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Assessment of biomarkers of cholesterol homeostasis and vitamin D metabolism in patients with colorectal cancer

dc.contributor.advisorSpasojević-Kalimanovska, Vesna
dc.contributor.otherZeljković, Aleksandra
dc.contributor.otherJelić-Ivanović, Zorana
dc.contributor.otherTrifunović, Bratislav
dc.creatorVladimirov, Sandra
dc.date.accessioned2020-10-06T11:37:38Z
dc.date.available2020-10-06T11:37:38Z
dc.date.issued2019
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=7341
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/12189
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:21578/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048435042
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3690
dc.description.abstractKolorektalni karcinom (CRC) je maligno oboljenje sa visokom prevalencijom urazvijenim zemljama. Holesterol poseduje mnogobrojne funkcije, te se pretpostavlja daima ulogu i u procesima maligne transformacije i proliferacije. Procena efikasnosti procesasinteze i apsorpcije holesterola, određivanjem cirkulišućih nivoa neholesterolskih sterola(NHS), može pružiti značajne podatke o metabolizmu holesterola, kao i njegovom uticajuna status drugih biomolekula (vitamin D, steroidni hormoni). Ciljevi ovog istraživanja bilisu uvođenje i validacija metoda tečne hromatografije sa tandem masenom detekcijom(HPLC-MS/MS) za kvantifikaciju markera sinteze (dezmosterol i latosterol) i apsorpcijeholesterola (kampesterol, β-sitosterol) u serumu i izolovanoj serumskoj frakcijilipoproteina visoke gustine (HDL), kao i razvoj i validacija metode za kvantifikacijuprekursora (7-dehidroholesterol, 7-DHC) i metabolita vitamina D (25(OH)D3,24,25(OH)2D3) u serumu. Osim toga, ispitivali smo i status markera sinteze i apsorpcijeholesterola, kao i metabolizma vitamina D kod osoba sa CRC, i nastojali da utvrdimopovezanost između metabolizma ovih jedinjenja, kao i da procenimo njihov prediktivnipotencijal za CRC.U istraživanju je učestvovao 101 pacijent sa dijagnozom CRC i 114 zdravihispitanika. Pacijenti su podeljeni prema patološkim karakteristikama na sledeće grupe:karcinom kolona (CA kolona) i karcinom rektuma (CA rektuma); gradus I i objedinjenigradusi II i III; stadijumi A i B, te stadijumi C i D. Koncentracije NHS u serumu i HDLfrakciji, kao i koncentracije parametara statusa vitamina D u serumu, određivani su HPLCMS/MS metodama. Na osnovu koncentracija NHS u serumu i HDL frakciji, izračunati surazličiti indeksi homeostaze holesterola, dok je odnos metabolita vitamina D (VDMR)izračunat na osnovu koncentracija 25(OH)D3 i 24,25(OH)2D3 u serumu.Rezultati studije su pokazali da je holesterol glavni interferent prilikom određivanjaNHS, pa je u tom smislu izvršena priprema odgovarajućeg matriksa za kvantitativnuanalizu. Varijacije unutar serije su bile 4.7-10.3% za NHS u serumu i 3.6-13.6% za NHS uHDL frakciji, a između serija 4.6-9.5% za NHS u serumu i 2.5–9.8% za NHS u HDLfrakciji. Studije prinosa analita su pokazale zadovoljavajuće rezultate: 89.8–113.1% zaNHS u serumu i 85.3–95.8% za NHS i HDL frakciji. Pacijenti su imali značajno nižekoncentracije NHS u serumu (p<0,001, za sve) i u HDL frakciji (p<0,001 za dezmosterol iβ-sitosterol, p<0,005 za kampesterol, p<0,05 za latosterol)...sr
dc.description.abstractColorectal cancer (CRC) is a malignancy highly prevalent in developed countries.Cholesterol is a biomolecule with multiple functions and suspected important role inmalignant transformation and proliferation. Assessing the efficiency of cholesterolsynthesis and absorption processes, by determining circulating levels of non-cholesterolsterols (NCS), can provide significant data on cholesterol metabolism as well as its effecton other biomolecules (vitamin D, steroid hormones). The objectives of this study were tointroduce and validate liquid chromatography - tandem mass detection (HPLC-MS/MS)methods for quantification of cholesterol synthesis (desmosterol and lathosterol) andcholesterol absorption (campesterol, β-sitosterol) markers in serum and serum high densitylipoprotein fraction (HDL), as well as the method for quantification of vitamin D statusparameters (7-dehydrocholesterol (7-DHC), 25(OH)D3, 24,25(OH)2D3). In addition, weexamined the status of cholesterol synthesis and absorption markers, as well as vitamin Dmetabolites in individuals with CRC, and explored the association between these twometabolic pathways, as well as evaluated their predictive potential for CRC.The study involved 101 patients with CRC diagnosis and 114 healthy subjects.Patients were divided according to pathological characteristics into the following groups:colon cancer (colon CA) and rectal cancer (rectal CA); grade I, and grade II and IIIcombined; stages A and B and stages C and D. NCS concentrations in serum and HDLfraction, as well as concentrations of serum vitamin D status parameters, were determinedby HPLC-MS/MS. Based on NCS concentrations in serum and HDL fraction, differentcholesterol homeostasis indices were calculated. Vitamin D metabolite ratio (VDMR) wascalculated based on serum 25(OH)D3 and 24,25(OH)2D3 concentrations.The study results showed that cholesterol was the main interferent in thedetermination of NCS, and in this respect, the appropriate matrix for quantitative analysiswas prepared. Within-series variations were 4.7-10.3% for serum NHS and 3.6-13.6% forNCS in HDL fraction, whereas between series variations were 4.6-9.5% for serum NHSand 2.5-9.8% for NCS in HDL fraction. Recovery study has shown satisfactory results:89.8–113.1% for serum NCS and 85.3–95.8% for NHS and HDL fraction.Patients had significantly lower NCS concentrations (p<0.001, for all) in serum andin the HDL fraction (p<0.001 for desmosterol and β-sitosterol, p<0.005 for campesterol,p<0.05 for latosterol)...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175035/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectkolorektalni karcinom; neholesterolski steroli u serumu i HDLfrakciji; promene nivoa sinteze i apsorpcije holesterola; metaboliti vitamina D; nezavisniprediktori kolorektalnog karcinomasr
dc.subjectcolorectal cancer; non-cholesterol sterols in serum and HDL fraction;changes in cholesterol synthesis and absorption; vitamin D metabolites; independentpredictors of colorectal canceren
dc.titleIspitivanje biomarkera homeostaze holesterola i metabolizma vitamina D kod pacijenata sa kolorektalnim karcinomomsr
dc.title.alternativeAssessment of biomarkers of cholesterol homeostasis and vitamin D metabolism in patients with colorectal canceren
dc.typedoctoralThesisen
dc.rights.licenseARR
dcterms.abstractСпасојевић-Калимановска, Весна; Трифуновић, Братислав; Зељковић, Aлександра; Јелић-Ивановић, Зорана; Владимиров, Сандра; Испитивање биомаркера хомеостазе холестерола и метаболизма витамина Д код пацијената са колоректалним карциномом; Испитивање биомаркера хомеостазе холестерола и метаболизма витамина Д код пацијената са колоректалним карциномом;
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8210/Disertacija-3.pdf
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8211/IzvestajKomisije22303.pdf
dc.type.versionpublishedVersion


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