Žádný z dosud studovaných biomarkerů v oblasti HCC nevykazuje pro časná stadia vyšší senzitivitu a specificitu než ultrasonografické vyšetření jater. Existuje tak naléhavá klinická potřeba zavedení laboratorního markeru pro HCC, který splňuje požadavky na vysokou senzitivitu a specificitu pro screening a včasnou diagnostiku rizikových pacientů. Protože různé patologické procesy, včetně karcinogeneze, mohou způsobit změny koncentrace i struktury a prostorového uspořádání tělních biomolekul, spektroskopická analýza krevní plazmy se jeví jako vhodný nástroj pro jejich včasnou detekci. V našem výzkumu se soustředíme na identifikaci nových biomarkerů v krevní plazmě, které by vykazovaly dostatečnou senzitivitu a specificitu k detekci časných a potenciálně léčitelných stadií HCC, a které by byly potenciálně užitečné pro rutinní screening tohoto onemocnění u rizikových pacientů. Pro tyto účely jsme využili unikátní kombinaci dvou chiroptických metod – elektronového cirkulárního dichroizmu (ECD) a Ramanovy optické aktivity (ROA) – doplněných nepolarizovanými variantami – infračervenou a Ramanovou spektroskopií. Metody: Krevní plazma 18 vybraných pacientů s cirhózou jater, z toho 8 pacientů s HCC, byla analyzována kombinací metod ECD, ROA, infračervené a Ramanovy spektroskopie. Výsledky: Získaná spektrální data byla zpracována vícerozměrnou statistickou analýzou s využitím analýzy hlavních komponent (PCA) a lineární diskriminační analýzy (LDA). Vizualizace výsledků LDA vykázala oddělení dvou sledovaných skupin jen s mírným překryvem. Na základě spektrální analýzy v rámci této předběžné studie dosáhla senzitivita a specificita pro diskriminaci mezi cirhotickými jedinci s HCC a bez HCC 88 %, resp. 90 % po křížové validaci. Hodnota plochy pod křivkou 0,975 prokázala vysokou spolehlivost navrženého modelu. Závěr: Na základě našich údajů by pokročilá spektroskopická analýza krevní plazmy mohla být slibným nástrojem při diagnostice HCC a potenciálně screeningu.
None of the biomarkers studied so far in the HCC area has yielded higher sensitivity and specificity in the early-stage diagnosis than the liver ultrasonography examination. There is an urgent clinical need for establishing a laboratory marker for HCC that meets the requirements for high sensitivity and specificity for the screening and early diagnosis of at-risk patients. As a variety of pathological processes, including carcinogenesis, may cause changes in both the concentration and the structure and spatial arrangement of body biomolecules, the spectroscopic analysis of blood-based derivatives appears to be an appropriate tool for the early detection thereof. In our research, the focus is on the identification of novel biomarkers in blood plasma, which would exhibit sufficient sensitivity and specificity to detect early and potentially curable HCC stages, and which would be potentially useful for routine screening of this disease in well-defined at-risk groups. For this purpose, we utilised a unique combination of two chiroptical methods – electronic circular dichroism (ECD) and Raman optical activity (ROA) – supplemented by non-polarised variants – infrared (IR) absorption and Raman spectroscopy. Methods: Blood plasma of 18 selected patients with liver cirrhosis, 8 of which also suffered from HCC, was analysed by a combination of ECD, ROA, IR and Raman spectroscopy. Results: The obtained spectral data were processed by a multivariate statistical evaluation using principal component analysis (PCA) and linear discriminant analysis (LDA). The visualisation of the LDA results showed the separation of the two monitored groups with only a slight overlap. Based on the spectral analysis within this preliminary study, sensitivity and specificity for the discrimination between cirrhotic individuals with and without HCC reached 88% and 90% after leave-one-out cross validation, respectively. The area under the ROC curve of 0.975 proved high reliability of the established model. Conclusion: Based on our findings, the combination of advanced spectroscopic methods for the analysis of blood plasma might be a promising tool in HCC diagnosis and potentially in the screening thereof.
PURPOSE: To determine whether the levels of circulating microRNAs (miRNAs) are altered in patients undergoing thermal ablation and chemoembolization and whether these changes are predictive of a clinical outcome. MATERIAL AND METHODS: This prospective study consisted of 43 patients diagnosed with hepatocellular carcinoma (n = 15) and intrahepatic colorectal cancer metastases (n = 28) treated with thermal ablation (n = 23; radiofrequency [n = 6] or microwave [n = 19]), chemoembolization using drug-eluting embolics (n = 18), or both (n = 2). Four blood samples (immediately before the intervention and 60-90 minutes, 24 hours, and 7 days after the intervention) were taken to measure the plasma concentrations of miRNAs related to hypoxia (miR-21 and miR-210), liver injury (miR-122), epithelial-mesenchymal transition (miR-200a), and apoptosis (miR-34a) using miRNA-specific TaqMan assays and quantitative real-time polymerase chain reaction. Tumor burden and treatment response at 3 months were evaluated using the modified response evaluation criteria in solid tumors. The miRNA results were compared with clinical outcomes (Mann-Whitney U test, Wilcoxon matched-pair test). RESULTS: Dynamic changes in the circulating miRNA levels were observed following both the interventions. For thermal ablation, significant increases in miR-21, miR-210, miR-122, miR-200a, and miR-34a concentrations peaked 60-90 minutes after the intervention (P < .01). However, for transarterial chemoembolization, maximum increases in the miRNA concentrations were observed at 24 hours after the intervention for miR-21, miR-210, miR-122, miR-200a, and miR-34a (P < .05). The increased concentrations of the circulating miRNAs were followed by a subsequent decline to baseline by 7 days. For the thermal ablation (but not chemoembolization) patients, elevations in the miR-210 and miR-200a levels were associated with early progressive disease at 3 months (P = .040 and P = .012, respectively). CONCLUSIONS: Increased but dynamic levels of circulating miRNAs are present following interventional oncologic procedures and may prove useful as biomarkers for the monitoring of clinical outcomes.
- MeSH
- časové faktory MeSH
- chemoembolizace * škodlivé účinky MeSH
- cirkulující mikroRNA krev MeSH
- hepatocelulární karcinom krev patologie terapie MeSH
- kolorektální nádory patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrovlny škodlivé účinky terapeutické užití MeSH
- nádorové biomarkery krev MeSH
- nádory jater krev patologie sekundární terapie MeSH
- prospektivní studie MeSH
- radiofrekvenční ablace * škodlivé účinky MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
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
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
AIM: The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence (PIVKA-II) for hepatocellular carcinoma (HCC) diagnostics and compare it with alpha-foetoprotein (AFP), a routinely used tumour marker. MATERIALS AND METHODS: A total of 332 participants were enrolled in this study: 64 with HCC, 48 with liver metastases of colorectal cancer origin, 42 with liver cirrhosis and 178 healthy individuals. Serum levels of PIVKA-II were measured using the chemiluminescent assay of the Architect 1000i System (Abbott, USA) and AFP levels using the chemiluminescent assay by DxI 800 (Beckman Coulter, USA). RESULTS: PIVKA-II achieved better clinical sensitivity than AFP and the difference in this sensitivity was statistically significant. PIVKA-II achieved the best sensitivity (96.9%) in distinguishing between the HCC and control groups with the proposed cut-off value of 60 mAU/ml. CONCLUSION: Our recommendation is for addition of PIVKA-II to the routine panel of HCC tumour markers.
- MeSH
- biologické markery krev MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- hepatocelulární karcinom krev genetika patologie MeSH
- jaterní cirhóza krev genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory jater krev genetika patologie MeSH
- pilotní projekty MeSH
- proteinové prekurzory krev genetika MeSH
- protrombin genetika MeSH
- senioři nad 80 let MeSH
- senioři 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
Cholinesterasy jsou enzymy nezastupitelné v některých nervových přenosech, kde hraje zásadní roli acetylcholinesterasa. Druhá cholinesterasa, butyrylcholinesterasa, pak není nezbytná pro neurotransmisi, ale může se podílet na některých detoxifikačních reakcích. V tomto přehledovém článku je provedeno shrnutí literatury, diskuze diagnostického významu a metod určení aktivity. Je tak nastíněno například rozpoznání jaterních selhání, expozice neurotoxickým látkám, geneticky podmíněné dispozice. V oblasti testování je diskutováno provádění spektrofotometrických, kolorimetrických a elektrochemických měření.
Cholinesterases are enzymes important for some nerve transmissions where the enzyme acetylcholinesterase plays a crucial role. The second enzyme, butyrylcholinesterase, is not necessary for the neurotransmission but it is involved in some detoxification reactions. A survey of literature, a discussion of diagnostic importance and the methods for an activity assay are presented in this review article. Liver failures, exposure to neurotoxic compounds, genetic dispositions are outlined here. In the field of assays, spectrophotometric, colorimetric and electrochemical tests are discussed.
Hepatocelulární karcinom jater je šestým nejčastějším nádorovým onemocněním celosvětově, v našich zeměpisných šířkách se však jedná o vzácnější chorobu téměř výlučně se vyskytující u pacientů s jaterní cirhózou. Pouze 10 % hepatocelulárních karcinomů vzniká bez souvislosti s chronickou hepatitidou či abúzem alkoholu a označuje se jako kryptogenní. Časná stadia tohoto onemocnění bývají asymptomatická a jsou odhalena náhodně nebo v rámci screeningových vyšetření pacientů s chronickým postižením jater. V naší kazuistice prezentujeme případ 65letého muže bez anamnézy jaterní cirhózy, přijatého na interní oddělení pro náhle vzniklou bolest epigastria při spontánní hemoragii kryptogenního hepatocelulárního karcinomu pravého jaterního laloku.
Hepatocellular carcinoma is the sixth most common cancer worldwide; however, in our region, it is less frequent and occurs almost exclusively in patients with liver cirrhosis. About 10% of hepatocellular carcinomas are observed in patients with no history of chronic hepatitis or alcohol abuse and are classified as cryptogenic. Early stages of this disease are usually asymptomatic and are found accidentally or through screening examinations of patients with chronic liver disease. We present a case of a 65 year old men with no history of liver cirrhosis, who was admitted to our department of internal medicine complaining of epigastric pain caused by spontaneous hemorrhage of a cryptogenic hepatocellular carcinoma in the right lobe of his liver.
- Klíčová slova
- spontánní krvácení, subkapsulární hematom jater,
- MeSH
- alfa-fetoproteiny analýza MeSH
- hematom * diagnóza MeSH
- hepatocelulární karcinom * chirurgie krev radiografie ultrasonografie MeSH
- krvácení etiologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nádorové biomarkery krev MeSH
- nádory jater chirurgie krev radiografie ultrasonografie MeSH
- obezita MeSH
- počítačová rentgenová tomografie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Introduction and aim. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, the aim of our study was to assess expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. MATERIAL AND METHODS: The study was performed on 32 patients with primary HCC (verified by liver histology in 29 patients) and 27 control subjects (in 11 subjects, liver histology was available either with no or minimal changes in the liver tissue). Gene expressions of heme oxygenase 1 (HMOX1), biliverdin reductase A/B (BLVRA/B), NADPH oxidase 2 (NOX2) and p22phox were analyzed in the liver and peripheral blood leukocytes (PBL) in the subjects. RESULTS: Compared to controls, almost a 3 times higher mRNA level of BLVRA was detected in livers of HCC patients (p = 0.002); while those of BLVRB as well as HMOX1 were unchanged (p > 0.05). In accord with these results in the liver tissue, BLVRA mRNA levels in PBL were also significantly increased in HCC patients (p = 0.012). mRNA levels of NOX2 and p22phox in the liver tissue, although higher in HCC patients, did not differ significantly compared to control subjects (p > 0.05). Nevertheless, NOX2 mRNA level in PBL was significantly higher in HCC patients (p = 0.003). CONCLUSIONS: BLVRA mRNA levels in the liver as well as in PBL are significantly higher in HCC patients most likely as a feedback mechanism to control increased oxidative stress associated with HCC progression.
- MeSH
- hemoxygenasa-1 genetika MeSH
- hepatocelulární karcinom krev enzymologie genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny genetika MeSH
- messenger RNA genetika MeSH
- nádorové biomarkery krev genetika MeSH
- nádory jater krev enzymologie genetika patologie MeSH
- NADPH-oxidasy genetika MeSH
- oxidační stres genetika MeSH
- oxidoreduktasy působící na CH-CH vazby krev genetika MeSH
- progrese nemoci MeSH
- regulace genové exprese enzymů MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- signální transdukce MeSH
- studie případů a kontrol MeSH
- upregulace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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
Glypican 3 is a membrane-bound heparan sulfate proteoglycan, which has recently been identified as a marker for liver cancer and germ cell malignancies. Individuals with loss-of-function mutations for the glypican 3 gene exhibit Simpson-Golabi-Behmel syndrome, a rare X-linked overgrowth disorder. Expression of glypican 3 mRNA and protein is normally silenced in most adult organs and may reappear during malignant transformation. In the past few years, immunohistochemical and molecular characteristics of glypican 3 in hepatocellular carcinoma have been elucidated. More recently, glypican 3 has been emerging as a new diagnostic marker for germ cell tumors and especially testicular and ovarian yolk sac tumors. However, in other tumors such as renal cell carcinomas, squamous cell carcinomas, and melanomas, studies disagree on the level of glypican 3 expression. Finally, there is the controversial notion of glypican 3 as a tumor suppressor gene. In this review article, we update current knowledge on glypican 3 expression in normal and neoplastic tissues, evaluate its utility as a tumor marker in clinical practice, and explore its role as a novel oncofetal protein with clinical implications. Our focus is on the diagnostic value of glypican 3 in germ cell tumors and other neoplasms in addition to hepatocellular carcinoma. In conclusion, glypican 3 has been proven to be a useful immunohistochemical marker in distinguishing yolk sac tumors, choriocarcinomas, and Wilms tumors from other malignancies histologically mimicking these primitive tumors. Clinically, we recommend that glypican 3 be used as part of a panel of markers in subtyping testicular germ cell tumors.
- MeSH
- biopsie MeSH
- genetické testování MeSH
- germinální a embryonální nádory krev chemie diagnóza genetika patologie MeSH
- glypikany * analýza krev genetika MeSH
- hepatocelulární karcinom krev chemie diagnóza genetika patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- nádorové biomarkery * analýza krev genetika MeSH
- nádory jater krev chemie diagnóza genetika patologie MeSH
- nádory vaječníků krev chemie diagnóza genetika patologie MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- testikulární nádory krev chemie diagnóza genetika patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
