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hypoxia cancer

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https://www.readbyqxmd.com/read/29684705/dual-tail-arylsulfone-based-benzenesulfonamides-differently-match-the-hydrophobic-and-hydrophilic-halves-of-human-carbonic-anhydrases-active-sites-selective-inhibitors-for-the-tumor-associated-hca-ix-isoform
#1
Hany S Ibrahim, Heba Abdelrasheed Allam, Walaa R Mahmoud, Alessandro Bonardi, Alessio Nocentini, Paola Gratteri, Eslam S Ibrahim, Hatem A Abdel-Aziz, Claudiu T Supuran
The synthesis and characterization of two new sets of arylsulfonehydrazone benzenesulfonamides (4a-4i with phenyl tail and 4j-4q with tolyl tail) are reported. The compounds were designed according to a dual-tails approach to modulate the interactions of the ligands portions at the outer rim of both hydrophobic and hydrophilic active site halves of human isoforms of carbonic anhydrase (CA, EC 4.2.1.1). The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IV and IX...
April 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29684361/high-frequency-of-ovarian-cyst-development-in-vhl-2b-snf5-mice
#2
Yasumichi Kuwahara, Leslie M Kennedy, Anthony N Karnezis, E Lorena Mora-Blanco, Arlin B Rogers, Christopher D Fletcher, David G Huntsman, Charles W M Roberts, W Kimryn Rathmell, Bernard E Weissman
The new paradigm of mutations in chromatin modifying genes as driver events in the development of cancers has proved challenging to resolve the complex influences over disease phenotypes. In particular, impaired activities of members of the SWI/SNF chromatin remodeling complex have appeared in an increasing variety of tumors. Mutations in SNF5, a member of this ubiquitously expressed complex, arise in almost all cases of malignant rhabdoid tumor in the absence of additional genetic alterations. Therefore, we studied how activation of additional oncogenic pathways might shift the phenotype of disease driven by SNF5 loss...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29682563/deregulation-of-hexokinase-ii-is-associated-with-glycolysis-autophagy-and-the-epithelial-mesenchymal-transition-in-tongue-squamous-cell-carcinoma-under-hypoxia
#3
Guanhui Chen, Yadong Zhang, Jianfeng Liang, Wenqing Li, Yue Zhu, Ming Zhang, Cheng Wang, Jinsong Hou
The glycolytic enzyme Hexokinase (HKII) participates in tumor glycolysis and the progression of various cancers, but its clinicopathological effect on the progression of tongue squamous cell carcinoma (TSCC) and its role in glycolysis, autophagy, and the epithelial-mesenchymal transition of TSCC in a hypoxic microenvironment remain unknown. Our results showed that HKII expression was dramatically increased in TSCC tissues and that its upregulation was significantly associated with the presence of pathological differentiation, lymph node metastasis, and clinical stage...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29680257/measurement-of-tumor-hypoxia-in-patients-with-locally-advanced-cervical-cancer-using-positron-emission-tomography-with-18-f-fluoroazomyin-arabinoside
#4
Kathy Han, Tina Shek, Douglass Vines, Brandon Driscoll, Anthony Fyles, David Jaffray, Harald Keller, Ur Metser, Melania Pintilie, Jason Xie, Ivan Yeung, Michael Milosevic
PURPOSE: To assess cervical tumor hypoxia using the hypoxia tracer 18 F-fluoroazomycin arabinoside (18 F-FAZA) and compare different reference tissues and thresholds for quantifying tumor hypoxia. METHODS AND MATERIALS: Twenty-seven patients with cervical cancer were studied prospectively by positron emission tomography (PET) imaging with 18 F-FAZA before starting standard chemoradiation. The hypoxic volume was defined as all voxels within a tumor (T) with standardized uptake values (SUVs) greater than 3 standard deviations from the mean gluteus maximus muscle SUV value (M) or SUVs greater than 1 to 1...
March 2, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29678527/the-effect-of-neoadjuvant-androgen-deprivation-therapy-on-tumor-hypoxia-in-high-grade-prostate-cancer-an-18-f-miso-pet-mri-study
#5
Ismini C Mainta, Thomas Zilli, Jean-Christophe Tille, Thomas De Perrot, Jean-Paul Vallée, Franz Buchegger, Valentina Garibotto, Raymond Miralbell
PURPOSE: Tumor hypoxia is associated with radioresistance and poor prognosis after radiation therapy for prostate cancer (PCa). In this prospective pilot study, we assessed the ability of 18 F-misonidazole (18 F-MISO) positron emission tomography (PET)-magnetic resonance imaging (MRI) to detect hypoxia in high-grade PCa patients who were candidates for curative radiation therapy, and we evaluated 18 F-MISO PET-MRI modulation after 3 months of neoadjuvant androgen deprivation therapy (nADT)...
March 8, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29675970/does-hypoxia-inducible-factor-1-%C3%AE-hif-1-%C3%AE-c1772t-polymorphism-predict-short-term-prognosis-in-patients-with-oral-squamous-cell-carcinoma-oscc
#6
Jitender Prasad, Binita Goswami, Srinivas H Gowda, Nikhil Gupta, Shilpa Kumar, Kiran Agarwal, Pravesh Mehra, Bindiya K Pahuja, Anju Chauhan
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF1 α levels as well as single nucleotide polymorphism of HIF1α gene in cancer and healthy controls. METHODS: Fifty newly diagnosed OSCC patients and 50 age and sex matched healthy control were included in the study. Serum concentrations of HIF1 α were measured by sandwich ELISA; whereas HIF1 α gene polymorphism study was done using restriction enzyme digestion by HpH I...
April 20, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29675438/fgfrl1-promotes-ovarian-cancer-progression-by-crosstalk-with-hedgehog-signaling
#7
Haiyan Tai, Zhiyong Wu, Su'an Sun, Zhigang Zhang, Congjian Xu
Fibroblast growth factor receptor-like-1 (FGFRL1) has been identified as the fifth fibroblast growth factor receptor. So far, little is known about its biological functions, particularly in cancer development. Here, for the first time, we demonstrated the roles of FGFRL1 in ovarian carcinoma (OC). An array and existing databases were used to investigate the expression profile of FGFRL1 and the relationship between FGFRL1 expression and clinicopathological parameters. FGFRL1 was significantly upregulated in OC patients, and high FGFRL1 expression was correlated with poor prognosis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29674477/blockade-of-myeloid-derived-suppressor-cell-expansion-with-all-trans-retinoic-acid-increases-the-efficacy-of-anti-angiogenic-therapy
#8
Raimund Bauer, Florian Udonta, Mark Wroblewski, Isabel Ben-Batalla, Ines Miranda Santos, Federico Taverna, Meike Kuhlencord, Victoria Gensch, Sarina Päsler, Stefan Vinckier, Johanna M Brandner, Klaus Pantel, Carsten Bokemeyer, Thomas Vogl, Johannes Roth, Peter Carmeliet, Sonja Loges
Intrinsic and adaptive resistance hamper the success of anti-angiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC) which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT...
April 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29672321/metabolic-plasticity-enables-circadian-adaptation-to-acute-hypoxia-in-zebrafish-cells
#9
Adolf M Sandbichler, Bianca Jansen, Bettina A Peer, Monika Paulitsch, Bernd Pelster, Margit Egg
BACKGROUND/AIMS: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. METHODS: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts...
April 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29669759/multi-kinase-inhibitor-ct-707-targets-liver-cancer-by-interrupting-the-hypoxia-activated-igf-1r-yap-axis
#10
Hong Zhu, Dan-Dan Wang, Tao Yuan, Fang-Jie Yan, Chen-Ming Zeng, Xiao-Yang Dai, Zi-Bo Chen, Ying Chen, Tianyi Zhou, Guang-Han Fan, Meidan Ying, Ji Cao, Peihua Luo, Xi-Jie Liu, Yuandong Hu, Yong Peng, Qiaojun He, Bo Yang
Given that YAP signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling...
April 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29665677/a-nanoscale-metal-organic-framework-overcomes-hypoxia-for-photodynamic-therapy-primed-cancer-immunotherapy
#11
Guangxu Lan, Kaiyuan Ni, Ziwan Xu, Samuel S Veroneau, Yang Song, Wenbin Lin
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal-organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions...
April 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29661250/isocitrate-dehydrogenase-1-snail-axis-dysfunction-significantly-correlates-with-breast-cancer-prognosis-and-regulates-cell-invasion-ability
#12
Wen-Shan Liu, Shih-Hsuan Chan, Hong-Tai Chang, Guan-Cheng Li, Ya-Ting Tu, Hui-Hwa Tseng, Ting-Ying Fu, Hui-Yu Chang, Huei-Han Liou, Luo-Ping Ger, Kuo-Wang Tsai
BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma...
April 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29658569/%C3%AE-%C3%A2-catenin-nuclear-translocation-induced-by-hif%C3%A2-1%C3%AE-overexpression-leads-to-the-radioresistance-of-prostate-cancer
#13
Yong Luo, Mingchuan Li, Xuemei Zuo, Spyridon P Basourakos, Jiao Zhang, Jiahui Zhao, Yili Han, Yunhua Lin, Yongxing Wang, Yongguang Jiang, Ling Lan
Hypoxia-inducible factor‑1α (HIF‑1α) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF‑1α remain unclear. β‑catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF‑1α and β‑catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4‑2B, were grouped as follows: Negative control (no treatment), HIF‑1α overexpression group (transfected with HIF‑1α overexpression plasmid) and β‑catenin silenced group (transfected with HIF‑1α plasmids and β‑catenin-shRNA)...
April 12, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29657306/hypoxia-induced-microrna-210-targets-neurodegenerative-pathways
#14
Michelle E Watts, Sarah M Williams, Jess Nithianantharajah, Charles Claudianos
Hypoxia-regulated microRNA-210 (miR-210) is a highly conserved microRNA, known to regulate various processes under hypoxic conditions. Previously we found that miR-210 is also involved in honeybee learning and memory, raising the questions of how neural activity may induce hypoxia-regulated genes and how miR-210 may regulate plasticity in more complex mammalian systems. Using a pull-down approach, we identified 620 unique target genes of miR-210 in humans, among which there was a significant enrichment of age-related neurodegenerative pathways, including Huntington's, Alzheimer's, and Parkinson's diseases...
March 27, 2018: Non-Coding RNA
https://www.readbyqxmd.com/read/29656756/correlation-of-tumor-related-immunity-with-18f-fdg-pet-in-pulmonary-squamous-cell-carcinoma
#15
Norimitsu Kasahara, Kyoichi Kaira, Pinjie Bao, Tetsuya Higuchi, Yukiko Arisaka, Bilguun Erkhem-Ochir, Noriaki Sunaga, Yoichi Ohtaki, Toshiki Yajima, Takayuki Kosaka, Tetsunari Oyama, Takehiko Yokobori, Takayuki Asao, Masahiko Nishiyama, Yoshito Tsushima, Hiroyuki Kuwano, Kimihiro Shimizu, Akira Mogi
OBJECTIVES: 2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission tomography (18 F-FDG-PET) is a clinically useful tool for cancer evaluation. 18 F-FDG accumulation in tumor cells is known to be correlated with the presence of glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody treatments have been approved, no suitable predictor of significant responders has been identified. Based on the existing information, we investigated the relationship between tumor immunity (including PD-L1) and 18 F-FDG uptake in patients with surgically resected pulmonary squamous-cell carcinoma (SQC)...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29656202/syntheses-and-anti-pancreatic-cancer-activities-of-rakicidin-a-analogues
#16
Jian Chen, Jingpei Li, Lingling Wu, Yan Geng, Jianming Yu, Chuanke Chong, Mengmeng Wang, Yuan Gao, Cuigai Bai, Yahui Ding, Yue Chen, Quan Zhang
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor and resistant to most therapies. Pancreatic cancer stem cells (PCSCs) had critical role in regulating PDAC progression, metastasis, and drug resistance. Therefore, targeting PCSCs is considered to be a promising strategy for treatment of PDAC. However, there is no effective drug that can selectively ablate PCSCs. A series of twenty rakicidin A analogues were synthesized via a combinatorial strategy and evaluated for their anti-PDAC activities, and the structure-activity relationship was also discussed...
March 29, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29656061/hypoxia-inducible-bidirectional-shrna-expression-vector-delivery-using-pei-chitosan-tba-copolymers-for-colorectal-cancer-gene-therapy
#17
Bita Javan, Fatemeh Atyabi, Majid Shahbazi
AIMS: This investigation was conducted to construct a hypoxia/colorectal dual-specific bidirectional short hairpin RNA (shRNA) expression vector and to transfect it into the colon cancer cell line HT-29 with PEI/chitosan-TBA nanoparticles for the simultaneous knock down of β-catenin and Bcl-2 under hypoxia. MAIN METHODS: To construct a pRNA-bipHRE-CEA vector, the carcinoma embryonic antigen (CEA) promoter designed in two directions and the vascular endothelial growth factor (VEGF) enhancer were inserted between two promoters for hypoxic cancer specific gene expression...
April 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29649636/a-microfluidic-oxygen-sink-to-create-a-targeted-cellular-hypoxic-microenvironment-under-ambient-atmospheric-conditions
#18
Samineh Barmaki, Ville Jokinen, Daniela Obermaier, Daria Blokhina, Matti Korhonen, Robin H A Ras, Jyrki Vuola, Sami Franssila, Esko Kankuri
Physiological oxygen levels within the tissue microenvironment are usually lower than 14 %, in stem cell niches these levels can be as low as 0-1 %. In cell cultures, such low oxygen levels are usually mimicked by altering the global culture environment either by O2 removal (vacuum or oxygen absorption) or by N2 supplementation for O2 replacement. To generate a targeted cellular hypoxic microenvironment under ambient atmospheric conditions, we characterized the ability of the dissolved oxygen-depleting sodium sulfite to generate an in-liquid oxygen sink...
April 9, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29644003/overexpression-of-plod3-promotes-tumor-progression-and-poor-prognosis-in-gliomas
#19
Chia-Kuang Tsai, Li-Chun Huang, Wen-Chiuan Tsai, Shih-Ming Huang, Jiunn-Tay Lee, Dueng-Yuan Hueng
High-grade gliomas are the most threatening brain tumors due to aggressive proliferation and poor prognosis. Thus, utilizing genetic glioma biomarkers to forecast prognosis and guide clinical management is crucial. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) modulates cancer progression and metastasis. However, its detailed function in cancer remains largely uninvestigated. PLOD3 expression was evaluated with real-time PCR in glioblastoma (GBM) cell lines and by Gene Expression Omnibus dataset analysis and immunohistochemistry of glioma tissues...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29628788/the-role-of-hypoxia-in-shaping-the-recruitment-of-proangiogenic-and-immunosuppressive-cells-in-the-tumor-microenvironment
#20
REVIEW
Salem Chouaib, Viktor Umansky, Claudine Kieda
Hypoxia characterizes growing tumors and contributes significantly to their aggressiveness. Hypoxia-inducible factors (HIFs 1 and 2) are stabilized and act differentially as transcription factors on tumor growth and are responsible for important cancer hallmarks such as pathologic angiogenesis, cellular proliferation, apoptosis, differentiation and genetic instability as well as affecting tumor metabolism, tumor immune responses, invasion and metastasis. Taking into account the tumor tissue as a whole and considering the interplay of the various partners which react with hypoxia in the tumor site lead to reconsideration of the treatment strategies...
March 2018: Contemporary Oncology Współczesna Onkologia
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