linkers with or without insertion of a disulfide bond...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767464/platinum-resistant-recurrent-ovarian-cancer-with-long-survival-on-bevacizumab-and-gemcitabine
#10
Shinichi Komiyama, Tsuyoki Kugimiya, Chiaki Takeya, Rena Takahashi, Kaneyuki Kubushiro
Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin...
May 16, 2018: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/29767267/hdac-inhibitors-trichostatin-a-and-valproic-acid-increase-e%C3%A2-cadherin-and-vimentin-expression-but-inhibit-migration-and-invasion-of-cholangiocarcinoma-cells
#11
Joon Ho Wang, Eun Jeoung Lee, Meiying Ji, Seon Mee Park
The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various cancers. E‑cadherin is a cell‑to‑cell adhesion protein, whereas accumulation of vimentin is related to the development of the spindle shape of the mesenchymal cell phenotype. We investigated the EMT phenotypes of human cholangiocellular carcinoma HuCC‑T1, JCK and SNU‑1079 cell lines. To this end, we measured the expression of E‑cadherin or zonula occludens (ZO)‑1 and vimentin, epithelial and mesenchymal cell markers, respectively, using real‑time reverse transcription‑polymerase chain reaction, western blotting, and immunofluorescence microscopy following treatment with trichostatin A (TSA, 200 nM) or valproic acid (VPA, 0...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29766468/gemcitabine-induced-thrombotic-microangiopathy-with-nephrotic-syndrome
#12
Daisuke Katagiri, Fumihiko Hinoshita
We encountered a case of gemcitabine (GEM)-induced secondary thrombotic microangiopathy (TMA) with nephrotic syndrome. Advanced pancreatic cancer with liver metastasis had originally been diagnosed. Renal biopsy showed focal reduplication of the glomerular basement membrane, endothelial cell swelling, and narrowed capillary lumens with fragmented erythrocytes and fibrin deposition, compatible with TMA. Regular monitoring of renal function during GEM treatment and discontinuation of treatment if acute kidney injury (AKI) might occur is crucial, because AKI combined with TMA is life-threatening...
May 15, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29766200/highly-enantioselective-synthesis-of-%C3%AE-tertiary-chiral-amino-acid-derivatives-through-rhodium-catalyzed-asymmetric-arylation-of-cyclic-n-sulfonyl-%C3%AE-ketimino-esters
#13
Zheng Wang, Ming-Hua Xu
By employing an easily available, exceptionally simple sulfur-olefin ligand, a highly enantioselective rhodium-catalyzed arylation of cyclic N-sulfonyl α-ketimino esters with arylboronic acids has been developed. The reaction allows facile access to a wide range of α,α-gem-diaryl substituted chiral amino esters in excellent yields with extremely high enantioselectivities (uniformly 98-99% ee). The synthetic utility of this approach was highlighted by the efficient synthesis of a series of interesting molecules including unique chiral spirocycles bearing 2,3-dihydrobenzofuran and 1H-isoindole skeletons...
May 16, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29763876/mercury-wet-deposition-and-speciated-mercury-air-concentrations-at-rural-and-urban-sites-across-new-york-state-temporal-patterns-sources-and-scavenging-coefficients
#14
Hao Zhou, Chuanlong Zhou, Philip K Hopke, Thomas M Holsen
Measurements of ambient speciated mercury (Hg) concentrations and Hg wet deposition were made at two urban sites (Bronx, NY and Rochester, NY) and one rural site (Potsdam, NY) in New York State in 2013 and 2014 to: 1) determine the factors influencing Hg wet deposition concentrations, 2) identify the contribution of gaseous oxidized Hg (GOM) and particulate bound Hg (PBM) scavenging to Hg wet deposition concentrations, and 3) identify potential source areas associated with high concentration events. The Bronx had the highest mean gaseous elemental Hg (GEM) and GOM concentrations, Rochester had the highest mean PBM and the lowest GOM concentrations, and Potsdam had the lowest mean GEM and PBM concentrations...
May 12, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29753029/inherited-genetic-variants-associated-with-melanoma-braf-nras-subtypes
#15
Nancy E Thomas, Sharon N Edmiston, Irene Orlow, Peter A Kanetsky, Li Luo, David C Gibbs, Eloise A Parrish, Honglin Hao, Klaus J Busam, Bruce K Armstrong, Anne Kricker, Anne E Cust, Hoda Anton-Culver, Stephen B Gruber, Richard P Gallagher, Roberto Zanetti, Stefano Rosso, Lidia Sacchetto, Terence Dwyer, David W Ollila, Colin B Begg, Marianne Berwick, Kathleen Conway
BRAF and NRAS mutations arise early in melanoma development but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features...
May 9, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29752104/antibody-fragment-conjugated-gemcitabine-and-paclitaxel-based-liposome-for-effective-therapeutic-efficacy-in-pancreatic-cancer
#16
Wentao Yang, Qian Hu, Yanmei Xu, Hailang Liu, Lin Zhong
In this study, we have developed an antibody fragment (AF)-conjugated gemcitabine (GEM) and paclitaxel (PTX)-loaded liposome (AF-GPL) to enhance the therapeutic efficacy in pancreatic cancer treatment. The maleimide-thiol chemistry was utilized to conjugate AF on the liposome surface. The dual-drug loaded liposome was nanosized and exhibited a controlled release of both the drugs. Importantly, two drugs have different release pattern over a period of time. The AF-conjugated liposome showed enhanced cellular uptake in pancreatic cancer cells compared to that of non-targeted liposome...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29752079/gemcitabine-loaded-gold-nanospheres-mediated-by-albumin-for-enhanced-anti-tumor-activity-combining-with-ct-imaging
#17
Zhiming Wang, Lina Chen, Zhongyun Chu, Chusen Huang, Yuankui Huang, Nengqin Jia
Currently, the development of a more effective therapy approach overcoming the resistance to chemotherapy for lung cancer still faces great challenges and requires further investigation. Herein, we fabricated gemcitabine (Gem) loaded gold nanospheres mediated by bovine serum albumin (Au@BSA) for the efficient delivery of therapeutic agents into the human pulmonary carcinoma cells (A549) and simultaneous computed tomography (CT) imaging. These nanoparticles (Au@BSA) with an approximate diameter of 10 nm were single crystals and prepared through a protein-directed facile one-pot synthesis via the reduction of chloroauric acid (HAuCl4 ) utilizing bovine serum albumin (BSA) as the stabilizer...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29749486/effects-of-obatoclax-combined-with-gemcitabine-on-the-biological-activity-of-pancreatic-cancer-cells-under-hypoxic-conditions
#18
Xin-Fang Hou, Shuai Li, Chen Wu, Ke Li, Shu-Ning Xu, Ju-Feng Wang
The present study aimed to investigate the effects of obatoclax (OBX) combined with gemcitabine (GEM) treatment on the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) related proteins of pancreatic cancer cell line BxPC‑3 under hypoxic conditions. Protein expression levels of hypoxia‑inducible factor 1α (HIF‑1α) in BxPC‑3 pancreatic cancer cells under normoxic and hypoxic conditions were detected by western blotting. Cells were divided into four groups: Normoxia group, hypoxia group, OBX group and OBX + GEM group...
April 26, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29749405/natural-compound-oblongifolin-c-confers-gemcitabine-resistance-in-pancreatic-cancer-by-downregulating-src-mapk-erk-pathways
#19
Yang Li, Zhichao Xi, Xiaoqiong Chen, Shuangfan Cai, Chen Liang, Zhen Wang, Yingyi Li, Hongsheng Tan, Yuanzhi Lao, Hongxi Xu
Gemcitabine (GEM)-induced drug resistance is the major reason for the failure of chemotherapy in pancreatic cancer (PC). In this study, we found that Oblongifolin C (OC) efficiently inhibited PC cell proliferation by inducing G0/G1 arrest and apoptosis. Also, our mechanism study demonstrated that OC re-sensitized the GEM-resistant PC cells through the ubiquitin-proteasome-dependent degradation of Src, and then downregulating the MAPK pathway. Knockdown of Src plus OC resulted in a greater inhibitory effect in GEM-resistant PC cells...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29747463/thiol-activated-hydrogen-sulfide-donors-antiviral-and-anti-inflammatory-activity-in-respiratory-syncytial-virus-infection
#20
Nikolay Bazhanov, Teodora Ivanciuc, Haotian Wu, Matteo Garofalo, Jianming Kang, Ming Xian, Antonella Casola
We have recently shown that endogenous hydrogen sulfide (H₂S), an important cellular gaseous mediator, exerts an antiviral and anti-inflammatory activity in vitro and in vivo, and that exogenous H₂S delivered via the synthetic H₂S-releasing compound GYY4137 also has similar properties. In this study, we sought to extend our findings to a novel class of H₂S donors, thiol-activated gem-dithiol-based (TAGDDs). In an in vitro model of human respiratory syncytial virus (RSV) infection, TAGDD-1 treatment significantly reduced viral replication, even when added up to six hours after infection...
May 10, 2018: Viruses
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