Introduction: Skin malignancy is one of the most common reasons for seeking out a plastic surgery clinic. This article presents an overview of the therapeutic results at Department of Plastic and Aesthetic Surgery Brno and includes an algorithm according to which we proceed in the treatment of patients with skin malignancy. Material and methods: Retrospective analysis of data for the year 2022, including a set of 791 patients with a total of 1,117 procedures to remove skin malignancy. The representation of cutaneous malignancy was as follows – basalioma (51%), squamous cell carcinoma (14%), and other malignancies including precancerous lesions were represented in 35%. Age, sex, a character and a number of procedures (excision, re-excision, controlled excision), and the histological results of resected specimens (with a sufficient margin or ingrowth) were evaluated. Based on the analysis of the patient cohort, an algorithm is presented to guide the surgical management of the patient. Results: Patients’ age ranged from 26 to 102 years. There was a discrete male predominance in the cohort (51%). Tumour localization was most frequently on the skin of the face, cleavage, and extremities. Regarding the spectrum of procedures, excision accounted for the largest proportion (83%). Re-excision accounted for the rest of the procedures (10%), controlled excision was performed in 6% and excisional biopsy accounted for 1%. Primary sanative excision with a histologically sufficient margin was performed in 96%. In the group of controlled excisions, 59% were sanative. Overall, 73% of patients in our cohort underwent a single operation only to remove a cutaneous malignancy. Conclusion: The results of the therapy and the algorithm of the care for patients with skin malignancy can be evaluated as successful based on the analysis performed. The determination of the surgical strategy according to the algorithm appears to be effective. The authors recommend its use in practice, especially with the current trend of the increasing incidence of skin malignancies and the desire to improve the effectiveness of surgical interventions.
- MeSH
- bazocelulární karcinom chirurgie patologie terapie MeSH
- lidé MeSH
- management nemoci MeSH
- nádory kůže * chirurgie patologie terapie MeSH
- retrospektivní studie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- spinocelulární karcinom chirurgie patologie terapie MeSH
- výsledek terapie MeSH
- zákroky plastické chirurgie * metody MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. METHODS: Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting. RESULTS: Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU-based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa. CONCLUSIONS: The observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naïve colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated.
- MeSH
- CpG ostrůvky MeSH
- fluoruracil farmakologie MeSH
- kolorektální nádory genetika metabolismus mortalita patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA MeSH
- promotorové oblasti (genetika) MeSH
- protinádorové antimetabolity farmakologie MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- ribonukleosiddifosfátreduktasa genetika metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- signální transdukce účinky léků MeSH
- staging nádorů MeSH
- stanovení celkové genové exprese * MeSH
- stupeň nádoru MeSH
- transkriptom * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The objective of this study was to investigate whether melamine (MEL) is biotransformed into cyanuric acid (CYA) in male broiler chickens. The effects of the dietary addition of MEL and CYA alone and in combination on the growth performance and mortality of the chickens were also investigated. The chickens were divided into six experimental groups and were fed diets with an addition of 50 or 100 mg/kg MEL or 50 or 100 mg/kg CYA of diet, with the contaminants added separately or in combination. The control group was fed a diet without MEL or CYA. At the end of the experiment (day 40), samples of liver, kidney and breast and thigh muscles were collected from 12 birds per treatment group and were analysed for the presence of MEL and CYA. This study showed that MEL is biotransformed into CYA in broilers. Higher concentrations of MEL or CYA in the diet increased the presence of their residues in tissues, and the CYA residue concentration was several times higher in the respective tissues than the MEL residue concentration. The dietary addition of MEL and CYA did not affect the mortality rate, feed conversion ratio or body weight of the chickens.
- MeSH
- biotransformace MeSH
- játra účinky léků metabolismus MeSH
- kontaminace potravin analýza MeSH
- kosterní svaly účinky léků metabolismus MeSH
- krmivo pro zvířata analýza MeSH
- kur domácí růst a vývoj metabolismus MeSH
- ledviny účinky léků metabolismus MeSH
- tělesná hmotnost účinky léků MeSH
- tkáňová distribuce MeSH
- triaziny aplikace a dávkování metabolismus farmakokinetika toxicita MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
l-asparaginase (ASNase), a key component in the treatment of childhood acute lymphoblastic leukemia (ALL), hydrolyzes plasma asparagine and glutamine and thereby disturbs metabolic homeostasis of leukemic cells. The efficacy of such therapeutic strategy will depend on the capacity of cancer cells to adapt to the metabolic challenge, which could relate to the activation of compensatory metabolic routes. Therefore, we studied the impact of ASNase on the main metabolic pathways in leukemic cells. Treating leukemic cells with ASNase increased fatty-acid oxidation (FAO) and cell respiration and inhibited glycolysis. FAO, together with the decrease in protein translation and pyrimidine synthesis, was positively regulated through inhibition of the RagB-mTORC1 pathway, whereas the effect on glycolysis was RagB-mTORC1 independent. As FAO has been suggested to have a pro-survival function in leukemic cells, we tested its contribution to cell survival following ASNase treatment. Pharmacological inhibition of FAO significantly increased the sensitivity of ALL cells to ASNase. Moreover, constitutive activation of the mammalian target of rapamycin pathway increased apoptosis in leukemic cells treated with ASNase, but did not increase FAO. Our study uncovers a novel therapeutic option based on the combination of ASNase and FAO inhibitors.
- MeSH
- akutní lymfatická leukemie farmakoterapie metabolismus patologie MeSH
- asparaginasa terapeutické užití MeSH
- autofagie účinky léků MeSH
- lidé MeSH
- mastné kyseliny metabolismus MeSH
- monomerní proteiny vázající GTP fyziologie MeSH
- multiproteinové komplexy fyziologie MeSH
- nádorové buněčné linie MeSH
- oxidace-redukce MeSH
- pyrimidiny biosyntéza MeSH
- TOR serin-threoninkinasy fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Integral membrane proteins are generally under-represented in routine proteomic analyses, mostly because of their relatively low abundance, hydrophobicity and lack of trypsin-cleavage sites. To increase the coverage of membrane proteomes, various strategies have been developed, targeting mostly the extra-membrane segments of membrane proteins. We focused our attention to the rather overlooked hydrophobic transmembrane segments. Such peptides can be isolated after carbonate stripping and protease "shaving" of membranes isolated by simple centrifugation procedure. The treated membranes with embedded hydrophobic peptides can then be solubilized in organic solvents, re-digested with CNBr, delipidated and subjected to LC-MS/MS analysis. We modified the original "hppK" method, and applied it for the analysis of human lymphoma cells. We identified 1224 proteins of which two-thirds were IMPs with 1-16 transmembrane segments. This method allowed us to identify 13 "missing proteins" - proteins with no previous evidence on protein level. BIOLOGICAL SIGNIFICANCE: Integral membrane proteins execute numerous essential functions and represent substantial part of eukaryotic proteomes. Our knowledge of their function and expression is, however, limited. Novel approaches extending our knowledge of membrane proteome are therefore highly desired. As we demonstrate here, a non-conventional method which targets rather overlooked hydrophobic transmembrane segments of integral membrane proteins has wide potential to provide the missing information on the membrane proteome. We show that it can deliver identification and potentially also quantification of hundreds of integral membrane proteins including the so called "missing proteins".
- MeSH
- chromatografie kapalinová metody MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- lymfom z plášťových buněk chemie MeSH
- membránové proteiny analýza MeSH
- nádorové proteiny analýza MeSH
- peptidy analýza MeSH
- proteom chemie MeSH
- proteomika metody MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- trypsin chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
1. The aim of the study was to investigate the effect of melamine-contaminated feed (100 mg/kg) on the distribution of melamine and cyanuric acid in the tissues of laying hens. The effect of a 5-week melamine administration in feed on the egg quality and blood variables of layers was also investigated. 2. A total of twenty 36-week-old ISA Brown layers were used in the experiment. The layers were equally divided into an experimental melamine group (n = 10) and a control group without melamine (n = 10). At the end of the experiment, samples of liver, kidney, breast and thigh muscles were collected from all hens and analysed for the presence of melamine and cyanuric acid by gas chromatography and tandem mass spectrometry. 3. Layers receiving the melamine-contaminated diet laid eggs with decreased eggshell strength. The decrease in shell strength was found in weeks 3 and 4 compared to the initial state (week 0) and week 1. 4. Hens receiving the melamine-contaminated diet also exhibited a higher total red blood cell count and lower mean corpuscular haemoglobin compared to the control group. However, melamine at 100 mg/kg feed had no effects on the blood variables of layers. 5. Melamine was detected in all analysed tissues of layers fed on the melamine-contaminated diet, with its mean concentrations decreasing in the following order: kidney (7.43 mg/kg) > breast muscle (3.88 mg/kg) > liver (3.11 mg/kg) > thigh muscle (1.91 mg/kg). The kidney and liver of layers fed on the melamine-contaminated diet also exhibited the presence of cyanuric acid. 6. On the basis of our results, it can be concluded that the biotransformation of melamine into cyanuric acid proceeded mainly in the liver, and cyanuric acid was eliminated in urine.
- MeSH
- biotransformace MeSH
- játra metabolismus MeSH
- krmivo pro zvířata * MeSH
- kur domácí růst a vývoj fyziologie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- počet erytrocytů MeSH
- testy toxicity MeSH
- triaziny metabolismus toxicita MeSH
- vaječná skořápka účinky léků fyziologie MeSH
- vejce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
