Lipidated anorexigenic peptides are highly promising compounds for the treatment of obesity and related diseases. However, their exact mechanism of action still remains unknown. We labelled a lipidated analogue of an anorexigenic prolactin-releasing peptide (palm11-PrRP31) with an extremely stable ClickZip lanthanide tag, facilitating tracking of the peptide within the organism. We then employed a separation method based on liquid chromatography combined with inductively coupled plasma mass spectrometry (LC-ICP-MS). This technique involved the use of an unconventional mobile phase containing 5 % 1,2-hexanediol in H2O (v/v) with the addition of 2 % formic acid. Using a rapid. 6-min analysis, we were able to quantify the ClickZip tag - and thus indirectly the fate of the labelled peptides in the living organism - independently of free Ln3+ ions. The detection limits for the various lanthanide chemical forms were extremely low, ranging between 0.9 and 3.4 ng/L. We demonstrated the suitability of the method for analysing real biological samples like blood plasma, and confirmed the accuracy of our results. Prior to LC-ICP-MS analysis, we optimised a process involving the microwave-assisted digestion of liver samples to preserve the integrity of the ClickZip tag. We also identified several metabolites of the labelled peptides in the liver, urine, and blood plasma, highlighting the utility of the method for revealing the mechanism of action behind the labelled lipopeptides.

• Klíčová slova
• 1,2-Hexanediol, Anorexigenic peptides, Method validation, Sample digestion,
• MeSH
• chromatografie kapalinová metody   MeSH
• click chemie MeSH
• hmotnostní spektrometrie * metody   MeSH
• lanthanoidy * chemie   MeSH
• myši MeSH
• peptidy * analýza   chemie   krev   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lanthanoidy * MeSH
• peptidy * MeSH

PURPOSE: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. METHODS: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. RESULTS: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. CONCLUSION: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

• Klíčová slova
• BALP, Bone status indices, Bone turnover markers, PINP, TRACP5b, β-CTX-I,
• MeSH
• biologické markery krev   MeSH
• hodnocení rizik metody   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• kolagen typu I krev   MeSH
• konsensus MeSH
• lidé MeSH
• osteoporotické fraktury prevence a kontrola   etiologie   MeSH
• osteoporóza * diagnóza   patofyziologie   farmakoterapie   krev   terapie   MeSH
• peptidové fragmenty krev   MeSH
• peptidy krev   MeSH
• prokolagen krev   MeSH
• remodelace kosti * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• inhibitory kostní resorpce MeSH
• kolagen typu I MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH

Ageing is associated with the accumulation of damage to all the macromolecules within and outside cells leading to progressively more cellular and tissue defects and resulting in age-related frailty, disability and disease. As a result of the aging process the bone deteriorates in composition, structure and function. Age-related musculoskeletal losses are a major public health burden because they can cause physical disability and increased mortality. We tried to find out on a small set of old women, without risk factors for osteoporosis, what caused them the loss of bone minerals. All 492 women had just only one risk factor - the old age. Laboratory findings have shown a decreased serum C telopeptide and low serum alkaline phosphatase circulating markers, used to quantify bone resorption and formation, and very low level of vitamin D. Very low level of vitamin D that disrupted calcium absorption through the intestine, and decreased calcemia increased parathyroid hormone levels with resulting bone effect. The manifestation of physiological aging is worsening eyesight, peripheral neuropathy, depression, worsening of physical condition, skin aging, sarcopenia and bone mineral loss. Senile osteoporosis, which is not caused by known risk factors for osteoporosis, does not appear to be a separate disease, but is part of the physiological process of aging. Treatment of senile osteoporosis should be focused on the control of secondary hyperparathyroidism by administration of vitamin D and calcium. The risk of fractures in the advanced age is determined by a large number of factors ranging from hazards in the home environment to frailty and poor balance.

• Klíčová slova
• Aging, Frailty, Osteoporosis, Sarcopenia,
• MeSH
• alkalická fosfatasa krev   MeSH
• kolagen typu I krev   MeSH
• kostní denzita MeSH
• lidé MeSH
• osteogeneze MeSH
• osteoporóza krev   MeSH
• parathormon krev   MeSH
• peptidy krev   MeSH
• stárnutí krev   patologie   MeSH
• vápník metabolismus   MeSH
• vitamin D krev   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• kolagen typu I MeSH
• parathormon MeSH
• peptidy MeSH
• vápník MeSH
• vitamin D MeSH

BACKGROUND/AIM: The aim of this study was to analyze the pretreatment cytokeratin serum levels in head and neck squamous cell carcinoma (HNSCC) by three assays in relation to selected clinicopathological characteristics in an effort to find diagnostic/prognostic biomarkers for HNSCC and determine the best assay. PATIENTS AND METHODS: In total, 46 patients with HNSCC with different subsite (oropharyngeal-21 cases, hypopharyngeal-4 and laryngeal-21) were included in this prospective study. MonoTotal, Cyfra 21-1, and TPS radioimmunoassay kits were used to analyze cytokeratin fragments serum levels. RESULTS: Statistically significant differences in serum levels of TPS and Cyfra 21-1 were found between low (stage I-II)- and high-stage (stage III-IV) tumors (p=0.0057; p=0.0138 respectively). Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors. CONCLUSION: The present study is the first to compare cytokeratin serum levels between various subgroups of HNSCC using three different assays. Cyfra 21-1 seems to be the most useful for clinical practice. The relation between elevated Cyfra 21-1 serum levels and p16 expression requires further investigation.

• Klíčová slova
• Cyfra 21-1, Head and neck squamous cell carcinoma, MonoTotal, TPS, p16, serum tumor marker,
• MeSH
• antigeny nádorové krev   MeSH
• dlaždicobuněčné karcinomy hlavy a krku krev   diagnóza   mortalita   terapie   MeSH
• keratin-19 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové biomarkery * MeSH
• peptidy krev   MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen CYFRA21.1 MeSH Prohlížeč
• antigeny nádorové MeSH
• keratin-19 MeSH
• nádorové biomarkery * MeSH
• peptidy MeSH
• tissue polypeptide specific antigen MeSH Prohlížeč

BACKGROUND/AIM: The results of surgical treatment of breast cancer liver metastases (BCLM) remain suboptimal. The search for perioperative prognostic factors could help determine high risk groups of patients. The aim of study was to evaluate the significance of tumour markers (TM) on long-term treatment results. PATIENTS AND METHODS: Liver surgery was carried out in 32 women for BCLM. The perioperative serum levels of CEA, CA19-9, TPA, TPS, CYFRA 21-1 and TK were determined. RESULTS: Preoperative levels of CA19-9 were significant for overall survival (OS)(p<0.05) and recurrence-free survival (RFS) (p<0.01). TPA, TPS and CYFRA 21-1 levels were significant for OS (p<0.05; p<0.04; p<0.05). Postoperative levels of CEA, TPS and CYFRA 21-1 were significant for RFS (p<0.04; p<0.01; p<0.02), while CA19-9 postoperative levels were significant for OS and RFS (p<0.03; p<0.01). CONCLUSION: Perioperative TM serum levels may represent prognostic indicators reflecting the results of surgical treatment of BCLM.

• Klíčová slova
• Breast cancer liver metastases, liver surgery, tumour markers,
• MeSH
• analýza přežití MeSH
• antigen CA-19-9 krev   MeSH
• antigeny nádorové krev   MeSH
• dospělí MeSH
• karcinoembryonální antigen krev   MeSH
• keratin-19 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory jater sekundární   chirurgie   MeSH
• nádory prsu patologie   chirurgie   MeSH
• peptidy krev   MeSH
• perioperační období * MeSH
• prognóza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen CA-19-9 MeSH
• antigen CYFRA21.1 MeSH Prohlížeč
• antigeny nádorové MeSH
• karcinoembryonální antigen MeSH
• keratin-19 MeSH
• nádorové biomarkery MeSH
• peptidy MeSH
• tissue polypeptide specific antigen MeSH Prohlížeč

Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m(2) of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan's multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7alpha-, 7beta-, and 16alpha-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with delta(5)-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs.

• MeSH
• androgeny krev   farmakologie   terapeutické užití   MeSH
• dospělí MeSH
• glukokortikoidy farmakologie   terapeutické užití   MeSH
• IgA nefropatie krev   farmakoterapie   MeSH
• imunologické faktory krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadledviny účinky léků   metabolismus   MeSH
• peptidy krev   MeSH
• prednisolon farmakologie   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgeny MeSH
• C19 peptide MeSH Prohlížeč
• glukokortikoidy MeSH
• imunologické faktory MeSH
• peptidy MeSH
• prednisolon MeSH

An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n=16) or alendronate-pretreated (ALN, n=29) at teriparatide initiation. Teriparatide (20μg/day) was given for 24months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P=0.039) and 55 (139)% (P<0.005) and trabecular thickness 30.4 (30)% (P<0.001) and 30.8 (53)% (P<0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor βCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r=0.502 (P<0.01) and r=0.378 (P<0.05), trabecular number, r=0.559 (P<0.01) and r=0.515 (P<0.01), and reduction of trabecular separation, r=-0.432 (P<0.05) and r=-0.530 (P<0.01), for PINP and βCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy irrespective of prior antiresorptive use.

• Klíčová slova
• Alendronate pretreatment, Cancellous bone microstructure, PINP, Teriparatide, Turnover markers,
• MeSH
• alendronát terapeutické užití   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• kolagen typu I krev   MeSH
• kostní denzita účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidové fragmenty krev   MeSH
• peptidy krev   MeSH
• postmenopauzální osteoporóza farmakoterapie   MeSH
• prokolagen krev   MeSH
• remodelace kosti účinky léků   MeSH
• senioři MeSH
• teriparatid terapeutické užití   MeSH
• trabekulární kostní tkáň účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alendronát MeSH
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• inhibitory kostní resorpce MeSH
• kolagen typu I MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH
• teriparatid MeSH

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

• Klíčová slova
• Beta-carboxyterminal cross-linked telopeptide of type I collagen, Bone scintigraphy, Human epididymis protein 4, Malignant melanoma, Osteocalcin,
• MeSH
• kolagen typu I krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom krev   patologie   MeSH
• nádorové biomarkery krev   MeSH
• nádory kostí krev   diagnostické zobrazování   sekundární   MeSH
• nádory kůže krev   patologie   MeSH
• osteokalcin krev   MeSH
• peptidy krev   MeSH
• radioisotopová scintigrafie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• kolagen typu I MeSH
• nádorové biomarkery MeSH
• osteokalcin MeSH
• peptidy MeSH

AIM: The aim of the study was to assess the degree to which tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), as well as carcinoembryonic antigen (CEA), can assist in the detection of distant metastases. PATIENTS AND METHODS: We assessed 157 patients with colorectal and breast cancer divided into two groups. The first was a group of patients with cancer at stages 1, 2 and 3; the second was a group of patients with cancer at stage 4 with metastasis. RESULTS: We found significantly higher levels of all biomarkers in the metastatic group compared to the group with cancer at stages 1-3 (p<0.0001). The calculated area under the receiver operating characteristic (ROC) curve was 0.9929 for TPS, 0.9337 for TPA and 0.7234 for CEA. The cut-off was calculated for each biomarker at 95% specificity, TPS cut-off=255 IU/l (sensitivity 95%), TPA cut-off=200 IU/l (sensitivity 70%) and CEA cut-off=18 μg/l (sensitivity 37%). CONCLUSION: We suggest combining CEA with TPS or TPA in the detection of distant metastases or using only cytokeratins. This approach can significantly increase the quality of detection of the metastatic process.

• Klíčová slova
• CEA, Colorectal cancer, TPA, TPS, breast cancer, distant metastasis,
• MeSH
• dospělí MeSH
• karcinoembryonální antigen krev   MeSH
• kolorektální nádory krev   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory jater krev   sekundární   MeSH
• nádory kostí krev   sekundární   MeSH
• nádory ledvin krev   sekundární   MeSH
• nádory plic krev   sekundární   MeSH
• nádory prsu krev   patologie   MeSH
• peptidy krev   MeSH
• plocha pod křivkou MeSH
• prediktivní hodnota testů MeSH
• reagenční diagnostické soupravy MeSH
• reprodukovatelnost výsledků MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• tkáňový polypeptidový antigen krev   MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• karcinoembryonální antigen MeSH
• peptidy MeSH
• reagenční diagnostické soupravy MeSH
• tissue polypeptide specific antigen MeSH Prohlížeč
• tkáňový polypeptidový antigen MeSH

The aim of our retrospective study was to analyze the association of selected tumor markers (TMs) including serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase, and tissue polypeptide specific antigen with outcomes in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab. There is an increasing body of evidence from retrospective/observational studies that some serum TMs may be predictive of effect of targeted therapies in mCRC. In our study, the cohort included 152 patients treated with bevacizumab-based therapy between years 2005 and 2014 at Department of Oncology and Radiotherapy, Medical School and Teaching Hospital Pilsen. Serum samples for measurement of TMs were collected within 1 month before the initiation of bevacizumab-based treatment. In multivariate Cox analysis that included serum tumor markers and clinical baseline parameters, the number of metastatic sites (hazard ratio [HR] = 2.00, p = 0.001) and CEA levels (HR = 2.80, p < 0.001) were significantly associated with progression-free survival, whereas CA 19-9 levels (HR = 2.25, p = 0.008) were the only studied parameter associated with overall survival. Quantification of serum CEA and CA 19-9 is simple and readily available, and their candidate prognostic importance in the setting of antiangiogenesis therapy deserves to be studied in prospective trials.

• MeSH
• antigen CA-19-9 krev   MeSH
• bevacizumab aplikace a dávkování   MeSH
• dospělí MeSH
• karcinoembryonální antigen krev   MeSH
• kohortové studie MeSH
• kolorektální nádory krev   farmakoterapie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové biomarkery krev   MeSH
• peptidy krev   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thymidinkináza krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CA-19-9 MeSH
• bevacizumab MeSH
• karcinoembryonální antigen MeSH
• nádorové biomarkery MeSH
• peptidy MeSH
• thymidinkináza MeSH
• tissue polypeptide specific antigen MeSH Prohlížeč