Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0-6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.
- MeSH
- aminokyseliny * moč krev MeSH
- antracykliny terapeutické užití aplikace a dávkování MeSH
- cyklofosfamid * terapeutické užití MeSH
- dospělí MeSH
- dusík * moč MeSH
- kreatinin moč krev MeSH
- krevní proteiny * metabolismus analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu * farmakoterapie krev moč MeSH
- neoadjuvantní terapie * MeSH
- paclitaxel * terapeutické užití aplikace a dávkování MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference 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.
- 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
The liver and the biliary tree form the main excretory route of manganese (Mn) and copper (Cu). Cholestasis, can lead to the accumulation of these trace elements in the organism, resulting in toxicity to the basal ganglia of the central nervous system. The aim of our study was to reveal the influence of long-term cholestasis on the Mn and Cu levels in the blood of patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We recruited patients with PBC (n = 20) and PSC (n = 32). A control group (n = 40) was also set up. We also examined serum bile acid concentrations and liver enzyme activities. We did not observe any significant differences in any of these parameters between the PBC and PSC groups. The Mn and Cu levels in the PBC and PSC patients differed significantly from the that in the control group (p < 0.0001 and p < .021, respectively). Patients in whom the laboratory cholestasis markers normalized during ursodeoxycholic acid treatment (18/52;35%) presented with significantly lower levels of Mn and Cu (p = .015 and p = .012, respectively). Ten PSC patients showed normal levels of Mn and Cu six months after liver transplantation. Fine tremors, rigidity, dysarthria, and hypomimia were reported in nine (23%), eight (20%), four (10%), and eight (20%) patients, respectively. In addition to monitoring the cholestasis levels, liver function, and Mn and Cu levels during the long-term treatment of PBC and PSC patients, it is important to also regularly monitor the occurrence and development of extrapyramidal symptoms of Parkinson's-like syndromes.
- MeSH
- biliární cirhóza krev terapie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mangan krev MeSH
- měď krev MeSH
- mladý dospělý MeSH
- senioři MeSH
- sklerozující cholangitida krev terapie MeSH
- studie případů a kontrol MeSH
- transplantace jater MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Lithium in the form of lithium carbonate (Li2CO3) has become one of the most effective and widely prescribed drugs for mood stabilization. However, lithium has adverse effects on renal tubular functions, such as decreased concentrating function of the kidneys, and even occasional symptoms of nephrogenous diabetes insipidus occur with additional evidence of glomerular disruption in lithium-treated patients. METHODS: We assessed the kidney function of patients with bipolar disorder who are under long-term lithium treatment using novel markers of kidney damage such as plasma neutrophil gelatinase-associated lipocalin, cystatin C, albuminuria, estimated glomerular filtration rate, Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, and serum and urinary osmolality, and compared the results with those of age-matched patients with bipolar disorder not treated with lithium. The study enrolled 120 patients with bipolar disorder, consisting of 80 (30 male and 50 female patients) who have been receiving lithium for 0.5 to 20 (mean, 7) years and 40 (10 male and 30 female patients) who had never been exposed to lithium treatment. RESULTS: Patients treated with lithium had significantly decreased urine osmolality (mean ± SD, 405 ± 164 vs 667 ± 174 mmol/kg) and urine-to-serum osmolality ratio (1.35 ± 0.61 vs 2.25 ± 0.96). No significant difference was found in creatinine, estimated glomerular filtration rate values calculated using the Chronic Kidney Disease-Epidemiology Investigation using creatinine and cystatin C, neutrophil gelatinase-associated lipocalin, cystatin C, and albuminuria between both groups. We found no significant difference in renal biomarkers between patients treated with lithium for 6 to 24 months and those treated for 25 to 240 months. CONCLUSIONS: We found significantly decreased kidney concentrating ability in the long-term lithium-treated patients compared with the control group. Other renal function markers did not indicate any significant signs of renal dysfunction.
- MeSH
- antimanika aplikace a dávkování škodlivé účinky MeSH
- biologické markery metabolismus MeSH
- bipolární porucha farmakoterapie MeSH
- časové faktory MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- lidé středního věku MeSH
- lidé MeSH
- lithiumkarbonát aplikace a dávkování škodlivé účinky MeSH
- nemoci ledvin chemicky indukované epidemiologie MeSH
- senioři MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
