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Abstracts
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Determination of hormone receptors in small specimen of cancer tissue
Author: Levin Vrhovec
Mentors: Meta Lavrenčak,. prof.
prof. dr. Janez Škrk, dipl.biol.
March, 1994
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We measured the estrogen receptor concentration
in cytosol of breast cancer tissue by using the dextran-coated
charcoal (DCC) assay. /2,4,6,7-3H/-estradiol was taken as a
radiolabeled estrogen hormone, and dietilstilbestrol (DES) as a
competitive binder for estrogen receptors.
The specific
binding potential of estrogen receptors was
observed in the concentrations within the range of 0,020 to 4 pmol
in each specimen. After having determined the range of saturation,
we measured the ER concentration at just one point.
Our
results were compared with those which were
obtained by Scatchard analysis method. A good correlation (r=0,967)
between the sample of our and Scatchard's method was established.
Having a large enough tumor tissue sample, it is reasonable to
use Scatchard analysis with six points of ligand
concentration. But in the case that such specimen of tumor tissue
cannot be obtained, we can determine the ER concentration by using
one point with the value of 2 pmol/100 ul.
The obtained
results are reliable enough to be used for clinical
purposes.
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Cystatin-C as a kidney-failure marker during chemotherapy
Author: Levin Vrhovec
Mentor: doc.dr. Borut Štabuc
December, 1997
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Many cytotoxic agents used
in antitumor therapies can cause a kidney damage. Therefore there is
a necessity for regular kidney function monitoring before and during
chemotherapy. Clearance tests have been proven to
be the most accurate indicators for clinical assessment of
glomerular filtration (GFR). Because of inconvenience of
exogene markers (inulin, 51Cr-EDTA), endogenous
creatinine clearance (ECC) is used in everyday routine work.
Results obtained from ECC analysis can often be
misleading due to inaccurate urine collecting. In order to avoid the
inconvenient urine collecting, we are trying to find an
easier and faster way of kidney function
assessment.
Cystatin C is a serum protein,
which is a member of the cysteine proteinase inhibitors. It is
produced by all nucleal cells and its production rate is independent
of sex, nutrition status, acute and chronic diseases and cancer.
Because it is freely filtered at the glomerulus, its serum
concentration correlates with glomerular filtration rate.
The purpose of this research was to find out if
the serum cystatin C concentration correlates with GFR and ECC
respectively.
We analysed 117 serum samples
taken from 56 patients. Serum and urine creatinine concentrations
were determined by method based on Jaffe reaction, ECC was
calculated from urine flow, surface area and the ratio between serum
and urine creatinine concentrations. We used particle enhanced
turbidimetric immunoassay (PET) for cystatin C determination. Data
were statistically analysed with SimStat computer program. We used
Pearson correlation method with 95 % confidence interval.
A good correlation coefficient (r=0.736)
between the values of serum creatinine and cystatin C was
established within the whole concentration interval. The relation
between cystatin C and ECC values was determined with correlation
coefficient r=0.792. Cystatin C differed from ECC values in 8 of 117
samples (6.8 %). Methods don't show significant statistical
difference in pathological results (hi square=0.86, p=0.35). An
increased cystatin C concentration corresponds to decreased ECC
values in 93 %.
We showed that serum cystatin C concentration can replace with great certainty the ECC method for clinical assessment of early kidney damage.
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Improved prediction of decreased creatinine clearance by serum cystatin C : Use in cancer patients before and during chemotherapy
Stabuc B, Vrhovec L, Stabuc-Silih M, Cizej TE. Improved prediction of decreased creatinine clearance by serum cystatin C : Use in cancer patients before and during chemotherapy.
Clin Chem 2000;46:193-7.
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Background: Serum cystatin C, a cysteine protease inhibitor has been suggested as a new marker of glomerular filtration rate (GFR). This study explores the possibility to replace the creatinine clearance (CrCl) estimation of GFR with the cystatin C in early detection of renal impairment in cancer patients on chemotherapy.
Methods: Serum creatinine and cystatin C concentrations as well as 24-hour CrCl were determined simultaneously in 72 cancer patients. Among them 60 were treated with combined chemotherapy with cisplatin (CDDP). Creatinine was determined enzymatically with a spectrophotometric method. Serum cystatin C was determined by a particle enhanced turbidimetric immunoassay.
Results: Cystatin C and creatinine correlated significantly (p=0.001) with CrCl. The correlation was significantly better for cystatin C than creatinine (r=0.84, r=0.74; p=0.01). Stepwise regression analysis identified no differences for the correlation between cystatin C and CrCl in patients with metastases or without them (r=0.82, r=0.84) as well as before treatment and before the fourth cycle of chemotherapy (r=0.70, r=0.75). A cystatin C cutoff concentration of 1.33 mg/L had 87% sensitivity and 100% specificity for detecting CrCl <78mL/min.
Conclusion: Serum cystatin C appears to be superior to serum creatinine and broadly equivalent to CrCl measurements for the estimation of GFR in cancer patients independently of the presence of metastases or chemotherapy.
Key words: cystatin C, creatinine, creatinine clearance, chemotherapy
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Pomen serumskega cistatina C za ugotavljanje okvare ledvic med kemoterapijo
Vrhovec L. Pomen serumskega cistatina C za ugotavljanje okvare ledvic med kemoterapijo.
Med Razgl 2000;39:33-50.
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Mnoge citotoksične učinkovine, ki jih uporabljamo pri zdravljenju raka, lahko okvarijo delovanje ledvic, zato moramo pred in med kemoterapijo redno spremljati delovanje ledvic. Za oceno njihovega delovanja in zgodnjih okvar so najpomembnejši testi očistkov. V vsakodnevni klinični praksi delovanje ledvic vrednotimo z očistkom kreatinina (endogenous creatinine clearance - ECC), saj so preiskave s pomočjo eksogenih označevalcev (npr. inulin, 51Cr-EDTA) nepraktične in obremenjujoče za bolnika.
Pri določanju ECC lahko pride do zavajajočih rezultatov zaradi nedoslednosti bolnika pri zbiranju celodnevnega urina. Da bolnikom ne bi bilo treba zbirati urina, poskušamo odkriti enostavnejši in hitrejši način ugotavljanja ledvične funkcije.
Cistatin C je serumska beljakovina, ki jo uvrščamo med inhibitorje cisteinskih proteaz. Nastaja v vseh jedrnih celicah. Njegova serumska koncentracija je neodvisna od spola, stanja prehranjenosti, akutnih in kroničnih bolezni ter raka. Ker se v večini izloča skozi glomerule, njegova serumska koncentracija korelira z glomerulno filtracijo (GFR).
Namen naloge je bil ugotoviti, ali koncentracija serumskega cistatina C korelira z GFR oziroma z ECC.
V raziskavi smo analizirali 117 vzorcev pri 56 bolnikih. Kreatinin v serumu in urinu smo določali z metodo, ki temelji na Jaffejevi reakciji, ECC smo izračunali iz volumskega pretoka urina, telesne površine in razmerja med koncentracijo kreatinina v serumu in urinu, cistatin C smo določili s turbidimetrično analizno tehniko PET.
Podatke smo statistično obdelali s programom SimStat. Korelacijske koeficiente smo računali po Pearsonu v 95 % intervalu zaupanja. Pri primerjavi vrednosti serumskega kreatinina in cistatina C smo ugotovili visoko povezanost (r = 0,736) za celotno koncentracijsko območje. Odnos med vrednostmi cistatina C in ECC je določen s korelacijskim koeficientom r = 0,792.
Pri 117 vzorcih se je cistatin C razlikoval od ECC v 8 primerih (6,8 %). Metodi se statistično pomembno ne razlikujeta v deležu patoloških rezultatov (c2 = 0,86, p = 0,35). Zvišana koncentracija cistatina C se ujema z znižanjem ECC v vsaj 93 %.
Raziskava je pokazala, da serumska koncentracija cistatina C lahko z veliko gotovostjo nadomesti dolgotrajno preiskavo ECC pri ugotavljanju zgodnje ledvične okvare.
Ključne besede: cistatin C, očistek kreatinina, ledvična okvara, kemoterapija
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