Haemophagocytic syndrome, diffuse alveolar haemorrhage, catastrophic antiphospholipid syndrome and various types of thrombotic microangiopathies are rare conditions with significant morbidity and mortality. A common feature is late diagnosis, which can affect the success of treatment. The aim of this review article is to summarize the basic diagnostic and therapeutic steps of the present subpopulation of critically ill patients.
- Klíčová slova
- HLH, Lens-Associated Uveitis, antiphospholipid syndrome, anti‑glomerular basement membrane (anti‑GBM) antibodies, caplacizumab, catastrophic antiphospholipid syndrome, cytokine storm syndrome, diffuse alveolar haemorrhage, eculizumab, eculizumab, etoposide, haemolytic‑uremic syndrome, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, immunosuppressive therapy, macrophage activation syndrome, plasma exchange, ravulizumab, recombinant factor VIIa, rituximab, thrombosis, thrombotic microangiopathies, thrombotic microangiopathy, thrombotic thrombocytopenic purpura, vasculitis,
- MeSH
- antifosfolipidový syndrom * komplikace diagnóza terapie MeSH
- dospělí MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * MeSH
- trombotické mikroangiopatie * diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post-treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow-up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more pronounced in a subgroup of patients who underwent radical prostatectomy, HR = 3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may become a possible predictor for patients' outcomes, because patients with elevated post-treatment sarcosine could be predicted to have recurrent relapses of the disease.
- Klíčová slova
- outcome, prostate cancer, relapse, sarcosine, survival,
- MeSH
- adenokarcinom chirurgie moč MeSH
- biologické markery moč MeSH
- hyperplazie prostaty chirurgie moč MeSH
- lidé MeSH
- lokální recidiva nádoru moč MeSH
- nádory prostaty chirurgie moč MeSH
- pooperační období MeSH
- prostatektomie MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- sarkosin moč MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- sarkosin MeSH
Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin ("Apodox" and "lip-8-dox") and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC50) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC50 = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC50 was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.
- MeSH
- apoferritiny * MeSH
- doxorubicin aplikace a dávkování chemie toxicita MeSH
- inhibiční koncentrace 50 MeSH
- koně MeSH
- lidé MeSH
- liposomy * MeSH
- nádorové buněčné linie MeSH
- nosiče léků MeSH
- příprava léků MeSH
- protinádorová antibiotika aplikace a dávkování chemie toxicita MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- apoferritiny * MeSH
- doxorubicin MeSH
- liposomy * MeSH
- nosiče léků MeSH
- protinádorová antibiotika MeSH
BACKGROUND AND OBJECTIVES: Current studies give us inconsistent results regarding the association of neoplasms and zinc(II) serum and tissues concentrations. The results of to-date studies using meta-analysis are summarized in this paper. METHODS: Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL were searched. Articles were reviewed by two evaluators; quality was assessed by Newcastle-Ottawa scale; meta-analysis was performed including meta-regression and publication bias analysis. RESULTS: Analysis was performed on 114 case control, cohort and cross-sectional studies of 22737 participants. Decreased serum zinc level was found in patients with lung (effect size = -1.04), head and neck (effect size = -1.43), breast (effect size = -0.93), liver (effect size = -2.29), stomach (effect size = -1.59), and prostate (effect size = -1.36) cancers; elevation was not proven in any tumor. More specific zinc patterns are evident at tissue level, showing increase in breast cancer tissue (effect size = 1.80) and decrease in prostatic (effect size = -3.90), liver (effect size = -8.26), lung (effect size = -3.12), and thyroid cancer (effect size = -2.84). The rest of the included tumors brought ambiguous results, both in serum and tissue zinc levels across the studies. The association between zinc level and stage or grade of tumor has not been revealed by meta-regression. CONCLUSION: This study provides evidence on cancer-specific tissue zinc level alteration. Although serum zinc decrease was associated with most tumors mentioned herein, further--prospective--studies are needed.
- MeSH
- epitel patologie MeSH
- lidé MeSH
- nádory krev patologie MeSH
- statistické modely MeSH
- zinek krev MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Názvy látek
- zinek MeSH
Differences in the antioxidant system, apoptotic mechanism and in cell cycle between prostatic cell lines could partially elucidate the development of cisplatin resistance. The aim of this study was to identify the most characteristic parameter for a particular cell line and/or a particular cisplatin treatment using a general regression model and to assess whether it is possible to use measured parameters as markers of cisplatin resistance. This study integrates the results of viability, antioxidant, flow cytometric and quantitative PCR assays in order to characterize the resistance of prostate cancer to cisplatin. Cell growth using metabolic- (MTT) and impedance-based assays, the expression of key cell death signaling proteins (p53, Bax and Bcl-2), cell cycle, activity of antioxidant system-related proteins (superoxide dismutase, glutathione peroxidase, glutathione reductase and metallothionein) and free radical scavenging capacity assays [free radicals (FR), ferric reducing antioxidant power (FRAP), ABTS] were analyzed in the cell lines 22Rv1, PC-3 and PNT1A with respect to rising concentrations (0-150 µM) and different length of cisplatin treatment (12-72 h). The non-functional-p53 PC-3 cell line showed decreased BAX (p<0.05) and, in contrast to PNT1A and 22Rv1, no cisplatin-induced effects on cell cycle. All cell lines showed increasing levels of free radical scavenging activity by ABTS, FRAP and FR assays in a time- and dose-dependent manner (r>0.76 at p<0.001 for ABTS, FRAP and FR at p<0.001). PC-3 showed increased (p<0.05) levels of free radical scavenging activity by ABTS and FR methods. These findings, together with significantly elevated MT, decreased p53 and Bax indicate PC-3 to be cisplatin-resistant. The differences in the antioxidant system and apoptotic mechanisms in PC-3 cells may elucidate the development of cisplatin resistance and indicate that this cell line may be further studied as a model of cytostatic resistance.
- MeSH
- antioxidancia metabolismus MeSH
- apoptóza účinky léků MeSH
- buněčný cyklus účinky léků genetika MeSH
- chemorezistence genetika MeSH
- cisplatina terapeutické užití MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory prostaty farmakoterapie genetika patologie MeSH
- proliferace buněk účinky léků MeSH
- signální transdukce genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- cisplatina MeSH
- nádorový supresorový protein p53 MeSH
Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03) and ovarian tumors (OR 7.83; 1.09-56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.
- MeSH
- databáze bibliografické MeSH
- imunohistochemie MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- metastázy nádorů MeSH
- nádorové biomarkery metabolismus MeSH
- nádory hlavy a krku diagnóza metabolismus patologie MeSH
- nádory jater diagnóza metabolismus patologie MeSH
- nádory vaječníků diagnóza metabolismus patologie MeSH
- odds ratio MeSH
- prognóza MeSH
- studie případů a kontrol MeSH
- stupeň nádoru MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Názvy látek
- metalothionein MeSH
- nádorové biomarkery MeSH
Guinea pigs (Cavia porcellus) were treated with haloperidol (HP), and free radical (FR) and ferric reducing antioxidant power (FRAP) assays were used to determine oxidative stress levels. Furthermore, the superoxide dismutase (SOD), glutathione reductase (GR) and glutathione-S-transferase (GST) activity levels were detected and glucose levels and the reduced and oxidized glutathione (GSH/GSSG) ratio were measured in HP-treated and untreated guinea pigs. The present study demonstrated that the administration of HP causes significant oxidative stress in guinea pigs (P=0.022). In animals treated with HP, the activity of GST was significantly increased compared with a placebo (P= 0.007). The elevation of SOD and GR activity levels and increase in the levels of glutathione (GSH) in HP-treated animals were not statistically significant. In the HP-untreated animals, a significant positive correlation was observed between oxidative stress detected by the FR method and GST (r=0.88, P=0.008) and SOD (r=0.86, P= 0.01) activity levels, respectively. A significant negative correlation between the levels of plasma glucose and oxidative stress detected by the FRAP method was observed (r=-0.78, P=0.04). Notably, no significant correlations were observed in the treated animals. In the HP-treated group, two subgroups of animals were identified according to their responses to oxidative stress. The group with higher levels of plasma HP had higher enzyme activity and reactive oxygen species production compared with the group with lower plasma levels of HP. The greatest difference in activity (U/μl) between the two groups of animals was for GR.
- Klíčová slova
- glutathione reductase, glutathione-S-transferase, guinea pig, haloperidol, oxidative stress, superoxide dismutase,
- Publikační typ
- časopisecké články MeSH
Current diagnostic techniques of prostate cancer cannot efficiently distinguish the latent and low-risk forms from the high-risk significant forms of prostate cancer. Caveolin-1 (Cav-1), except other functions, plays an important role in cell transformation and the process of tumorigenesis. Furthermore, Cav-1 is involved in metastatic processes. It has also been shown that Cav-1 expression is induced under stress conditions, such as oxidative stress. The present study focused on the determination of prognostic markers of aggressive (high-grade) forms of prostate cancer. We determined serum Cav-1 and serum markers of antioxidant activity-glutathione (GSH), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC), ferric-reducing antioxidant power (FRAP), N,N-dimethyl-1,4-diaminobenzene (DMPD), free radicals method (FRK) and blue chromium peroxide (Cro) in 97 serum samples (82 prostate cancer patients and 15 controls). We found insignificant differences in Cav-1 between the sera of patients and controls (5.69 in the cancer group vs. 5.42 ng/ml in the control group). However, we found a significant (p<0.004) 2.8-fold elevation of Cav-1 in high tumour stages (TNM T4) compared to lower stages and a significant positive association with histological grading (r=0.29, p=0.028). We also found that in patients with high serum Cav-1 the antioxidant capacity of the body is reduced. These findings indicate that Cav-1 may be an interesting tool for the prediction of disease burden.
- MeSH
- antioxidancia metabolismus MeSH
- bifenylové sloučeniny krev MeSH
- chromany (dihydrobenzopyrany) krev metabolismus MeSH
- glutathion krev MeSH
- kaveolin 1 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty krev MeSH
- oxidační stres MeSH
- peroxidy krev MeSH
- pikráty krev MeSH
- senioři MeSH
- sloučeniny chromu krev MeSH
- volné radikály krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,1-diphenyl-2-picrylhydrazyl MeSH Prohlížeč
- 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid MeSH Prohlížeč
- antioxidancia MeSH
- bifenylové sloučeniny MeSH
- chromany (dihydrobenzopyrany) MeSH
- chromium peroxide MeSH Prohlížeč
- glutathion MeSH
- kaveolin 1 MeSH
- nádorové biomarkery MeSH
- peroxidy MeSH
- pikráty MeSH
- sloučeniny chromu MeSH
- volné radikály MeSH