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Tumor hypoxia

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https://www.readbyqxmd.com/read/28544853/microrna-34a-protect-myocardial-cells-against-ischemia-reperfusion-injury-through-inhibiting-autophagy-via-regulating-tnf%C3%AE-expression
#1
Haifeng Shao, Lili Yang, Li Wang, Bozan Tang, Jian Wang, Qiang Li
BACKGROUND: Ischemia/reperfusion (I/R) accompanying with the blood supply restored after myocardial infarction. Myocardial I/R injury relieves when autophagy decreased. MicroRNA-34a(miR-34a) regulate autophagy in renal I/R injury model. But whether it can affect cardiac I/R injury remains studying. This study investigated how miR-34a in protecting myocardial cells against I/R injury through inhibit autophagy via regulating tumor necrosis factor α (TNFα) . METHODS: Constructed the I/R model in vivo with Langendorff; treated Neonatal Rat cardiomyocyte to make H/R injury model in vitro with hypoxia/reoxygenation (H/R) method...
May 25, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28544324/albumin-templated-manganese-dioxide-nanoparticles-for-enhanced-radioisotope-therapy
#2
Longlong Tian, Qian Chen, Xuan Yi, Jiawen Chen, Chao Liang, Yu Chao, Kai Yang, Zhuang Liu
Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide (131) I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles ((131) I-HSA-MnO2 ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME)...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28543796/mxd1-mediates-hypoxia-induced-cisplatin-resistance-in-osteosarcoma-cells-by-repression-of-the-pten-tumor-suppressor-gene
#3
Datong Zheng, Weiling Wu, Na Dong, Xiuqin Jiang, Jinjin Xu, Xi Zhan, Zhengdong Zhang, Zhenzhen Hu
Hypoxia-induced chemoresistance remains a major obstacle to treating osteosarcoma effectively. Mxd1, a member of the Myc/Max/Mxd family, was shown to be involved in the development of drug resistance under hypoxia. However, the effect of Mxd1 on hypoxia-induced cisplatin (CDDP) resistance and its mechanism in osteosarcoma have not been fully elucidated. In this study, we demonstrated that HIF-1α-induced Mxd1 contributed to CDDP resistance in hypoxic U-2OS and MG-63 cells. The knockdown of Mxd1 expression elevated PTEN expression at both protein and RNA levels in these hypoxic cells...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28540524/changes-in-tumor-biology-during-chemoradiation-of-cervix-cancer-assessed-by-multiparametric-mri-and-hypoxia-pet
#4
Petra Georg, Piotr Andrzejewski, Pascal Baltzer, Michaela Daniel, Wolfgang Wadsak, Markus Mitterhauser, Alina Sturdza, Katarina Majercakova, Georgios Karanikas, Richard Pötter, Marcus Hacker, Thomas Helbich, Dietmar Georg, Katja Pinker
PURPOSE: Imaging biomarkers assessed with magnetic resonance imaging (MRI) and/or positron emission tomography (PET) enable non-invasive tumor characterization in cervix cancer patients. We investigated the spatio-temporal stability of hypoxia, perfusion, and the cell density of tumors over time by repetitive imaging prior to, during, and after radio-chemotherapy. PROCEDURES: Thirteen patients were included in this prospective study. The imaging protocol included the following: [(18)F]fluoromisonidazole ([(18)F]FMISO)-PET/x-ray computed tomography (CT) and multiparametric (mp)-MRI at four time-points (TP): baseline (BL); and weeks 2 (TP1), 5 (TP2), and 19 after treatment start (follow-up FU)...
May 24, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28540417/monitoring-early-response-to-chemoradiotherapy-with-18-f-fmiso-dynamic-pet-in-head-and-neck-cancer
#5
Milan Grkovski, Nancy Y Lee, Heiko Schöder, Sean D Carlin, Bradley J Beattie, Nadeem Riaz, Jonathan E Leeman, Joseph A O'Donoghue, John L Humm
PURPOSE: There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of (18)F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC. EXPERIMENTAL DESIGN: Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy...
May 24, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28539466/modeling-the-cellular-response-of-lung-cancer-to-radiation-therapy-for-a-broad-range-of-fractionation-schedules
#6
Jeho Jeong, Jung Hun Oh, Jan-Jakob Sonke, José S A Belderbos, Jeffrey D Bradley, Andrew N Fontanella, Shyam S Rao, Joe Deasy
To demonstrate that a mathematical model can be used to quantitatively understand tumor cellular dynamics during a course of radiotherapy, and to predict the likelihood of local control as a function of dose and treatment fractions.<br /><br />Experimental Design: We model outcomes for early-stage, localized non-small cell lung cancer (NSCLC), by fitting a mechanistic, cellular dynamics-based tumor control probability that assumes a constant local supply of oxygen and glucose. In addition to standard radiobiological effects such as repair of sub-lethal damage and the impact of hypoxia, we also accounted for proliferation as well as radiosensitivity variability within the cell cycle...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28538666/melatonin-attenuates-pulmonary-hypertension-in-chronically-hypoxic-rats
#7
Ming Wai Hung, Hang Mee Yeung, Chi Fai Lau, Angela Ming See Poon, George L Tipoe, Man Lung Fung
Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O₂ for 14 days...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#8
REVIEW
Nathalie Dehne, Javier Mora, Dmitry Namgaladze, Andreas Weigert, Bernhard Brüne
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming...
May 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28537911/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#9
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew Wb Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537679/mir-15a-expression-analysis-in-non-small-cell-lung-cancer-a549-cells-under-local-hypoxia-microenvironment
#10
X-G Jing, T-F Chen, C Huang, H Wang, L An, Z Cheng, G-J Zhang
OBJECTIVE: Lung cancer is a common tumor in the clinic. Hypoxia is an important biological characteristic in the solid malignant tumor. MiRNA participates in cell proliferation, differentiation, and apoptosis. This study tested hypoxia-inducible factor 1-α (HIF-1α) in lung cancer patients and analyzed the microRNA-15a (miR-15a) expression in A549 cells under different local hypoxia microenvironments. PATIENTS AND METHODS: A total of 40 non-small cell lung cancer (NSCLC) patients in First Affiliated Hospital of Zhengzhou University between Jan 2015 and Jan 2016 were involved in this study...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28537472/a-novel-role-for-a-glycolytic-pathway-kinase-in-regulating-autophagy-has-implications-in-cancer-therapy
#11
Aileen R Ariosa, Daniel J Klionsky
When it comes to cancer initiation and progression, macroautophagy/autophagy seemingly acts in a contradictory fashion, serving either as a suppressive factor that functions to protect against tumor formation or as a support mechanism that sustains the disease itself through its cytoprotective functions. In tumor suppression, autophagy assists by restricting oxidative stress and curbing genomic instability that could possibly cause oncogenic mutations. However, in certain circumstances, autophagy can also promote cancer by providing nourishment and by limiting stress-response pathways, leading to cancer cell survival and rapid proliferation...
May 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28536635/the-regulatory-mechanisms-of-ng2-cspg4-expression
#12
REVIEW
Emmanuel Ampofo, Beate M Schmitt, Michael D Menger, Matthias W Laschke
Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28536481/trpv4-dependent-induction-of-a-novel-mammalian-cold-inducible-protein-srsf5-as-well-as-cirp-and-rbm3
#13
Takanori Fujita, Hiroaki Higashitsuji, Hisako Higashitsuji, Yu Liu, Katsuhiko Itoh, Toshiharu Sakurai, Takahiro Kojima, Shuya Kandori, Hiroyuki Nishiyama, Motoi Fukumoto, Manabu Fukumoto, Koji Shibasaki, Jun Fujita
Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are structurally related to hnRNPs and upregulated in response to moderately low temperatures in mammalian cells. Although contributions of splicing efficiency, the gene promoters activated upon mild hypothermia and the transcription factor Sp1 to induction of CIRP have been reported, precise mechanisms by which hypothermia and other stresses induce the expression of mammalian cold-inducible proteins (CIPs) are poorly understood...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536432/nuclear-translocation-of-hif-1%C3%AE-induced-by-influenza-a-h1n1-infection-is-critical-to-the-production-of-proinflammatory-cytokines
#14
Xinkun Guo, Zhaoqin Zhu, Wanju Zhang, Xiaoxiao Meng, Yong Zhu, Peng Han, Xiaohui Zhou, Yunwen Hu, Ruilan Wang
Infection with the influenza A (H1N1) virus is a major challenge for public health because it can cause severe morbidity and even mortality in humans. The over-secretion of inflammatory cytokines (cytokine storm) is considered to be a key contributor to the severe pneumonia caused by H1N1 infection. It has been reported that hypoxia-inducible factor 1-alpha (HIF-1α) is associated with the production of proinflammatory molecules, but whether HIF-1α participates in the acute inflammatory responses against H1N1 infection is still unclear...
May 24, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28536391/glioma-fmiso-pet-mr-imaging-concurrent-with-antiangiogenic-therapy-molecular-imaging-as-a-clinical-tool-in-the-burgeoning-era-of-personalized-medicine
#15
Ramon F Barajas, Kenneth A Krohn, Jeanne M Link, Randall A Hawkins, Jennifer L Clarke, Miguel H Pampaloni, Soonmee Cha
The purpose of this article is to provide a focused overview of the current use of positron emission tomography (PET) molecular imaging in the burgeoning era of personalized medicine in the treatment of patients with glioma. Specifically, we demonstrate the utility of PET imaging as a tool for personalized diagnosis and therapy by highlighting a case series of four patients with recurrent high grade glioma who underwent 18F-fluoromisonidazole (FMISO) PET/MR (magnetic resonance) imaging through the course of antiangiogenic therapy...
October 31, 2016: Biomedicines
https://www.readbyqxmd.com/read/28534992/hif-1%C3%AE-inhibits-idh-1-expression-in-osteosarcoma
#16
Deng-Cheng Liu, Xun Zheng, Yong Zho, Wan-Rong Yi, Zong-Huan Li, Xiang Hu, Ai-Xi Yu
Recently, hypoxia inducible factor-1 (HIF-1) was reported to be correlated with isocitrate dehydrogenase 1 (IDH-1) in several types of tumors. However, the expression and significance of HIF-1 and IDH-1 in osteosarcoma is still unknown. In the present study, the expression levels of IDH-1 and HIF-1α in 35 formalin-fixed paraffin-embedded sections from osteosarcoma patients were investigated by immunohistochemistry. The expression levels of IDH-1 and HIF-1α in human osteosarcoma cell lines (MG-63 and 143B) were further detected by western blotting under normal and hypoxic conditions...
May 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#17
J-Y Lee, J-H Park, H-J Choi, H-Y Won, H-S Joo, D-H Shin, M K Park, B Han, K P Kim, T J Lee, C M Croce, G Kong
Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534419/correlation-between-hypoxic-area-in-primary-brain-tumors-and-who-grade-differentiation-from-malignancy-using-18f-fluoromisonidazole-positron-emission-tomography
#18
Masafumi Kanoto, Kazukuni Kirii, Toshitada Hiraka, Yuuki Toyoguchi, Yukio Sugai, Kenichiro Matsuda, Kaori Sakurada, Yukihiko Sonoda, Jun Hatazawa, Takaaki Hosoya
Background 18F-fluoromisonidazole positron emission tomography (FMISO-PET) has been used for identification of hypoxic areas in tumors, and since hypoxia causes hypoxia-inducible factor-1 and enhancement of tumor growth, identifying the hypoxic area in the tumor tissue is important. Purpose To evaluate the usefulness of FMISO-PET in the grading of primary brain tumors. Material and Methods FMISO-PET was performed preoperatively on 41 consecutive patients with pathologically confirmed brain tumor. A neuroradiologist retrospectively measured both maximum standardized uptake value (SUVmax) and mean SUV (SUVmean) in the tumor and normal cerebellar parenchyma...
January 1, 2017: Acta Radiologica
https://www.readbyqxmd.com/read/28533661/macrophage-inflammatory-protein-2-as-mediator-of-inflammation-in-acute-liver-injury
#19
REVIEW
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen
Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28530543/using-properties-of-tumor-microenvironments-for-controlling-local-on-demand-delivery-from-biopolymer-based-nanocarriers
#20
Abdullah K Alshememry, Suleiman S El-Tokhy, Larry D Unsworth
BACKGROUND: The 'tumor microenvironment' comprised of tumor cells, non-malignant stromal tissues, signaling molecules and the extracellular matrix. Tumor microenvironment has unique physical and physiological characteristics including vascular abnormalities, hypoxia, acidic pH, specific enzymes and growth factors upregulation and high reducing potential. It is these endogenous properties of the tumor environment that can be used to trigger the release of cancer therapeutics both locally and as a function of disease state...
May 21, 2017: Current Pharmaceutical Design
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