BACKGROUND: 68 Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is a recommended imaging modality for patients with recurrent prostate cancer (PCa). Its routine implementation before radical prostatectomy (RP) may allow avoiding undertreatment. We aimed to analyze the diagnostic accuracy of 68 Ga-PSMA-PET/CT for pelvic lymph node metastases in a large cohort of patients treated with RP and extended pelvic lymph node dissection (ePLND) for high-risk PCa. METHODS: This is a retrospective analysis of an institutional database of patients who underwent 68 Ga-PSMA-PET/CT before RP and ePLND for high-risk PCa. The diagnostic estimates of 68 Ga-PSMA-PET/CT with 95% confidence intervals (CIs) for lymph node involvement were calculated. RESULTS: We included 165 high-risk PCa patients. The median PSA value was 24.5 ng/mL (range: 6.7-185) and all the patients had biopsy Grade Group 4-5. In total, 46 (28%) of patients had clinical lymph node involvement at 68 Ga-PSMA-PET/CT. A mean number of resected lymph nodes per patient was 22 (range: 15-45) and 149 (4.2%) of all resected nodes were positive for lymph node metastasis at final pathology. The diagnostic estimates for the detection of pN+ disease at RP were as follows: sensitivity 63% (95% CI: 51-75), specificity 97% (95% CI: 91-99), positive predictive value 94% (95% CI: 82-99), and negative predictive value 79% (95% CI: 70-86). The total accuracy of PSMA-PET was 83% (95% CI: 76-88). CONCLUSION: Our analyses support high specificity and positive predictive value of pretreatment 68 Ga-PSMA PET/CT for the detection of pelvic lymph node metastasis in patients treated with RP for high-risk PCa. While a positive finding should be considered as robust indicator for clinical decision-making, a negative result cannot reliably rule out the presence of lymph node involvement in high-risk PCa; there is a need for advanced risk stratification in those patients.

• MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• lymfatické metastázy diagnostické zobrazování   patologie   MeSH
• nádory prostaty * diagnostické zobrazování   chirurgie   patologie   MeSH
• PET/CT * metody   MeSH
• prostata diagnostické zobrazování   chirurgie   patologie   MeSH
• prostatektomie MeSH
• radioizotopy galia MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Class I histone deacetylases (HDACs) are key regulators of cell proliferation and they are frequently dysregulated in cancer cells. We report here the synthesis of a novel series of class-I selective HDAC inhibitors (HDACi) containing a 2-aminobenzamide moiety as a zinc-binding group connected with a central (piperazin-1-yl)pyrazine or (piperazin-1-yl)pyrimidine moiety. Some of the compounds were additionally substituted with an aromatic capping group. Compounds were tested in vitro against human HDAC1, 2, 3, and 8 enzymes and compared to reference class I HDACi (Entinostat (MS-275), Mocetinostat, CI994 and RGFP-966). The most promising compounds were found to be highly selective against HDAC1, 2 and 3 over the remaining HDAC subtypes from other classes. Molecular docking studies and MD simulations were performed to rationalize the in vitro data and to deduce a complete structure activity relationship (SAR) analysis of this novel series of class-I HDACi. The most potent compounds, including 19f, which blocks HDAC1, HDAC2, and HDAC3, as well as the selective HDAC1/HDAC2 inhibitors 21a and 29b, were selected for further cellular testing against human acute myeloid leukemia (AML) and erythroleukemic cancer (HEL) cells, taking into consideration their low toxicity against human embryonic HEK293 cells. We found that 19f is superior to the clinically tested class-I HDACi Entinostat (MS-275). Thus, 19f is a new and specific HDACi with the potential to eliminate blood cancer cells of various origins.

• MeSH
• benzamidy chemická syntéza   chemie   farmakologie   MeSH
• HEK293 buňky MeSH
• inhibitory histondeacetylas chemická syntéza   chemie   farmakokinetika   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• ortoaminobenzoáty chemická syntéza   chemie   MeSH
• protinádorové látky chemická syntéza   chemie   farmakokinetika   farmakologie   MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• pyraziny chemie   MeSH
• pyridiny chemická syntéza   chemie   farmakologie   MeSH
• simulace molekulového dockingu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Hyperintenzity bíle hmoty (HBH) patří mezi nejčastěji replikované nálezy získané zobrazovacími metodami u bipolární poruchy (BP). Není jasné, zda jsou tyto leze artefaktem souvisejícím se souběžnými somatickými či duševními nemocemi, nebo mají přímý vztah k BP, nebo dokonce představují biologický rizikový faktor nemoci. Abychom zhodnotili, zda HBH splňují kritéria pro biologický znak BP, vyšetřili jsme magnetickou rezonancí 15 potomků rodičů s BP, kteří sami trpěli afektivní poruchou, 20 zdravých potomků rodičů s BP a 18 zdravých osob bez výskytu duševních poruch v rodině. Výskyt HBH byl určen z FLAIR (Fluid Attenuated Inversion Recovery) obrazu pořízených na 1,5T skeneru a jejich rozsah byl hodnocen dle semikvantitativní stupnice. Celkově jsme nalezli nízkou frekvenci HBH a převažovaly hyperintenzity malého rozsahu. Dále nebyl zjištěn rozdíl ve výskytu těchto hyperintenzit mezi skupinami postižených a zdravých potomků rodičů s bipolární poruchou a zdravých kontrol. Naše výsledky tedy nepotvrdily předpoklad, že by HBH mohly představovat biologický marker vulnerability pro bipolární poruchu. Studie byla součástí mezinárodního projektu, v tomto textu jsou prezentovány výsledky souboru získané v Psychiatrickém centru Praha.

White matter hyperintensities (WMHs) are among the most replicated neuroimaging findings in bipolar disorders (BD). It is not clear whether these lesions are an artifact of comorbid conditions, directly associated with the illness and even possibly represent biologic al markers for the illness. To test whether WMHs meet criteria for a biological marker, we recruited 15 affected and 20 unaffected offspring of bi polar probands, and 18 healthy controls without any personal or family history of psychiatric disorders. We used FLAIR (Fluid Attenuated Invers ion Recovery) images obtained at a 1.5T scaner to determine presence of WMHs. Lesions were rated by using a validated semi-quantitative scale . We found a low rate of low grade WMHs in all groups. The proportion of WMH-positive participants was comparable between the unaffected, affected high-risk groups and healthy controls. Therefore, WMHs do not appear to be a biological vulnerability marker of BD. The study w as part of an international project, in this paper we presented results obtained in Prague Psychiatric Center.

• Klíčová slova
• hyperintenzity bílé hmoty, MR, bipolární afektivní porucha, endofenotyp,
• MeSH
• bipolární porucha diagnóza   genetika   MeSH
• depresivní poruchy diagnóza   epidemiologie   MeSH
• dítě MeSH
• dospělí MeSH
• financování organizované MeSH
• genetická predispozice k nemoci epidemiologie   genetika   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek patologie   růst a vývoj   MeSH
• prediktivní hodnota testů MeSH
• rizikové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH