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https://www.readbyqxmd.com/read/28651237/the-many-postures-of-noncanonical-wnt-signaling-in-development-and-diseases
#1
REVIEW
Qian Xiao, Zhengxi Chen, Xiaozhuang Jin, Runyi Mao, Zhenqi Chen
Wnt signaling regulates many aspects of vertebrate development. Its dysregulation causes developmental defects and diseases including cancer. The signaling can be categorized in two pathways: canonical and noncanonical. Canonical pathway plays a key role in regulating proliferation and differentiation of cells whilst noncanonical Wnt signaling mainly controls cellular polarity and motility. During development, noncanonical Wnt signaling is required for tissue formation. Recent studies have shown that noncanonical Wnt signaling is involved in adult tissue development and cancer progression...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28651144/improved-anticancer-effects-of-albumin-bound-paclitaxel-nanoparticle-via-augmentation-of-epr-effect-and-albumin-protein-interactions-using-s-nitrosated-human-serum-albumin-dimer
#2
Ryo Kinoshita, Yu Ishima, Victor T G Chuang, Hideaki Nakamura, Jun Fang, Hiroshi Watanabe, Taro Shimizu, Keiichiro Okuhira, Tatsuhiro Ishida, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama
In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane(®)). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models...
June 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28651126/tnf-%C3%AE-exerts-cytotoxic-effects-on-multidrug-resistant-breast-cancer-mcf-7-mx-cells-via-a-non-apoptotic-death-pathway
#3
Morteza Ghandadi, Javad Behravan, Khalil Abnous, Melika Ehtesham Gharaee, Fatemeh Mosaffa
Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed. Although, treatment of MCF-7 cells with TNF-α activated NF-kB and caused RIP1 ubiquitination, TNF-α exposure led to JNK and RIP1 phosphorylation in MCF-7/MX cells...
June 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28651088/genetic-and-epigenetic-alterations-in-normal-and-sensitive-copd-diseased-human-bronchial-epithelial-cells-repeatedly-exposed-to-air-pollution-derived-pm2-5
#4
B Leclercq, A Platel, S Antherieu, L Y Alleman, E M Hardy, E Perdrix, N Grova, V Riffault, B M Appenzeller, M Happillon, F Nesslany, P Coddeville, J-M Lo-Guidice, G Garçon
Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface...
June 23, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28651025/invasive-cx43-high-sub-line-of-human-prostate-du145-cells-displays-increased-nanomechanical-deformability
#5
Katarzyna Piwowarczyk, Michał Sarna, Damian Ryszawy, Jarosław Czyż
Connexin(Cx)43(high) cells are preferentially recruited to the invasive front of prostate cancer in vitro and in vivo. To address the involvement of Cx43 in the regulation of human prostate cancer DU145 cell invasiveness, we have analysed the nanoelasticity of invasive Cx43(high) sub-sets of DU145 cells by atomic force microscopy (AFM). The Cx43(high) DU145 cells displayed considerably higher susceptibility to mechanical distortions than the wild type DU145 cells. Transient Cx43 silencing had no effect on their elastic properties...
June 24, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28650865/effect-of-obesity-on-bladder-cancer-and-renal-cell-carcinoma-incidence-and-survival
#6
Philipp Gild, Behfar Ehdaie, Luis A Kluth
PURPOSE OF REVIEW: The prevalence of obesity has risen dramatically in the general population and among cancer survivors in the last three decades. In this review, we highlight the impact of obesity on carcinogenesis and survival with a focus on bladder cancer and renal cell carcinoma (RCC). RECENT FINDINGS: Obesity presents an established risk factor for an up to 1.8-fold relative risk of RCC. Data with regard to bladder cancer are less abundant but support this association as well...
June 24, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28650823/bi-level-and-bi-objective-p-median-type-problems-for-integrative-clustering-application-to-analysis-of-cancer-gene-expression-and-drug-response-data
#7
Anton V Ushakov, Xenia Klimentova, Igor Vasilyev
Recent advances in high-throughput technologies have given rise to collecting large amounts of multidimensional heterogeneous data that provide diverse information on the same biological samples. Integrative analysis of such multisource datasets may reveal new biological insights into complex biological mechanisms and therefore remains an important research field in systems biology. Most of the modern integrative clustering approaches rely on independent analysis of each dataset and consensus clustering, probabilistic or statistical modeling, while flexible distance-based integrative clustering techniques are sparsely covered...
October 27, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28650702/a-case-report-of-methadone-associated-hypoglycemia-in-an-11-month-old-male
#8
Michael S Toce, Margaret A Stefater, David T Breault, Michele M Burns
BACKGROUND: Methadone is a synthetic μ-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence. Overdose can cause miosis, respiratory depression, and central nervous system depression. Rarely, hypoglycemia has been reported. We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. CASE DETAILS: The patient was a previously healthy 11-month-old male who presented in respiratory failure...
June 26, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28650658/a-potent-selective-and-cell-active-protein-arginine-methyltransferase-5-prmt5-inhibitor-developed-by-structure-based-virtual-screening-and-hit-optimization
#9
Ruifeng Mao, Jingwei Shao, Kongkai Zhu, Yuanyuan Zhang, Hong Ding, Chenhua Zhang, Zhe Shi, Hualiang Jiang, De-Qun Sun, Wenhu Duan, Cheng Luo
PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as anti-cancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0...
June 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28650573/factors-associated-with-thromboembolic-events-following-cytoreductive-surgery-and-hyperthermic-intraperitoneal-chemotherapy
#10
Amihai Rottenstreich, Yosef Kalish, Geffen Kleinstern, Almog Ben Yaacov, Joseph Dux, Aviram Nissan
BACKGROUND AND OBJECTIVES: We investigated the risk factors, incidence, and role of thromboprophylaxis in the development of thrombosis following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: We reviewed data of patients with CRS/HIPEC in three hospitals. RESULTS: Overall, 192 patients underwent CRS/HIPEC during 2007-2016. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h before surgery until discharge) was provided for all patients; and 116 (60...
June 26, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28650473/testes-specific-protease-50-promotes-cell-proliferation-via-inhibiting-activin-signaling
#11
Z-B Song, P Wu, J-S Ni, T Liu, C Fan, Y-L Bao, Y Wu, L-G Sun, C-L Yu, Y-X Huang, Y-X Li
Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650469/a-compartmentalized-phosphoinositide-signaling-axis-at-cilia-is-regulated-by-inpp5e-to-maintain-cilia-and-promote-sonic-hedgehog-medulloblastoma
#12
S E Conduit, V Ramaswamy, M Remke, D N Watkins, B J Wainwright, M D Taylor, C A Mitchell, J M Dyson
Sonic Hedgehog (SHH) signaling at primary cilia drives the proliferation and progression of a subset of medulloblastomas, the most common malignant paediatric brain tumor. Severe side effects associated with conventional treatments and resistance to targeted therapies has led to the need for new strategies. SHH signaling is dependent on primary cilia for signal transduction suggesting the potential for cilia destabilizing mechanisms as a therapeutic target. INPP5E is an inositol polyphosphate 5-phosphatase that hydrolyses PtdIns(4,5)P2 and more potently, the phosphoinositide (PI) 3-kinase product PtdIns(3,4,5)P3...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650468/mkp-1-suppresses-parp-1-degradation-to-mediate-cisplatin-resistance
#13
J Wang, D H Kho, J-Y Zhou, R J Davis, G S Wu
Understanding the mechanisms of platinum compound resistance, including cisplatin resistance, has important implications for improving cancer treatments. Previous studies identified a potential role for mitogen-activated protein kinase phosphatase-1 (MKP-1) in cisplatin resistance. This work focuses on the regulation of poly(ADP-ribose) polymerase-1 (PARP-1) expression by MKP-1. We found that MKP-1 overexpression stimulates PARP-1 and poly(ADP-ribose) (PAR) protein expression and cisplatin resistance while its downregulation suppresses PARP-1 and PAR protein expression and cisplatin resistance...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#14
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650464/%C3%AE-catenin-downregulates-dicer-to-promote-ovarian-cancer-metastasis
#15
S K Y To, A S C Mak, Y M Eva Fung, C-M Che, S-S Li, W Deng, B Ru, J Zhang, A S T Wong
Ovarian cancer is a nearly uniform lethal disease and its highly aggressive metastatic phenotype portends a poor prognosis. Lack of a well-controlled, relevant experimental model has been a major obstacle to identifying key molecules causing metastasis. Here we describe the creation of a new isogenic model of spontaneous human ovarian cancer metastasis exhibiting opposite phenotypes-highly metastatic (HM) and non-metastatic (NM)-both in vitro and in vivo. HM was unique in its ability to metastasize consistently to the peritoneum, mimicking the major dissemination route of human ovarian cancer...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650334/expression-of-twist-protein-in-colorectal-carcinoma-and-its-effect-on-proliferation-and-invasion-of-colorectal-cancer-cells
#16
Chuanyao Cheng, Yaguang Qin, Yanhua Li, Jia Pan, Jianjun Wang
This paper aims to study Twist protein expression in colorectal carcinoma and its effect on the proliferation and invasion of colorectal cancer cells, and to explore its specific mechanism of promoting cancer. Tissues of 20 patients and specimens of 20 normal people were examined by colonoscopy biopsy; the Twist mRNA expression level was detected by real-time quantitative PCR; the RNA interference in colorectal carcinoma cell line CT-26 cells was performed by lipid transfection method; the effects of Twist interference on proliferation and invasion of colorectal cancer cells were observed by CCK8 assay and tran swell assay; the mRNA and protein levels of mRNA in CT-26 cells were detected by RT-PCR and Western blot...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28650043/heme-containing-enzymes-and-inhibitors-for-tryptophan-metabolism
#17
REVIEW
Daojing Yan, Ying-Wu Lin, Xiangshi Tan
Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies...
June 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28650030/carbon-nanoscroll-silk-crystallite-hybrid-structures-with-controllable-hydration-and-mechanical-properties
#18
Yuan Cheng, Leng-Duei Koh, Fan Wang, Dechang Li, Baohua Ji, Jingjie Yeo, Guijian Guan, Ming-Yong Han, Yong-Wei Zhang
Hybrid structures of nanomaterials (e.g. tubes, scrolls, threads, cages) and biomaterials (e.g. proteins) hold tremendous potential for applications as drug carriers, biosensors, tissue scaffolds, cancer therapeutic agents, etc. However, in many cases, the interacting forces at the nano-bio interfaces and their roles in controlling the structures and dynamics of nano-bio-hybrid systems are very complicated but poorly understood. In this study, we investigate the structure and mechanical behavior of a protein-based hybrid structure, i...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28649895/the-safety-and-efficacy-of-palbociclib-in-the-treatment-of-metastatic-breast-cancer
#19
Johannes Ettl, Nadia Harbeck
Palbociclib (Ibrance(®)) is the first-in-class CDK4/6 inhibitor which has been introduced into clinical practice for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). It is an orally administered drug, which acts by selectively inhibiting cyclin-dependant kinases CDK4 and CDK6. Given together with anti-estrogens like letrozole and fulvestrant it enhances the antiproliferative effect of these drugs without compromising the favorable toxicity profile of endocrine therapy...
June 26, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28649661/inflammatory-breast-cancer-a-model-for-investigating-cluster-based-dissemination
#20
Mohit Kumar Jolly, Marcelo Boareto, Bisrat G Debeb, Nicola Aceto, Mary C Farach-Carson, Wendy A Woodward, Herbert Levine
Metastases claim more than 90% of cancer-related patient deaths and are usually seeded by a subset of circulating tumor cells shed off from the primary tumor. In circulation, circulating tumor cells are found both as single cells and as clusters of cells. The clusters of circulating tumor cells, although many fewer in number, possess much higher metastatic potential as compared to that of individual circulating tumor cells. In this review, we highlight recent insights into molecular mechanisms that can enable the formation of these clusters-(a) hybrid epithelial/mesenchymal phenotype of cells that couples their ability to migrate and adhere, and (b) intercellular communication that can spatially coordinate the cluster formation and provide survival signals to cancer cells...
2017: NPJ Breast Cancer
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