BACKGROUND/OBJECTIVE: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer. MATERIALS AND METHODS: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019. RESULTS: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039). CONCLUSIONS: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions.

• Klíčová slova
• breast cancer metastases, hormone receptor status, receptor status discrepancy,
• Publikační typ
• časopisecké články MeSH

CONTEXT: Ticagrelor, a novel, reversible, and oral P2Y12 receptor antagonist, was claimed to reduce all-cause mortality compared to clopidogrel in the PLATO trial. OBJECTIVE: We sought to ascertain vital status follow-up for clopidogrel and ticagrelor to determine if any discrepancy existed by reviewing data from the FDA Complete Response Review. RESULTS: The FDA Complete Response Review indicated misrepresentation of vital status follow-up by the sponsor's presenter at the Cardiovascular and Renal Drugs Advisory Committee. Instead of five patients with missing vital status follow-up, the FDA primary efficacy reviewer indicated that there was a minimum of 106 patients. Additionally and more concerning was the fact that significantly more patients on ticagrelor (3.1%, n = 289 patients) had incomplete vital status follow-up versus clopidogrel (2.6%, n = 242 patients, p = 0.04 for the difference). CONCLUSIONS: The Advisory Committee that voted in favor to approve ticagrelor was given misrepresented data, which may have affected the approval of ticagrelor. The fact that significantly more patients on ticagrelor had incomplete vital status follow-up versus clopidogrel challenges the claimed mortality benefit of ticagrelor and the approval of the PLATO trial.

• Klíčová slova
• Clopidogrel, Misrepresentations, Ticagrelor,
• MeSH
• adenosin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• antagonisté purinergních receptorů P2Y terapeutické užití   MeSH
• hodnocení rizik MeSH
• klinické zkoušky jako téma etika   normy   MeSH
• klopidogrel MeSH
• kontraindikace MeSH
• lidé MeSH
• mortalita trendy   MeSH
• následné studie MeSH
• poradní výbory normy   MeSH
• schvalování léčiv * MeSH
• statistika přirozeného pohybu MeSH
• ticagrelor MeSH
• tiklopidin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• adenosin MeSH
• antagonisté purinergních receptorů P2Y MeSH
• klopidogrel MeSH
• ticagrelor MeSH
• tiklopidin MeSH

The option to treat patients suffering from ERBB-2 protein-positive invasive duct carcinomas of the breast (IDC) with Herceptin requires a precise determination of the ERBB2 status. The aim of the study was to evaluate the ERBB2 mRNA level, placing emphasis on cases with discordant findings between ERBB-2 protein expression (IHC) and a copy number of the ERBB2 gene (FISH). Thirty-nine IDCs (21 cases IHC and FISH concordant, 15 cases moderately discordant, 3 cases markedly discordant) were investigated. ERBB2 mRNA expression was determined using quantitative real-time RT-PCR (Q-RT-PCR). IDCs with negative ERBB-2 protein and without ERBB2 gene amplification had a low ERBB2 mRNA level. Cases with 3+ overexpression of the protein and with strong gene amplification (> 10 copies/tumor cell) had a significantly increased expression of ERBB2 mRNA. In 13 of 15 IDCs with moderate discrepancies (up to 10 copies of the gene per one tumor cell/negative ERBB-2 protein; without amplification/2+ protein) mRNA was low, comparable to that in cases with negative ERBB-2 protein and without ERBB2 gene amplification. In three cases with markedly discordant findings (the gene amplified/protein negative--one case; protein 3+/no amplification--2 cases), Q-RT-PCR results were within a "normal" limit. Ineffective gene amplification and protein accumulation are suggested explanations. Q-RT-PCR revealed two cases with highly expressed ERBB2 mRNA and discordant FISH and/or IHC findings. Increased effectiveness of transcription (protein 2+/high mRNA/without the gene amplification), and combined dysregulation (protein negative/high mRNA/no amplification) are possible causes of these findings. Q-RT-PCR appears useful in clarifying borderline or discrepant IHC and FISH findings.

• MeSH
• dospělí MeSH
• duktální karcinom prsu genetika   metabolismus   sekundární   MeSH
• genová dávka * MeSH
• geny erbB-2 * MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• receptor erbB-2 * genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• RNA nádorová chemie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• receptor erbB-2 * MeSH
• RNA nádorová MeSH

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) prevents the binding of corticosterone to mineralocorticoid receptors by reversible conversion of biologically active corticosterone to inactive 11-dehydrocorticosterone. To clarify the relationship between high plasma concentrations of corticosterone during weaning and high activity of intestinal transport pathways that are induced by aldosterone in immature intestine, we have studied the distribution, developmental pattern and regulation of 11 beta-OHSD in intestinal segments that possess mineralocorticoid target epithelium. Dehydrogenase activity was already high in the caecum, and the proximal and distal colon on the second postnatal day and altered little until adulthood. In contrast, the activity in the ileum was low during the first two weeks of life, rose more than 5-fold in the next 20 days to attain a peak in 30-day-old rats, and thereafter declined to the values of adult animals. There was no significant reductase activity (conversion of 11-dehydrocorticosterone to corticosterone) in any intestinal segment of young and adult rats. The regulation of intestinal 11 beta-OHSD by corticosteroids and thyroid hormones was studied in the ileum and distal colon. In weanling rats, adrenalectomy or a high-salt diet decreased 11 beta-OHSD activities in both intestinal segments whereas dexamethasone administration prevented this decline in adrenalectomized rats and administration of deoxycorticosterone acetate led to a significant increase of intestinal 11 beta-OHSD activities in rats kept on a high-salt diet. Dexamethasone administration to intact adult rats also stimulated 11 beta-OHSD activity in the ileum and distal colon. The changes in thyroid status of weanling rats did not change the 11 beta-OHSD activities. We conclude that (1) the developmental patterns of 11 beta-OHSD activity in the small and large intestine are not identical and this discrepancy may facilitate the maturation effect of glucocorticoids in the small intestine and the stimulatory effect of aldosterone in the large intestine and (2) corticosteroids but not thyroid hormones can modulate 11 beta-OHSD activity in the developing intestine.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasy MeSH
• adrenalektomie MeSH
• cékum enzymologie   růst a vývoj   MeSH
• deoxykortikosteron farmakologie   MeSH
• dexamethason farmakologie   MeSH
• hydroxysteroiddehydrogenasy metabolismus   MeSH
• hypotyreóza metabolismus   MeSH
• ileum enzymologie   růst a vývoj   MeSH
• kolon enzymologie   růst a vývoj   MeSH
• krysa rodu Rattus MeSH
• kuchyňská sůl aplikace a dávkování   MeSH
• novorozená zvířata metabolismus   MeSH
• odstavení * MeSH
• potkani Wistar MeSH
• střeva enzymologie   růst a vývoj   MeSH
• trijodthyronin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasy MeSH
• deoxykortikosteron MeSH
• dexamethason MeSH
• hydroxysteroiddehydrogenasy MeSH
• kuchyňská sůl MeSH
• trijodthyronin MeSH