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https://www.readbyqxmd.com/read/28324887/association-between-hypoxic-volume-and-underlying-hypoxia-induced-gene-expression-in-oropharyngeal-squamous-cell-carcinoma
#1
Yae-Eun Suh, Katherine Lawler, Rhonda Henley-Smith, Lucy Pike, Russell Leek, Sally Barrington, Edward W Odell, Tony Ng, Francesco Pezzella, Teresa Guerrero-Urbano, Mahvash Tavassoli
BACKGROUND: Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with (64)Cu-ATSM PET/CT. METHODS: (64)Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients...
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28319066/nucleus-accumbens-associated-protein-1-promotes-glycolysis-and-survival-of-hypoxic-tumor-cells-via-the-hdac4-hif-1%C3%AE-axis
#2
Y Zhang, Y-J Ren, L-C Guo, C Ji, J Hu, H-H Zhang, Q-H Xu, W-D Zhu, Z-J Ming, Y-S Yuan, X Ren, J Song, J-M Yang
Nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer. In this study, we identified the NAC1-HDAC4-HIF-1α axis as an important pathway in regulating glycolysis and hypoxic adaptation in tumor cells. We show that nuclear NAC1 binds to histone deacetylase type 4 (HDAC4), hindering phosphorylation of HDAC4 at Ser(246) and preventing its nuclear export that leads to cytoplasmic degradation of the deacetylase. Accumulation of HDAC4 in the nuclei results in an attenuation of HIF-1α acetylation, enhancing the stabilization and transcriptional activity of HIF-1α and strengthening adaptive response of cells to hypoxia...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318896/role-of-ahr-and-hif-1%C3%AE-in-glioblastoma-metabolism
#3
REVIEW
Galina Gabriely, Michael A Wheeler, Maisa C Takenaka, Francisco J Quintana
Glioblastoma (GBM) progression is associated with metabolic remodeling in both glioma and immune cells, resulting in the use of aerobic glycolysis as the main source of energy and biosynthetic molecules. The transcription factor hypoxia-inducible factor (HIF)-1α drives this metabolic reorganization. Oxygen levels, as well as other factors, control the activity of HIF-1α. In addition, the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) modulates tumor-specific immunity and can also participate in metabolic remodeling...
March 16, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28317592/long-term-prognostic-value-of-preoperative-anemia-in-patients-with-colorectal-cancer-a-systematic-review-and-meta-analysis
#4
REVIEW
M J Wilson, M van Haaren, J J Harlaar, Hee Chul Park, H J Bonjer, J Jeekel, J J Zwaginga, M Schipperus
OBJECTIVE: To evaluate the long-term prognostic factor of preoperative anemia in colorectal cancer patients. BACKGROUND: Anemia is frequently observed in colorectal cancer patients, with a case incidence of 30 to 67 percent. Besides an indicator of tumor-induced blood loss and inflammation, anemia in cancer is also suggested to be a cause of inferior outcome, possibly via worsening of tumor hypoxia. As surgery is likely to enhance anemia, the long-term prognostic value of preoperative anemia seems most interesting...
March 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28317401/biological-implications-and-clinical-value-of-mir-210-in-gastrointestinal-cancer
#5
Wanli Yang, Jiaojiao Ma, Wei Zhou, Xin Zhou, Bo Cao, Daiming Fan, Liu Hong
Introduction Hypoxia, a common feature of tumor microenvironment, is known to accelerate tumor development and growth by promoting the formation of a neoplastic environment. Recent studies have provided a wealth of evidence that miRNAs are significant members of the adaptive response to low oxygen in tumors. miR-210 is one of the hypoxia-induced miRNAs, which has been reported extensively in cancer researches. However, there is no systematic discussion about the role of miR-210 in gastrointestinal cancer. We conducted a literature research in database including PubMed, Elsevier Science Direct and Medline before September 16, 2016, in order to collect articles of miR-210 in gastrointestinal cancer...
March 18, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28317128/comparison-of-dce-mri-kinetic-parameters-and-fmiso-pet-uptake-parameters-in-head-and-neck-cancer-patients
#6
Urban Simoncic, Sara Leibfarth, Stefan Welz, Nina Schwenzer, Holger Schmidt, Gerald Reischl, Christina Pfannenberg, Christian la Fougère, Konstantin Nikolaou, Daniel Zips, Daniela Thorwarth
PURPOSE: Tumour hypoxia is a major cause of radiation resistance, often present in various solid tumours. Dynamic [(18) F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumour hypoxia. Comprehensive characterization of tumour microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters...
March 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28315669/cell-survival-interplay-between-hypoxia-and-pre-mrna-splicing
#7
Arvydas Kanopka
RNA splicing takes place in the nucleus and occurs either coor post-transcriptionally. Noncoding sequences (introns) in nuclear mRNA precursors (pre-mRNA) are removed by dedicated splicing machinery. The coding sequences (exons) are joined to generate the mature mRNA that is exported to the cytoplasm and translated into protein. Splicing events are tissue-specific. This process plays an important role in cellular differentiation and organism development. The splicing machinery heavily contributes to biological complexity and especially to the ability of cells to adapt to different developmental stages and altered cellular conditions...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28314789/non-invasive-imaging-of-cycling-hypoxia-in-head-neck-cancer-using-intrinsic-susceptibility-mri
#8
Rafal Panek, Liam Welsh, Lauren Cj Baker, Maria A Schmidt, Kee H Wong, Angela Riddell, Dow-Mu Koh, Alex Dunlop, Dualta Mcquaid, James A d'Arcy, Shreerang Bhide, Kevin J Harrington, Christopher M Nutting, Georgina Hopkinson, Cheryl Richardson, Carol Box, Suzanne A Eccles, Martin O Leach, Simon P Robinson, Katie L Newbold
PURPOSE: To evaluate intrinsic susceptibility (IS) MRI for the identification of cycling hypoxia, and the assessment of its extent and spatial distribution, in head and neck squamous cell carcinoma (HNSCC) xenografts and patients. EXPERIMENTAL DESIGN: Quantitation of the transverse relaxation rate R2*, which is sensitive to paramagnetic deoxyhemoglobin, using serial IS-MRI acquisitions, was used to monitor temporal oscillations in levels of paramagnetic deoxyhemoglobin in human CAL(R) xenografts and patients with HNSCC at 3T...
March 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28314267/induced-pluripotent-stem-cell-related-genes-contribute-to-de-differentiation-in-oral-squamous-cell-carcinoma
#9
Daisuke Takeda, Takumi Hasegawa, Takeshi Ueha, Eiji Iwata, Risa Harada, Akiko Sakakibara, Teruya Kawamoto, Tsutomu Minamikawa, Yoshitada Sakai, Takahide Komori
BACKGROUND/AIM: Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304334/kdm2-family-members-are-regulated-by-hif-1-in-hypoxia
#10
Michael Batie, Jimena Druker, Laura D'Ignazio, Sonia Rocha
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase...
March 17, 2017: Cells
https://www.readbyqxmd.com/read/28303266/novel-hypoxia-targeting-pt-iv-prodrugs
#11
Zichen Xu, Jian Zhao, Shaohua Gou, Gang Xu
Novel Pt(iv) prodrugs targeting hypoxia inducible factor HIF-1α were prepared for evaluating their antitumor activity on hypoxic cancer cells for the first time. The resulting Pt(iv) prodrug exhibited effective inhibition on tumor growth in the HCT-116 xenograft mouse model with low toxicity in vivo.
March 17, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#12
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μM cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to anti-tumor drugs...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302670/modelling-pulmonary-microthrombosis-coupled-to-metastasis-distinct-effects-of-thrombogenesis-on-tumorigenesis
#13
Colin E Evans, Asis Palazon, Jingwei Sim, Petros A Tyrakis, Alice Prodger, Xiao Lu, Saria Chan, Pär-Ola Bendahl, Mattias Belting, Love Von Euler, Helene Rundqvist, Randall S Johnson, Cristina Branco
Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumor cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we model the effect of microvascular occlusion in metastatic efficiency, by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumor cell injection...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28302582/characterization-of-pegylated-and-non-pegylated-liposomal-formulation-for-the-delivery-of-hypoxia-activated-vinblastine-n-oxide-for-the-treatment-of-solid-tumors
#14
Vidhi M Shah, Duc X Nguyen, Adel Alfatease, Shay Bracha, Adam Wg Alani
Solid tumors often contain hypoxic regions which are resistant to standard chemotherapy and radiotherapy. We have developed a liposomal delivery system for a prodrug of vinblastine (CPD100) which converts to the parent compound only in the presence of lower oxygen levels. As a part of this work we have developed and optimized two formulations of CPD100: one composed of sphingomyelin/cholesterol (55/45; mol/mol) (CPD100Li) and the other composed of sphingomyelin/cholesterol/PEG (55/40/5; mol/mol) (CPD100 PEGLi)...
March 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28302216/-association-of-indoor-air-pollution-single-nucleotide-polymorphism-of-hif-1%C3%AE-gene-with-susceptibility-to-lung-cancer-in-han-population-in-fujian-province
#15
Fei He, Qi Qi, Xu Li, Rendong Xiao, Qiuping Xu, Weimin Xiong, Zhiqiang Liu, Lin Cai
BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is associated with the progression and metastasis of lung cancer. There are, however, few studies on the relationship between the single nucleotide polymorphisms of HIF-1α and susceptibility to lung cancer. Therefore, we aimed to investigate the relationship between indoor air pollution, HIF-1α rs2057482, and the susceptibility to primary lung cancer of the Fujian Han population. METHODS: The present study is a hospital-based case-control study...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28301873/personalising-and-targeting-antiangiogenic-resistance-a-complex-and-multifactorial-approach
#16
REVIEW
Maria J Bueno, Silvana Mouron, Miguel Quintela-Fandino
Pathological angiogenesis involves complex and dynamic interactions between tumour cells and other lineages existing in the microenvironment of the tumour. Preclinical and clinical data suggest that tumours can show dual, different adaptive responses against antiangiogenic agents: one successful adaptation is vascular normalisation, whereas the second adaptation is elicited through vascular trimming and increased hypoxia. These phenomena depend on the type of tumour and the type of agent. The classical approach for investigating acquired resistance against antiangiogenic agents is to identify compensatory signalling pathways emerging in response to VEGF blockade, which has led to the development of highly effective drugs; however, ultimately these drugs fail...
March 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28300223/role-of-cyclooxygenase-2-on-intermittent-hypoxia-induced-lung-tumor-malignancy-in-a-mouse-model-of-sleep-apnea
#17
Noelia Campillo, Marta Torres, Antoni Vilaseca, Paula Naomi Nonaka, David Gozal, Jordi Roca-Ferrer, César Picado, Josep Maria Montserrat, Ramon Farré, Daniel Navajas, Isaac Almendros
An adverse role for obstructive sleep apnea (OSA) in cancer epidemiology and outcomes has recently emerged from clinical and animal studies. In animals, intermittent hypoxia (IH) mimicking OSA promotes tumor malignancy both directly and via host immune alterations. We hypothesized that IH could potentiate cancer aggressiveness through activation of the cyclooxygenase-2 (COX-2) pathway and the concomitant increases in prostaglandin E2 (PGE2). The contribution of the COX-2 in IH-induced enhanced tumor malignancy was assessed using celecoxib as a COX-2 specific inhibitor in a murine model of OSA bearing Lewis lung carcinoma (LLC1) tumors...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295307/high-expression-of-insulin-receptor-on-tumor-associated-blood-vessels-in-invasive-bladder-cancer-predicts-poor-overall-and-progression-free-survival
#18
Filip Roudnicky, Lothar C Dieterich, Cedric Poyet, Lorenz Buser, Peter Wild, Dave Tang, Peter Camenzind, Chien Hsien Ho, Vivianne I Otto, Michael Detmar
Bladder cancer is a frequently recurring disease with a very poor prognosis when progressed to invasive stages, and tumor-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumor-associated BECs greatly upregulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival...
March 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28294076/microrna-biogenesis-in-hypoxia
#19
Veronika Bandara, Michael Zenon Michael, Jonathan Mark Gleadle
MicroRNAs (miRNAs) are 17-22 nucleotide, non-coding, single stranded RNA molecules that play a key role in post-transcriptional gene regulation. Hypoxia is a reduction in the normal level of tissue oxygen (O2) tension, and is a feature of chronic vascular disease, pulmonary disease and many cancers. Tissue hypoxia can have widespread effects on cellular functions, as O2 availability is critical for many cellular processes. Cells respond to changes in O2 tension through multiple molecular and cellular mechanisms, including changes in gene expression through transcriptional and translational mechanisms...
March 13, 2017: MicroRNA
https://www.readbyqxmd.com/read/28294075/%C3%AE-18f-fluoro-azomycin-arabinoside-%C3%AE-18f-faza-synthesis-radiofluorination-and-preliminary-pet-imaging-of-murine-a431-tumors
#20
Piyush Kumar, Peter Roselt, Gerald Reischl, Carlene Cullinane, Davood Beiki, Walter Ehrlichmann, David Binns, Ebrahim Naimi, Jennifer Yang, Rodney Hicks, Hans-Juergen Machulla, Leonard I Wiebe
BACKGROUND: 1-α-D-(5-Deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole ([18F]FAZA) is a PET radiotracer that demonstrates excellent potential in imaging regional hypoxia, and is clinically used in diagnosing a wide range of solid tumors in cancer patients. [18F]FAZA, however, is radiofluorinated in only moderate recovered radiochemical yield (rRCY, ~12%). It is postulated that the relative stability of the C1' β-anomeric bond at C5' will make 1-β-D-(5-fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (β-FAZA), the β-conformer of FAZA, an attractive candidate for clinical hypoxia imaging...
March 13, 2017: Current Radiopharmaceuticals
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