Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3-10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20-56%), breast (5-20%), and melanoma (7-16%) tumors, although they can arise from other cancer types less frequently. The metastatic cascade is a multistep process involving local invasion, intravasation into the bloodstream or lymphatic system, extravasation into normal tissue, and colonization of the distal site. After reaching the brain, circulating tumor cells (CTCs) breach the blood-brain barrier (BBB).The selective permeability of the BBB poses a significant challenge for therapeutic compounds, limiting the treatment efficacy of BMs. Understanding the mechanisms of tumor cell interactions with the BBB is crucial for the development of effective treatments. This review provides an in-depth analysis of the brain barriers, including the BBB, blood-spinal cord barrier, blood-meningeal barrier, blood-arachnoid barrier, and blood-cerebrospinal fluid barrier. It explores the molecular and cellular components of these barriers and their roles in brain metastasis, highlighting the importance of this knowledge for identifying druggable targets to prevent or limit BM formation.

• Klíčová slova
• Blood-cerebrospinal fluid barrier, Blood-spinal cord barrier, Blood–brain barrier, Brain Metastasis, Cancer,
• MeSH
• hematoencefalická bariéra * metabolismus   patologie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové cirkulující buňky patologie   MeSH
• nádory mozku * sekundární   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35-45 % of colorectal cancer (CRC) cases. Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p < 0.001 and p < 0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR = 2.18, p < 0.001) and OS (HR = 2.58, p < 0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild-type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.

• Klíčová slova
• Bevacizumab, Chemotherapy, Colorectal cancer, KRAS, Mutation,
• MeSH
• alely * MeSH
• bevacizumab terapeutické užití   MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• kodon MeSH
• kolorektální nádory farmakoterapie   genetika   mortalita   patologie   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mutace * MeSH
• opakovaná terapie MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• Ras proteiny genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bevacizumab MeSH
• kodon MeSH
• Ras proteiny MeSH

BACKGROUND: It is mandatory to confirm the absence of mutations in the KRAS gene before treating metastatic colorectal cancers with epidermal growth factor receptor inhibitors, and similar regulations are being considered for non-small cell lung carcinomas (NSCLC) and other tumor types. Routine diagnosis of KRAS mutations in NSCLC is challenging because of compromised quantity and quality of biological material. Although there are several methods available for detecting mutations in KRAS, there is little comparative data regarding their analytical performance, economic merits, and workflow parameters. METHODS: We compared the specificity, sensitivity, cost, and working time of five methods using 131 frozen NSCLC tissue samples. We extracted genomic DNA from the samples and compared the performance of Sanger cycle sequencing, Pyrosequencing, High-resolution melting analysis (HRM), and the Conformité Européenne (CE)-marked TheraScreen DxS and K-ras StripAssay kits. RESULTS AND CONCLUSIONS: Our results demonstrate that TheraScreen DxS and the StripAssay, in that order, were most effective at diagnosing mutations in KRAS. However, there were still unsatisfactory disagreements between them for 6.1% of all samples tested. Despite this, our findings are likely to assist molecular biologists in making rational decisions when selecting a reliable, efficient, and cost-effective method for detecting KRAS mutations in heterogeneous clinical tumor samples.

• MeSH
• analýza nákladů a výnosů MeSH
• DNA nádorová analýza   genetika   MeSH
• kolorektální nádory * genetika   sekundární   MeSH
• lidé MeSH
• mutace MeSH
• nemalobuněčný karcinom plic genetika   MeSH
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny genetika   MeSH
• Ras proteiny genetika   MeSH
• sekvenční analýza DNA * ekonomika   metody   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA nádorová MeSH
• KRAS protein, human MeSH Prohlížeč
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny MeSH
• Ras proteiny MeSH

MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that act as post-transcriptional regulators of gene expression. Dysregulation of these molecules has been indicated in the development of many cancers. Altered expression levels of several miRNAs were identified also in glioblastoma. It was repeatedly found that miRNAs are involved in important signalling pathways, which play roles in crucial cellular processes, such as proliferation, apoptosis, cell cycle regulation, invasion, angiogenesis and stem cell behaviour. Therefore, miRNAs represent promising therapeutic targets in glioblastoma. In this review, we summarize the current knowledge about miRNAs significance in glioblastoma, with special focus on their involvement in core signalling pathways, their roles in drug resistance and potential clinical implications.

• MeSH
• down regulace MeSH
• glioblastom genetika   patologie   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• modely genetické MeSH
• regulace genové exprese u nádorů * MeSH
• signální transdukce genetika   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN197 microRNA, human MeSH Prohlížeč
• MIRN21 microRNA, human MeSH Prohlížeč