Dysregulation of gap junction intercellular communication (GJIC) is recognized as one of the key hallmarks for identifying non-genotoxic carcinogens (NGTxC). Currently, there is a demand for in vitro assays addressing the gap junction hallmark, which would have the potential to eventually become an integral part of an integrated approach to the testing and assessment (IATA) of NGTxC. The scrape loading-dye transfer (SL-DT) technique is a simple assay for the functional evaluation of GJIC in various in vitro cultured mammalian cells and represents an interesting candidate assay. Out of the various techniques for evaluating GJIC, the SL-DT assay has been used frequently to assess the effects of various chemicals on GJIC in toxicological and tumor promotion research. In this review, we systematically searched the existing literature to gather papers assessing GJIC using the SL-DT assay in a rat liver epithelial cell line, WB-F344, after treating with chemicals, especially environmental and food toxicants, drugs, reproductive-, cardio- and neuro-toxicants and chemical tumor promoters. We discuss findings derived from the SL-DT assay with the known knowledge about the tumor-promoting activity and carcinogenicity of the assessed chemicals to evaluate the predictive capacity of the SL-DT assay in terms of its sensitivity, specificity and accuracy for identifying carcinogens. These data represent important information with respect to the applicability of the SL-DT assay for the testing of NGTxC within the IATA framework.

• Klíčová slova
• carcinogenesis, carcinogens, gap junction intercellular communication, scrape loading-dye transfer,
• MeSH
• barvicí látky metabolismus   MeSH
• biotest metody   MeSH
• buněčné linie MeSH
• fluorescenční mikroskopie metody   MeSH
• játra patologie   MeSH
• karcinogeny MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• mezerový spoj metabolismus   MeSH
• mezibuněčná komunikace účinky léků   fyziologie   MeSH
• testy karcinogenity metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• barvicí látky MeSH
• karcinogeny MeSH

Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon. Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses. Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner. Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique. Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.

• Klíčová slova
• CD44 isoforms, RNA splicing, cancer markers, colon polyps, colorectal precancerosis,
• MeSH
• antigeny CD44 genetika   metabolismus   MeSH
• kolon metabolismus   patologie   MeSH
• kolorektální nádory diagnóza   genetika   metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• polypy tlustého střeva metabolismus   patologie   MeSH
• prognóza MeSH
• protein - isoformy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD44 MeSH
• CD44 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein - isoformy MeSH

The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics.

• Publikační typ
• časopisecké články MeSH