Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.

• MeSH
• buněčná diferenciace MeSH
• chordom * patologie   genetika   diagnóza   metabolismus   MeSH
• fetální proteiny * genetika   metabolismus   MeSH
• gen SMARCB1 * genetika   MeSH
• lidé MeSH
• metylace DNA * MeSH
• nádorové biomarkery * analýza   genetika   MeSH
• nádory měkkých tkání patologie   diagnóza   genetika   metabolismus   MeSH
• proteiny T-boxu * genetika   metabolismus   MeSH
• senioři MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Ataxie­‐telangiektázie (AT) je autozomálně recesivně děděné onemocnění charakterizované pomalu progredující mozečkovou ataxií, telangiektáziemi a zvýšenou citlivostí k ionizačnímu záření. Často se vyvíjí imunodeficit projevující se opakujícími respiračními infekcemi. Dalšími klinickými projevy může být okulomotorická apraxie nebo extrapyramidové projevy. Pacienti jsou predisponováni ke vzniku hematologických malignit i solidních nádorů. AT je nejčastější příčinou progresivní ataxie u dětí mladších 10 let. Cílem tohoto článku je upozornit na toto onemocnění a poukázat na diagnostiku a možnosti symptomatické terapie. Jako příklad uvádím dvě kazuistiky z našeho oddělení.

Ataxia-telangiectasia (AT) is an autosomal recessively disorder characterized by slowly progressive cerebellar ataxia, telangiectasia and heightended sensitivity to ionizing radiation. The condition often leads to immunodeficiency, presenting as recurrent respiratory infections. Other clinical manifestations may include oculomotor apraxia or extrapyramidal symptoms. Furthermore, patients are predisposed to hematological malignancies and solid tumors. In children under the age of 10, AT represents the most prevalent cause of progressive ataxia. This article aims to raise awareness of AT, providing an overview of its diagnosis and available options for symptomatic therapy. To illustrate these aspects, I present two case reports from our department.

• MeSH
• alfa-fetoproteiny analýza   MeSH
• apraxie diagnóza   etiologie   klasifikace   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• kazuistiky jako téma MeSH
• lidé MeSH
• mezioborová komunikace MeSH
• motorické poruchy diagnóza   etiologie   MeSH
• předškolní dítě MeSH
• teleangiektatická ataxie * diagnóza   farmakoterapie   genetika   MeSH
• teleangiektazie diagnóza   klasifikace   MeSH
• těžká kombinovaná imunodeficience diagnóza   etiologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• přehledy MeSH

Hepatocelulární karcinom (HCC) je nejčastější primární zhoubný nádor jater, který se ve většině případů rozvíjí v terénu jaterní cirhózy různé etiologie. Jen časná stadia onemocnění jsou indikována k chirurgické, potenciálně kurativní léčbě. Jen přibližně třetina HCC je zachycena v časných stadiích. Screeningovým vyšetřením rizikových skupin pacientů je ultrasonografie jater (USG) v 6měsíčních intervalech. USG má vedle svých známých výhod i značné limitace. Senzitivita USG pro časná stadia HCC se pohybuje pouze okolo 60 %. Vzhledem k tomu a i proto, že se jedná o expert dependentní metodu, existuje naléhává potřeba objektivního biomarkeru HCC. Alfa-fetoprotein je obecně vnímán jako biomarker HCC, nicméně jeho senzitivita a specificita pro účely diagnostiky či dokonce screeningu je nedostatečná. Byly zkoumány i jiné další biomarkery s různými výsledky, ale žádný nedosáhl efektivity USG. Poměrně novým přístupem k této problematice je spektroskopie krevní plazmy, která prokázala svoji účinnost u různých onemocnění. Z pohledu HCC se spektroskopii krevní plazmy věnovalo jen málo studií. Autoři prezentují v přehledu i vlastní práci, kdy spektroskopie krevní plazmy dosáhla senzitivity a specificity v odlišení nemocných s jaterní cirhózou bez HCC a s ním 88 %, respektive 90 %. Přes veškeré snahy nebyl dosud dostatečně spolehlivý a validovaný biomarker HCC použitelný pro účely časné diagnostiky a screeningu identifikován.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, which in most cases develops in the field of liver cirrhosis of various etiologies. Only the early stages of the disease are indicated for surgical, potentially curative treatment. Only about a third of cases of HCC are caught in the early stages. The screening examination of risk groups of patients is liver ultrasonography (USG) at 6-month intervals. Besides its well-known advantages, USG has significant limitations. The sensitivity of USG for the early stages of HCC is only around 60 %. Considering this and also because it is an expert-dependent method, there is an urgent need for an objective HCC biomarker. Alpha-fetoprotein is generally perceived as a biomarker of HCC, however, its sensitivity and specificity for diagnostic or even screening purposes are insufficient. Other biomarkers have been investigated with varying results, but none have reached the effectiveness of USG. A relatively new approach to this problem is blood plasma spectroscopy, which has proven its effectiveness in various diseases. From the perspective of HCC, few studies have focused on blood plasma spectroscopy. In the review, the authors also present their work, where blood plasma spectroscopy achieved a sensitivity and specificity of 88 % and 90 %, respectively, in differentiating patients with liver cirrhosis without and with HCC. Despite all efforts, a sufficiently reliable and validated biomarker of HCC usable for early diagnosis and screening has not yet been identified.

• MeSH
• alfa-fetoproteiny analýza   MeSH
• časná detekce nádoru metody   MeSH
• hepatocelulární karcinom * diagnóza   MeSH
• jaterní cirhóza komplikace   MeSH
• karcinogeneze MeSH
• krevní plazma MeSH
• lidé MeSH
• nádorové biomarkery analýza   klasifikace   MeSH
• spektrální analýza metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Several single-nucleotide polymorphisms (SNPs) and rare variants of non-receptor tyrosine kinase 1 gene (TNK1) have been associated with Alzheimer's disease (AD). To date, none of the associations have proven to be of practical importance in predicting the risk of AD either because the evidence is not conclusive, or the risk alleles occur at very low frequency. In the present study, we are evaluating the associations between rs11867353 polymorphism of TNK1 gene and both AD and mild cognitive impairment (MCI) in a group of 1656 persons. While the association with AD was found to be highly statistically significant (p < 0.0001 for the risk genotype CC), no statistically significant association with MCI could be established. Possible explanation of the apparent discrepancy could be rapid progression of MCI to AD in persons with the CC genotype. Additional findings of the study are statistically significant associations of rs11867353 polymorphism with body mass index, body weight, and body height. The patients with AD and CC genotype had significantly lower values of body mass index and body weight compared with patients with other genotypes. The main outcome of the study is the finding of a previously never described association between the rs11867353 polymorphism of the TNK1 gene and AD. The rs11867353 polymorphism has a potential to become a significant genetic marker when predicting the risk of AD.

• MeSH
• Alzheimerova nemoc genetika   MeSH
• fetální proteiny genetika   MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie MeSH
• genetické markery MeSH
• index tělesné hmotnosti MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kognitivní dysfunkce diagnóza   genetika   MeSH
• lidé MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tělesná hmotnost MeSH
• tělesná výška MeSH
• tyrosinkinasy genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Several single-nucleotide polymorphisms (SNPs) and rare variants of non-receptor tyrosine kinase 1 gene (TNK1) have been associated with Alzheimer's disease (AD). To date, none of the associations have proven to be of practical importance in predicting the risk of AD either because the evidence is not conclusive, or the risk alleles occur at very low frequency. In the present study, we are evaluating the associations between rs11867353 polymorphism of TNK1 gene and both AD and mild cognitive impairment (MCI) in a group of 1656 persons. While the association with AD was found to be highly statistically significant (p < 0.0001 for the risk genotype CC), no statistically significant association with MCI could be established. Possible explanation of the apparent discrepancy could be rapid progression of MCI to AD in persons with the CC genotype. Additional findings of the study are statistically significant associations of rs11867353 polymorphism with body mass index, body weight, and body height. The patients with AD and CC genotype had significantly lower values of body mass index and body weight compared with patients with other genotypes. The main outcome of the study is the finding of a previously never described association between the rs11867353 polymorphism of the TNK1 gene and AD. The rs11867353 polymorphism has a potential to become a significant genetic marker when predicting the risk of AD.

• MeSH
• Alzheimerova nemoc genetika   MeSH
• fetální proteiny genetika   MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie MeSH
• genetické markery MeSH
• index tělesné hmotnosti MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kognitivní dysfunkce diagnóza   genetika   MeSH
• lidé MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tělesná hmotnost MeSH
• tělesná výška MeSH
• tyrosinkinasy genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile, and their oocytes fail to complete meiosis I. In determining AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers (aMTOCs; meiotic spindle poles). This activation induces fragmentation of the aMTOCs, a step essential for building a bipolar spindle. We also show that AURKA is required for regulating localization of TACC3, another protein required for spindle building. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.

• MeSH
• aparát dělícího vřeténka genetika   MeSH
• aurora kinasa A genetika   MeSH
• aurora kinasa B genetika   MeSH
• aurora kinasa C genetika   MeSH
• dělení bunečného jádra genetika   MeSH
• fetální proteiny genetika   MeSH
• lidé MeSH
• meióza genetika   MeSH
• myši MeSH
• oocyty růst a vývoj   metabolismus   MeSH
• organizační centrum mikrotubulů metabolismus   MeSH
• póly dělícího vřeténka genetika   MeSH
• protein-serin-threoninkinasy genetika   MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• protoonkogenní proteiny genetika   MeSH
• segregace chromozomů genetika   MeSH
• vývojová regulace genové exprese genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Východiská: Pretrvávanie zvýšenej hladiny alfa-fetoproteínu u pacienta s neseminómovým germinatívnym tumorom semenníka po orchiektómii a chemoterapii je výnimočný stav, kedy je potrebné odlíšiť pretrvávanie nádoru od falošnej pozitivity onkomarkera. Táto situácia často vedie k nadliečeniu pacienta, čo môže spôsobiť závažnú akútnu aj neskorú toxicitu a iné komplikácie spojené s liečbou. Prípad: Prezentujeme prípad pacienta s vyššie uvedeným ochorením a priebehom liečby. Vzhľadom na to, že pretrvávanie ochorenia nebolo rádiologicky dokázané a hladina alfa-fetoproteínu bola mierne stabilne zvýšená, bol zvýšený onkomarker vyhodnotený ako falošne pozitívny. Možné príčiny zvýšenej hodnoty onkomarkera boli analyzované, keďže môže byť markerom aj iných závažných ochorení. Hladina alfa-fetoproteínu sa nezmenila ani pri abstinencii od alkoholu, ani pri podávaní hepatoprotektívnej liečby silymarínom. Sérológické testy hepatitíd B a C boli negatívne. Iný malígny tumor nebol identifikovaný. Na CT bolo nájdené zhrubnutie a stratifikácia cirkulárnej steny terminálneho ilea a reakcia okolitého viscerálneho tuku a lymfatických uzlín, ktoré pripomína nešpecifické zápaly čreva, ktoré by mohli vysvetľovať vyššiu hladinu alfa-fetoproteínu. Viac ako 14 mesiacov po ukončení liečby chemoterapiou pacient nemá žiaden dôkaz aktivity ochorenia, hladina alfa-fetoproteínu pretrváva nezmenená. Záver: Ak nie je po ukončení liečby prítomný iný znak prítomnosti nádoru semenníka, ako zvýšený onkomarker, pacient by mal byť ďalej prísne observovaný.

Background: Persistent alpha-fetoprotein elevation in a patient following orchiectomy and chemotherapy for non-seminomatous testicular germ cell tumor is a rare condition when persistence of the tumor and false positivity of tumor marker elevation has to be differentiated. This situation often leads to over-treatment and potential toxicity with adverse events which can be severe. Case: A case of a patient with the abovementioned disease and course of treatment is presented. As no radiological signs of the disease were present and the level of alpha-fetoprotein was mild and stable, the tumor marker elevation was evaluated as false positive. Possible causes of the tumor marker elevation were identified as other serious diseases are known to cause such a false positivity. The level of alpha-fetoprotein remained unchanged despite alcohol abstinence and hepatoprotective treatment by silymarin. Hepatitis B and C serological tests were negative, and no other malignant tumor was identified. Finding of terminal ileum circular wall thickening and stratification with a reaction of surrounding visceral fat and lymph nodes persisting in CT scans suggests the presence of inflammatory bowel disease, possibly explaining the alpha-fetoprotein elevation. The patient has no evidence of the disease more than 14 months after the end of chemotherapy treatment with no change in the elevation of alpha-fetoprotein. Conclusion: After the treatment, when no other indication of testicular cancer than an elevated alpha-fetoprotein level is present, the patient should be managed by ongoing surveillance.

• MeSH
• alfa-fetoproteiny analýza   MeSH
• chybná diagnóza MeSH
• dospělí MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• testikulární nádory * diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866) and ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years.

• MeSH
• alfa-fetoproteiny MeSH
• hepatocelulární karcinom * farmakoterapie   MeSH
• humanizované monoklonální protilátky MeSH
• lidé MeSH
• nádory jater * farmakoterapie   MeSH
• senioři MeSH
• sorafenib MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované 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

• MeSH
• alfa-fetoproteiny MeSH
• analýza přežití MeSH
• chemoembolizace metody   škodlivé účinky   MeSH
• doxorubicin aplikace a dávkování   MeSH
• fatální výsledek MeSH
• hepatocelulární karcinom * diagnóza   farmakoterapie   terapie   MeSH
• katetrizační ablace metody   MeSH
• lidé MeSH
• opožděná diagnóza MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH