Endocrine-disrupting chemicals (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoblastoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.
- Klíčová slova
- High-content imaging, In vitro testing, Lipid droplets, Metabolism-disrupting chemicals, NAFLD, NAMs,
- MeSH
- benzhydrylové sloučeniny toxicita MeSH
- buňky Hep G2 MeSH
- diacylglycerol-O-acyltransferasa genetika metabolismus MeSH
- diethylhexylftalát toxicita MeSH
- endokrinní disruptory * toxicita MeSH
- fenoly toxicita MeSH
- fluorokarbony toxicita MeSH
- kapryláty toxicita MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- viabilita buněk účinky léků MeSH
- ztučnělá játra * chemicky indukované metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- Bisphenol A Compounds MeSH
- bisphenol A MeSH Prohlížeč
- DGAT1 protein, human MeSH Prohlížeč
- diacylglycerol-O-acyltransferasa MeSH
- diethylhexylftalát MeSH
- endokrinní disruptory * MeSH
- fenoly MeSH
- fluorokarbony MeSH
- kapryláty MeSH
- perfluorooctanoic acid MeSH Prohlížeč
Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized and subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, and related derivatives. A total of 55 new compounds were prepared and tested for in vitro cytotoxic activity against eight cancer cell lines and two non-cancerous cell lines. Four compounds with IC50 values of 5 μM or lower were selected for further investigation. These compounds induced apoptosis in CCRF-CEM cells in a concentration-dependent manner, accompanied by mitochondrial depolarization and altered expression of key proteins involved in mitochondrial apoptosis. The compounds also disrupted DNA replication and transcriptional activity. Modulation of key proliferation pathways, including PI3K/Akt and STAT3, further supported the antiproliferative potential of these derivatives. Considering their high cytotoxicity and antiproliferative activity in CCRF-CEM cells, compounds 19, 26, 28, and 30 have been identified as promising candidates for further development.
- Klíčová slova
- Apoptosis, Betulin, Betulinic acid, Cancer, Cell cycle regulation, Diels-Alder reaction, Mitochondria, Phthalates, Triterpenoids, Wittig reaction,
- MeSH
- antitumorózní látky * farmakologie chemie chemická syntéza MeSH
- apoptóza * účinky léků MeSH
- ftalimidy * farmakologie chemie chemická syntéza MeSH
- léky antitumorózní - screeningové testy * MeSH
- lidé MeSH
- mitochondrie * účinky léků metabolismus MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- triterpeny * farmakologie chemie chemická syntéza MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky * MeSH
- ftalimidy * MeSH
- triterpeny * MeSH
Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.
- Klíčová slova
- lenalidomide maintenance, minimal residual disease (MRD), multiparameter flow cytometry, multiple myeloma, overall survival (OS), progression‐free survival (PFS), real‐world,
- MeSH
- autologní transplantace MeSH
- dospělí MeSH
- lenalidomid aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * diagnóza mortalita terapie patologie MeSH
- prognóza MeSH
- průtoková cytometrie * metody MeSH
- retrospektivní studie MeSH
- reziduální nádor * diagnóza MeSH
- senioři MeSH
- staging nádorů MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- lenalidomid MeSH
We performed retrospective analysis of relapsed/refractory multiple myeloma (RRMM) patients previously exposed to daratumumab treated with ixazomib, lenalidomide, dexamethasone (IRd) regimen in real clinical practice. Our aim was to evaluate efficacy of IRd in these patients and select a subset of patients that would benefit from this treatment the most. In total, we analyzed 43 daratumumab-exposed RRMM patients treated in our center. Minimal response or better was achieved by 53.5% of patients from the cohort. Median progression free survival (PFS) was 4.56 months (95% CI: 2.56, 8.03) and median overall survival (OS) was 28.92 months (95% CI: 5.4, NR). Duration of response (DOR) was evaluable in 28 patients and reached a median of 21.3 months (95% CI: 6.85, NR). Next, we evaluated hazard ratios (HR) for OS and PFS. There was improved OS in patients that were not-triple refractory or worse (HR = 0.39, 95%Cl (0.14; 1.10), p = .07) and in patients, that had less than three previous lines of treatment (LOT) (HR = 0.13, 95%Cl (0.03; 0.6) p = .003). Similar to OS, there was improved PFS in patients, that were not triple-refractory or worse (HR = 0.52, 95%Cl (0.25; 1.10), p = .08). We concluded, that the best survival benefit for RRMM patients pretreated with daratumumab to IRd regimen was observed in patients that were not triple-refractory and had less than three previous lines of treatment (LOT). The DOR in these patients was 21.3 months (95% CI: 6.85, NR).
- Klíčová slova
- daratumumab, ixazomib, relapsed/refractory multiple myeloma,
- MeSH
- chemorezistence * MeSH
- dexamethason * aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- glycin * analogy a deriváty aplikace a dávkování terapeutické užití MeSH
- lenalidomid * aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * farmakoterapie mortalita MeSH
- monoklonální protilátky * terapeutické užití aplikace a dávkování MeSH
- opakovaná terapie MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sloučeniny boru * aplikace a dávkování terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- daratumumab MeSH Prohlížeč
- dexamethason * MeSH
- glycin * MeSH
- ixazomib MeSH Prohlížeč
- lenalidomid * MeSH
- monoklonální protilátky * MeSH
- sloučeniny boru * MeSH
A human biomonitoring study was conducted to assess the exposure of Hungarian children aged 8-11 years to ten phthalate esters (PEs) and DINCH between 2017 and 2018. In addition to collecting urine samples from 262 participants, a questionnaire was completed by the parents or legal guardians to identify potential determinants of exposure. The highest geometric mean concentration was observed for MiBP, followed by MBP, cx- MEHP, OH-MEHP and MEP. Three out of the four DINCH metabolites were detected in more than 90% of the samples. The comparison of the urinary concentrations measured in this study with those observed in the DEMOCOPHES study revealed a significant decreasing trend in all PE metabolites investigated in both studies between 2011/2012 and 2017/2018. Different approaches were used to assess the health risks associated with the exposure to PEs and DINCH. Our results highlighted that the hazard index (HI) values were higher than 1 in 17.6% of the children when the human biomonitoring guidance values were applied. In contrast, less than 3% of the children had HI values exceeding 1 when other sources of reference values were used. By applying a safety factor of 10 for the risk assessment, 17.6-91.6% of the children were characterized by HI values higher than 0.1, indicating the need for risk reduction measures. Overall, DnBP, DiBP and DEHP were identified as the main drivers of the mixture risk. Although PEs and DINCH are ubiquitous contaminants, there are still inconsistencies and gaps in our understanding of the determinants of exposure. The results of the multivariate regression analysis showed significant associations between PE or DINCH metabolite concentrations and certain individual characteristics, use of personal care products, home and school environment and food and beverages consumption 24 h prior to sample collection.
- Klíčová slova
- Children, DINCH, Environmental health, Human biomonitoring, Phthalates, Risk assessment,
- MeSH
- biologický monitoring * MeSH
- dítě MeSH
- hodnocení rizik MeSH
- kyseliny ftalové * moč MeSH
- látky znečišťující životní prostředí * moč MeSH
- lidé MeSH
- vystavení vlivu životního prostředí * analýza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Maďarsko MeSH
- Názvy látek
- kyseliny ftalové * MeSH
- látky znečišťující životní prostředí * MeSH
- phthalic acid MeSH Prohlížeč
Phthalic acid isomers are the monomers of phthalate molecules, also known as phthalic acid esters, widely employed in the plastics industry. This study aims to investigate the biodegradation of phthalic acid (PA) and terephthalic acid (TPA) by five industry-borne Comamonas testosteroni strains: 3APTOL, 3ABBK, 2B, 3A1, and C8. To assess the ability of C. testosteroni strains to biodegrade phthalic acid isomers in fermentation media, an analytical method was employed, consisting of high-performance liquid chromatography (HPLC) analyses. Subsequently, molecular screening of the genomic and plasmid DNA was conducted to identify the degradative genes responsible for the breakdown of these chemicals. The genes of interest, including ophA2, tphA2, tphA3, pmdA, and pmdB, were screened by real-time PCR. The five C. testosteroni strains effectively degraded 100% of 100 mg/L PA (p = 0.033) and TPA (p = 0.0114). Molecular analyses indicated that all C. testosteroni strains contained the pertinent genes at different levels within their genomes and plasmids, as reflected in the threshold cycle (Ct) values. Additionally, DNA temperature of melting (Tm) analyses uncovered minor differences between groups of genes in genomic and plasmid DNA. C. testosteroni strains could be excellent candidates for the removal of phthalic acid isomers from environmental systems.
- Klíčová slova
- Comamonas testosteroni, Biodegradation, Gene detection, Phthalic acid isomers, Real-time PCR,
- MeSH
- biodegradace MeSH
- Comamonas testosteroni * genetika metabolismus MeSH
- fermentace MeSH
- kyseliny ftalové * metabolismus MeSH
- plazmidy genetika MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyseliny ftalové * MeSH
- phthalic acid MeSH Prohlížeč
- terephthalic acid MeSH Prohlížeč
The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab-pomalidomide-dexamethasone vs. pomalidomide-dexamethasone) and IKEMA (isatuximab-carfilzomib-dexamethasone vs. carfilzomib-dexamethasone) studies provide large datasets for retrospectively validating the prognostic value of the R2-ISS in relapsed/refractory multiple myeloma. Of 609 pooled patients, 68 (11.2%) were reclassified as R2-ISS stage I, 136 (22.3%) as R2-ISS stage II, 204 (33.5%) as R2-ISS stage III, 55 (9.0%) as stage IV, and 146 (24.0%) "Not classified". Median progression-free survival was shorter among those reclassified as R2-ISS stage II (HR 1.52, 95% CI 0.979-2.358), stage III (HR 2.59, 95% CI 1.709-3.923), and stage IV (HR 3.51, 95% CI 2.124-5.784) versus stage I. Adding isatuximab led to longer progression-free survival versus doublet therapy (adjusted HR 0.544 [95% CI 0.436-0.680]), with a consistent treatment effect observed across all R2-ISS stages. This is the first study to validate the R2-ISS with novel agents, including anti-CD38 monoclonal antibodies, and to show that R2-ISS, as a prognostic scoring system, can be applied to patients with relapsed/refractory multiple myeloma.
- MeSH
- dexamethason terapeutické užití aplikace a dávkování MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * patologie farmakoterapie mortalita diagnóza MeSH
- oligopeptidy terapeutické užití MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři MeSH
- staging nádorů * MeSH
- thalidomid analogy a deriváty terapeutické užití aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
- validační studie MeSH
- Názvy látek
- carfilzomib MeSH Prohlížeč
- dexamethason MeSH
- humanizované monoklonální protilátky * MeSH
- isatuximab MeSH Prohlížeč
- oligopeptidy MeSH
- pomalidomide MeSH Prohlížeč
- thalidomid MeSH
Diethyl phthalate (DEP) has been widely used as a plasticiser in various consumer products, including cosmetics, personal care items, and pharmaceuticals, and recent studies reported a higher abundance of this priority phthalate in the aquatic environment. DEP is a potential endocrine disruptor, affecting immune systems in humans and wildlife even at low-level chronic exposure. As concern over phthalates increases globally, regulatory bodies focus more on their environmental impact. However, limited research is available, particularly using model organisms like planarians. Planarians are ideal for toxicological studies and may provide insightful information on pollutants' neurotoxic, developmental, and ecological effects, especially in freshwater environments where planarians play a vital role in ecosystem balance. Therefore, the objective of the current study was to examine the toxicity of DEP using the freshwater Dugesia sp., as an experimental animal. The LC50 for the test organism was calculated using DEP concentrations of 800, 400, 200, 100, and 50 µM, with an estimated LC50 of 357.24 µM. Furthermore, planarians were exposed to sub-lethal DEP concentration (178.62 µM) for one day as well as eight days to evaluate the impact of DEP on planarian locomotion, feeding behaviour, and regeneration ability. At sub-lethal concentration, locomotion and feeding ability were decreased, and regeneration was delayed. Furthermore, neuro-transmittance in planaria was altered by sub-lethal DEP concentration, as indicated by a reduced acetylcholinesterase (AChE) activity. DEP exposure induced oxidative damage in the tested planarians as shown by a marked increase in stress biomarkers, including lipid peroxidation levels and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), and glutathione S-transferase (GST). Our study revealed that DEP exposure may prove fatal to freshwater organisms, such as planarians. The observed alterations in behaviour and regeneration ability demonstrate the severity of the effects exerted by DEP as a toxicant in aquatic ecosystems, thereby indicating the need to restrict its usage to protect aquatic environments.
- Klíčová slova
- Acetylcholinesterase, Environmental contamination, Phthalate, Plasticiser, Stress biomarkers,
- MeSH
- antioxidancia * metabolismus MeSH
- chemické látky znečišťující vodu * toxicita MeSH
- chování zvířat účinky léků MeSH
- kyseliny ftalové * toxicita MeSH
- lokomoce účinky léků MeSH
- oxidační stres účinky léků MeSH
- ploštěnky * účinky léků fyziologie MeSH
- regenerace * účinky léků MeSH
- sladká voda MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia * MeSH
- chemické látky znečišťující vodu * MeSH
- diethyl phthalate MeSH Prohlížeč
- kyseliny ftalové * MeSH
BACKGROUND: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear. METHODS: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)-negative status in patients with a complete response. RESULTS: A total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; P<0.001). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P = 0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P = 0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups. CONCLUSIONS: Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. (Funded by Sanofi and a Cancer Center Support Grant; IMROZ ClinicalTrials.gov number, NCT03319667.).
- MeSH
- bortezomib * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dexamethason * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- humanizované monoklonální protilátky terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- Kaplanův-Meierův odhad MeSH
- lenalidomid * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * farmakoterapie mortalita MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- reziduální nádor MeSH
- senioři nad 80 let MeSH
- senioři 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
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- bortezomib * MeSH
- dexamethason * MeSH
- humanizované monoklonální protilátky MeSH
- isatuximab MeSH Prohlížeč
- lenalidomid * MeSH
Twice-weekly carfilzomib (27 mg/m2) plus lenalidomide and dexamethasone (KRd27) is a standard of care in relapsed/refractory multiple myeloma (RRMM). Once-weekly carfilzomib regimens have shown clinical benefits with improved patient convenience. This open-label, phase 3, multicenter, randomized study aimed to demonstrate noninferiority of the overall response rate (ORR) for once-weekly carfilzomib (56 mg/m2) plus Rd (KRd56) vs twice-weekly KRd27 in RRMM. A total of 454 patients were randomized (1:1) to receive carfilzomib as once-weekly 30-minute infusions of 56 mg/m2 (KRd56; n = 228) or twice-weekly 10-minute infusions of 27 mg/m2 (KRd27; n = 226). Baseline characteristics were balanced between groups. ORR was 82.5% (95% confidence interval [CI], 76.9-87.2) in the once-weekly group vs 86.3% (95% CI, 81.1-90.5) in the twice-weekly group (risk ratio, 0.954 [95% CI, 0.882-1.032]) and did not meet the threshold for statistical significance of noninferiority (P = .0666). Complete response (CR) or better was obtained in 46.9% of patients in the once-weekly arm and 36.3% in the twice-weekly arm. The proportions of patients who achieved CR and were also assessed negative for minimal residual disease were 21.5% and 18.1%, respectively (odds ratio, 1.235 [95% CI, 0.775-1.970]). Progression-free survival was comparable between groups (hazard ratio, 0.945 [95% CI, 0.617-1.447]). The safety profile was similar for both groups. In conclusion, although statistical significance for noninferiority of ORR was not achieved, the efficacy and safety of once-weekly KRd56 were similar to those of twice-weekly KRd27, and once-weekly KRd56 may be an effective and convenient treatment option for patients with RRMM. This trial was registered at www.ClinicalTrials.gov as #NCT03859427.
- MeSH
- dexamethason * aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- lenalidomid * aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * farmakoterapie mortalita MeSH
- oligopeptidy * aplikace a dávkování terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- recidiva MeSH
- rozvrh dávkování léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- carfilzomib MeSH Prohlížeč
- dexamethason * MeSH
- lenalidomid * MeSH
- oligopeptidy * MeSH