Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.
- Klíčová slova
- Cancer cells, Carcinogenesis, Flavonoids, Metabolic reprogramming, Metabolism,
- MeSH
- aminokyseliny * MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- flavonoidy farmakologie MeSH
- ketolátky metabolismus MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- nádorová transformace buněk metabolismus MeSH
- nádory * farmakoterapie metabolismus MeSH
- oxidace-redukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- aminokyseliny * MeSH
- faktor 2 související s NF-E2 MeSH
- flavonoidy MeSH
- ketolátky MeSH
BACKGROUND: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. To date, the role of the combined application of long non-coding RNAs (PCA3, DLX1, HOXC6, TMPRSS2:ERG) for obtaining the most accurate method of detection of PCa has not yet been comprehensively investigated. METHODS: In total 240 persons were included in the retrospective study. Among them were 150 patients with confirmed PCa, 30 patients with benign prostatic hyperplasia, 30 patients with active chronic prostatitis and 30 healthy volunteers. In all patients, the urine samples were collected prior to biopsy or treatment. Polymerase chain reaction with reverse transcription was performed to detect the expression level of PCA3, HOXC6, DLX1 and the presence of the TMPRSS2:ERG transcript. RESULTS: PCA3 was detected in urine samples in all cases. Using a PCA3 score of 56 allowed the differentiation between PCa and all other cases with a sensitivity of 61% and specificity of 96% (p < 0.001) while a PCA3 score threshold value of 50 resulted in a differentiation between clinically significant PCa (ISUP grades 2-5) and all other cases with a sensitivity of 93% and specificity of 93% (p < 0.001). The TMPRSS2:ERG expression in urine was detected exclusively in the group of patients with PCa and only in 16% of all cases. CONCLUSIONS: PCA3 score detected in urine demonstrated moderate sensitivity and good specificity in differentiation between PCa and non-PCa and high sensitivity and specificity in differentiation between clinically significant PCa and non-PCa.
- Klíčová slova
- DLX1, Diagnostics, HOXC6, PCA3, Prostate cancer, RNA, TMPRSS2:ERG, Urinary marker,
- MeSH
- antigeny nádorové * genetika MeSH
- fúzní onkogenní proteiny genetika moč MeSH
- homeodoménové proteiny genetika MeSH
- lidé MeSH
- nádorové biomarkery moč MeSH
- nádory prostaty * diagnóza genetika MeSH
- prostata patologie MeSH
- prostatický specifický antigen MeSH
- retrospektivní studie MeSH
- serinové endopeptidasy genetika MeSH
- transkripční regulátor ERG MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny nádorové * MeSH
- ERG protein, human MeSH Prohlížeč
- fúzní onkogenní proteiny MeSH
- homeodoménové proteiny MeSH
- HOXC6 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- prostatický specifický antigen MeSH
- serinové endopeptidasy MeSH
- TMPRSS2 protein, human MeSH Prohlížeč
- transkripční regulátor ERG MeSH
BACKGROUND: Atherosclerosis and coronary artery disease (CAD) are a common condition and cause of death in the elderly population. There are difficulties with risk assessment in the elderly as the objectification of their symptomatic status can be challenging due to neuromuscular weakness, physical deconditioning or neurological, orthopaedic, peripheral vascular, or respiratory limitations. Non-invasive coronary artery velocity assessment by Doppler method at rest could be helpful in the elderly population. To evaluate the prognostic role of coronary artery ultrasound assessment in a non-selected elderly population in everyday clinical practice. METHODS: One hundred forty-five patients, aged ≥75years (99 women; 80 ± 4 years), formed the study group. Left coronary artery flows were scanned in addition to conventional echocardiography. During a median follow-up of 26 months, 16 deaths and 2 non-fatal MI occurred. RESULTS: In multivariable analysis, maximal coronary velocity was the only independent predictor for mortality (heart rate [HR]: 1.02, 95%, CI: 1.01-1.04, p < .0005) and for mortality/MI (HR: 1.02, 95%, CI: 1.01-1.03, p < .0001). The value of 110 cm/s maximal coronary flow velocity (CFL) in the proximal segments of left arteries was the best predictor for death, sensitivity 50%, specificity 90%, p < .005. The annual mortality rate was 16.6% persons/year for patients with elevated CFL ≥110 cm/s. The value 81 cm/s was the best predictor for death/MI, sensitivity 61%, specificity 80%, p < .0005; annual mortality rate was 11.2% persons/year for patients with elevated CFL ≥81 cm/s (p < .0001). CONCLUSION: Doppler CFL scanning during routine echocardiography is a feasible and valuable tool for assessment of short-term prognosis in elderly patients.
- Klíčová slova
- Echocardiography, coronary flow: coronary Doppler, elderly, outcome,
- MeSH
- dopplerovská echokardiografie * metody MeSH
- echokardiografie MeSH
- koronární cirkulace fyziologie MeSH
- lidé MeSH
- nemoci koronárních tepen * MeSH
- prognóza MeSH
- rychlost toku krve fyziologie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: There is a lack of information about the prognostic value of high velocity in coronary arteries during echocardiography. The present study was aimed at investigating the three-year prognostic value of coronary velocity assessment in all patients who were referred for echocardiography examination. METHODS: The prospective study comprises 747 consecutive patients. Death, myocardial infarction (MI), acute coronary syndrome (ACS), and/or revascularisation were defined as major adverse cardiac events (MACE). Routine echocardiography was added with coronary velocity assessment in the left main, anterior descending, or circumflex coronary arteries by the Doppler method. RESULTS: During a median follow-up of 36 months, 192 patients experienced MACE. Deaths occurred more frequently in patients with high local velocity in proximal left-sided segments vs. in middle left-sided segments vs. patients without high coronary velocity (9 vs. 3 vs. 1%, p < 0.0001). Death/MI/ACS occurred in 17 vs. 7 vs. 1%, p < 0.0001, respectively. Age (HR 1.04, 95% CI 1.00; 1.06; p < 0.04), a velocity more than 65 cm/s in any proximal segments of the arteries (HR 4.7, 95% CI 1.9; 11.9; p < 0.002), ejection fraction (HR 0.97, 95% CI 0.94; 0.99; p < 0.007) were strong independent prognostic predictors of death/MI/ACS. The maximal velocity of coronary flow velocity had a significant additive prognostic value to ejection fraction. CONCLUSIONS: The coronary velocity parameters give long-term prognostic information that can be used to identify persons with a high risk of MACE in consecutive non-selected patients.
- Klíčová slova
- Coronary artery flow velocity, cardiovascular prognosis, coronary Doppler, coronary stenoses, transthoracic echocardiography,
- MeSH
- echokardiografie * MeSH
- infarkt myokardu * MeSH
- koronární cévy diagnostické zobrazování MeSH
- koronární cirkulace MeSH
- lidé MeSH
- prognóza MeSH
- prospektivní studie MeSH
- rychlost toku krve MeSH
- tepový objem MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A lot of people with coronary artery disease do not have specific symptoms, and myocardial infarction or death are the first manifestation of the disease. New accurate, non-invasive and safe screening methods are required that can assess the prognosis of patients during routine examinations performed on millions of people. The aim of this review was to discuss the current literature regarding the utility of non-invasive ultrasound imaging of the coronary artery in assessing a patient's prognosis in daily practice. Assessment of coronary artery flow during common stress echocardiography or echocardiography can provide additive incremental prognostic information without the burden of radiation. Exercise or pharmacologic stress echocardiography tests combined with coronary flow velocity reserve assessment has advantages over stress tests based only on regional wall motion abnormalities. Scanning of main coronary arteries as an addition to routine echocardiography can reveal patients at high risk of adverse cardiac events in the near future.
- Klíčová slova
- CFR, Coronary artery disease, coronary Doppler, coronary artery velocity, coronary flow velocity reserve, prognosis, transthoracic echo,
- MeSH
- echokardiografie MeSH
- koronární cévy * diagnostické zobrazování MeSH
- koronární cirkulace MeSH
- lidé MeSH
- nemoci koronárních tepen * diagnostické zobrazování MeSH
- prognóza MeSH
- rychlost toku krve MeSH
- zátěžová echokardiografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.
- Klíčová slova
- B-type natriuretic peptide, clinical effectiveness, heart failure, pharmacotherapy,
- MeSH
- akutní nemoc MeSH
- lidé MeSH
- natriuretický peptid typu B * terapeutické užití krev MeSH
- srdeční selhání * farmakoterapie patofyziologie krev MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- natriuretický peptid typu B * MeSH
Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration-7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05-11.61), 7.40 ± 2.50 months (95% CI = 5.61-9.19) and 4.20 ± 1.99 months (95% CI = 2.78-5.62) accordingly (p < 0.05). There was no difference in change of main lesions' longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35-25.87) and by 7.66 ± 6.72% (95% CI = 2.86-12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.
- Klíčová slova
- Apparent diffusion coefficient, Diffusion-weighted imaging, Early response, Imaging biomarker, MRI, Prediction, Progress, Renal cell carcinoma, Systemic treatment, Targeted therapy, Tyrosine kinase inhibitor,
- MeSH
- difuzní magnetická rezonance metody MeSH
- indazoly MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- karcinom z renálních buněk diagnostické zobrazování farmakoterapie mortalita patologie MeSH
- ledviny diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin diagnostické zobrazování farmakoterapie mortalita patologie MeSH
- pyrimidiny terapeutické užití MeSH
- retrospektivní studie MeSH
- ROC křivka MeSH
- senioři MeSH
- sulfonamidy terapeutické užití MeSH
- výsledek terapie MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- Názvy látek
- indazoly MeSH
- inhibitory angiogeneze MeSH
- pazopanib MeSH Prohlížeč
- pyrimidiny MeSH
- sulfonamidy MeSH
BACKGROUND: Exercise capacity is well known to be an important prognostic factor in patients with cardiovascular disease and among healthy persons. AIM: To determine if there are any differences between the peak exercise response during exercise treadmill testing with the individualized ramp protocol and the modified Bruce protocol in elderly patients. MATERIALS AND METHODS: The study included 40 patients (both male and female), aged 70 years and older, who had not had a baseline history of the confirmed coronary artery disease or heart failure diagnoses. All patients underwent exercise treadmill testing using modified Bruce protocol and individualized ramp protocol for 2 consecutive days. Peak heart rate, peak systolic and diastolic blood pressure, peak pressure-rate double product, exercise duration, and peak metabolic equivalents were recorded in both tests. Perceived level of exertion was evaluated using the Borg 10-point scale. RESULTS: The average duration of exercise was longer for the ramp protocol than for the modified Bruce protocol. When the modified Bruce protocol was used, patients achieved a lower workload than they did in using the ramp protocol. The rating of perceived exertion using the revised Borg scale (0 to 10) was 5.6±1.4 for the ramp protocol and 8.7±1.4 for the modified Bruce protocol, which indicates that the patients found the ramp protocol easier. CONCLUSION: In elderly patients the individualized ramp treadmill protocol allows to achieve the optimal test duration with higher degrees of workload and greater patient comfort during the test more often than does the modified Bruce protocol.
- Klíčová slova
- elderly adults, exercise capacity, exercise treadmill testing, individualized ramp protocol, modified Bruce protocol,
- MeSH
- krevní tlak * MeSH
- lidé MeSH
- metabolický ekvivalent MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spotřeba kyslíku * MeSH
- srdeční frekvence * MeSH
- tělesná námaha MeSH
- tolerance zátěže * MeSH
- zátěžový test metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan-Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E - 03 ± 3.11E - 03 RU (p < 0.001). Overexpression of miR-15a was strongly associated with poor histologic prognostic features of ccRCC. Poorly differentiated tumors tend to have more pronounced upregulation of miR-15a compared to highly differentiated lesions: Mean expression values were 4.57 ± 3.19 RU for Fuhrman grade 4 versus 0.02 ± 0.01 RU for Fuhrman grade 1 (p < 0.001). The metastatic involvement of the regional lymphatic nodules (N +) was associated with significantly upregulated miRNA-15a in comparison with N - cases: Mean expression values were 4.92 ± 2.80 RU versus 1.10 ± 2.29 RU, respectively (p < 0.001). In patients with miR-15a expression in RCC tissues ≤ 0.10 RU, mean 5-year CSS was significantly longer compared to patients with expression levels above this threshold: 92.31% (mean duration of survival-59.88 ± 0.12 months) versus 54.8% (mean duration of survival-49.74 ± 2.16 months), respectively (p < 0.001). The tissue expression of miR-15a could be used as a potential prognostic molecular biomarker for conventional RCC.
- Klíčová slova
- Biomarker, Cancer, Clear cell, Genetic, MicroRNA-15a, Prediction, Prognosis, Renal cell carcinoma, Survival, miRNA-15a,
- MeSH
- analýza přežití MeSH
- karcinom z renálních buněk genetika mortalita chirurgie MeSH
- ledviny chemie MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mikro RNA genetika MeSH
- nádorové biomarkery genetika MeSH
- nádory ledvin genetika mortalita chirurgie MeSH
- nefrektomie MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- retrospektivní studie MeSH
- upregulace * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA MeSH
- MIRN15 microRNA, human MeSH Prohlížeč
- nádorové biomarkery MeSH
Atherosclerosis is a major contributor to morbidity and mortality worldwide. With therapeutic consequences in mind, several risk scores are being used to differentiate individuals with low, intermediate or high cardiovascular (CV) event risk. The most appropriate management of intermediate risk individuals is still not known, therefore, novel biomarkers are being sought to help re-stratify them as low or high risk. This narrative review is presented in two parts. Here, in Part 1, we summarise current knowledge on serum (serological) biomarkers of atherosclerosis. Among novel biomarkers, high sensitivity C-reactive protein (hsCRP) has emerged as the most promising in chronic situations, others need further clinical studies. However, it seems that a combination of serum biomarkers offers more to risk stratification than either biomarker alone. In Part 2, we address genetic and imaging markers of atherosclerosis, as well as other developments relevant to risk prediction.
- Klíčová slova
- Atherosclerosis, Biomarkers, High sensitivity C-reactive protein,
- MeSH
- ateroskleróza krev MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- lidé MeSH
- rizikové faktory MeSH
- zánět krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
