BACKGROUND: The roles of sphingosine in various cancers have not been fully investigated. Our aim was to identify the relationship between serum sphingosine and the risk of hepatocellular carcinoma (HCC). METHODS: Serum sphingosine in 34 normal people and 73 HCC patients were reviewed retrospectively. Receiver operating characteristic curve analysis was performed to determine the cut-off values of sphingosine in the serum. Chi-square test, t test and regression analysis were used to test the association between serum sphingosine and individual clinicopathologic parameters. RESULTS: Serum sphingosine was higher in HCC patients (155.91±331.5 ng/mL) with normal persons as the control (30.92±29.4 ng/mL). The sphingosine threshold according to ROC curve was set at 22.5 ng/mL with a sensitivity of 74%, and a specificity of 55.9%. Meanwhile, sphingosine in HCC patients with abnormal albumin was significantly higher than that in patients with normal albumin (t=2.452, P=0.019). When HCC patients were divided into two groups serum sphingosine was negatively associated with albumin in HCC patients (χ2=4.469, P=0.035). Moreover, the logistic regression analysis showed that large tumor size (P=0.018, OR=0.13) and a low albumin (P=0.005, OR=8.856) were two independent risk factors for serum sphingosine upregulation. High AFP coupled with high serum sphingosine, high sphingosine and high AFP respectively were found in 91.2%, 75.4%, 73% of the HCC patients. CONCLUSIONS: These results suggest that serum sphingosine could be treated as a marker for the risk of HCC. AFP and sphingosine in the serum could be used together for HCC diagnosis.

• MeSH
• alfa-fetoproteiny metabolismus   MeSH
• hepatocelulární karcinom krev   komplikace   diagnóza   patologie   MeSH
• jaterní cirhóza krev   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetné primární nádory krev   komplikace   diagnóza   MeSH
• nádory jater krev   komplikace   diagnóza   patologie   MeSH
• riziko MeSH
• ROC křivka MeSH
• sérový albumin metabolismus   MeSH
• sfingosin krev   MeSH
• studie případů a kontrol MeSH
• tumor burden MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Herbal medicines have been increasingly used in the last three decades. Despite their popularity, safety issues with herbal products need to be addressed. We performed a feasibility study of the toxic responses of human induced pluripotent stem cell-derived hepatocytes (iHep cells) to phytochemicals in comparison with hepatoblasoma-derived HepG2 cells and long-term human hepatocytes (LTHHs). The iHep cells expressed typical hepatocyte markers cytochrome P450 3A4 (CYP3A4), hepatocyte nuclear factor 4α, and albumin despite the expression of immature markers α-fetoprotein and cytokeratin 19. We studied the responses of iHep cells to phytochemicals saikosaponin D, triptolide, deoxycalyciphylline B, and monocrotaline with different mode of toxicity employing MTS and lactate dehydrogenase (LDH) assays. Saikosaponin D and triptolide caused dose-dependent cytotoxicity in the iHep cells, which were more sensitive than LTHHs and HepG2 cells. Saikosaponin D-induced cytotoxicity tightly correlated with increased LDH leakage in the iHep cells. Although deoxycalyciphylline B did not exhibit toxic effect on the iHep and HepG2 cells when compared with LTHHs, it decreased CYP3A7 expression in the iHep cells and increased CYP1A2 expression in HepG2 cells. We hereby show the feasibility of using iHep cells to detect toxic effects of phytochemicals.

• MeSH
• albuminy metabolismus   MeSH
• alfa-fetoproteiny metabolismus   MeSH
• dospělí MeSH
• fytonutrienty toxicita   MeSH
• hepatocytární jaderný faktor 4 metabolismus   MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• indukované pluripotentní kmenové buňky cytologie   MeSH
• keratin-19 metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladiství MeSH
• studie proveditelnosti MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. METHODS: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. RESULTS: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). CONCLUSIONS: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.

• MeSH
• alfa-fetoproteiny metabolismus   MeSH
• dospělí MeSH
• hepatocelulární karcinom krev   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nádory jater krev   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• rentgendiagnostika metody   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Prezentujeme kazuistiku 41letého pacienta, který byl přivezen do našeho zdravotnického zařízení pro podezření na krvácení do horní části gastrointestinálního traktu. Gastroskopicky byla nalezena exulcerovaná infiltrace na zadní stěně subkardiální části žaludku. Histologicky byl prokázán vzácný adenokarcinom žaludku s yolk sac diferenciací. Tento typ nádoru patří mezi malignity se špatnou prognózou. V době diagnózy bývá již přítomna generalizace s jaterním metastatickým postižením.

We present the case of a 41-year-old patient who was brought to our hospital because of suspected bleeding into the upper part of gastrointestinal tract. Gastroscopy found an ulcerated infiltration at the posterior wall of the subcardial stomach. Histological analysis showed the presence of an adenocarcinoma of the stomach with yolk sac differentiation, which is a rare type of malignant tumor with a poor prognosis that has usually metastasized to secondary sites such as the liver at the time of diagnosis.

• Klíčová slova
• protokol BEP,
• MeSH
• adenokarcinom diagnóza   farmakoterapie   patologie   MeSH
• alfa-fetoproteiny * metabolismus   MeSH
• bleomycin aplikace a dávkování   MeSH
• cisplatina aplikace a dávkování   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• etoposid aplikace a dávkování   MeSH
• fatální výsledek MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádor z entodermálního sinusu * diagnóza   farmakoterapie   patologie   MeSH
• nádorové biomarkery krev   MeSH
• nádory jater sekundární   MeSH
• nádory žaludku * diagnóza   farmakoterapie   patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

If diagnosed at early stages, patients with hepatocellular carcinoma (HCC) can receive curative therapies, whereas therapeutic options at later stages are very limited. Here, we addressed the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. Serum concentrations of sAxl were significantly increased in HCC (18.575 ng/mL) as compared to healthy (13.388 ng/mL) or cirrhotic (12.169 ng/mL) controls. Receiver operating characteristic curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. α-Fetoprotein (AFP)-negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon. In summary, sAxl outperforms AFP in detecting very early HCC as compared to healthy or cirrhotic controls and shows high diagnostic accuracy for AFP-negative patients. sAxl is specific for HCC and suggested as a biomarker for routine clinical use.

• MeSH
• alfa-fetoproteiny metabolismus   MeSH
• buňky Hep G2 MeSH
• časná diagnóza MeSH
• diferenciální diagnóza MeSH
• ELISA MeSH
• hepatocelulární karcinom krev   diagnóza   MeSH
• jaterní cirhóza krev   diagnóza   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory jater krev   diagnóza   MeSH
• protoonkogenní proteiny krev   metabolismus   MeSH
• ROC křivka MeSH
• rozpustnost MeSH
• staging nádorů MeSH
• tyrosinkinasové receptory krev   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α(1) fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α(1) fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure.

• MeSH
• akutní selhání jater krev   imunologie   terapie   MeSH
• alfa-fetoproteiny metabolismus   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• časové faktory MeSH
• design vybavení MeSH
• dospělí MeSH
• ELISA MeSH
• hemoperfuze přístrojové vybavení   MeSH
• hepatocytární růstový faktor krev   MeSH
• interleukiny krev   MeSH
• játra umělá MeSH
• kalcitonin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• proteinové prekurzory krev   MeSH
• regenerace jater MeSH
• TNF-alfa krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVE: To investigate the relationship of urine fetuin-A and other promotors and inhibitors of urine crystalization with urolithiasis, as fetuin-A inhibits the precipitation of hydroxyapatite from supersaturated solutions of calcium and phosphate in vitro but no information on urine fetuin-A in patients with urolithiasis is available. PATIENTS AND METHODS: In all, 39 patients with urolithiasis and 22 individuals with no urolithiasis or probands with undetected stones were involved. All patients underwent kidney ultrasonography and X-ray examination, and body mass index (BMI) was calculated. Serum creatinine, parathyroid hormone, calcium, magnesium, anorganic phosphate, uric acid and urine creatinine, albumin, alpha(1)-microglobulin, sulphate, oxalate, citrate and fetuin-A (ELISA) were determined. RESULTS: The patients with urolithiasis had lower urine fetuin-A levels (median 4.9 vs 0.77 mg/day; P < 0.01) and citraturia levels (1.7 vs 5.1 mmol/day; P = 0.02); and higher calciuria (6.5 vs 5.2 mmol/day) and oxaluria (0.47 vs 0.25; P = 0.04). Patients with fetuin-A levels in the lowest quartile had an odds ratio of 36 compared with individuals in the highest quartile. The sensitivity of the urine fetuin-A level for urolithiasis was 97.4% and specificity was 100% (area under the curve 0.99; 95% confidence interval 0.94-1.0) using a urine fetuin-A threshold of

• MeSH
• alfa-fetoproteiny metabolismus   moč   MeSH
• ELISA MeSH
• krystalizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• recidiva MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• urolitiáza krev   moč   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH