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https://www.readbyqxmd.com/read/28823141/targeted-therapy-of-ovarian-cancer-including-immune-check-point-inhibitor
#1
Jin Young Kim, Chi Heum Cho, Hong Suk Song
Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects...
August 22, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28821270/calmodulin-like-protein-3-is-an-estrogen-receptor-alpha-coregulator-for-gene-expression-and-drug-response-in-a-snp-estrogen-and-serm-dependent-fashion
#2
Sisi Qin, James N Ingle, Mohan Liu, Jia Yu, D Lawrence Wickerham, Michiaki Kubo, Richard M Weinshilboum, Liewei Wang
BACKGROUND: We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1...
August 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28820388/blockade-of-the-lrp16-pkr-nf-%C3%AE%C2%BAb-signaling-axis-sensitizes-colorectal-carcinoma-cells-to-dna-damaging-cytotoxic-therapy
#3
Xiaolei Li, Zhiqiang Wu, Xiaojing An, Qian Mei, Miaomiao Bai, Leena Hanski, Xiang Li, Tero Ahola, Weidong Han
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies. The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined. Here, we report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKβ, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-κB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820090/description-of-conyzicola-nivalis-sp-nov-isolated-from-glacial-snow-and-emended-description-of-the-genus-conyzicola-and-conyzicola-lurida
#4
Zhengquan Gu, Yongqin Liu, Baiqing Xu, Ninglian Wang, Liang Shen, Hongcan Liu, Yuguang Zhou, Tingting Xing, Bixi Guo, Xiaobo Liu
A cold-tolerant, translucent, yellow-pigmented, Gram-stain-positive, non-motile, rod-shaped bacteria was isolated from snow of the Zadang Glacier on the Tibetan Plateau, PR China. 16S rRNA gene sequence similarity analysis indicated that the isolate was closely related to Conyzicola lurida KCTC 29231T and Leifsonia psychrotolerans DSM 22824T at a level of 97.72 and 97.49 %, respectively. Other close relatives had a 16S rRNA gene sequence similarity of less than 97 %. The major cell-wall amino acid was 2,4-diaminobutyric acid...
August 18, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28818686/methyleugenol-and-selected-oxidative-metabolites-affect-dna-damage-signalling-pathways-and-induce-apoptosis-in-human-colon-tumour-ht29-cells
#5
Isabel Anna Maria Groh, Melanie Esselen
Previously the food carcinogen methyleugenol was found to be cytotoxic and genotoxic in multiple cell lines and in primary hepatocytes. In this study, the question addressed was whether methyleugenol and the selected oxidative metabolites, 1'-hydroxymethyleugenol, methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol trigger a DNA damage response in the human colon carcinoma HT29 cell line. Most notably investigations by flow cytometry revealed that the metabolites induce an accumulation of HT29 cells in the G2 phase of the cell cycle...
August 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28817076/spirulina-maxima-extract-prevents-neurotoxicity-via-promoting-activation-of-bdnf-creb-signaling-pathways-in-neuronal-cells-and-mice
#6
Eun-Jeong Koh, Young-Jin Seo, Jia Choi, Hyeon Yong Lee, Do-Hyung Kang, Kui-Jin Kim, Boo-Yong Lee
Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin (TMT)-induced neurotoxicity in HT-22 cells. SM70EE inhibited the cleavage of poly-ADP ribose polymerase (PARP). Besides, ROS production was decreased by down-regulating oxidative stress-associated enzymes...
August 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28815913/metastatic-triple-negative-breast-cancer-optimizing-treatment-options-new-and-emerging-targeted-therapies
#7
REVIEW
Parham Khosravi-Shahi, Luis Cabezón-Gutiérrez, Sara Custodio-Cabello
Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab...
August 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#8
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In the present study we examined the role of LPA receptors in the regulation of ERK1/2 activity and neuronal survival by the tetracyclic antidepressants mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28812304/management-of-castration-resistant-taxane-resistant-prostate-cancer
#9
Tomasz M Beer
Metastatic castration-resistant prostate cancer that is progressing despite docetaxel chemotherapy is difficult to treat and often aggressive. If not previously used, modern androgen signaling inhibitors have established clinical activity in this setting. Cabazitaxel and radium-223 have also been shown to extend survival in appropriately selected patients. Carboplatin-containing chemotherapy regimens have not been studied in randomized trials with a survival endpoint, but they have demonstrated activity in phase II trials and are occasionally considered in the post-docetaxel setting...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28811867/modulation-of-glutathione-hemostasis-by-inhibition-of-12-15-lipoxygenase-prevents-ros-mediated-cell-death-after-hepatic-ischemia-and-reperfusion
#10
Moritz Drefs, Michael N Thomas, Markus Guba, Martin K Angele, Jens Werner, Marcus Conrad, Christian J Steib, Lesca M Holdt, Joachim Andrassy, Andrej Khandoga, Markus Rentsch
BACKGROUND: Reactive oxygen species- (ROS-) mediated ischemia-reperfusion injury (IRI) detrimentally impacts liver transplantation and resection. 12/15-Lipoxygenase (12/15-LOX), an antagonistic protein of the glutathione peroxidase 4 (GPX4) signaling cascade, was proven to mediate cell death in postischemic cerebral and myocardial tissue. The aim of this study was to investigate the impact of 12/15-LOX inhibition on hepatic IRI. METHODS: Livers of C57BL/6 mice were exposed to 60 minutes of partial warm ischemia and 90 minutes of reperfusion after previous Baicalein administration, an inhibitor of 12/15-LOX...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811596/complete-alanine-scanning-of-the-escherichia-coli-rbsb-ribose-binding-protein-reveals-residues-important-for-chemoreceptor-signaling-and-periplasmic-abundance
#11
Artur Reimer, Vitali Maffenbeier, Manupriyam Dubey, Vladimir Sentchilo, Diogo Tavares, Manuel Hernandez Gil, Siham Beggah, Jan Roelof van der Meer
The Escherichia coli RbsB ribose binding protein has been used as a scaffold for predicting new ligand binding functions through in silico modeling, yet with limited success and reproducibility. In order to possibly improve the success of predictive modeling on RbsB, we study here the influence of individual residues on RbsB-mediated signaling in a near complete library of alanine-substituted RbsB mutants. Among a total of 232 tested mutants, we found 10 which no longer activated GFPmut2 reporter expression in E...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811296/a-novel-d2o-tracer-method-to-quantify-rna-turnover-as-a-biomarker-of-de-novo-ribosomal-biogenesis-in-vitro-in-animal-models-and-in-human-skeletal-muscle
#12
Matthew S Brook, Daniel J Wilkinson, W Kyle Mitchell, Jonathan L Lund, Bethan E Phillips, Nathaniel J Sweczyk, Heikki Kainulainen, Sanna Lensu, Lauren G Koch, Steve L Britton, Paul L Greenhaff, Kenneth Smith, Philip J Atherton
Current methods to quantify RNA dynamics are beset with limitations. Here, we developed a novel stable isotope (D2O)-methodology to quantify RNA synthesis (i.e. ribosomal biogenesis) in cells, animal models, and humans. Firstly, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes (±) 50ng.ml(-1) IGF-1. Secondly, rat quadriceps [untrained n=9; 7-wks interval-"like" training n=13] were collected after ~3-wks D2O (70-Atom%) administration, with body-water enrichment (BWE) monitored via blood sampling...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811071/biological-evaluation-of-2-pyrazolinyl-1-carbothioamide-derivatives-against-hct116-human-colorectal-cancer-cell-lines-and-elucidation-on-qsar-and-molecular-binding-modes
#13
Beom Soo Kim, Soon Young Shin, Seunghyun Ahn, Dongsoo Koh, Young Han Lee, Yoongho Lim
In the search of compounds exhibiting anticancer activity, 37 derivatives of 2-pyrazolinyl-1-carbothioamide were designed and synthesized. Clonogenic cell survival assays were adapted to measure the cytotoxicities of the synthetic derivatives against HCT116 human colon cancer cell lines. Half-maximal cell growth inhibitory concentrations (GI50) ranged from 0.49 to 41.22µM. The compound with the lowest GI50 value, 3-(2-hydroxy-4,5-dimethoxyphenyl)-5-(naphthalen-1-yl)-N-(3,4,5-trimethoxyphenyl)-pyrazolinyl-1-carbothioamide, was subjected to further biological studies, including cell viability and apoptosis assays to examine levels of annexin-V in the outer plasma membrane layer and poly ADP-ribose polymerase cleavage...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28810554/beneficial-effects-of-dried-pomegranate-juice-concentrated-powder-on-ultraviolet-b-induced-skin-photoaging-in-hairless-mice
#14
Su-Jin Kang, Beom-Rak Choi, Seung-Hee Kim, Hae-Yeon Yi, Hye-Rim Park, Chang-Hyun Song, Sae-Kwang Ku, Young-Joon Lee
The present study investigated the anti-aging effects of pomegranate juice concentrated powder (PCP) in hairless mice following 15 weeks of UVB irradiation (three times a week; 0.18 J/cm(2)). Skin moisturizing effects were evaluated through skin water, collagen type I and hyaluronan contents, as well as collagen type I and hyaluronan synthesis-related transcript levels. Wrinkle formation and edema scores (skin weights) were also assessed, along with skin matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13 transcript levels...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809140/planococcus-ruber-sp-nov-isolated-from-a-polluted-farmland-soil-sample
#15
Xu Wang, Zhi Wang, Xueqiu Zhao, Xing Huang, Yu Zhou, Wen-Jun Li
A pale-red-pigmented bacterial strain, designated CW1T, was isolated from a polluted soil sample in China and was characterized by a polyphasic taxonomic approach. Strain CW1T was Gram-stain-positive (or variable), coccoid, motile by a single polar flagellum and non-spore-forming. Growth was observed at 15-37 °C, but not at 10 °C or 40 °C, at pH 5.0-9.0 and with 0-5 % NaCl (w/v). Phylogenetic analysis showed that strain CW1T belongs to the genus Planococcus. The 16S rRNA gene sequence similarities between CW1T and the four most closely related type strains, Planococcus antarcticus DSM 14505T, Planococcus halocryophilus DSM 24743T, Planomicrobium soli XN13T and Planomicrobium okeanokoites NBRC 12536T were 97...
August 15, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28809055/apoptotic-effect-of-astragalin-in-melanoma-skin-cancers-via-activation-of-caspases-and-inhibition-of-sry-related-hmg-box-gene-10
#16
Ok Heui You, Eun Ah Shin, Hyemin Lee, Ju-Ha Kim, Deok Yong Sim, Jung Hyo Kim, Younghwan Kim, Jae-Ho Khil, Nam-In Baek, Sung-Hoon Kim
Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner...
August 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28808400/induction-of-apoptosis-and-cell-cycle-arrest-by-flavokawain-c-on-ht-29-human-colon-adenocarcinoma-via-enhancement-of-reactive-oxygen-species-generation-upregulation-of-p21-p27-and-gadd153-and-inactivation-of-inhibitor-of-apoptosis-proteins
#17
Chung-Weng Phang, Saiful Anuar Karsani, Sri Nurestri Abd Malek
Chalcones have been shown to exhibit anti-cancer properties by targeting multiple molecular pathways. It was, therefore, of interest to investigate flavokawain C (FKC), a naturally occurring chalcone, which can be isolated from Kava (Piper methysticum Forst) root extract. The aim of this study was to investigate the inhibitory effect of FKC on the growth of HT-29 cells and its underlying mechanism of action. Cell viability of HT-29 cells was assessed by Sulforhodamine B assay after FKC treatment. Induction of apoptosis was examined by established morphological and biochemical assays...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808137/regulatory-rnps-a-novel-class-of-ribonucleoproteins-that-potentially-contribute-to-ribosome-heterogeneity
#18
Aaron R Poole, Ian Vicino, Hironori Adachi, Yi-Tao Yu, Michael D Hebert
Many ribonucleoproteins (RNPs), which are comprised of non-coding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP), which contributes to the biogenesis of small nuclear RNPs (snRNPs) that are central components of the spliceosome. Three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here we provide data that these RNAs become part of RNPs we term regulatory RNPs (regRNPs)...
August 14, 2017: Biology Open
https://www.readbyqxmd.com/read/28807785/blocking-the-cd38-cadpr-pathway-plays-a-double-edged-role-in-lps-stimulated-microglia
#19
Yi-Min Wang, Zhi-Yong Liu, Yu-Hang Ai, Li-Na Zhang, Yu Zou, Qian-Yi Peng
Whether the CD38/cyclic ADP-ribose (cADPR) pathway plays a protective or detrimental role in neuroinflammation remains controversial. This study aimed to determine the role of CD38 in neuroinflammation using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and co-cultured Neuro-2a (N2a) cells. In monoculture experiments, BV2 cells were divided into control, CD38 interference (CD38Ri), negative control (NC), LPS, CD38Ri+LPS, NC+LPS and 8-Br-cADPR+LPS groups. In co-culture experiments, N2a cells were co-cultured with BV2 cells for 48h...
August 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28807574/synthesis-and-evaluation-of-analogs-of-5-z-4-amino-2-butenyl-methylamino-5-deoxyadenosine-mdl-73811-or-abeado-an-inhibitor-of-s-adenosylmethionine-decarboxylase-with-antitrypanosomal-activity
#20
Anthony J Brockway, Oleg A Volkov, Casey C Cosner, Karen S MacMillan, Stephen A Wring, Thomas E Richardson, Michael Peel, Margaret A Phillips, Jef K De Brabander
We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood-brain barrier permeation...
August 3, 2017: Bioorganic & Medicinal Chemistry
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