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Tumor hypoxia

Danielle E Jenkins, Dharshini Sreenivasan, Fiona Carman, Samal Babru, Lee E Eiden, Stephen J Bunn
The pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-1β/α modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Since interleukin-6 (IL6) also plays a key integrative role during inflammation, we have examined its ability to affect both tyrosine hydroxylase activity and adrenomedullary gene transcription in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine/tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3)...
October 22, 2016: Journal of Neurochemistry
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
Guosheng Song, Chenghong Ji, Chao Liang, Xuejiao Song, Xuan Yi, Ziliang Dong, Kai Yang, Zhuang Liu
Cancer radiotherapy (RT) is a clinically used tumor treatment strategy applicable for a wide range of solid tumors. However, during RT treatment of tumors, only a small portion of applied ionizing irradiation energy is absorbed by the tumor, in which the largely hypoxic microenvironment also limits the anti-tumor efficacy of RT. In this work, we rationally fabricate polyethylene glycol (PEG) stabilized perfluorocarbon (PFC) nano-droplets decorated with TaOx nanoparticles (TaOx@PFC-PEG) as a multifunctional RT sensitizer...
October 11, 2016: Biomaterials
Yun-Wen Yang, Chun-Mei Zhang, Xian-Jie Huang, Xiao-Xin Zhang, Lin-Kai Zhang, Jia-Huang Li, Zi-Chun Hua
Fas-associated protein with death domain (FADD), a pivotal adaptor protein transmitting apoptotic signals, is indispensable for the induction of extrinsic apoptosis. However, overexpression of FADD can form large, filamentous aggregates, termed death effector filaments (DEFs) by self-association and initiate apoptosis independent of receptor cross-linking. A mutant of FADD, which is truncated of the C-terminal tail (m-FADD, 182-205 aa) named N-FADD (m-FADD, 1-181 aa), can dramatically up-regulate the strength of FADD self-association and increase apoptosis...
October 21, 2016: Scientific Reports
Mark A Applebaum, Aashish R Jha, Clara Kao, Kyle M Hernandez, Gillian DeWane, Helen R Salwen, Alexandre Chlenski, Marija Dobratic, Christopher J Mariani, Lucy A Godley, Nanduri Prabhakar, Kevin White, Barbara E Stranger, Susan L Cohn
Neuroblastoma is notable for its broad spectrum of clinical behavior ranging from spontaneous regression to rapidly progressive disease. Hypoxia is well known to confer a more aggressive phenotype in neuroblastoma. We analyzed transcriptome data from diagnostic neuroblastoma tumors and hypoxic neuroblastoma cell lines to identify genes whose expression levels correlate with poor patient outcome and are involved in the hypoxia response. By integrating a diverse set of transcriptome datasets, including those from neuroblastoma patients and neuroblastoma derived cell lines, we identified nine genes (SLCO4A1, ENO1, HK2, PGK1, MTFP1, HILPDA, VKORC1, TPI1, and HIST1H1C) that are up-regulated in hypoxia and whose expression levels are correlated with poor patient outcome in three independent neuroblastoma cohorts...
October 17, 2016: Oncotarget
Minghui Ou, Xuezhi Sun, Jiancheng Liang, Fei Liu, Liqin Wang, Xiaomin Wu, Jie Tu
A water-soluble polysaccharide (STPC2) was isolated from the boiling-water extract of Sargassum thunbergii, purified by CaCl2 precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 column. It was found that STPC2, with a molecular weight of 57kD, was composed of fucose, xylose, galactose and glucuronic acid, in a ratio of 8.1: 3.8: 2.1: 1.0. Additionally, we found that STPC2 significantly inhibited endothelial cell migration and tube formation without toxicity. Moreover, STPC2 significantly inhibited lung cancer cell A549 migration and proliferation...
October 17, 2016: International Journal of Biological Macromolecules
Naoshi Nishida, Masatoshi Kudo
Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with advanced stage of disease remains unfavorable. Several immune therapies have been applied to HCC, and their responses have not been satisfactory. The immune response to cancer is determined by the balance between the antigenicity of the tumor and the microenvironment of cancer tissues. Generally, accumulated genetic mutations are observed in HCC, which may lead to increased neoantigens on cancer cells with high antigenicity...
October 21, 2016: Oncology
Tong Zhou, Luke Erber, Bing Liu, Yankun Gao, Hai-Bin Ruan, Yue Chen
Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs...
October 13, 2016: Oncotarget
Shasha Li, Hao Hu, Zhiheng He, Deguang Liang, Rui Sun, Ke Lan
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation...
October 2016: PLoS Pathogens
Lin Chen, Jie Li, Fei Wang, Chengliang Dai, Fan Wu, Xiaoman Liu, Taotao Li, Rainer Glauben, Yi Zhang, Guangjun Nie, Yulong He, Zhihai Qin
Tumor relapse after chemotherapy is a major hurdle for successful cancer therapy. Chemotherapeutic drugs select for resistant tumor cells and reshape tumor microenvironment, including the blood supply system. Using animal models, we observed on macrophages in tumor tissue a close correlation between upregulated Tie2 expression and tumor relapse upon chemotherapy. Conditional deletion of Tie2 expression in macrophages significantly prohibited blood supply and regrowth of tumors. Tie2+ macrophages were derived from tumor infiltrating Tie2-CD11b+ cells, and hypoxia induced Tie2 expression on these cells...
October 10, 2016: Cancer Research
Azhar Z Abbasi, Claudia R Gordijo, Mohammad Ali Amini, Azusa Maeda, Andrew M Rauth, Ralph S DaCosta, Xiao Yu Wu
Hypoxia in the tumor microenvironment (TME) mediates resistance to radiotherapy (RT) and contributes to poor prognosis in patients receiving RT. Here we report the design of clinically suitable formulations of hybrid manganese dioxide (MnO2) nanoparticles (MDNP) using biocompatible materials to re-oxygenate the TME by reacting with endogenous H2O2. MDNP containing hydrophilic terpolymer-protein-MnO2 or hydrophobic polymer-lipid-MnO2 provided different oxygen generation rates in the TME relevant to different clinical settings...
October 6, 2016: Cancer Research
Edem Dovlo, Bahman Lashkari, Sung Soo Sean Choi, Andreas Mandelis, Wei Shi, Fei-Fei Liu
Overcoming the limitations of conventional linear spectroscopy used in multispectral photoacoustic imaging, wherein a linear relationship is assumed between the absorbed optical energy and the absorption spectra of the chromophore at a specific location, is crucial for obtaining accurate spatially-resolved quantitative functional information by exploiting known chromophore-specific spectral characteristics. This study introduces a non-invasive phase-filtered differential photoacoustic technique, wavelength-modulated differential photoacoustic radar (WM-DPAR) imaging that addresses this issue by eliminating the effect of the unknown wavelength-dependent fluence...
October 19, 2016: Journal of Biophotonics
Perparim Limani, Michael Linecker, Philipp Kron, Panagiotis Samaras, Bernhard Pestalozzi, Roger Stupp, Alexander Jetter, Philipp Dutkowski, Beat Müllhaupt, Andrea Schlegel, Claude Nicolau, Jean-Marie Lehn, Henrik Petrowsky, Bostjan Humar, Rolf Graf, Pierre-Alain Clavien
BACKGROUND: Solid tumors, such as hepato-pancreato-biliary cancer, develop tumor hypoxia with tumor growth. Despite advances in surgery, a majority of these patients are in an unresectable condition. At this stage standard cytotoxic chemotherapy regimens are applied with limited success. Novel biological treatment options based on an antiangiogenic mechanism of action neglect other hypoxia mediated mechanisms (e.g. epithelial-mesenchymal transition, Warburg effect, and immunological response) leading to an increased invasiveness with a poor outcome...
October 19, 2016: BMC Cancer
Maud-Emmanuelle Gilles, Federica Maione, Mélissande Cossutta, Gilles Carpentier, Laure Caruana, Sylvia Di Maria, Claire Houppe, Damien Destouches, Ksenya Shchors, Christopher Prochasson, Fabien Mongelard, Simona Lamba, Alberto Bardelli, Philippe Bouvet, Anne Couvelard, José Courty, Enrico Giraudo, Ilaria Cascone
Pancreatic cancer is a highly aggressive tumor, mostly resistant to the standard treatments. Nucleolin (NCL) is overexpressed in cancers and its inhibition impairs tumor growth. Herein we showed that NCL was overexpressed in human specimens of pancreatic ductal adenocarcinoma (PDAC) and that the overall survival significantly increased in patients with low levels of NCL. The NCL antagonist N6L strongly impaired the growth of primary tumors and liver metastasis in an orthotopic mouse model of PDAC (mPDAC). Similar anti-tumor effect of N6L has been observed in a highly angiogenic mouse model of pancreatic neuroendocrine tumor RIP-Tag2...
October 17, 2016: Cancer Research
Jonas Magno Santos Cesário, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Chrisna Souza Silva, Yves Silva Teles Matos, Tânia Cristina Macedo Kunz, Jessica Julioti Urbano, Luis Vicente Franco Oliveira, Maria Aparecida Dalboni, Humberto Dellê
Angiogenesis is an essential process for the establishment, development, and dissemination of several malignant tumors including bladder cancer. The hypoxic condition promotes the stabilization of hypoxia-inducible factor 1 alpha (HIF-1α), which translocates to the nucleus to mediate angiogenic factors including the vascular endothelial growth factor A (VEGF-A). AnaeroGen system was developed for microbiology area to create a low oxygen tension required to the growth of anaerobic bacteria. Here, we hypothesized the use of AnaeroGen system to induce hypoxia in T24 human bladder carcinoma cells, in order to promote the overexpression of VEGF-A...
October 17, 2016: In Vitro Cellular & Developmental Biology. Animal
Takuya Toyonaga, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Osamu Manabe, Shiro Watanabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Shinya Tanaka, Yoichi M Ito, Nagara Tamaki
PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention...
October 18, 2016: European Journal of Nuclear Medicine and Molecular Imaging
Ashley M Stokes, Charles P Hart, C Chad Quarles
High-grade gliomas are often characterized by hypoxia, which is associated with both poor long-term prognosis and therapy resistance. The adverse role hypoxia plays in treatment resistance and disease progression has led to the development of hypoxia imaging methods and hypoxia-targeted treatments. Here, we determined the tumor hypoxia and vascular perfusion characteristics of 2 rat orthotopic glioma models using 18-fluoromisonidozole positron emission tomography. In addition, we determined tumor response to the hypoxia-activated prodrug evofosfamide (TH-302) in these rat glioma models...
September 2016: Tomography: a Journal for Imaging Research
Qing Zhang, Qing Zhang, Yanxing Guan, Shaozheng Liu, Qingjie Chen, Xiangmin Li
BACKGROUND This study was specifically designed to develop a new 99mTc compound with 3-amino-4-[2-(2-methyl-5-nitro-1H-imidazol)-ethylamino]-4-oxo-butyrate (5-ntm-asp) and to verify whether this compound is feasible to be a radiopharmaceutical for hypoxic tumors. MATERIAL AND METHODS Metronidazole derivative 5-ntm-asp was synthesized and then radio-labeled by Na [99mTcO4], forming 99mTc-5-ntm-asp. Another two complexes of 99mTc-2- and 99mTc-5-nitroimidazole-iminodiacetic acid (99mTc-2-ntm-IDA and 99mTc-5-ntm-IDA) were also synthesized based on previous studies...
October 18, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ying Wang, Tao Liu, Ning Yang, Shuo Xu, Xingang Li, Donghai Wang
Glioblastoma (GBM) is a highly malignant brain tumor characterized by invasion tendency. Macrophage infiltration is associated with GBM invasion, but the mechanisms remain unclear. Hypoxia is an outstanding characteristic of GBM tissue. Hypoxia microenvironment modulates the biological behaviors of both tumor cells and infiltrated immune cells, including macrophages. In the present study, we analyzed the effects of hypoxia and macrophages on invasion of GBM cells and its potential mechanisms. We found that both hypoxia and macrophage supernatant promoted GBM cells invasion and matrix metalloproteinase (MMP)-9 expression, and hypoxia modulated the invasive activity of GBM cells by upregulating their CCR5 expression...
October 13, 2016: Oncology Reports
A Cacace, M Sboarina, T Vazeille, P Sonveaux
Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glutamine, and this addiction is observed in oxidative as well as in glycolytic cells. Although both oxidative and bioreductive glutamine metabolism can contribute to cancer progression and glutamine can further serve to generate peptides (including glutathione) and proteins, we report that glutamine promotes the proliferation of cancer cells independently of its use as a metabolic fuel or as a precursor of glutathione...
October 17, 2016: Oncogene
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