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https://www.readbyqxmd.com/read/28423062/filamentous-fungal-carbon-catabolite-repression-supports-metabolic-plasticity-and-stress-responses-essential-for-disease-progression
#1
Sarah R Beattie, Kenneth M K Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna K Caffrey-Carr, Chao Cheng, Candice C Black, Paul Bowyer, Michael J Bromley, Joshua J Obar, Gustavo H Goldman, Robert A Cramer
Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28420351/prognostic-significance-of-trail-r3-and-ccr-2-expression-in-tumor-epithelial-cells-of-patients-with-early-breast-cancer
#2
Vivian Labovsky, Leandro Marcelo Martinez, Kevin Mauro Davies, María de Luján Calcagno, Hernán García-Rivello, Alejandra Wernicke, Leonardo Feldman, Ayelén Matas, María Belén Giorello, Francisco Raúl Borzone, Hosoon Choi, Scott C Howard, Norma Alejandra Chasseing
BACKGROUND: Tumor epithelial cells (TEpCs) and spindle-shaped stromal cells, not associated with the vasculature, of patients with early breast cancer express osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), receptor activator of nuclear factor kappa B ligand, stromal cell derived factor-1, interleukin-6, macrophage colony stimulating factor, chemokine (C-C motif) ligand-2 (CCL-2) and their receptors at significantly higher levels compared with non-neoplastic breast tissues...
April 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28414588/prehospital-predictors-of-traumatic-spinal-cord-injury-in-victoria-australia
#3
Alaa O Oteir, Karen Smith, Johannes Stoelwinder, James W Middleton, Shelley Cox, Lisa N Sharwood, Paul A Jennings
OBJECTIVES: To identify the predictors of traumatic spinal cord injury (TSCI) and describe the differences between confirmed and potential TSCI cases in the prehospital setting. METHODS: A retrospective cohort study including all adult patients over a six-year period (2007-12) with potential TSCI who were attended and transported by Ambulance Victoria (AV). We extracted potential TSCI cases from the AV data warehouse and linked with the Victorian State Trauma Registry to compare with final hospital diagnosis...
April 17, 2017: Prehospital Emergency Care
https://www.readbyqxmd.com/read/28409543/ccr-2-neutralization-augments-murine-fresh-bmc-activation-by-staphylococcus-aureus-via-two-distinct-mechanisms-at-the-level-of-ros-production-and-cytokine-response
#4
Ajeya Nandi, Biswadev Bishayi
CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the bloodstream and then to sites of infection. We sought to determine whether CCL-2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)-NF-κB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to determine whether neutralization of CCR-2 augments the response of murine fresh BMCs (FBMCs) after S. aureus infection...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28406084/evidence-that-tmp-gfr-can-be-estimated-with-the-walton-bijvoet-nomogram-in-chronic-kidney-disease%C3%A2
#5
Kenneth R Phelps, Darius L Mason
BACKGROUND: The Walton--Bijvoet nomogram incorporates the assumption that GFR = creatinine clearance (Ccr). It determines phosphate tubular maximum per volume of filtrate (TmP/GFR) from serum phosphorus ([P]s) and fractional excretion of P (FEP), and equates TmP/GFR with actual reabsorption per volume of filtrate (TRP/Ccr) at FEP ≥ 20%. It has not been validated in chronic kidney disease (CKD). METHODS: We studied 28 controls and 30 patients with stages 3 - 4 CKD...
April 13, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28400785/dihydroflavonol-4-reductase-genes-from-freesia-hybrida-play-important-and-partially-overlapping-roles-in-the-biosynthesis-of-flavonoids
#6
Yueqing Li, Xingxue Liu, Xinquan Cai, Xiaotong Shan, Ruifang Gao, Song Yang, Taotao Han, Shucai Wang, Li Wang, Xiang Gao
Dihydroflavonol-4-reductase (DFR) is a key enzyme in the reduction of dihydroflavonols to leucoanthocyanidins in both anthocyanin biosynthesis and proanthocyanidin accumulation. In many plant species, it is encoded by a gene family, however, how the different copies evolve either to function in different tissues or at different times or to specialize in the use of different but related substrates needs to be further investigated, especially in monocot plants. In this study, a total of eight putative DFR-like genes were firstly cloned from Freesia hybrida...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28400046/atgl-gene-deletion-predisposes-to-proximal-tubule-damage-by-impairing-the-fatty-acid-metabolism
#7
Wen Chen, Qiong Zhang, Shiwu Cheng, Jie Huang, Ge Diao, Jian Han
Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl(-/-) mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr)...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28390955/evidence-that-compatibility-of-closely-related-replicons-in-clostridium-perfringens-depends-on-linkage-to-parmrc-like-partitioning-systems-of-different-subfamilies
#8
Thomas D Watts, Priscilla A Johanesen, Dena Lyras, Julian I Rood, Vicki Adams
Clostridium perfringens produces an extensive repertoire of toxins and extracellular enzymes, many of which are intimately involved in the progression of disease and are encoded by genes on conjugative plasmids. In addition, many C. perfringens strains can carry up to five of these conjugative toxin or antimicrobial resistance plasmids, each of which has a similar 35kb backbone. This conserved backbone includes the tcp conjugation locus and the central control region (CCR), which encodes genes involved in plasmid regulation, replication and partitioning, including a parMRC partitioning locus...
April 6, 2017: Plasmid
https://www.readbyqxmd.com/read/28387853/cxcl8-antagonist-improves-diabetic-nephropathy-in-male-mice-of-diabetes-and-attenuates-high-glucose-induced-mesangial-injury
#9
Siyuan Cui, Yujie Zhu, Jianling Du, Muhammad Noman Khan, Bing Wang, Jing Wei, Jya-Wei Cheng, John R Gordon, Yutian Mu, Fang Li
Inflammation is recognized as a crucial contribution to diabetic nephropathy (DN). CXCL8 binds to its CXC chemokine receptors (CXCR1 and CXCR2) for recruiting neutrophils infiltration and initiates tissue inflammation. Therefore, we explored the effect of CXCR1 and CXCR2 inhibition on diabetic nephropathy. This was achieved by CXCL8 (3-72) K11R/G31P (G31P), an antagonist of CXCL8, which has exhibited therapeutic efficacy in inflammatory diseases and malignancies. In this study, we found renal leukocytes accumulation and rapid increases of CXCL8 occurred in HFD/STZ-induced diabetic mice...
April 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28385713/genome-wide-top2a-dna-cleavage-is-biased-towards-translocated-and-highly-transcribed-loci
#10
Xiang Yu, James W Davenport, Karen A Urtishak, Marie L Carillo, Sager J Gosai, Christos P Kolaris, Jo Ann W Byl, Eric F Rappaport, Neil Osheroff, Brian D Gregory, Carolyn Ann Felix
Type II topoisomerases orchestrate proper DNA topology and they are the targets of anticancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single base precision and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs) and is enriched in introns and lincRNA loci...
April 6, 2017: Genome Research
https://www.readbyqxmd.com/read/28383652/th1-and-innate-lymphoid-cells-accumulate-in-primary-sclerosing-cholangitis-associated-inflammatory-bowel-disease
#11
Agnes Gwela, Priya Siddhanathi, Roger W Chapman, Simon Travis, Fiona Powrie, Carolina V Arancibia-Cárcamo, Alessandra Geremia
Background and Aims: Primary sclerosing cholangitis (PSC) is an idiopathic chronic disorder of the hepatobiliary system associated with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). Colitis in patients with PSC and UC (PSC-UC) exhibits characteristic features and is linked to increased colon cancer risk. Genetic studies have identified immune-related susceptibility genes that only partially overlap with those involved in IBD. These observations suggest that PSC-UC may represent a distinct form of IBD...
April 5, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28382399/ccr5-in-recruitment-and-activation-of-myeloid-derived-suppressor-cells-in-melanoma
#12
REVIEW
Viktor Umansky, Carolin Blattner, Christoffer Gebhardt, Jochen Utikal
Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, leading to the accumulation of myeloid-derived suppressor cells (MDSCs). Using ret transgenic mouse melanoma model, we found a significant migration of MDSCs expressing C-C chemokine receptor (CCR)5 into primary tumors and metastatic lymph nodes, which was correlated with tumor progression. An increased CCR5 expression on MDSCs was associated with elevated concentrations of CCR5 ligands in melanoma microenvironment...
April 5, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28380674/metformin-use-and-survival-after-non-small-cell-lung-cancer-a-cohort-study-in-the-u-s-military-health-system
#13
Jie Lin, Abegail Gill, Shelia H Zahm, Corey A Carter, Craig D Shriver, Joel A Nations, William F Anderson, Katherine A McGlynn, Kangmin Zhu
Research suggests that metformin may be associated with improved survival in cancer patients with type II diabetes. This study assessed whether metformin use after non-small cell lung cancer (NSCLC) diagnosis is associated with overall survival among type II diabetic patients with NSCLC in the U.S. military health system (MHS). The study included 636 diabetic patients with histologically confirmed NSCLC diagnosed between 2002 and 2007, identified from the linked database from the Department of Defense's Central Cancer Registry (CCR) and the Military Health System Data Repository (MDR)...
April 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28373962/the-influence-of-different-calorie-restriction-protocols-on-serum-pro-inflammatory-cytokines-adipokines-and-igf-i-levels-in-female-c57bl6-mice-short-term-and-long-term-diet-effects
#14
Soner Dogan, Amitabha Ray, Margot P Cleary
Calorie restriction (CR) is an effective intervention to prevent chronic diseases including cancer. Although many factors, i.e., sex hormones, IGF-I and mTOR have been studied in response to CR, the molecular mechanisms of CR remain to be identified. Our objective was to determine the short and long-term effects of different CR protocols on pro-inflammatory cytokines. Our hypothesis was that Intermittent CR (ICR) would result in greater inhibition of pro-inflammatory serum cytokines compared to Chronic CR (CCR) as we previously found ICR to be more protective in the prevention of mammary tumor development...
June 2017: Meta Gene
https://www.readbyqxmd.com/read/28373365/current-and-emerging-therapies-in-metastatic-pancreatic-cancer
#15
EDITORIAL
Gulam Abbas Manji, Kenneth P Olive, Yvonne M Saenger, Paul Oberstein
Targeted therapies and immunotherapy have changed the face of multiple solid malignancies, including metastatic melanoma and lung cancer, but no such therapies exist for pancreatic ductal adenocarcinoma (PDAC) despite the knowledge of key mutations and an increasing understanding of the tumor microenvironment. Until now, most clinical studies have not been biomarker driven in this highly immunosuppressive and heterogeneous cancer. Ongoing basic and translational studies are better classifying the disease in hopes of identifying critical pathways that distinguish the unique PDAC subtypes, which will lead to personalized therapies...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373364/strategies-for-increasing-pancreatic-tumor-immunogenicity
#16
EDITORIAL
Burles A Johnson, Mark Yarchoan, Valerie Lee, Daniel A Laheru, Elizabeth M Jaffee
Immunotherapy has changed the standard of care for multiple deadly cancers, including lung, head and neck, gastric, and some colorectal cancers. However, single-agent immunotherapy has had little effect in pancreatic ductal adenocarcinoma (PDAC). Increasing evidence suggests that the PDAC microenvironment is comprised of an intricate network of signals between immune cells, PDAC cells, and stroma, resulting in an immunosuppressive environment resistant to single-agent immunotherapies. In this review, we discuss differences between immunotherapy-sensitive cancers and PDAC, the complex interactions between PDAC stroma and suppressive tumor-infiltrating cells that facilitate PDAC development and progression, the immunologic targets within these complex networks that are druggable, and data supporting combination drug approaches that modulate multiple PDAC signals, which should lead to improved clinical outcomes...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373363/re-engineering-the-pancreas-tumor-microenvironment-a-regenerative-program-hacked
#17
EDITORIAL
Gerard I Evan, Nasun Hah, Trevor D Littlewood, Nicole M Sodir, Tania Campos, Michael Downes, Ronald M Evans
The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373362/pancreatic-cancer-genomes-implications-for-clinical-management-and-therapeutic-development
#18
EDITORIAL
Stephan B Dreyer, David K Chang, Peter Bailey, Andrew V Biankin
Pancreatic cancer has become the third leading cause of cancer-related death, with little improvement in outcomes despite decades of research. Surgery remains the only chance of cure, yet only 20% of patients will be alive at 5 years after pancreatic resection. Few chemotherapeutics provide any improvement in outcome, and even then, for approved therapies, the survival benefits are marginal. Genomic sequencing studies of pancreatic cancer have revealed a small set of consistent mutations found in most pancreatic cancers and beyond that, a low prevalence for targetable mutations...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373361/pancreatic-cancer-a-riddle-wrapped-in-a-mystery-inside-an-enigma
#19
EDITORIAL
Erkut Borazanci, Chi V Dang, Robert W Robey, Susan E Bates, John A Chabot, Daniel D Von Hoff
Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult-to-treat cancers. With an increasing incidence and inability to make major progress, it represents the very definition of unmet medical need. Progress has been made in understanding the basic biology-systematic genomic sequencing has led to the recognition that PDAC is not typically a heavily mutated tumor, although there are exceptions. The most consistently mutated genes are KRAS, CDKN2A, TP53, and SMAD4/DPC4 Study of familial PDAC has led to the recognition that a variety of defects in DNA repair genes can be associated with the emergence of pancreatic cancer...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28370680/rapid-and-sensitive-determination-of-multiple-endocrine-disrupting-chemicals-by-ultrasound-assisted-in-situ-derivatization-dispersive-liquid-liquid-microextraction-coupled-with-uhplc-ms-ms
#20
Na Wei, Zhenjia Zheng, Yuhua Wang, Yanduo Tao, Yun Shao, Shuyun Zhu, Jinmao You, Xian-En Zhao
RATIONALE: Endocrine disrupting chemicals (EDCs) in environment samples and food stuffs are an increasing serious public health issue due to their potency to interfere and deregulate several aspects of the endocrine system. Because of their extremely low abundance, it remains a challenging task to develop a sensitive detection method. METHODS: 4'-Carbonyl chloride rosamine (CCR) was used as a derivatization reagent for EDCs for the first time. A new ultrasound-assisted in situ derivatization-dispersive liquid-liquid microextraction (UA-DLLME with in situ derivatization) method for multiple EDCs including five estrogens, two alkylphenols, eight bisphenols, seven parabens and triclosan coupled with ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed and validated...
March 31, 2017: Rapid Communications in Mass Spectrometry: RCM
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