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https://www.readbyqxmd.com/read/28813782/urea-cycle-pathway-targeted-therapeutic-action-of-naringin-against-ammonium-chloride-induced-hyperammonemic-rats
#1
Arumugam Ramakrishnan, Natesan Vijayakumar
Ammonia is a well-known neurotoxin that causes liver disease and urea cycle disorder. Excessive ammonia content in the blood leads to hyperammonemic condition and affects both excitatory and inhibitory neurotransmission including brain edema and coma. Naringin, a plant bioflavonoid present in various citrus fruits and mainly extracted from the grape fruit. This study was designed to assess the protective effect of naringin on ammonium chloride (NH4Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitoneal injections (i...
August 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28813743/combined-melanocytic-nevus-superficial-congenital-and-deep-penetrating-types-with-fibroepithelioma-of-pinkus-collision-tumor-a-case-report
#2
Ashwyna Sunassee, Amy M Kerkvliet, Ali D Jassim
We present a case of collision tumor composed of a combined melanocytic nevus with superficial congenital and deep penetrating components and a fibroepithelioma of Pinkus on the left lumbar back of a 21-year-old male. He presented to the dermatologist for evaluation of numerous moles, and the lesion in question was described as a brown variegated papule with slightly irregular shape and irregular borders. This case is being reported as it is very unusual to see a fibroepithelioma of Pinkus in conjunction with a melanocytic lesion...
August 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28813706/carts-for-solid-tumors-feasible-or-infeasible
#3
Wei Li, Xiujun Song, Yanwen Jin, Fengsheng Li, Huijie Yu, Cheng Cao, Qisheng Jiang
No abstract text is available yet for this article.
August 17, 2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28813705/the-lncrna-tug1-ezh2-axis-promotes-pancreatic-cancer-cell-proliferation-migration-and-emt-phenotype-formation-through-sponging-mir-382
#4
Liang Zhao, Hongwei Sun, Hongru Kong, Zongjing Chen, Bicheng Chen, Mengtao Zhou
BACKGROUND/AIMS: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#5
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813678/therapeutic-antibodies-to-ganglioside-gd2-evolved-from-highly-selective-germline-antibodies
#6
Eric Sterner, Megan L Peach, Marc C Nicklaus, Jeffrey C Gildersleeve
Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#7
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813675/cd44-interacts-with-hif-2%C3%AE-to-modulate-the-hypoxic-phenotype-of-perinecrotic-and-perivascular-glioma-cells
#8
Elinn Johansson, Elisa S Grassi, Vasiliki Pantazopoulou, Bei Tong, David Lindgren, Tracy J Berg, Elin J Pietras, Håkan Axelson, Alexander Pietras
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813674/an-integrated-systems-biology-approach-identifies-trim25-as-a-key-determinant-of-breast-cancer-metastasis
#9
Logan A Walsh, Mariano J Alvarez, Erich Y Sabio, Marsha Reyngold, Vladimir Makarov, Suranjit Mukherjee, Ken-Wing Lee, Alexis Desrichard, Şevin Turcan, Martin G Dalin, Vinagolu K Rajasekhar, Shuibing Chen, Linda T Vahdat, Andrea Califano, Timothy A Chan
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813666/microrna-9-couples-brain-neurogenesis-and-angiogenesis
#10
Romain Madelaine, Steven A Sloan, Nina Huber, James H Notwell, Louis C Leung, Gemini Skariah, Caroline Halluin, Sergiu P Paşca, Gill Bejerano, Mark A Krasnow, Ben A Barres, Philippe Mourrain
In the developing brain, neurons expressing VEGF-A and blood vessels grow in close apposition, but many of the molecular pathways regulating neuronal VEGF-A and neurovascular system development remain to be deciphered. Here, we show that miR-9 links neurogenesis and angiogenesis through the formation of neurons expressing VEGF-A. We found that miR-9 directly targets the transcription factors TLX and ONECUTs to regulate VEGF-A expression. miR-9 inhibition leads to increased TLX and ONECUT expression, resulting in VEGF-A overexpression...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813665/lineage-restricted-mammary-stem-cells-sustain-the-development-homeostasis-and-regeneration-of-the-estrogen-receptor-positive-lineage
#11
Alexandra Van Keymeulen, Marco Fioramonti, Alessia Centonze, Gaëlle Bouvencourt, Younes Achouri, Cédric Blanpain
The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER)(+) and ER(-) cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER(+) lineage is maintained by multipotent SCs or by lineage-restricted SCs...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813661/tissue-resident-macrophages-in-pancreatic-ductal-adenocarcinoma-originate-from-embryonic-hematopoiesis-and-promote-tumor-progression
#12
Yu Zhu, John M Herndon, Dorothy K Sojka, Ki-Wook Kim, Brett L Knolhoff, Chong Zuo, Darren R Cullinan, Jingqin Luo, Audrey R Bearden, Kory J Lavine, Wayne M Yokoyama, William G Hawkins, Ryan C Fields, Gwendalyn J Randolph, David G DeNardo
Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813659/the-dna-methylcytosine-dioxygenase-tet2-sustains-immunosuppressive-function-of-tumor-infiltrating-myeloid-cells-to-promote-melanoma-progression
#13
Wen Pan, Shu Zhu, Kun Qu, Katrina Meeth, Jijun Cheng, Kaixin He, Hongdi Ma, Yan Liao, Xizhi Wen, Christine Roden, Zuzana Tobiasova, Zheng Wei, Jun Zhao, Jun Liu, Ji Zheng, Bo Guo, Sajid A Khan, Marcus Bosenberg, Richard A Flavell, Jun Lu
Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813653/the-yolk-sac-feeds-pancreatic-tumors
#14
Jeffrey W Pollard
In this issue of Immunity, Zhu et al. (2017) report that tumor-associated macrophages in a mouse model of pancreatic ductal adenocarcinoma (PDAC) originate from both the yolk sac (YS) and bone marrow. Differential ablation of these populations indicates that only the YS-derived macrophages promote PDAC progression and growth.
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813646/antihelminthic-drug-niclosamide-inhibits-cip2a-and-reactivates-tumor-suppressor-protein-phosphatase-2a-in-non-small-cell-lung-cancer-cells
#15
Myeong-Ok Kim, Min Ho Choe, Yi Na Yoon, Jiyeon Ahn, Minjin Yoo, Kwan-Young Jung, Sungkwan An, Sang-Gu Hwang, Jeong Su Oh, Jae-Sung Kim
Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged as an anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28813640/innate-immune-signaling-in-the-ventral-tegmental-area-contributes-to-drug-primed-reinstatement-of-cocaine-seeking
#16
Kyle T Brown, Sophia C Levis, Casey E O'Neill, Alexis L Northcutt, Timothy J Fabisiak, Linda R Watkins, Ryan K Bachtell
Cocaine addiction is a chronic relapsing disorder characterized by persistent perturbations to an organism's homeostatic processes that result in maladaptive drug seeking. Although considerable attention has been directed at the consequences of neuronal changes following chronic cocaine taking, few studies have examined the role of microglia, the brain's resident immune cells, following chronic cocaine administration. Toll-Like Receptor 4 (TLR4) is a molecular pattern receptor that recognizes pathogens, danger signals, and xenobiotics and induces proinflammatory signaling in the central nervous system...
August 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28813596/molecular-imaging-of-p-glycoprotein-in-chemoresistant-tumors-using-a-dual-modality-pet-fluorescence-probe
#17
Mengzhe Wang, Chengqiong Mao, Hui Wang, Xueying Ling, Zhanhong Wu, Zi-Bo Li, Xin Ming
Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28813586/breast-cancer-and-exposure-to-aircraft-road-and-railway-noise-a-case-control-study-based-on-health-insurance-records
#18
Janice Hegewald, Melanie Schubert, Mandy Wagner, Patrik Dröge, Ursel Prote, Enno Swart, Ulrich Möhler, Hajo Zeeb, Andreas Seidler
Objectives Aircraft, road, and rail traffic noise can cause sleep disturbances. Since night work and shorter sleep durations have been linked to increased risks of breast cancer, we examined if 24-hour, or day- or night-time traffic noise exposure may also increase the risk of breast cancer. Methods To investigate the noise-related risks of breast cancer, the pseudonymized insurance records of three large statutory health companies (2005-2010) for women aged ≥40 years living in the region surrounding the Frankfurt international airport were analyzed with address-specific acoustic data representing aircraft, road, and rail-traffic noise...
August 16, 2017: Scandinavian Journal of Work, Environment & Health
https://www.readbyqxmd.com/read/28813519/expression-and-inhibition-of-brd4-ezh2-and-top2a-in-neurofibromas-and-malignant-peripheral-nerve-sheath-tumors
#19
Azadeh Amirnasr, Rob M Verdijk, Patricia F van Kuijk, Walter Taal, Stefan Sleijfer, Erik A C Wiemer
Malignant peripheral nerve sheath tumors (MPNST) are rare, highly aggressive sarcomas that can occur spontaneously or from pre-existing plexiform neurofibromas in neurofibromatosis type1 (NF1) patients. MPNSTs have high local recurrence rates, metastasize easily, are generally resistant to therapeutic intervention and frequently fatal for the patient. Novel targeted therapeutic strategies are urgently needed. Standard treatment for patients presenting with advanced disease is doxorubicin based chemotherapy which inhibits the actions of the enzyme topoisomerase IIα (TOP2A)...
2017: PloS One
https://www.readbyqxmd.com/read/28813492/point-prevalence-survey-of-healthcare-facility-onset-healthcare-associated-clostridium-difficile-infection-in-greek-hospitals-outside-the-intensive-care-unit-the-c-define-study
#20
Athanasios Skoutelis, Angelos Pefanis, Sotirios Tsiodras, Nikolaos V Sipsas, Moyssis Lelekis, Marios C Lazanas, Panagiotis Gargalianos, George N Dalekos, Emmanuel Roilides, George Samonis, Efstratios Maltezos, Dimitrios Hatzigeorgiou, Malvina Lada, Symeon Metallidis, Athena Stoupis, Georgios Chrysos, Lazaros Karnesis, Styliani Symbardi, Chariclia V Loupa, Helen Giamarellou, Ioannis Kioumis, Helen Sambatakou, Epameinondas Tsianos, Maria Kotsopoulou, Areti Georgopali, Klairi Liakou, Stavroula Perlorentzou, Stamatina Levidiotou, Marina Giotsa-Toutouza, Helen Tsorlini-Christoforidou, Ilias Karaiskos, Georgia Kouppari, Eleftheria Trikka-Graphakos, Maria-Anna Ntrivala, Kate Themeli-Digalaki, Anastasia Pangalis, Melina Kachrimanidou, Maria Martsoukou, Stergios Karapsias, Maria Panopoulou, Sofia Maraki, Anagnostina Orfanou, Efthymia Petinaki, Maria Orfanidou, Vasiliki Baka, Antonios Stylianakis, Iris Spiliopoulou, Stavroula Smilakou, Loukia Zerva, Evangelos Vogiatzakis, Eleni Belesiotou, Charalambos A Gogos
BACKGROUND: The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. METHODS: There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI...
2017: PloS One
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