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hypoxia tumor

Xiaolan Zhu, Huiling Shen, Xinming Yin, Meiling Yang, Hong Wei, Qi Chen, Fan Feng, Yueqin Liu, Wenlin Xu, Yuefeng Li
BACKGROUND: How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood. METHODS: The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
David Ball, G Tao Mai, Shalini Vinod, Scott Babington, Jeremy Ruben, Tomas Kron, Brent Chesson, Alan Herschtal, Marijana Vanevski, Angela Rezo, Christine Elder, Marketa Skala, Andrew Wirth, Greg Wheeler, Adeline Lim, Mark Shaw, Penelope Schofield, Louis Irving, Benjamin Solomon
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques. METHODS: We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand...
February 12, 2019: Lancet Oncology
Fanghui Zhang, Rongrong Li, Yunshan Yang, Chunhui Shi, Yingying Shen, Chaojie Lu, Yinghu Chen, Wu Zhou, Aifu Lin, Lei Yu, Wanjing Zhang, Zhenwei Xue, Jianli Wang, Zhijian Cai
Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19+ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8+ T cell responses. Serum CD19+ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19+ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19+ EVs by inducing Rab27a mRNA transcription...
February 6, 2019: Immunity
Ruben D Addie, Yvonne de Jong, Gaia Alberti, Alwine B Kruisselbrink, Ivo Que, Hans Baelde, Judith V M G Bovée
Background: Chondrosarcomas are malignant cartilage-producing tumors showing mutations and changes in gene expression in metabolism related genes. In this study, we aimed to explore the metabolome and identify targetable metabolic vulnerabilities in chondrosarcoma. Methods: A custom-designed metabolic compound screen containing 39 compounds targeting different metabolic pathways was performed in chondrosarcoma cell lines JJ012, SW1353 and CH2879. Based on the anti-proliferative activity, six compounds were selected for validation using real-time metabolic profiling...
April 2019: Journal of Bone Oncology
Jun Suzuki, Motohiro Kojima, Keiju Aokage, Takashi Sakai, Hiroshi Nakamura, Yuuki Ohara, Kenta Tane, Tomohiro Miyoshi, Masato Sugano, Satoshi Fujii, Takeshi Kuwata, Atsushi Ochiai, Masaaki Ito, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
Metastatic lung cancers from the colon and rectum (MLCR) frequently have necrotic components. The aim of this study is to elucidate clinicopathological factors associated with the amount of necrosis in MLCR. Ninety patients who underwent the first pulmonary metastasectomy for MLCR with a tumor diameter ≦ 3.0 cm and without chemotherapy were enrolled in this study. Analyzing digitally scanned pathological slides, we calculated the necrosis percentage (NP, the necrosis area divided by the tumor area). The relationship between NP and clinicopathological factors was analyzed...
February 14, 2019: Virchows Archiv: An International Journal of Pathology
Wafaa Al Tameemi, Tina P Dale, Rakad M Kh Al-Jumaily, Nicholas R Forsyth
While oxygen is critical to the continued existence of complex organisms, extreme levels of oxygen within a system, known as hypoxia (low levels of oxygen) and hyperoxia (excessive levels of oxygen), potentially promote stress within a defined biological environment. The consequences of tissue hypoxia, a result of a defective oxygen supply, vary in response to the gravity, extent and environment of the malfunction. Persistent pathological hypoxia is incompatible with normal biological functions, and as a result, multicellular organisms have been compelled to develop both organism-wide and cellular-level hypoxia solutions...
2019: Frontiers in Cell and Developmental Biology
Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chang Dong Yeo, Chan Kwon Park, Young Kyoon Kim, Tae-Jung Kim, Seong-Beom Lee, Sug Hyung Lee, Jong Y Park, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim
BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood. METHODS: Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed...
February 13, 2019: BMC Cancer
Ying Xiong, Li Liu, Yu Xia, Yangyang Qi, Yifan Chen, Lingli Chen, Peipei Zhang, Yunyi Kong, Yang Qu, Zewei Wang, Zhiyuan Lin, Xiang Chen, Zhuoyi Xiang, Jiajun Wang, Qi Bai, Weijuan Zhang, Yuanfeng Yang, Jianming Guo, Jiejie Xu
PURPOSE: Hypoxia-inducible factor 2α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mechanisms. EXPERIMENTAL DESIGN: We immunohistochemically evaluated immune cells infiltrations and prognostic value of HIF-2α expression in a retrospective Zhongshan Hospital cohort of 280 ccRCC patients...
February 13, 2019: Cancer Immunology, Immunotherapy: CII
Nak-Kyun Soung, Hye-Min Kim, Yukihiro Asami, Dong Hyun Kim, Yangrae Cho, Ravi Naik, Yerin Jang, Kusic Jang, Ho Jin Han, Srinivas Rao Ganipisetti, Hyunjoo Cha-Molstad, Joonsung Hwang, Kyung Ho Lee, Sung-Kyun Ko, Jae-Hyuk Jang, In-Ja Ryoo, Yong Tae Kwon, Kyung Sang Lee, Hiroyuki Osada, Kyeong Lee, Bo Yeon Kim, Jong Seog Ahn
Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460...
February 12, 2019: Experimental & Molecular Medicine
Felicitas Bossler, Bianca J Kuhn, Thomas Günther, Stephen J Kraemer, Prajakta Khalkar, Svenja Adrian, Claudia Lohrey, Angela Holzer, Mitsugu Shimobayashi, Matthias Dürst, Arnulf Mayer, Frank Rösl, Adam Grundhoff, Jeroen Krijgsveld, Karin Hoppe-Seyler, Felix Hoppe-Seyler
Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia...
February 12, 2019: MBio
Stoyan Dimitrov, Tanja Lange, Cécile Gouttefangeas, Anja T R Jensen, Michael Szczepanski, Jannik Lehnnolz, Surjo Soekadar, Hans-Georg Rammensee, Jan Born, Luciana Besedovsky
Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of β2 -integrins. Gαs -coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of β2 -integrins-we show that the Gαs -coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2 , PGD2 , and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner...
February 12, 2019: Journal of Experimental Medicine
Sha Zhao, Shengxiang Ren, Tao Jiang, Bo Zhu, Xuefei Li, Chao Zhao, Yijun Jia, Jinpeng Shi, Limin Zhang, Xiaozhen Liu, Meng Qiao, Xiaoxia Chen, Chunxia Su, Hui Yu, Caicun Zhou, Jun Zhang, D Ross Camidge, Fred R Hirsch
Lack of response to treatment in most lung cancer patients suggests the value of broadening the benefit of anti-PD-1/PD-L1 monotherapy. Judicious dosing of anti-angiogenic agents such as apatinib (VEGFR2-TKI) can modulate the tumor immunosuppressive microenvironment, which contributes to resistance to anti-PD-1/PD-L1 treatment. We therefore hypothesized that inhibiting angiogenesis could enhance therapeutic efficacy of PD-1/PD-L1 blockade. Here, using a syngeneic lung cancer mouse model, we demonstrated that low-dose apatinib alleviated hypoxia, increased infiltration of CD8+ T cells, reduced recruitment of tumor-associated macrophages (TAMs) in tumor and decreased TGF-β amounts both in tumor and serum...
February 12, 2019: Cancer Immunology Research
Muhannad Abu-Remaileh, Monther Abu-Remaileh, Rania Akkawi, Ibrahim Knani, Shiran Udi, Micheal E Pacold, Joseph Tam, Rami I Aqeilan
OBJECTIVE: WWOX, a well-established tumor suppressor, is frequently lost in cancer and plays important roles in DNA damage response and cellular metabolism. METHODS: We re-analyzed several genome-wide association studies (GWAS) using the Type 2 Diabetes Knowledge Portal website to uncover WWOX's association with metabolic syndrome (MetS). Using several engineered mouse models, we studied the effect of somatic WWOX loss on glucose homeostasis. RESULTS: Several WWOX variants were found to be strongly associated with MetS disorders...
January 31, 2019: Molecular Metabolism
Sandhya Chipurupalli, Elango Kannan, Vinay Tergaonkar, Richard D'Andrea, Nirmal Robinson
It is evident that regions within tumors are deprived of oxygen, which makes the microenvironment hypoxic. Cancer cells experiencing hypoxia undergo metabolic alterations and cytoprotective adaptive mechanisms to survive such stringent conditions. While such mechanisms provide potential therapeutic targets, the mechanisms by which hypoxia regulates adaptive responses-such as ER stress response, unfolded protein response (UPR), anti-oxidative responses, and autophagy-remain elusive. In this review, we summarize the complex interplay between hypoxia and the ER stress signaling pathways that are activated in the hypoxic microenvironment of the tumors...
February 11, 2019: International Journal of Molecular Sciences
Yan Wang, Zihao Qi, Menglong Zhou, Wang Yang, Ran Hu, Guichao Li, Xuejun Ma, Zhen Zhang
Gastric cancer (GC) is one of the most lethal diseases worldwide, but the mechanism of GC development remains elusive. In the present study, the roles of stanniocalcin‑1 (STC1) in GC were investigated. It was demonstrated that overexpression of STC1 mRNA and protein were associated with poor survival of patients with GC. The expression of STC1 was enhanced in hypoxic GC cells and overexpression of STC1 facilitated cell proliferation in hypoxia but not in normoxia. Furthermore, STC1 promoted chemoresistance, migration and invasion in hypoxia...
January 23, 2019: Oncology Reports
Chao Liu, Shengfeng Li, Fawei Pang, Haiwei Wu, Li Chai, Cheng Liang, Dongsheng Zhang
OBJECTIVES: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia-induced autophagy was up-regulated in the progression of SACC. MATERIALS AND METHODS: We performed differentially expressed gene analysis, pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF-1ɑ and MAP1LC3B was analyzed in the paraffin-embedded specimens by immunohistochemical method and in the hypoxic SACC-LM cells by immunofluorescence...
February 11, 2019: Oral Diseases
Zaira Rehman, Ammad Fahim, Attya Bhatti, Hajra Sadia, Peter John
The hypoxic tumor microenvironment is the major contributor of chemotherapy resistance in solid tumors. One of the key regulators of hypoxic responses within the cell is the hypoxia inducible factor-1α (HIF-1α) that is involved in transcription of genes promoting cell survival and chemotherapy resistance. Multidrug resistance gene-1 (MDR1) and Lysosome-associated protein transmembrane 4B-35 (LAPTM4B-35) are among those notable players which augment their responses to cellular hypoxia. MDR1 is the hypoxia responsive gene involved in multidrug resistance phenotype while LAPTM4B-35 is involved in chemotherapy resistance by stabilizing HIF-1α and overexpressing MDR1...
2019: PeerJ
Fan Liu, Ting-Wei Liu, Jian Kang
Background: The aim of this study is to determine the role of nuclear factor kappa B (NF-κB)-mediated c-Jun N-terminal kinase (JNK) pathway in cognitive impairment induced by chronic intermittent hypoxia (CIH). Methods: Ninety-six male Sprague-Dawley rats were randomly divided into 8 groups: sham group, sustained hypoxia (SH) group, CIH group, CIH + melatonin group, CIH + vitamin E group, CIH + DMSO group, CIH + BAY 11-7082 group and CIH + normal saline (NS) group...
December 2018: Journal of Thoracic Disease
Baoan Hong, Jingcheng Zhou, Kaifang Ma, Jiufeng Zhang, Haibiao Xie, Kenan Zhang, Lei Li, Lin Cai, Ning Zhang, Zhongyuan Zhang, Kan Gong
Tribbles pseudokinase 3 (TRIB3) is a member of the mammalian pseudokinase tribbles family and is involved in multiple biological processes. However, the role of TRIB3 in renal cell carcinoma (RCC) remains unclear. In this study, we aimed to elucidate the biological functions of TRIB3 in RCC and explore its underlying mechanisms. TRIB3 expression and its correlation with clinicopathological features was evaluated in 123 patients with RCC. A series of cytological experiments were performed to clarify the biological functions of TRIB3, and potential molecular regulatory mechanisms were explored using transcriptome sequencing...
2019: International Journal of Biological Sciences
Yinjie Su, Weiping Yang, Ning Jiang, Juanyi Shi, Luping Chen, Guangzheng Zhong, Junming Bi, Wei Dong, Qiong Wang, Chunhui Wang, Tianxin Lin
Hypoxia plays a critical role in cancer biology. It induces genomic instability, which in turn helps cancer cells respond adaptively to meet the needs of carcinogenesis, cancer progression and relapse. Circular RNA has not been reported among the variety of downstream factors in this adaptive response. Although a few studies have demonstrated the important role of circular RNAs in driving human bladder cancer progression, their carcinogenic roles are still under investigated. Here, we identified a hypoxia-elevated circular RNA, circELP3, that contributes to bladder cancer progression and cisplatin resistance...
2019: International Journal of Biological Sciences
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