BACKGROUND: In this study, some important biological characteristics of two radiolabelled somatostatin analogues 111In-DOTA-1-Nal3-octreotide (DOTA-NOC) and 111In-DOTA-Tyr3-octreotate (DOTA-TATE) were compared. MATERIALS AND METHODS: Rats were used for in vivo biodistribution experiments and in vitro cell models (OK and AR42J cell lines) were used for simulating the internalization in the kidney and in subtype 2 somatostatin receptor (SSTR2)-positive tissues, respectively. RESULTS: Significantly higher radioactivity concentrations in rat organs with high density of somatostatin receptors after 111In-DOTA-NOC administration in comparison with 111In-DOTA-TATE were observed. The predominant urine excretion was associated with accumulation of the radioactivity in the kidney, where higher retention of 111In-DOTA-TATE compared to 111In-DOTA-NOC was detected. In the OK cell line the opposite results were found. No significant differences in the in vitro internalization and externalization of radioactivity to AR42J cell line were found for either peptide suggesting their same affinity for SSTR2. CONCLUSION: Preclinical experiments indicated that 111In-DOTA-NOC is a very promising peptide for somatostatin receptor-positive tumour visualization. The conflict between the in vitro and in vivo kidney handling showed that the transfer of results from in vitro to in vivo conditions and their interpretation should be performed very carefully because both types of experiments can be affected by different factors, making their simple comparison difficult.

• MeSH
• buněčné linie MeSH
• krysa rodu Rattus MeSH
• ledvinové kanálky metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní metabolismus   MeSH
• oktreotid analogy a deriváty   chemie   farmakokinetika   MeSH
• organokovové sloučeniny chemie   farmakokinetika   MeSH
• potkani Wistar MeSH
• radiofarmaka farmakokinetika   MeSH
• radioizotopy india MeSH
• receptory somatostatinu metabolismus   MeSH
• tkáňová distribuce MeSH
• vačicovití MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 111In-DOTA-1-Nal(3)-octreotide MeSH Prohlížeč
• 111In-octreotate, DOTA(0)-Tyr(3)-Thr(8)- MeSH Prohlížeč
• oktreotid MeSH
• organokovové sloučeniny MeSH
• radiofarmaka MeSH
• radioizotopy india MeSH
• receptory somatostatinu MeSH
• somatostatin receptor 2 MeSH Prohlížeč

BACKGROUND: In this study, two octreotate derivatives N-[4-carboxy-4-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]butanoyl]-Tyr(3)-octreotate (DOTAGA-tate) and N-[[4,10-bis(carboxymethyl)-7-(1(1,3-dicarboxypropyl))-1,4,7,10-tetraaza-cyclododec-1-yl]acetyl]-Tyr(3)-octreotate (DOTA-t-GA-tate) were radio-labeled with (111)In or (88)Y and their biodistribution profiles together with their elimination characteristics in rats were compared. MATERIALS AND METHODS: Radiolabeling of the peptides with high radiochemical purity was carried out in an acetate buffer with gentisic acid as radioprotective compound. Biodistribution profiles of the radiolabeled peptides were determined in intact male Wistar rats after an intravenous dose of 1 microg/kg. For elimination pathways analysis, studies in intact rats in metabolic cages and perfused rat kidney and liver were carried out. RESULTS: Fast radioactivity clearance from rat tissues (excepting somatostatin receptor-rich organs and the kidney) was determined for all agents under study. Profound radioactivity uptake in organs with a high density of somatostatin receptors (namely the adrenals and pancreas as biomarkers of somatostatin receptor-positive tissue) was slightly higher for radiolabeled DOTAGA-tate when compared with DOTA-t-GA-tate. Significantly higher accumulation in kidney and somewhat lower urinary elimination of (111)In-labeled peptides in comparison with that of (88)Y-agents were determined. Perfused rat kidney experiments confirmed that glomerular filtration was the main elimination mechanism for the compounds under study; their bile clearances in the perfused rat liver were negligible. CONCLUSION: (111)In((88)Y)-DOTAGA-tates exhibited higher distribution into somatostatin receptor-rich organs when compared with the corresponding radiolabeled DOTA-t-GA-tates. Higher uptake of (111)In-labeled peptides in the kidney is attributed to its different coordination properties.

• MeSH
• krysa rodu Rattus MeSH
• ledviny metabolismus   MeSH
• oktreotid analogy a deriváty   chemie   farmakokinetika   MeSH
• potkani Wistar MeSH
• radiofarmaka chemie   farmakokinetika   MeSH
• radioizotopy india * MeSH
• radioizotopy ytria * MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• oktreotid MeSH
• radiofarmaka MeSH
• radioizotopy india * MeSH
• radioizotopy ytria * MeSH
• Y-DOTA-t-GA-tate MeSH Prohlížeč
• Y-DOTAGA-tate MeSH Prohlížeč

Distribution profiles and elimination pathways in rats of two new octreotate derivatives radiolabeled with yttrium, namely Y-DOTAGA-tate and Y-DOTA-t-GA-tate, were compared with those of Y-DOTA-octreotide and Y-DOTA-Tyr(3)-octreotide. All synthetic somatostatin analogues under study were rapidly cleared from the blood and most organs of rats. The main elimination pathway for all peptides under study was urine excretion. High and long-term uptakes of radioactivity in the kidneys and also in organs with high density of somatostatin receptors (the adrenals and pancreas) were found. Radioactivity concentrations in these somatostatin receptor-rich organs were substantially higher for octreotate derivatives in comparison with octreotide analogues; the highest values for Y-DOTAGA-tate were determined. The octreotate derivatives under study appear to be specific ligands for treatment of somatostatin receptor-positive tumors if some mechanism to decrease their kidney retention is provided.

• MeSH
• krevní proteiny metabolismus   MeSH
• krysa rodu Rattus MeSH
• oktreotid analogy a deriváty   farmakokinetika   MeSH
• potkani Wistar MeSH
• radioizotopy ytria MeSH
• receptory somatostatinu metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• krevní proteiny MeSH
• oktreotid MeSH
• radioizotopy ytria MeSH
• receptory somatostatinu MeSH
• Y-DOTA-t-GA-tate MeSH Prohlížeč
• Y-DOTAGA-tate MeSH Prohlížeč

BACKGROUND: Eye tumors are moving targets, but there have been no reports of radiation therapy with real-time monitoring. CASE: A 54-year-old woman with metastatic breast cancer was referred for treatment of diplopia due to choroidal metastasis after hippocampal avoiding whole brain radiotherapy. Since visual acuity was preserved and long-term survival was expected, real-time MRI-guided intensity-modulated radiation therapy (36 Gy in 20 fractions) was performed. No adverse events occurred during treatment or during the subsequent one-year follow-up period. The patient's diplopia resolved and no choroidal recurrence was observed during the follow-up period. CONCLUSION: MRI-guided radiation therapy may be a safe and effective treatment for choroidal metastases after hippocampal avoiding whole brain radiotherapy.

• Klíčová slova
• choroidal tumor, image guided radiotherapy, image-guided radiotherapy, intensity-modulated radiation therapy, retinal neoplasms,
• MeSH
• hipokampus MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• nádory choroidey * radioterapie   sekundární   MeSH
• nádory mozku sekundární   radioterapie   MeSH
• nádory prsu * patologie   MeSH
• radioterapie řízená obrazem * MeSH
• radioterapie s modulovanou intenzitou * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: There are no reports of concurrent chemoradiotherapy for gastric cancer with peritoneal oligometastases. CASE DESCRIPTION: A 70-year-old man with gastric cancer and peritoneal oligometastases received concurrent adaptive radiotherapy and oral S-1. After radiotherapy, S-1 was discontinued, and 2 years later the tumor had completely regressed, with no recurrence or metastasis 6 years after radiotherapy. CONCLUSION: Peritoneal oligometastatic gastric cancer may be a candidate for curative treatment with concurrent adaptive radiotherapy and oral S-1.

• Klíčová slova
• Drug therapy, image-guided radiotherapy, intensity-modulated radiotherapy, stomach neoplasms,
• MeSH
• chemoradioterapie * MeSH
• fixní kombinace léků MeSH
• ftorafur * terapeutické užití   aplikace a dávkování   MeSH
• kyselina oxonová * terapeutické užití   aplikace a dávkování   MeSH
• lidé MeSH
• nádory žaludku * patologie   terapie   farmakoterapie   MeSH
• peritoneální nádory * sekundární   terapie   MeSH
• protinádorové antimetabolity terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• fixní kombinace léků MeSH
• ftorafur * MeSH
• kyselina oxonová * MeSH
• protinádorové antimetabolity MeSH
• S 1 (combination) MeSH Prohlížeč

BACKGROUND: Benign lymphoid hyperplasia (BLH) is a rare lymphoproliferative disorder of normal polyclonal B lymphocytes, but is sometimes difficult to distinguish from malignancy. CASE: An 87-year-old man with a history of localized non-small cell lung cancer (NSCLC) was referred for evaluation and treatment of an elastic hard tumor in the left supraclavicular fossa one year after stereotactic ablative radiotherapy (SABR). Whole-body PET scan showed high 18F-fluorodeoxyglucose uptake in the left supraclavicular fossa, and a dia-gnosis of oligometastasis was made. The tumor was homogeneously high signal on T2-weighted image with homogeneous enhancement after contrast administration. Since the palpation and MRI findings were inconsistent with those of metastatic NSCLC, a bio-psy was performed. Pathological and immunohistochemical investigation revealed the lesion to be BLH. CONCLUSION: In a patient with suspected oligometastasis after SABR for NSCLC, caution should be exercised before undergoing SABR for oligometastasis because BLH may be present.

• Klíčová slova
• lymph node metastasis, oligometastatic disease, pseudolymphoma, reactive lymphoid hyperplasia, stereotactic body radiotherapy,
• MeSH
• fluorodeoxyglukosa F18 MeSH
• hyperplazie MeSH
• lidé MeSH
• nádory plic * patologie   MeSH
• nemalobuněčný karcinom plic * diagnostické zobrazování   chirurgie   patologie   MeSH
• radiochirurgie * metody   MeSH
• senioři nad 80 let MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• fluorodeoxyglukosa F18 MeSH

BACKGROUND: Soft tissue tumors near metal implants are sometimes difficult to treat with real-time image-guided radiation therapy. Low-field MRI was utilized to clearly delineate the tumor and spinal cord while avoiding metal artifacts, and re-irradiation was performed for recurrent spinal metastases. CASE DESCRIPTION: A 57-year-old woman with a history of thyroid cancer was referred for re-irradiation for recurrent painful bone metastases in the thoracolumbar spine. She had already undergone conventional radiation therapy followed by stereotactic ablative radiotherapy and multiple fusion surgeries. Since the radiation dose to the spinal cord should have been limited, metal artifact-free low-field MRI-guided re-irradiation was performed with no significant adverse events. CONCLUSION: Low-field MRI-guided re-irradiation may be feasible for recurrent spinal metastases, even after metal implants have been placed.

• Klíčová slova
• image-guided, magnetic resonance, magnetic resonance imaging, radiotherapy, radiotherapy –intensity-modulated,
• MeSH
• artefakty MeSH
• kovy MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru radioterapie   sekundární   MeSH
• magnetická rezonanční tomografie * MeSH
• nádory páteře radioterapie   sekundární   MeSH
• nádory štítné žlázy patologie   radioterapie   MeSH
• protézy a implantáty MeSH
• radioterapie řízená obrazem * MeSH
• reiradiace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• kovy MeSH

Transposable elements (TEs) have the ability to move and amplify inside the host genome, making them a pivotal source of genome plasticity. Presently, only 4 TE clades (all classified as Class I retrotransposons) have been identified in trypanosomatids. We predicted repeat content and manually curated TEs across the genomes of 57 trypanosomatids, shedding light on their proportions, diversity and dynamics. Our analysis yielded 214 TE consensus sequence models across the dataset, with abundance ranging from 0.1% to 7.2%. We found evidence of recent transposon activity in most species, with notable bursts in the Vickermania, Lafontella, Porcisia and Angomonas spp., along with Leishmania (Mundinia) chancei, L. (M.) orientalis and L. (M.) procaviensis. We confirmed that the 4 TE clades have colonized virtually all lineages of trypanosomatids, potentially playing a role in shaping their genome architecture. The effort of this work culminated in the establishment of the Trypanosomatid TE Database 1.0, a resource designed to standardize the TE annotation process that can serve as a foundation for future studies on trypanosomatid TEs.

• Klíčová slova
• CRE, INGI, SLACS, TATE, VIPER, mobilome, transposable elements, trypanosomatids,
• Publikační typ
• časopisecké články MeSH

In yeast physiology, a commonly used reference condition for many experiments, including those involving nitrogen catabolite repression (NCR), is growth in synthetic complete (SC) medium. Four SC formulations, SCCSH,1990, SCCSH,1994, SCCSH,2005, and SCME, have been used interchangeably as the nitrogen-rich medium of choice [Cold Spring Harbor Yeast Course Manuals (SCCSH) and a formulation in the methods in enzymology (SCME)]. It has been tacitly presumed that all of these formulations support equivalent responses. However, a recent report concluded that (i) TorC1 activity is downregulated by the lower concentration of primarily leucine in SCME relative to SCCSH. (ii) The Whi2-Psr1/2 complex is responsible for this downregulation. TorC1 is a primary nitrogen-responsive regulator in yeast. Among its downstream targets is control of NCR-sensitive transcription activators Gln3 and Gat1. They in turn control production of catabolic transporters and enzymes needed to scavenge poor nitrogen sources (e.g., Proline) and activate autophagy (ATG14). One of the reporters used in Chen et al. was an NCR-sensitive DAL80-GFP promoter fusion. This intrigued us because we expected minimal if any DAL80 expression in SC medium. Therefore, we investigated the source of the Dal80-GFP production and the proteomes of wild-type and whi2Δ cells cultured in SCCSH and SCME. We found a massive and equivalent reorientation of amino acid biosynthetic proteins in both wild-type and whi2Δ cells even though both media contained high overall concentrations of amino acids. Gcn2 appears to play a significant regulatory role in this reorientation. NCR-sensitive DAL80 expression and overall NCR-sensitive protein production were only marginally affected by the whi2Δ. In contrast, the levels of 58 proteins changed by an absolute value of log2 between 3 and 8 when Whi2 was abolished relative to wild type. Surprisingly, with only two exceptions could those proteins be related in GO analyses, i.e., GO terms associated with carbohydrate metabolism and oxidative stress after shifting a whi2Δ from SCCSH to SCME for 6 h. What was conspicuously missing were proteins related by TorC1- and NCR-associated GO terms.

• Klíčová slova
• DAL80, Gat1, Gcn2, Gln3, TorC1 complex, Whi2, nitrogen metabolism, nuclear translocation, signal transduction, synthetic complete medium,
• MeSH
• dusík metabolismus   farmakologie   MeSH
• katabolická represe * MeSH
• proteom metabolismus   MeSH
• regulace genové exprese u hub MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• transkripční faktory GATA chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• dusík MeSH
• proteom MeSH
• Saccharomyces cerevisiae - proteiny MeSH
• transkripční faktory GATA MeSH
• Whi2 protein, S cerevisiae MeSH Prohlížeč

BACKGROUND: Tragopogon mirus and T. miscellus are allotetraploids (2n = 24) that formed repeatedly during the past 80 years in eastern Washington and adjacent Idaho (USA) following the introduction of the diploids T. dubius, T. porrifolius, and T. pratensis (2n = 12) from Europe. In most natural populations of T. mirus and T. miscellus, there are far fewer 35S rRNA genes (rDNA) of T. dubius than there are of the other diploid parent (T. porrifolius or T. pratensis). We studied the inheritance of parental rDNA loci in allotetraploids resynthesized from diploid accessions. We investigate the dynamics and directionality of these rDNA losses, as well as the contribution of gene copy number variation in the parental diploids to rDNA variation in the derived tetraploids. RESULTS: Using Southern blot hybridization and fluorescent in situ hybridization (FISH), we analyzed copy numbers and distribution of these highly reiterated genes in seven lines of synthetic T. mirus (110 individuals) and four lines of synthetic T. miscellus (71 individuals). Variation among diploid parents accounted for most of the observed gene imbalances detected in F1 hybrids but cannot explain frequent deviations from repeat additivity seen in the allotetraploid lines. Polyploid lineages involving the same diploid parents differed in rDNA genotype, indicating that conditions immediately following genome doubling are crucial for rDNA changes. About 19% of the resynthesized allotetraploid individuals had equal rDNA contributions from the diploid parents, 74% were skewed towards either T. porrifolius or T. pratensis-type units, and only 7% had more rDNA copies of T. dubius-origin compared to the other two parents. Similar genotype frequencies were observed among natural populations. Despite directional reduction of units, the additivity of 35S rDNA locus number is maintained in 82% of the synthetic lines and in all natural allotetraploids. CONCLUSIONS: Uniparental reductions of homeologous rRNA gene copies occurred in both synthetic and natural populations of Tragopogon allopolyploids. The extent of these rDNA changes was generally higher in natural populations than in the synthetic lines. We hypothesize that locus-specific and chromosomal changes in early generations of allopolyploids may influence patterns of rDNA evolution in later generations.

• MeSH
• Asteraceae genetika   MeSH
• diploidie MeSH
• hybridizace genetická genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• molekulární evoluce * MeSH
• ribozomální DNA genetika   MeSH
• Southernův blotting MeSH
• tetraploidie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• ribozomální DNA MeSH