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https://www.readbyqxmd.com/read/28944843/microarray-and-bioinformatics-analyses-of-gene-expression-profiles-in-balb-c-murine-macrophage-polarization
#1
Li Jiang, Xueqin Li, Yingying Zhang, Mengying Zhang, Zongsheng Tang, Kun Lv
Macrophages possess the hallmark feature of plasticity, allowing them to undergo a dynamic transition between M1 and M2 polarized phenotypes. The aim of the present study was to screen for differentially-expressed genes (DEGs) that were associated with BALB/c murine macrophage polarization. The transcription profiles of three M1 and three M2 samples were obtained using microarray analysis. Based on the threshold of fold‑change >2.0 and P‑value <0.05, a total of 1,253 DEGs were identified, of which 696 were upregulated and 557 downregulated in M1 macrophages compared with M2 macrophages...
September 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944496/the-unidirectional-hypoxia-activated-prodrug-oct1002-inhibits-growth-and-vascular-development-in-castrate-resistant-prostate-tumors
#2
Heather Nesbitt, Jenny Worthington, Rachel J Errington, Laurence H Patterson, Paul J Smith, Stephanie R McKeown, Declan J McKenna
BACKGROUND: OCT1002 is a unidirectional hypoxia-activated prodrug (uHAP) OCT1002 that can target hypoxic tumor cells. Hypoxia is a common feature in prostate tumors and is known to drive disease progression and metastasis. It is, therefore, a rational therapeutic strategy to directly target hypoxic tumor cells in an attempt to improve treatment for this disease. Here we tested OCT1002 alone and in combination with standard-of-care agents in hypoxic models of castrate-resistant prostate cancer (CRPC)...
September 24, 2017: Prostate
https://www.readbyqxmd.com/read/28943924/network-based-analysis-of-the-molecular-mechanisms-of-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance
#3
Zhi Liu, Jing Huang, Qi Zhong, Yanling She, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to reveal the molecular mechanisms of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). This was a secondary study on microarray dataset GSE80608, downloaded from the Gene Expression Omnibus database, which included 10 control samples, 10 MGUS samples and 10 MM samples. Differentially expressed genes (DEGs) were identified between control and MGUS samples, and between control and MM samples. A protein-protein interaction (PPI) network was built for studying the interactions between the DEGs...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28942194/the-2-oxoglutarate-carrier-promotes-liver-cancer-by-sustaining-mitochondrial-gsh-despite-cholesterol-loading
#4
Anna Baulies, Joan Montero, Nuria Matías, Naroa Insausti, Oihana Terrones, Gorka Basañez, Carmen Vallejo, Laura Conde de La Rosa, Laura Martinez, David Robles, Albert Morales, Joaquin Abian, Montserrat Carrascal, Keigo Machida, Dinesh B U Kumar, Hidekazu Tsukamoto, Neil Kaplowitz, Carmen Garcia-Ruiz, José C Fernández-Checa
Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC), by depleting mitochondrial GSH (mGSH) due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown...
September 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28940980/sulfocoumarin-coumarin-4-sulfamoylphenyl-bearing-indazole-3-carboxamide-hybrids-synthesis-and-selective-inhibition-of-tumor-associated-carbonic-anhydrase-isozymes-ix-and-xii
#5
Srinivas Angapelly, P V Sri Ramya, Andrea Angeli, Claudiu T Supuran, Mohammed Arifuddin
A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a-g (amide derivatives) and 7 a-h (triazoles) act as "prodrugs", and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets...
September 2, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28938563/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#6
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew W B 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...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937321/enhancement-of-radiotherapy-efficacy-by-pleiotropic-liposomes-encapsulated-paclitaxel-and-perfluorotributylamine
#7
Xing Jiang, Baoli Zhang, Zaigang Zhou, Lingtong Meng, Zhiling Sun, Yun Xu, Qiuping Xu, Ahu Yuan, Lixia Yu, Hanqing Qian, Jinhui Wu, Yiqiao Hu, Baorui Liu
Paclitaxel (PTX) is widely used as a radiosensitizer in the clinical treatment of cancer. However, the efficacy of chemoradiotherapy is limited by the hostility of the tumor microenvironment such as hypoxia. To overcome this constraint, we designed pleiotropic radiotherapy sensitized liposomes containing perfluorotributylamine (PFTBA) and PTX. The results showed that liposomes significantly accumulated in the tumor site. PFTBA in liposomes dramatically reversed tumor hypoxia and improved the sensitivity of tumor radiotherapy...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28936522/a-novel-hif-1%C3%AE-vmp1-autophagic-pathway-induces-resistance-to-photodynamic-therapy-in-colon-cancer-cells
#8
M E Rodríguez, C Catrinacio, A Ropolo, V A Rivarola, M I Vaccaro
Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as an adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumors and leads to chemo/radioresistance. Recently, it has been shown that in response to hypoxia, cells can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment...
September 22, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28936211/regulation-of-human-macrophage-m1-m2-polarization-balance-by-hypoxia-and-the-triggering-receptor-expressed-on-myeloid-cells-1
#9
Federica Raggi, Simone Pelassa, Daniele Pierobon, Federica Penco, Marco Gattorno, Francesco Novelli, Alessandra Eva, Luigi Varesio, Mirella Giovarelli, Maria Carla Bosco
Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28929492/potent-antitumor-effect-of-tumor-microenvironment-targeted-oncolytic-adenovirus-against-desmoplastic-pancreatic-cancer
#10
Yan Li, JinWoo Hong, Joung-Eun Oh, A-Rum Yoon, Chae-Ok Yun
Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT-driven transgene expression was highly cancer-specific and was superior to that of H(mT)E-driven expression...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28929255/carbonic-anhydrase-ix-inhibition-affects-viability-of-cancer-cells-adapted-to-extracellular-acidosis
#11
Elena Andreucci, Silvia Peppicelli, Fabrizio Carta, Giulia Brisotto, Eva Biscontin, Jessica Ruzzolini, Francesca Bianchini, Alessio Biagioni, Claudiu T Supuran, Lido Calorini
Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity...
September 19, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28927099/interleukin-6-identified-as-an-important-factor-in-hypoxia-and-aldehyde-dehydrogenase-based-gefitinib-adaptive-resistance-in-non-small-cell-lung-cancer-cells
#12
Shi-Min An, Hui-Min Lei, Xu-Ping Ding, Fan Sun, Chun Zhang, Ya-Bin Tang, Hong-Zhuan Chen, Ying Shen, Liang Zhu
Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues in vivo, roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926956/carbonic-anhydrase-inhibition-and-the-management-of-hypoxic-tumors
#13
REVIEW
Claudiu T Supuran
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors...
September 16, 2017: Metabolites
https://www.readbyqxmd.com/read/28925921/au-pt-nanoparticles-as-catalase-mimics-to-attenuate-tumor-hypoxia-and-enhance-immune-cell-mediated-cytotoxicity
#14
Juan Li, Hong Liang, Ying Wu, Xiang-Yu Ou, Jingying Li
Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor (HIF)-1α expression...
September 19, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28925397/coactosin-like-protein-clp-cotl1-suppresses-breast-cancer-growth-through-activation-of-il-24-perp-and-inhibition-of-non-canonical-tgf%C3%AE-signaling
#15
L Xia, X Xiao, W L Liu, Y Song, T J J Liu, Y J Li, E Zacksenhaus, X J Hao, Y Ben-David
Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924948/magnetic-nanoparticles-for-the-delivery-of-dapagliflozin-to-hypoxic-tumors-physicochemical-characterization-and-cell-studies
#16
Athina Angelopoulou, Efstathia Voulgari, Argiris Kolokithas-Ntoukas, Aristides Bakandritsos, Konstantinos Avgoustakis
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors...
September 18, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28923859/upregulation-of-cystathionine-%C3%AE-synthase-in-colonic-epithelia-reprograms-metabolism-and-promotes-carcinogenesis
#17
Ches'Nique M Phillips, John Zatarain, Michael E Nicholls, Craig Porter, Steve G Widen, Ketan Thanki, Paul Johnson, Muhammad U Jawad, Mary Pat Moyer, James W Randall, Judith L Hellmich, Manjit Maskey, Suimin Qiu, Thomas Wood, Nadiya Druzhyna, Bartosz Szczesny, Katalin Modis, Csaba Szabo, Celia Chao, Mark R Hellmich
The transsulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28922791/targeting-hypoxia-to-improve-non-small-cell-lung-cancer-outcome
#18
Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O'Connor, Corinne Faivre-Finn
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922619/identification-of-angiogenesis-inhibitors-using-a-co-culture-cell-model-in-a-high-content-and-high-throughput-screening-platform
#19
Shuaizhang Li, Chia-Wen Hsu, Srilatha Sakamuru, Chaozhong Zou, Ruili Huang, Menghang Xia
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28918350/expression-and-functional-characterization-of-the-bnip3-protein-in-renal-cell-carcinomas
#20
Stephan Macher-Goeppinger, Martina Keith, Gencay Hatiboglu, Markus Hohenfellner, Peter Schirmacher, Wilfried Roth, Katrin E Tagscherer
BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a BH3-only protein that regulates apoptosis and autophagy. BNIP3 plays also an important role in hypoxia-induced cell response and is regulated by HIF1. Here, we studied a possible association of BNIP3 expression and the prognosis of patients with renal cell carcinomas (RCCs) and examined the functional relevance of BNIP3 in the regulation of cell survival and apoptosis of renal carcinoma cells. BNIP3 expression was determined by immunohistochemistry in RCC tumor tissue samples of 569 patients using a tissue microarray...
September 14, 2017: Translational Oncology
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