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HIF-1α AND tumor

Annasofia Anemone, Lorena Consolino, Francesca Arena, Martina Capozza, Dario Livio Longo
Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic products, resulting in enhanced acidification of the extracellular pH (pHe ~ 6.5), which is a salient feature of the tumor microenvironment. Despite the importance of pH and tumor acidosis, there is currently no established clinical tool available to image the spatial distribution of tumor pHe...
February 14, 2019: Cancer Metastasis Reviews
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
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
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
Yongsheng Wang, Yinliang Qi, Xiang Wei, Shaolong Chen, Ning Jia, Qing Zhou, Sumei Zhang, Shuyu Gui, Yuan Wang
Hypoxia induces vigorous growth and a higher malignant phenotype in solid tumors. Hyperoxic treatment using hyperbaric oxygen (HBO) has previously been shown as a highly effective method to attenuate hypoxia. We aimed to investigate the effect of HBO on hypoxia-induced malignancy of lung cancer cells. Cobalt chloride (CoCl2 ) was used to induce chemical hypoxia in lung cancer cell line A549. Hypoxic inducible factor-1α (HIF-1α) expression, lactate dehydrogenase (LDH) activity, migration and invasion capacity, expression profiles of epithelial-mesenchymal transition (EMT) markers and apoptotic markers were assessed in CoCl2 -treated A549 cells, with or without HBO treatment...
February 10, 2019: Experimental Lung Research
Min Deng, Yong-Ju Xue, Le-Rong Xu, Qiang-Wu Wang, Jun Wei, Xi-Quan Ke, Jian-Chao Wang, Xiao-Dong Chen
Colorectal cancer (CRC) is a common human malignancy, accounting for 600,000 death cases annually worldwide. Chrysophanol is a naturally occurring anthraquinone compound and exhibits anti-neoplastic activities. This study aims to explore the biological effects of chrysophanol on CRC metastasis and the relevant underlying mechanism. Cell proliferation assay, Wound scratch assay and Transwell invasion assay were used to examine the effect of chrysophanol on proliferation, migration and invasion of CRC cells. Hypoxia-inducible factor-1α (HIF-1α) shRNA was utilized to transfect CRC cells in order to examine the role of HIF-1α in chrysophanol suppression of hypoxia-induced epithelial to mesenchymal transition (EMT)...
February 8, 2019: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Qi Yang, Xuejun Li
Cases with pituitary adenoma comprise 10-25% of intracranial neoplasm, being the third most common intracranial tumor, most of the adenomas are considered to be benign. About 35% of pituitary adenomas are invasive. This review summarized the known molecular basis of the invasiveness of pituitary adenomas. The study pointed out that hypoxia-inducible factor-1α, pituitary tumor transforming gene, vascular endothelial growth factor, fibroblast growth factor-2, and matrix metalloproteinases (MMPs, mainly MMP-2, and MMP-9) are core molecules responsible for the invasiveness of pituitary adenomas...
2019: Frontiers in Endocrinology
Lifei Meng, Xuhui Yang, Xiao Xie, Mingsong Wang
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for a significant proportion of cancer-related deaths and lacks an effective treatment strategy. NSCLC tissues are generally found in a low oxygen environment. The NDUFA4L2 protein, located in the mitochondria, is encoded by the nucleus genome and is considered a crucial mediator that regulates cell survival. A better understanding of the mechanism of NDUFA4L2 in NSCLC survival in hypoxic environments is essential to design new therapeutic methods...
February 2, 2019: Thoracic Cancer
Valerio Ciccone, Erika Terzuoli, Sandra Donnini, Antonio Giachetti, Lucia Morbidelli, Marina Ziche
February 1, 2019: Journal of Experimental & Clinical Cancer Research: CR
Fangxiong Wu, Hongyan Gao, Kaige Liu, Baohua Gao, Hezhuang Ren, Zheng Li, Fengrui Liu
Background: Growing evidence has implicated the important role of the long non-coding RNAs (lncRNAs) in gastric cancer progression. In this study, we examined the expression of lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in gastric cancer tissues and elucidated the molecular mechanisms underlying ZEB2-AS1-mediated gastric cancer progression. Methods: Quantitative real-time PCR measured the gene expression level; CCK-8, colony formation and cell invasion assays determined gastric cancer cell proliferation, growth and invasion, respectively; the xenograft nude mice model was used to determine in vivo tumor growth; Bioinformatics analysis and luciferase reporter assay determined the downstream targets of ZEB2-AS1 and miR-143-5p...
2019: OncoTargets and Therapy
Yangsook Song Green, Timothy Sargis, Ethan Conrad Reichert, Eleanor Rudasi, Daniel Fuja, Eric Jonasch, Mei Yee Koh
Low oxygen or hypoxia is a feature of all solid tumors, and has been associated with aggressive disease. Here, we describe a novel mechanism for the hypoxia-dependent degradation of the Ras-GTPase activating protein neurofibromin, by hypoxia-associated factor (HAF). We have previously characterized HAF as an oxygen-independent ubiquitin ligase for HIF-1α. Here, we show that HAF promotes neurofibromin ubiquitination and degradation independently of oxygen and pVHL, resulting in Ras-ERK pathway activation. Hypoxia enhanced HAF:neurofibromin binding independently of HAF-SUMOylation, whereas HAF knockdown increased neurofibromin levels primarily in hypoxia, supporting the role of HAF as a hypoxia-specific neurofibromin regulator...
January 31, 2019: Molecular Cancer Research: MCR
Saki Maeda-Otsuka, Ikko Kajihara, Yukino Tasaki, Saori Yamada-Kanazawa, Ryoko Sakamoto, Soichiro Sawamura, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Yoshihiro Komohara, Hironobu Ihn
BACKGROUND: Angiosarcoma is a rare malignant tumor with a poor prognosis. It is known that hypoxic condition activates tumor progression in several cancers. Additionally, hypoxic tumor microenvironment accelerates immune escape. However, the presence and significance of hypoxia in angiosarcoma has not been adequately investigated. OBJECTIVE: To study the role of hypoxia in the progression of angiosarcoma. METHODS: The protein level of hypoxia inducible factor-1α (HIF-1α) in angiosarcoma was examined using immunohistochemistry and immunoblotting...
January 15, 2019: Journal of Dermatological Science
Jérémy Lavigne, Alexandra Suissa, Nicolas Verger, Morgane Dos Santos, Mohamedamine Benadjaoud, Laurence Mille-Hamard, Iman Momken, Frédéric Soysouvanh, Valérie Buard, Olivier Guipaud, Vincent Paget, Georges Tarlet, Fabien Milliat, Agnès François
PURPOSE: Stereotactic body radiation therapy (SBRT) offers good lung local tumor control by the administration of a high dose per fraction in small volumes. SBRT preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional HIF-1α deletion in the endothelium on radiation-induced tissue damage. METHODS AND MATERIALS: The Small Animal Radiation Research Platform (SARRP) was used to create a mouse model of focal irradiation of the lung using arc therapy...
January 28, 2019: International Journal of Radiation Oncology, Biology, Physics
Joan Cao, Zhou Zhu, Hui Wang, Timothy C Nichols, Goldie Y L Lui, Shibing Deng, Paul A Rejto, Todd VanArsdale, James S Hardwick, Scott L Weinrich, Ping Wei
The CDK4/6 inhibitor palbociclib reduces tumor growth by decreasing retinoblastoma (RB) protein phosphorylation and inducing cell cycle arrest at the G1/S phase transition. Palbociclib in combination with anti-hormonal therapy brings significant benefit to breast cancer patients. In this study, novel combination approaches and underlying molecular/cellular mechanisms for palbociclib were explored in squamous cell lung cancer (SqCLC), the second most common subtype of non-small cell lung cancer. While approximate 20% lung patients benefit from immunotherapy, most SqCLC patients who receive platinum-doublet chemotherapy as first-line treatment, which often includes a taxane, are still in need of more effective combination therapies...
January 30, 2019: Oncogene
Marijke I Zonneveld, Tom G H Keulers, Kasper M A Rouschop
Tumour hypoxia is a common feature of solid tumours that contributes to poor prognosis after treatment. This is mainly due to increased resistance of hypoxic cells to radio- and chemotherapy and the association of hypoxic cells with increased metastasis development. It is therefore not surprising that an increased hypoxic tumour fraction is associated with poor patient survival. The extent of hypoxia within a tumour is influenced by the tolerance of individual tumor cells to hypoxia, a feature that differs considerably between tumors...
January 29, 2019: Cancers
Jianye Liang, Rong Ma, Heru Chen, Dongmei Zhang, Wencai Ye, Changzheng Shi, Liangping Luo
OBJECTIVE: This study aimed to investigate the feasibility of intravoxel incoherent motion (IVIM) DWI and R2* (transverse relaxation rate) mapping to monitor the hyperacute therapeutic efficacy of desacetylvinblastine monohydrazide (DAVLBH) on an experimental hepatocellular carcinoma mouse model within 24 hours. MATERIALS AND METHODS: Forty-four mice were implanted with hepatocellular carcinoma and divided into three random groups. A treatment group and a control group underwent IVIM-DWI and R2* mapping examinations before and after a single injection of DAVLBH or saline at 1, 2, 4, and 24 hours...
January 30, 2019: AJR. American Journal of Roentgenology
Zheng-Lin Ou, Min Zhang, Lian-Dong Ji, Zhen Luo, Tong Han, Ye-Bin Lu, Yi-Xiong Li
Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions...
January 28, 2019: Journal of Cellular Physiology
Hiroyuki Suzuki, Mitsutake Yano, Mariko Miyazawa, Masaki Miyazawa, Naoki Ogane, Kosei Hasegawa, Hitoshi Tsuda, Masayuki Yoshida, Ryugo Okagaki, Osamu Ishihara, Masanori Yasuda
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Japan. OCCC has a more unfavorable clinical outcome due to a poor response to platinum-based chemotherapy, compared with serous carcinoma. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of cellular response to hypoxia and plays an important role in tumor growth, and HIF-1α gene single-nucleotide polymorphisms (SNPs) adversely affect the outcome in some cancers...
January 24, 2019: Journal of Ovarian Research
Jingli Gong, Shengxue Zhou, Shihai Yang
Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tumor adaptation to microenvironmental hypoxia, and it also exerts important roles in angiogenesis and tumor development. Vanillic acid is a dietary phenolic compound reported to exhibit anticancer properties. However, the mechanisms by which vanillic acid inhibits tumor growth are not fully understood. Here, we investigated the effect of vanillic acid on HIF-1α activation. Vanillic acid significantly inhibits HIF-1α expression induced by hypoxia in various human cancer cell lines...
January 22, 2019: International Journal of Molecular Sciences
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