Basal cell carcinoma (BCC) is the most common cancer worldwide, and its current treatment options are insufficient and toxic. Surprisingly, unlike several other malignancies, chemopreventive efforts against BCC are almost lacking. Silibinin, a natural agent from milk thistle seeds, has shown strong efficacy against several cancers including ultraviolet radiation-induced skin (squamous) cancer; however, its potential activity against BCC is not yet examined. Herein, for the first time, we report the efficacy of silibinin and its oxidation product 2,3-dehydrosilibinin (DHS) against BCC both in vitro and in vivo using ASZ (p53 mutated) and BSZ (p53 deleted) cell lines derived from murine BCC tumors. Both silibinin and DHS significantly inhibited cell growth and clonogenicity while inducing apoptosis in a dose- and time-dependent manner, with DHS showing higher activity at lower concentrations. Both agents also inhibited the mitogenic signaling by reducing EGFR, ERK1/2, Akt, and STAT3 phosphorylation and suppressed the activation of transcription factors NF-κB and AP-1. More importantly, in an ectopic allograft model, oral administration of silibinin and DHS (200 mg/kg body weight) strongly inhibited the ASZ tumor growth by 44% and 71% (P < 0.05), respectively, and decreased the expression of proliferation biomarkers (PCNA and cyclin D1) as well as NF-κB p50 and c-Fos in the tumor tissues. Taken together, these results provide the first evidence for the efficacy and usefulness of silibinin and its derivative DHS against BCC, and suggest the need for additional studies with these agents in pre-clinical and clinical BCC chemoprevention and therapy models.

• MeSH
• aktivace enzymů účinky léků   MeSH
• alografty MeSH
• antioxidancia chemie   farmakologie   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• bazocelulární karcinom farmakoterapie   metabolismus   patologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory kůže farmakoterapie   metabolismus   patologie   MeSH
• NF-kappa B metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• silymarin chemie   farmakologie   MeSH
• testy nádorových kmenových buněk MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• Klíčová slova
• mikrobiochronometrie, měření cirkadiánního a cirkasemiseptánního cyklu adaptace vaskulárního systému při cestování přes časová pásma,
• MeSH
• cestování letadlem * MeSH
• chronobiologické jevy fyziologie   MeSH
• cirkadiánní rytmus fyziologie   MeSH
• financování organizované MeSH
• jet lag syndrom * etiologie   komplikace   prevence a kontrola   MeSH
• koronární nemoc komplikace   MeSH
• lidé MeSH
• měření krevního tlaku MeSH
• statistika jako téma MeSH
• telemetrie metody   využití   MeSH
• určení tepové frekvence metody   přístrojové vybavení   využití   MeSH
• Check Tag
• lidé MeSH

In the 13th Edition, Dr. Brian Coley leads a team of experts to bring you up to date with today's practice standards in pediatric imaging. This two-volume bestselling reference is a must-have resource for pediatric radiologists, general radiologists, pediatric subspecialists, pediatricians, hospitals, and more. Nakladatelská anotace. Kráceno.

• MeSH
• diagnostické zobrazování metody   MeSH
• dítě MeSH
• kojenec MeSH
• nemoci plodu diagnostické zobrazování   diagnóza   MeSH
• prenatální diagnóza metody   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH

• Konspekt
• Patologie. Klinická medicína
• Pediatrie
• NLK Obory
• pediatrie
• radiologie, nukleární medicína a zobrazovací metody
• perinatologie a neonatologie
• NLK Publikační typ
• kolektivní monografie

• MeSH
• autofagie * fyziologie   MeSH
• biotest metody   normy   MeSH
• lidé MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• směrnice MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• autofagie * fyziologie   MeSH
• autofagozomy MeSH
• biologické markery MeSH
• biotest normy   MeSH
• lidé MeSH
• lyzozomy MeSH
• proteiny spojené s autofagií metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• směrnice MeSH