Chromophobe renal cell carcinoma (CRCC) with neuroendocrine differentiation (CRCCND) has only recently been described. Eighteen cases of CRCC with morphologic features suggestive of neuroendocrine differentiation were selected from among 624 CRCCs in our registry. The tissues were fixed in neutral formalin, embedded in paraffin, cut into 4- to 5-μm-thick sections, and stained with hematoxylin and eosin. As CRCC with neuroendocrine features, tumors with following morphology were suggested: (1) trabecular/palisading/ribbon-like, gyriform, insular, glandular, and solid pattern; (2) uniform polygonal cells formed in small islets; and (3) cribriform pattern in combination with palisading. Selected cases were further analyzed using immunohistochemistry, electron microscopy, array comparative genomic hybridization, and fluorescence in situ hybridization. Cases were classified as CRCCND or CRCC with neuroendocrine-like features (CRCCND-L) based on the immunohistochemical expression of neuroendocrine markers: CRCCND, 4 cases, age range 49 to 79 years, size ranged from 2.2 to 22 cm, and CRCCND-L, 14 cases, age range 34 to 74 years, size range 3.8 to 16.5 cm. Follow-up information was available for 11 of 18 patients aged 0.5 to 12 years. Two of 4 CRCCNDs showed aggressive clinical course with metastatic spreading. Chromophobe renal cell carcinomas with neuroendocrine differentiation were focally positive for CD56 (4/4), synaptophysin (4/4), chromogranin A (1/4), and neuron-specific enolase (3/4). All 14 CRCCND-Ls were mostly negative or very weakly focally positive for some of the aforementioned markers. All 18 tumors were positive for cytokeratin 7 and CD117. Ultrastructural analysis showed poorly preserved neuroendocrine granules only in 2 of 4 analyzed CRCCNDs. Losses of chromosomes 1, 2, 6, and 10 were found in all analyzable CRCCNDs, whereas multiple losses (chromosomes 1, 2, 6, 10, 13, 17, and 21) and gains (chromosomes 4, 11, 12, 14, 15, 16, 19, and 20) were found in CRCCND-L.

• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk genetika   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory ledvin genetika   metabolismus   patologie   MeSH
• neuroendokrinní nádory genetika   metabolismus   patologie   MeSH
• senioři MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• deoxycytidin analogy a deriváty   MeSH
• dospělí MeSH
• epitelové buňky patologie   MeSH
• lidé MeSH
• nádory močového měchýře patologie   MeSH
• neuroendokrinní karcinom MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH

Neuroendocrine prostate cancer (NEPC) represents a variant of prostate cancer that occurs in response to treatment resistance or, to a much lesser extent, de novo. Unravelling the molecular mechanisms behind transdifferentiation of cancer cells to neuroendocrine-like cancer cells is essential for development of new treatment opportunities. This review focuses on summarizing the role of small molecules, predominantly microRNAs, in this phenomenon. A published literature search was performed to identify microRNAs, which are reported and experimentally validated to modulate neuroendocrine markers and/or regulators and to affect the complex neuroendocrine phenotype. Next, available patients' expression datasets were surveyed to identify deregulated microRNAs, and their effect on NEPC and prostate cancer progression is summarized. Finally, possibilities of miRNA detection and quantification in body fluids of prostate cancer patients and their possible use as liquid biopsy in prostate cancer monitoring are discussed. All the addressed clinical and experimental contexts point to an association of NEPC with upregulation of miR-375 and downregulation of miR-34a and miR-19b-3p. Together, this review provides an overview of different roles of non-coding RNAs in the emergence of neuroendocrine prostate cancer.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress; (2) stress-axis functionality; and (3) dopaminergic and glutamatergic neuroadaptation in the NAc. We also assess the potential effects of the non-intoxicating phytocannabinoid cannabidiol, to counteract (or reverse) the development of detrimental consequences of binge-like alcohol exposure. Our results show that adolescent binge-like alcohol exposure alters the sensitivity to positive stimuli, exerts social and novelty-triggered anxiety-like behaviour, and passive stress-coping during early and prolonged withdrawal. In addition, serum corticosterone and hypothalamic and NAc corticotropin-releasing hormone levels progressively increase during withdrawal. Besides, NAc tyrosine hydroxylase levels increase at late withdrawal, while the expression of dopamine transporter, D1 and D2 receptors is dynamically altered during binge and withdrawal. Furthermore, the expression of markers of excitatory postsynaptic signaling-PSD95; Homer-1 and -2 and the activity-regulated spine-morphing proteins Arc, LIM Kinase 1 and FOXP1-increase at late withdrawal. Notably, subchronic cannabidiol, during withdrawal, attenuates social- and novelty-induced aversion and passive stress-coping and rectifies the hyper-responsive stress axis and NAc dopamine and glutamate-related neuroplasticity. Overall, the exposure to binge-like alcohol levels in adolescent rats makes the NAc, during withdrawal, a locus minoris resistentiae as a result of perturbations in neuroplasticity and in stress-axis homeostasis. Cannabidiol holds a promising potential for increasing behavioural, neuroendocrine and molecular resilience against binge-like alcohol harmful effects.

• Publikační typ
• časopisecké články MeSH

This article provides a general overview of radiopharmaceuticals for diagnostics and therapy of neuroendocrine tumors. These agents employ specific differences between neuroendocrine tumors and normal tissues on the cellular level. Individual radiopharmaceuticals demonstrate examples of typical strategies for targeted radionuclide accumulation in tumor cells.

• MeSH
• 3-jodobenzylguanidin farmakologie   terapeutické užití   MeSH
• 5-hydroxytryptofan farmakologie   terapeutické užití   MeSH
• glukagonu podobný peptid 1 farmakologie   terapeutické užití   MeSH
• lidé MeSH
• neuroendokrinní nádory * farmakoterapie   radioterapie   MeSH
• radiofarmaka * farmakologie   terapeutické užití   MeSH
• somatostatin farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• glukokortikoidy farmakologie   MeSH
• hypopituitarismus imunologie   MeSH
• imunitní systém fyziologie   MeSH
• insulinu podobný růstový faktor I fyziologie   MeSH
• lidé MeSH
• modely u zvířat MeSH
• neurosekreční systémy fyziologie   MeSH
• přirozená imunita MeSH
• prolaktin fyziologie   MeSH
• růstový hormon fyziologie   MeSH
• systém hypotalamus-hypofýza fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

• Klíčová slova
• tirzepatid,
• MeSH
• cystatin C analýza   MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• hodnoty glomerulární filtrace * účinky léků   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor pro glukagonu podobný peptid 2 terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, βTSH). Sox2+ cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2+ cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2+ and Sox2- groups with respect to the age, initial levels of GH, IGF1, prolactin, βTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2+ cell count and βTSH immunoreactive cells (r = 0.459, p < 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2+ cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2+ cells are thus commonly present in growth hormone-producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.

• MeSH
• akromegalie etiologie   metabolismus   MeSH
• dospělí MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• kmenové buňky metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský růstový hormon metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory hypofýzy komplikace   patologie   MeSH
• neuroendokrinní nádory komplikace   patologie   MeSH
• transkripční faktory SOXB1 metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The authors describe 2 tumors that, to the best of their knowledge, are hitherto undescribed. The predominant cell type was small round to fusiform dark blue cells. The dark blue cells formed distinct epithelial cords with gland-like formations with mucicarmine-positive mucus. Another distinctive component of the tumors was a mesenchymal one. The mesenchymal areas appeared benign and could be likened to a fibroma having a densely collagenous stroma, or they had spindle cells set in the myxoid background, rendering a myxoma-like appearance. Another distinctive feature was ganglion cell differentiation. Mitotic figures, including atypical forms, were found only in the small cell component. All cells were immunohistochemically negative for actin, calponin, desmin, HMB45, neurofilament protein, CD99/MIC2, Melan A, tyrosinase, serotonin, CD56, Melan A, GFAP, and S-100 protein. Cytokeratin, synaptophysin, FLI1 protein, and chromogranin antibodies reacted only in the primitive small round cells, while all the other components were cytokeratin negative. Fluorescence in situ hybridization showed that the tumors are without the EWSR1 gene translocation and gain 12p. Ultrastructurally, the cells were endowed with well-formed intercellular desmosomes membrane-bound secretory in the cytoplasm. Granules were found in the cytoplasm. We suggest the name "primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation" for this neoplasm.

• MeSH
• aneuploidie MeSH
• desmozomy ultrastruktura   MeSH
• epitelové buňky metabolismus   patologie   MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• lidské chromozomy, pár 12 MeSH
• malobuněčný karcinom genetika   metabolismus   patologie   terapie   MeSH
• malobuněčný sarkom genetika   metabolismus   patologie   terapie   MeSH
• nádorová transformace buněk MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory měkkých tkání genetika   metabolismus   patologie   terapie   MeSH
• neuroendokrinní nádory genetika   metabolismus   patologie   terapie   MeSH
• předškolní dítě MeSH
• sekreční vezikuly ultrastruktura   MeSH
• transmisní elektronová mikroskopie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• kazuistiky MeSH

The revised Fourth Edition of this highly acclaimed reference is a practical, state-of-the-art, superbly illustrated guide to the evaluation and clinical correlates of prostate biopsy findings. This edition features expanded coverage of mimickers of prostate cancer, a new chapter on immunohistochemistry and molecular techniques, a major update to the Gleason grading system, new information on histologic changes following radiation therapy, and an expanded section on tumors of specialized prostatic stroma. The book contains nearly 300 full-color illustrations. A companion online image bank provides over 1,800 full-color images of specimens at various magnifications, plus a question-and-answer review of prostate pathology.

• Klíčová slova
• prostata,
• MeSH
• nádory prostaty * MeSH
• nemoci prostaty MeSH
• prostata MeSH