The incidence of malignant melanoma is rapidly increasing and current medicine is offering only limited options for treatment of the advanced disease. For B‑Raf mutated melanomas, treatment with mutation‑specific drug inhibitors may be used. Unfortunately, tumors frequently acquire resistance to the treatment. Tumor microenvironment, namely cancer‑associated fibroblasts, largely influence this acquired resistance. In the present study, fibroblasts were isolated from a patient suffering from acrolentiginous melanoma (Breslow, 4.0 mm; Clark, IV; B‑Raf V600E mutated). The present study focused on the expression of structural and functional markers of fibroblast activation in melanoma‑associated fibroblasts (MAFs; isolated prior to therapy initiation) as well as in autologous control fibroblasts (ACFs) of the same patient isolated during B‑Raf inhibitor therapy, yet before clinical progression of the disease. Analysis of gene transcription was also performed, as well as DNA methylation status analysis at the genomic scale of both isolates. MAFs were positive for smooth muscle actin (SMA), which is a marker of myofibroblasts and the hallmark of cancer stoma. Surprisingly, ACF isolated from the distant uninvolved skin of the same patient also exhibited strong SMA expression. A similar phenotype was also observed in control dermal fibroblasts (CDFs; from different donors) exclusively following stimulation by transforming growth factor (TGF)‑β1. Immunohistochemistry confirmed that melanoma cells potently produce TGF‑β1. Significant differences were also identified in gene transcription and in DNA methylation status at the genomic scale. Upregulation of SMA was observed in ACF cells at the protein and transcriptional levels. The present results support recent experimental findings that tumor microenvironment is driving resistance to B‑Raf inhibition in patients with melanoma. Such an activated microenvironment may be viable for the growth of circulating melanoma cells.

• MeSH
• bodová mutace MeSH
• chemorezistence * MeSH
• fibroblasty asociované s nádorem účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• melanom farmakoterapie   genetika   patologie   MeSH
• metylace DNA MeSH
• nádorové buňky kultivované MeSH
• nádorové mikroprostředí * MeSH
• nádory kůže farmakoterapie   genetika   patologie   MeSH
• protoonkogenní proteiny B-raf antagonisté a inhibitory   genetika   MeSH
• senioři MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Endogenous retroviruses (ERVs) were acquired during evolution of their host organisms after infection and mendelian inheritance in the germline by their exogenous counterparts. The ERVs can spread in the host genome and in some cases they affect the host phenotype. The cervid endogenous gammaretrovirus (CrERV) is one of only a few well-defined examples of evolutionarily recent invasion of mammalian genome by retroviruses. Thousands of insertionally polymorphic CrERV integration sites have been detected in wild ranging mule deer (Odocoileus hemionus) host populations. Here, we describe for the first time induction of replication competent CrERV by cocultivation of deer and human cells. We characterize the physical properties and tropism of the induced virus. The genomic sequence of the induced virus is phylogenetically related to the evolutionarily young endogenous CrERVs described so far. We also describe the level of replication block of CrERV on deer cells and its capacity to establish superinfection interference.

• MeSH
• biologická evoluce MeSH
• endogenní retroviry klasifikace   genetika   izolace a purifikace   ultrastruktura   MeSH
• epitelové buňky ultrastruktura   virologie   MeSH
• fylogeneze MeSH
• Gammaretrovirus klasifikace   genetika   izolace a purifikace   ultrastruktura   MeSH
• genom virový * MeSH
• HEK293 buňky MeSH
• kokultivační techniky MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• replikace viru MeSH
• virion genetika   izolace a purifikace   ultrastruktura   MeSH
• vysoká zvěř virologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Achromobacter xylosoxidans strain A8 was isolated from soil contaminated with polychlorinated biphenyls. It can use 2-chlorobenzoate and 2,5-dichlorobenzoate as sole sources of carbon and energy. This property makes it a good starting microorganism for further development toward a bioremediation tool. The genome of A. xylosoxidans consists of a 7-Mb chromosome and two large plasmids (98 kb and 248 kb). Besides genes for the utilization of xenobiotic organic substrates, it contains genes associated with pathogenesis, toxin production, and resistance. Here, we report the complete genome sequence.

• MeSH
• Achromobacter denitrificans genetika   izolace a purifikace   metabolismus   MeSH
• bakteriální chromozomy MeSH
• chlorbenzoáty metabolismus   MeSH
• DNA bakterií chemie   genetika   MeSH
• energetický metabolismus MeSH
• genom bakteriální MeSH
• molekulární sekvence - údaje MeSH
• plazmidy MeSH
• půdní mikrobiologie MeSH
• sekvenční analýza DNA MeSH
• uhlík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH