{"id":"https://openalex.org/W1736614021","doi":null,"title":"Regulation of Hypoxia-Inducible Factor-Mediated Tumour Growth by Ascorbate","display_name":"Regulation of Hypoxia-Inducible Factor-Mediated Tumour Growth by Ascorbate","publication_year":2015,"publication_date":"2015-01-01","ids":{"openalex":"https://openalex.org/W1736614021","mag":"1736614021"},"language":"en","primary_location":{"id":"pmh:oai:ourarchive.otago.ac.nz:10523/5882","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10523/5882","pdf_url":null,"source":{"id":"https://openalex.org/S4306402094","display_name":"Otago University Research Archive (University of Otago)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I80281795","host_organization_name":"University of Otago","host_organization_lineage":["https://openalex.org/I80281795"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Thesis or Dissertation"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5103629521","display_name":"Elizabeth J. Campbell","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Elizabeth J. Campbell","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5103629521"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.7773000001907349,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.7773000001907349,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12554","display_name":"Vitamin C and Antioxidants Research","score":0.20649999380111694,"subfield":{"id":"https://openalex.org/subfields/2916","display_name":"Nutrition and Dietetics"},"field":{"id":"https://openalex.org/fields/29","display_name":"Nursing"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10422","display_name":"Angiogenesis and VEGF in Cancer","score":0.002099999925121665,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/vitamin-c","display_name":"vitamin C","score":0.9399999976158142},{"id":"https://openalex.org/keywords/tumor-growth","display_name":"tumor growth","score":0.9169999957084656},{"id":"https://openalex.org/keywords/hif-1alpha-hydroxylation","display_name":"HIF-1\u03b1 hydroxylation","score":0.8109999895095825},{"id":"https://openalex.org/keywords/2-oxoglutarate-dependent-oxygenases","display_name":"2-oxoglutarate-dependent dioxygenase","score":0.8769999742507935},{"id":"https://openalex.org/keywords/ascorbate-deficiency","display_name":"ascorbate deficiency","score":0.8090000152587891},{"id":"https://openalex.org/keywords/high-dose-vitamin-c","display_name":"high-dose vitamin C","score":0.8090000152587891},{"id":"https://openalex.org/keywords/tumor-hypoxia","display_name":"tumor hypoxia","score":0.7260000109672546},{"id":"https://openalex.org/keywords/tumor-angiogenesis","display_name":"tumor angiogenesis","score":0.4749999940395355},{"id":"https://openalex.org/keywords/vascular-endothelial-growth-factor","display_name":"vascular endothelial growth factor","score":0.5360000133514404},{"id":"https://openalex.org/keywords/vegfr2","display_name":"VEGFR2","score":0.45100000500679016},{"id":"https://openalex.org/keywords/vegfr-3","display_name":"VEGFR-3","score":0.5830000042915344},{"id":"https://openalex.org/keywords/vegf-c","display_name":"VEGF-C","score":0.3919999897480011},{"id":"https://openalex.org/keywords/vegf-d","display_name":"VEGF-D","score":0.6629999876022339},{"id":"https://openalex.org/keywords/vegf-a","display_name":"VEGF-A","score":0.4350000023841858},{"id":"https://openalex.org/keywords/tumour-metastasis","display_name":"tumour metastasis","score":0.335999995470047}],"concepts":[{"id":"https://openalex.org/C160450060","wikidata":"https://www.wikidata.org/wiki/Q104598479","display_name":"Hypoxia-inducible factors","level":3,"score":0.6287003755569458},{"id":"https://openalex.org/C7836513","wikidata":"https://www.wikidata.org/wiki/Q1641506","display_name":"Hypoxia (environmental)","level":3,"score":0.5989471077919006},{"id":"https://openalex.org/C2909350873","wikidata":"https://www.wikidata.org/wiki/Q104598479","display_name":"Hypoxia-Inducible Factor 1","level":4,"score":0.546406090259552},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4505050480365753},{"id":"https://openalex.org/C2775960820","wikidata":"https://www.wikidata.org/wiki/Q408378","display_name":"Growth factor","level":3,"score":0.4427202641963959},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4387474060058594},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4367665648460388},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.34460583329200745},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3203356862068176},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.2870580554008484},{"id":"https://openalex.org/C540031477","wikidata":"https://www.wikidata.org/wiki/Q629","display_name":"Oxygen","level":2,"score":0.15201550722122192},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.11562281847000122},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:ourarchive.otago.ac.nz:10523/5882","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10523/5882","pdf_url":null,"source":{"id":"https://openalex.org/S4306402094","display_name":"Otago University Research Archive (University of Otago)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I80281795","host_organization_name":"University of Otago","host_organization_lineage":["https://openalex.org/I80281795"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Thesis or Dissertation"},{"id":"mag:1736614021","doi":null,"is_oa":false,"landing_page_url":"https://ourarchive.otago.ac.nz/handle/10523/5882","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.8371999859809875,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W1965079032","https://openalex.org/W1992980936","https://openalex.org/W2593622942","https://openalex.org/W7035978305","https://openalex.org/W109391890","https://openalex.org/W2515343504","https://openalex.org/W1602815497","https://openalex.org/W7199793863","https://openalex.org/W1984689645","https://openalex.org/W2120742250"],"abstract_inverted_index":{"The":[0,58,209,555,590],"transcription":[1,56],"factor":[2],"hypoxia-inducible":[3],"factor-1":[4],"(HIF-1)":[5],"upregulates":[6],"the":[7,15,20,38,51,71,84,141,153,177,187,225,247,260,284,320,376,379,396,401,413,488,506,510,522,537,543,571,588,612,632,667,676,704,707,750,776,785],"expression":[8],"of":[9,11,17,32,50,53,73,112,143,176,189,249,262,381,403,432,470,524,531,539,593,678,713,749,768,775,787,800],"hundreds":[10],"genes":[12],"involved":[13],"in":[14,45,123,136,161,171,182,206,295,341,345,416,505,513,521,582,598,634,654,662,732,756],"adaptation":[16],"tumours":[18,205,389,464],"to":[19,70,103,119,146,202,245,329,355,385,435,465,509,535,546,565,570,603,699,764],"hypoxic":[21],"microenvironment.":[22],"HIF-1":[23,121,162,229,363,373,471,561,737,777],"levels":[24,368,518,738,799],"and":[25,34,48,60,77,83,97,125,216,223,231,276,302,322,325,348,362,392,405,472,477,527,551,574,595,629,694,739,773,789],"transcriptional":[26,741],"activity":[27,99,131,230],"are":[28],"determined":[29],"by":[30,333,439,448,684,718,735],"hydroxylation":[31],"proline":[33,59],"asparagine":[35,61],"residues":[36],"on":[37,79,251,269,542],"regulatory":[39],"alpha":[40],"subunit.":[41],"These":[42,351],"signals":[43],"result":[44,581],"HIF-1\u03b1":[46,404,689],"degradation":[47],"prevention":[49],"formation":[52],"an":[54,528],"active":[55],"complex.":[57],"hydroxylases":[62],"that":[63,128,293,394,421,495,560,575,617,645,669,711],"carry":[64],"out":[65],"these":[66,326,642],"signalling":[67],"reactions":[68],"belong":[69],"family":[72],"iron-containing":[74],"2-oxoglutarate-dependent":[75],"dioxygenases,":[76],"depend":[78],"oxygen,":[80],"iron":[81],"(Fe),":[82],"metabolic":[85],"intermediate":[86],"2-oxoglutarate":[87],"for":[88,228,462,557,637,784],"activity.":[89,374,742],"They":[90],"also":[91,238,406,480],"require":[92],"ascorbate":[93,107,115,150,179,221,250,257,292,334,360,367,384,398,424,434,453,484,499,501,517,541,579,619,647,670,700,753,801],"as":[94,482,651],"a":[95,129,159,174,342,567,583,599,652,730,765],"cofactor":[96],"enzyme":[98],"has":[100,116,212,615,659],"been":[101,117],"shown":[102,118,683],"be":[104,156,330,727,803],"compromised":[105],"when":[106,754],"is":[108,502,563,671],"limiting.":[109],"Adequate":[110],"supplementation":[111,442,721],"cells":[113,313,573],"with":[114,158,279,290,319,336,358,365,371,387,427,459,578,587,729,758,762],"reduce":[120],"activation":[122,562],"vitro,":[124],"we":[126,184,745],"hypothesise":[127],"similar":[130,600],"could":[132],"affect":[133],"tumour":[134,154,165,197,214,220,252,346,359,397,408,423,429,433,483,544,572,733,798],"growth":[135,215,349],"vivo.":[137,655],"Therefore,":[138],"it":[139],"was":[140,169,237,390,425,456,534,559,682,690,695],"aim":[142],"this":[144,417,532,558,577,638,657],"thesis":[145,658],"investigate":[147,246,536],"if":[148],"increased":[149,422,460,540],"uptake":[151],"into":[152],"would":[155],"associated":[157,370,426,458,728],"reduction":[160],"activity,":[163],"slowing":[164],"progression.":[166],"This":[167,681,779],"hypothesis":[168,668],"tested":[170],"Gulo-/-":[172,207],"mice,":[173],"model":[175],"human":[178,791,797],"deficiency":[180],"condition,":[181],"which":[183,665],"can":[185,726,802],"manipulate":[186],"amount":[188],"vitamin":[190,265],"C":[191,266],"(ascorbate)":[192],"delivered.":[193],"Three":[194],"syngeneic":[195],"mouse":[196],"cell":[198,627],"lines":[199],"were":[200,243,288,314,327,353,479],"used":[201,755],"implant":[203],"subcutaneous":[204],"mice.":[208],"current":[210,613,708],"study":[211,418,490,533,614,709],"monitored":[213],"take":[217],"rates,":[218],"measured":[219],"content":[222,361,399],"analysed":[224],"harvested":[226],"tissues":[227],"related":[232],"gene":[233],"expression.":[234],"Tumour":[235],"morphology":[236],"investigated.":[239],"Several":[240],"different":[241],"approaches":[242],"taken":[244],"effect":[248,261,380,538,586,592],"growth,":[253],"including":[254],"manipulating":[255],"dietary":[256,291,441,720],"intake,":[258],"modelling":[259],"high":[263,451,497],"dose":[264,452,498],"(HDVC)":[267],"administration":[268,725],"pre-established":[270],"tumours,":[271],"changing":[272],"HDVC":[273,278,594,606],"dosage":[274],"schedules":[275],"combining":[277],"chemotherapy":[280,547,596,608,760],"agents.":[281],"\\n":[282,410,702],"\\nIn":[283],"initial":[285],"study,":[286],"mice":[287,386],"supplemented":[289],"resulted":[294,597],"optimal,":[296],"sub-optimal":[297],"or":[298,309,447,607,625,722],"low":[299],"tissue":[300,338],"levels,":[301,339],"B16-F10":[303,321],"(melanoma),":[304],"LL/2":[305,323,377,463],"(Lewis":[306],"lung":[307],"carcinoma)":[308],"CMT-93":[310],"(colon":[311],"cancer)":[312],"implanted":[315],"subcutaneously.":[316],"Tumours":[317],"formed":[318],"cells,":[324],"found":[328,354,616],"dramatically":[331],"affected":[332],"availability,":[335],"optimal":[337,440,714],"resulting":[340],"measurable":[343],"delay":[344],"initiation":[347],"rates.":[350],"effects":[352],"correlate":[356],"closely":[357],"activation,":[364],"higher":[366],"being":[369],"lower":[372],"Using":[375],"model,":[378],"administering":[382],"pharmacological":[383,618,646,724],"established":[388],"investigated,":[391],"showed":[393],"raising":[395],"decreased":[400],"level":[402],"slowed":[407],"growth.":[409,430],"\\nTaken":[411],"together,":[412,641],"results":[414,643],"presented":[415,660],"have":[419,630,746,782],"demonstrated":[420],"reduced":[428,481],"Restoration":[431],"0.6":[436],"\u03bcmol/g":[437],"either":[438,605,717],"(3300":[443],"mg/L;":[444],"per":[445],"OS)":[446],"daily":[449,525,723],"intra-peritoneal":[450],"(1":[454],"g/kg),":[455],"significantly":[457],"time":[461],"reach":[466],"4x":[467],"volume.":[468],"Levels":[469],"its":[473,673,740],"downstream":[474],"targets":[475],"CA-IX":[476],"VEGF,":[478],"increased.":[485],"In":[486,610,743],"addition,":[487,611,744],"pharmacokinetic":[489],"presents":[491],"novel":[492],"findings,":[493,664],"demonstrating":[494],"after":[496],"administration,":[500],"preferentially":[503],"retained":[504],"tumour,":[507],"compared":[508],"transient":[511],"elevation":[512],"normal":[514],"tissue.":[515],"\\nTumour":[516],"remained":[519],"elevated":[520],"presence":[523],"intervention,":[526],"important":[529],"aspect":[530],"response":[545],"(cisplatin":[548],"(2":[549],"mg/kg)":[550],"paclitaxel":[552],"(4":[553],"mg/kg)).":[554],"rationale":[556],"thought":[564],"confer":[566],"survival":[568],"advantage":[569],"decreasing":[576],"may":[580,781],"synergistic":[584],"anti-tumour":[585,601],"chemotherapy.":[589],"combined":[591],"outcome":[602],"using":[604],"alone.":[609],"does":[620,648],"not":[621,649],"induce":[622],"DNA":[623,771],"damage":[624,772],"caspase-mediated":[626],"death,":[628],"provided":[631,747],"first":[633],"vivo":[635],"evidence":[636,748],"effect.":[639],"Taken":[640],"suggest":[644],"behave":[650],"pro-oxidant":[653],"Finally,":[656],"preliminary":[661],"vitro":[663],"support":[666],"mediating":[672],"actions":[674],"through":[675],"maintenance":[677],"HIF-hydroxylase":[679],"function.":[680],"transfection":[685],"experiments,":[686],"where":[687],"mutated":[688],"stabilised":[691],"under":[692],"normoxia":[693],"no":[696],"longer":[697],"sensitive":[698],"availability.":[701],"\\nTherefore,":[703],"data":[705,780],"from":[706],"indicates":[710],"restoration":[712],"intracellular":[715],"ascorbate,":[716],"continuous":[719],"decline":[731],"aggression":[734],"dampening":[736],"complexity":[751],"surrounding":[752],"combination":[757],"other":[759],"agents,":[761],"regard":[763],"potential":[766],"mechanism":[767],"action":[769],"via":[770],"inhibition":[774],"response.":[778],"implications":[783],"management":[786],"cancer,":[788],"future":[790],"clinical":[792],"trials":[793],"will":[794],"determine":[795],"whether":[796],"similarly":[804],"manipulated.":[805]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2016-06-24T00:00:00"}
