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https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#1
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
#2
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/28537761/correlation-analysis-of-18-f-fluorodeoxyglucose-and-18-f-fluoroazomycin-arabinoside-uptake-distributions-in-lung-tumours-during-radiation-therapy
#3
Dario Di Perri, John A Lee, Anne Bol, François-Xavier Hanin, Guillaume Janssens, Daniel Labar, Annie Robert, Edmond Sterpin, Xavier Geets
BACKGROUND: PET-guided dose painting (DP) aims to target radioresistant tumour regions in order to improve radiotherapy (RT) outcome. Besides the well-known [(18)F]fluorodeoxyglucose (FDG), the hypoxia positron emission tomography (PET) tracer [(18)F]fluoroazomycin arabinoside (FAZA) could provide further useful information to guide the radiation dose prescription. In this study, we compare the spatial distributions of FDG and FAZA PET uptakes in lung tumours. MATERIAL AND METHODS: Fourteen patients with unresectable lung cancer underwent FDG and FAZA 4D-PET/CT on consecutive days at three time-points: prior to RT (pre), and during the second (w2), and the third (w3) weeks of RT...
May 24, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28534514/integration-of-hypoxic-hif-%C3%AE-signaling-in-blood-cancers
#4
REVIEW
L Schito, S Rey, M Konopleva
Hypoxia (low O2) is a fundamental microenvironmental determinant of bone marrow (BM) pathophysiology. Recent data from molecular and clinical studies indicate that hematopoiesis and leukemogenesis are dependent upon hypoxia-inducible factors (HIFs), a family of essential transcriptional activators mediating the metazoan hypoxic response. In blood cancers, the synergism between HIF overexpression and stabilization within the hypoxic BM microenvironment promotes disease progression, therapy resistance and relapse...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#5
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/28530543/using-properties-of-tumor-microenvironments-for-controlling-local-on-demand-delivery-from-biopolymer-based-nanocarriers
#6
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
https://www.readbyqxmd.com/read/28529605/mutual-regulation-of-mir-199a-5p-and-hif-1%C3%AE-modulates-the-warburg-effect-in-hepatocellular-carcinoma
#7
Binkui Li, Liru He, Dinglan Zuo, Wei He, Yongjin Wang, Yuanping Zhang, Wenwu Liu, Yunfei Yuan
The Warburg effect is one of the major metabolic changes of cancer cells, which characterized by high level of glycolysis even in the presence of oxygen. However, the role of microRNAs (miRNAs) in regulating the glycolytic switch in cancer cells has not been well explored. In this study, we demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in hepatocellular carcinoma (HCC). MiR-199a-5p directly targets the 3'-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529559/fbp1-expression-is-associated-with-basal-like-breast-carcinoma
#8
Lei Shi, Chunbo Zhao, Haihong Pu, Qingyuan Zhang
The present study aimed to investigate the value of liver fructose 1,6-bisphophatase (FBP1) and hypoxia-inducible factor-1α (HIF-1α) in the molecular subtyping of breast carcinoma. Tissue obtained from 60 surgical specimens from patients with breast carcinoma underwent immunohistochemical staining for cytokeratin 5/6, HIF-1α and FBP1. The variation in the expression levels of these markers and clinicopathological factors were compared between molecular subtypes. In addition, disease-free survival was compared between basal-like and luminal breast carcinoma, according to differing expression levels of HIF-1α and FBP1...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28527256/-stat3-activation-by-hypoxia-in-in-vitro-models-of-cervix-cancer-and-endothelial-cells
#9
Óscar Ortega, Alejandro Ondo-Méndez, Ruth Garzón
INTRODUCTION: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. OBJECTIVE: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526370/synthesis-and-biological-evaluation-of-kresoxim-methyl-analogues-as-novel-inhibitors-of-hypoxia-inducible-factor-hif-1-accumulation-in-cancer-cells
#10
Sanghyuck Lee, Oh Seok Kwon, Chang-Soo Lee, Misun Won, Hyun Seung Ban, Choon Sup Ra
We designed and synthesized strobilurin analogues as hypoxia-inducible factor (HIF) inhibitors based on the molecular structure of kresoxim-methyl. Biological evaluation in human colorectal cancer HCT116 cells showed that most of the synthesized kresoxim-methyl analogues possessed moderate to potent inhibitory activity against hypoxia-induced HIF-1 transcriptional activation. Three candidates, compounds 11b, 11c, and 11d were identified as potent inhibitors against HIF-1 activation with IC50 values of 0.60-0...
May 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28526262/hypoxic-pathobiology-of-breast-cancer-metastasis
#11
REVIEW
Luana Schito, Sergio Rey
Dissemination of breast cancer cells (BCCs) to distant sites (metastasis) is the ultimate cause of mortality in patients with breast cancer. Hypoxia (low O2) is a microenvironmental hallmark of most solid cancers arising as a mismatch between cellular O2 consumption and supply. Hypoxic selection of BCCs triggers molecular and cellular adaptations dependent upon hypoxia-inducible factors (HIFs), a family of evolutionarily conserved transcriptional activators that coordinate the expression of numerous genes controlling each step of the metastatic process...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28525507/subcellular-energetics-and-metabolism-a-cross-species-framework
#12
Robert H Thiele
Although it is generally believed that oxidative phosphorylation and adequate oxygenation are essential for life, human development occurs in a profoundly hypoxic environment and "normal" levels of oxygen during embryogenesis are even harmful. The ability of embryos not only to survive but also to thrive in such an environment is made possible by adaptations related to metabolic pathways. Similarly, cancerous cells are able not only to survive but also to grow and spread in environments that would typically be fatal for healthy adult cells...
June 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28525452/concomitant-lung-cancer-and-gastrointestinal-stromal-tumor-first-report-of-hypoxia-imaging-with-18f-faza-pet-ct
#13
Paola Mapelli, Elena Incerti, Federico Fallanca, Valentino Bettinardi, Antonia Compierchio, Valeria Masiello, Claudio Doglioni, Francesca Rossetti, Giampiero Negri, Luigi Gianolli, Maria Picchio
A 76-year-old man underwent F-FDG PET/CT to complete staging and characterize a suspicious lung mass. Images showed intense uptake in the lung lesion and faint uptake in correspondence of a gastric mass, which was subsequently biopsied revealing a gastrointestinal stromal tumor. A F-FAZA PET/CT was also performed because of patient's enrollment in a prospective clinical trial (trial registration no. EudraCT 2011-002647-98), showing heterogeneous uptake of F-FAZA in the pulmonary lesion and faint uptake in correspondence of the gastrointestinal stromal tumor...
May 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28524177/role-of-carbonic-anhydrases-in-skin-wound-healing
#14
Harlan Barker, Marleena Aaltonen, Peiwen Pan, Maria Vähätupa, Pirkka Kaipiainen, Ulrike May, Stuart Prince, Hannele Uusitalo-Järvinen, Abdul Waheed, Silvia Pastoreková, William S Sly, Seppo Parkkila, Tero Ah Järvinen
Skin wound closure occurs when keratinocytes migrate from the edge of the wound and re-epithelialize the epidermis. Their migration takes place primarily before any vascularization is established, that is, under hypoxia, but relatively little is known regarding the factors that stimulate this migration. Hypoxia and an acidic environment are well-established stimuli for cancer cell migration. The carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28523727/synthesis-and-antineoplastic-evaluation-of-mitochondrial-complex-ii-succinate-dehydrogenase-inhibitors-derived-from-atpenin-a5
#15
Hezhen Wang, Bader Huwaimel, Kshitij Verma, James Miller, Todd Germain, Nihar Kinarivala, Dimitri Pappas, Paul Brookes, Paul Charles Trippier
Mitochondrial complex II (CII) is an emerging target for numerous human diseases. Sixteen analogues of the CII inhibitor natural product atpenin A5 were prepared to evaluate the structure-activity relationship of the C-5 pyridine side chain. The side chain ketone moiety was determined to be pharmacophoric, engendering a bioactive conformation. Analogue 16c displayed CII IC50 = 64 nM, retained selectivity for CII over mitochondrial complex I (>156-fold) and possessed a ligand-lipophilicity efficiency of 5...
May 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28523294/autophagy-in-aging-and-disease
#16
Mădălina Fîlfan, Raluca Elena Sandu, Alexandra Daniela Zăvăleanu, Andrei GreşiŢă, Daniela Gabriela Glăvan, Denissa Greta Olaru, Aurel Popa-Wagner
Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28522758/regulation-of-erythropoiesis-after-normoxic-return-from-chronic-sustained-and-intermittent-hypoxia
#17
Jihyun Song, Krishna Sundar, Radhika Gangaraju, Josef T Prchal
Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF) which regulate erythropoietin (EPO) transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia (CSH) by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species (ROS) in reticulocytes mediated by down-regulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#18
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522191/enhanced-tumor-therapy-via-drug-co-delivery-and-in-situ-vascular-promoting-strategy
#19
Mingxing Yin, Songwei Tan, Yuling Bao, Zhiping Zhang
Conventional tumor starving therapy by reducing its vessel density may be effective at early treatment but potentially contributes to tumor hypoxia, drug resistance and metastasis. A new strategy through enhancing tumor angiogenesis in combination with effective chemotherapeutic drugs, has shown successful tumor growth and spread inhibition. To achieve in situ release of angiogenic and antitumor drugs in tumor, we designed a precise ratiometric polymeric hybrid micelle system for co-delivering nitric oxide and paclitaxel...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28521491/hif-1%C3%AE-acts-as-a-molecular-target-for-simvastatin-cytotoxicity-in-b16-f10-melanoma-cells-cultured-under-chemically-induced-hypoxia
#20
Emilia Licarete, Alina Sesarman, Valentin Florian Rauca, Lavinia Luput, Laura Patras, Manuela Banciu
Our previous studies reported that one of the main mechanisms of the antitumor activity of simvastatin (SIM) in B16.F10 murine melanoma cells was associated with strong suppression of the constitutive cell production of the α subunit of the heterodimeric transcription factor hypoxia-inducible factor (HIF)-1. Thus, the present study aimed to broaden this finding under hypoxic conditions induced by incubation of B16.F10 cells with cobalt chloride, when the constitutive production of HIF-1α in these melanoma cells is amplified by inducible expression of this factor...
May 2017: Oncology Letters
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