{"title":"Abstract PO-035: Understanding the role of hypoxia and PTEN loss in driving prostate cancer progression","authors":"Alexandru Suvac, R. Rebello, S. Lyons, R. Bristow","doi":"10.1158/1557-3265.RADSCI21-PO-035","DOIUrl":"https://doi.org/10.1158/1557-3265.RADSCI21-PO-035","url":null,"abstract":"","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45529910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstract PO-032: Mechanistic studies of hypoxia as a driver of genomic instability in prostate cancer","authors":"J. Ashton, R. Rebello, S. Lyons, R. Bristow","doi":"10.1158/1557-3265.RADSCI21-PO-032","DOIUrl":"https://doi.org/10.1158/1557-3265.RADSCI21-PO-032","url":null,"abstract":"","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48683020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstract PO-034: Changes in cancer associated fibroblast subsets following angiotensin II type I receptor blocker (ARB) treatment reduces transient hypoxia and radiation resistance","authors":"Che-Min Lee, Brennan J. Wadsworth, K. Bennewith","doi":"10.1158/1557-3265.RADSCI21-PO-034","DOIUrl":"https://doi.org/10.1158/1557-3265.RADSCI21-PO-034","url":null,"abstract":"","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43639898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Koritzinsky, P. Jain, A. Dvorkin-Gheva, Lucie Malbeteau, Piriththiv Dhavarasa, K. Brown, G. Jang, P. Vora, F. Notta, J. Moffat, P. Boutros
{"title":"Abstract IA-016: Metabolic deregulation drives a redox vulnerability in pancreatic cancer","authors":"M. Koritzinsky, P. Jain, A. Dvorkin-Gheva, Lucie Malbeteau, Piriththiv Dhavarasa, K. Brown, G. Jang, P. Vora, F. Notta, J. Moffat, P. Boutros","doi":"10.1158/1557-3265.RADSCI21-IA-016","DOIUrl":"https://doi.org/10.1158/1557-3265.RADSCI21-IA-016","url":null,"abstract":"","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44337548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypoxia (Auckland, N.Z.)Pub Date : 2020-02-10eCollection Date: 2020-01-01DOI: 10.2147/HP.S219049
Edwin F deZoeten, Kayla D Battista, Steven B Colson, Mark A Lovell, Brittelle E Kessler, Robert W Isfort, Blair P Fennimore, Joseph C Onyiah, Daniel J Kao, Alyson Yeckes, Simon Keely, Monica Murray, Edward J Hoffenberg, Sean P Colgan, Mark E Gerich
{"title":"Markers of Hypoxia Correlate with Histologic and Endoscopic Severity of Colitis in Inflammatory Bowel Disease.","authors":"Edwin F deZoeten, Kayla D Battista, Steven B Colson, Mark A Lovell, Brittelle E Kessler, Robert W Isfort, Blair P Fennimore, Joseph C Onyiah, Daniel J Kao, Alyson Yeckes, Simon Keely, Monica Murray, Edward J Hoffenberg, Sean P Colgan, Mark E Gerich","doi":"10.2147/HP.S219049","DOIUrl":"10.2147/HP.S219049","url":null,"abstract":"<p><strong>Background: </strong>Inflammation results in significant shifts in tissue metabolism. Recent studies indicate that inflammation and hypoxia occur concomitantly. We examined whether circulating and tissue markers of hypoxia could serve as surrogate indicators of disease severity in adult and pediatric patients with inflammatory bowel disease (IBD).</p><p><strong>Methods: </strong>Serum and colonic biopsies were obtained from pediatric subjects with active IBD colitis and adult subjects with active and inactive ulcerative colitis, along with healthy non-colitis controls of all ages. Disease activity was evaluated by endoscopy and histopathology. Levels of serum hypoxia markers (macrophage inflammatory protein-3α [MIP-3α], vascular endothelial growth factor [VEGF], and erythropoietin [EPO]) were measured.</p><p><strong>Results: </strong>Children with active IBD colitis had higher levels of serum MIP-3α and VEGF compared to non-colitis controls (p<0.01 and p<0.05, respectively). In adult subjects with endoscopically active ulcerative colitis, serum MIP-3α and EPO were significantly elevated compared to non-colitis controls (both p<0.01). In parallel, analysis of colon tissue MIP-3α mRNA and protein in pediatric subjects revealed increased expression in those with IBD colitis compared to controls (p<0.05 and p<0.01 for mRNA and protein, respectively). Serum MIP-3α and VEGF significantly increased with histology grade.</p><p><strong>Conclusion: </strong>Peripheral blood hypoxia markers may be useful indicators of disease activity for pediatric and adult IBD patients.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":"8 ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2020-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/24/hp-8-1.PMC7026141.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37683409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypoxia (Auckland, N.Z.)Pub Date : 2019-12-24eCollection Date: 2019-01-01DOI: 10.2147/HP.S235967
Eleni-Anastasia Triantafyllou, Ilias Mylonis, George Simos, Efrosyni Paraskeva
{"title":"Hypoxia Induces Pro-Fibrotic and Fibrosis Marker Genes in Hepatocellular Carcinoma Cells Independently of Inflammatory Stimulation and the NF-κΒ Pathway.","authors":"Eleni-Anastasia Triantafyllou, Ilias Mylonis, George Simos, Efrosyni Paraskeva","doi":"10.2147/HP.S235967","DOIUrl":"https://doi.org/10.2147/HP.S235967","url":null,"abstract":"<p><p>Hypoxia and its key mediators hypoxia inducible Factors (HIFs) are implicated in the development of liver diseases of diverse etiologies, often in interplay with inflammatory mediators. We investigated the interplay between hypoxia and proinflammatory mediators in the development of liver fibrosis, using human hepatocellular carcinoma Huh7 cells as a model. Treatment of Huh7 with DMOG or under hypoxia, induced HIF-1α protein levels and the expression of genes for pro-fibrotic (TGF-β1, PDGFC, PAI-1) and fibrosis (LOX, P4HA1, P4HB) markers. Knockdown of HIF-1α decreased the induction of PDGFC, LOX and P4HA1, showing the involvement of HIF-1 in their regulation. Interestingly, incubation of Huh7 cells under hypoxia did not cause activation of the NF-κΒ pathway. In contrast, inflammatory mediators such as tumor necrosis factor α (TNFα) and lipopolysaccharides (LPS) activated the NF-κΒ pathway, but failed to increase HIF-1α protein levels. Moreover, TNFα had a weaker effect than hypoxia on the induction or did not induce pro-fibrotic and fibrosis markers, respectively, while LPS enhanced only the hypoxic induction of P4HB. In conclusion, the above findings suggest that hypoxia and HIF-1 play an important role in the development of fibrosis in hepatocellular carcinoma, which appears to be independent of the activation of the NF-κΒ pathway.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":"7 ","pages":"87-91"},"PeriodicalIF":0.0,"publicationDate":"2019-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S235967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37529724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypoxia (Auckland, N.Z.)Pub Date : 2019-12-13eCollection Date: 2019-01-01DOI: 10.2147/HP.S230502
Daisheng Song, Wei Guan, Lea M Coon, Aref Al-Kali, Jennifer L Oliveira, Frank S Lee
{"title":"An Erythrocytosis-Associated Mutation in the Zinc Finger of PHD2 Provides Insights into Its Binding of p23.","authors":"Daisheng Song, Wei Guan, Lea M Coon, Aref Al-Kali, Jennifer L Oliveira, Frank S Lee","doi":"10.2147/HP.S230502","DOIUrl":"https://doi.org/10.2147/HP.S230502","url":null,"abstract":"<p><strong>Background: </strong>Loss of function mutations in the <i>EGLN1</i> gene are a cause of erythrocytosis. <i>EGLN1</i> encodes for prolyl hydroxylase domain protein 2 (PHD2). PHD2 hydroxylates and downregulates hypoxia-inducible factor-2α (HIF-2α), a transcription factor that regulates erythropoiesis. While the large majority of erythrocytosis-associated <i>EGLN1</i> mutations occur within its catalytic domain, rare mutations reside in its zinc finger. This zinc finger binds a Pro-Xaa-Leu-Glu motif in p23, an HSP90 cochaperone that facilitates hydroxylation of HIF-α, an HSP90 client. Essentially nothing is known about the specific interactions between the PHD2 zinc finger and p23.</p><p><strong>Results: </strong>Here, we characterize an erythrocytosis-associated mutation in the zinc finger, K55N, that abolishes interaction with p23. We provide evidence that the affected residue, Lys-55, interacts with Asp-152 of p23. We also present results that indicate that PHD2 Arg-32 interacts with p23 Glu-160.</p><p><strong>Conclusion: </strong>These studies not only reinforce the importance of the PHD2 zinc finger in the control of erythropoiesis, but also lead to a model in which a peptide motif in p23 binds in a specific orientation to a predicted groove in the zinc finger of PHD2.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":"7 ","pages":"81-86"},"PeriodicalIF":0.0,"publicationDate":"2019-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S230502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37471385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}