Používání cytotoxických léčiv (CL) v chemoterapii nádorových onemocnění je spojeno s potenciálním ohrožením zdraví zdravotnického personálu v důsledku profesní expozice těmto nebezpečným léčivům. Hlavním cílem této práce bylo popsat distribuci vybraného zástupce CL (cyklofosfamidu, CP) mezi jednotlivými složkami pracovního prostředí s vazbou na posouzení významnosti příjmu CL inhalací a dermální cestou. Distribuce CP v pracovním prostředí byla studována kombinací metod pro stanovení CP v ovzduší a na povrchu vybavení pracoviště. Stanovení vzdušné kontaminace bylo založeno na sledování CP ve vzorcích odebraných pomocí aktivního čerpání vzduchu přes PTFE filtr, pevný sorbent (Anasorb 708 a Strata-X) a promývačku vzduchu naplněnou destilovanou vodou. Povrchová kontaminace pracoviště byla sledována v místech intenzivní manipulace s CL využitím stěrů pracovního prostředí. Četnost nálezů CP v ovzduší byla nízká a pozorované koncentrace byly hluboko pod hodnotou rovnovážné koncentrace odvozené z tlaku par (0,36 mg/m3 při 20 °C). Měřitelné koncentrace plynného CP (? 0,1 ng/m3) byly zjištěny pouze na chemoterapeutickém stacionáři (max. 4,3 ng/m3). Četnost nálezů CP ve stěrech pracovního prostředí byla vyšší. Měřitelné koncentrace CP (? 20 ng/m2) byly zjištěny u 75 % vzorků (medián 750 ng/m2). Z provedených měření vyplývá, že při dodržení předepsaných podmínek pro zacházení s CL (používání podtlakových izolátorů pro přípravu CL, centralizace přípravy CL v nemocniční lékárně) má inhalační příjem v oblasti profesní expozice CL relativně malý význam. Naprostá většina zjištěné kontaminace byla zjištěna na povrchu vybavení pracoviště. Velká pozornost by proto měla být věnována především eliminaci zdrojů povrchové kontaminace a ochraně pracovníků před dermální expozicí.

Manipulation with cytotoxic drugs (CDs) during the preparation and administration of chemotherapy to cancer patients can potentially lead to contamination of working areas and consequently to occupational exposure of hospital staff. This study aimed to assess the potential of inhalation and dermal contact with CDs. For this purpose, distribution of the marker drug (cyclophosphamide, CP) in the working environment of the Masaryk Memorial Cancer Institute (Czech Republic) was studied. The study determined airborne and surface contamination of the hospital pharmacy and the outpatient clinic. Determination of airborne contamination was based on active stationary sampling of air using a PTFE filter, an impinger filled with distilled water and two solid sorbent tubes (Anasorb 708 and Strata-X) as sampling devices. Surface contamination was determined by the wipe sampling method. The airborne contamination was rare and the concentrations were many times lower than the maximal value calculated from the vapour pressure (0.36 mg/m3 at 20 °C). Detectable airborne CP was found in Strata-X samples collected at the outpatient clinic (n = 5, all samples positive at concentrations from 0.3 to 4.3 ng/m3). Surface contamination was determined at 75% of wipe samples (n = 65) with a median concentration of 750 ng/m2. In conclusion, inhalation of CDs seems to be of low importance at our hospital, which is up to the standard specified by current legislation (drug preparation performed in a clean room equipped with negative pressure isolators). The main proportion of contamination was present on the surfaces at all workplaces studied. Consequently, attention should be given to the elimination of the sources of surface contamination and to the prevention of dermal contact with contaminated material.

• Klíčová slova
• kontaminace ovzduší, povrchová kontaminace, profesní expozice, cytotoxická léčiva,
• MeSH
• alkylační protinádorové látky analýza   MeSH
• cyklofosfamid analýza   MeSH
• kontaminace zdravotnického vybavení MeSH
• látky znečišťující vzduch v pracovním prostředí analýza   MeSH
• lidé MeSH
• onkologická péče - zařízení MeSH
• pracovní expozice MeSH
• Check Tag
• lidé MeSH

• MeSH
• cefoperazon škodlivé účinky   terapeutické užití   MeSH
• gramnegativní bakterie účinky léků   MeSH
• hematologické nádory komplikace   terapie   MeSH
• kombinovaná terapie metody   využití   MeSH
• lidé MeSH
• neutropenie etiologie   komplikace   mikrobiologie   MeSH
• retrospektivní studie MeSH
• sulbaktam škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Identification of novel proteins with changed expression in resistant cancer cells could be helpful in elucidation mechanisms involved in the development of acquired resistance to paclitaxel. In this study, we carried out a 2D-PAGE using the mitochondrial-enriched fraction from paclitaxel-resistant MCF7/PacR cells compared to original paclitaxel-sensitive MCF7 breast cancer cells. Differentially expressed proteins were identified employing mass spectrometry. We found that lysosomal cathepsin D and mitochondrial abhydrolase-domain containing protein 11 (ABHD11) had decreased expression in MCF7/PacR cells. On the other hand, mitochondrial carbamoyl-phosphate synthetase 1 (CPS1) and ATPase family AAA-domain containing protein 3A and 3B (ATAD3A, ATAD3B) were overexpressed in MCF7/PacR cells. Further, we showed that there was no difference in localization of CPS1 in MCF7 and MCF7/PacR cells. We demonstrated a significant increase in the number of CPS1 positive MCF7/PacR cells, using FACS analysis, compared to the number of CPS1 positive MCF7 cells. Silencing of CPS1 expression by specific siRNA had no significant effect on the resistance of MCF7/PacR cells to paclitaxel. To summarize, we identified several novel proteins of a mitochondrial fraction whose role in acquired resistance to paclitaxel in breast cancer cells should be further assessed.

• MeSH
• chemorezistence * účinky léků   MeSH
• frakcionace buněk MeSH
• karbamoylfosfátsynthasa (amoniak) genetika   metabolismus   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• mitochondriální proteiny genetika   metabolismus   MeSH
• mitochondrie genetika   metabolismus   MeSH
• nádory prsu farmakoterapie   genetika   metabolismus   MeSH
• paclitaxel farmakologie   MeSH
• proteom MeSH
• proteomika metody   MeSH
• regulace genové exprese u nádorů MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• tandemová hmotnostní spektrometrie MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy. OBJECTIVE: With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women. METHODS: PK data from 9, 20, 22 and 16 pregnant cancer patients from the International Network of Cancer, Infertility and Pregnancy (INCIP) were available for docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. These samples were combined with available PK data from non-pregnant patients. Empirical non-linear mixed-effects models were developed, evaluating fixed pregnancy effects and gestational age as covariates. RESULTS: Overall, 82, 189, 271, and 227 plasma samples were collected from pregnant patients treated with docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. The plasma PK data were adequately described by the respective models for all cytotoxic drugs. Typical increases in central and peripheral volumes of distribution of pregnant women were identified for docetaxel, paclitaxel, doxorubicin and epirubicin. Additionally, docetaxel, doxorubicin and paclitaxel clearance were increased in pregnant patients, resulting in lower exposure in pregnant women compared with non-pregnant patients. CONCLUSION: Given the interpatient variability, the identified pregnancy-induced changes in PK do not directly warrant dose adjustments for the studied drugs. Nevertheless, these results underscore the need to investigate the efficacy of chemotherapy, when administered during pregnancy.

• MeSH
• docetaxel terapeutické užití   MeSH
• doxorubicin terapeutické užití   MeSH
• epirubicin MeSH
• infertilita * MeSH
• lidé MeSH
• nádory prsu * MeSH
• nádory * farmakoterapie   MeSH
• paclitaxel MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• taxoidy MeSH
• těhotenství MeSH
• těhotné ženy MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In recent years, multifunctional nanocarriers that provide simultaneous drug delivery and imaging have attracted enormous attention, especially in cancer treatment. In this research, a biocompatible fluorescent multifunctional nanocarrier is designed for the co-delivery of capsaicin (CPS) and nitrogen-doped graphene quantum dots (N-GQDs) using the pH sensitive amphiphilic block copolymer (poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone), PEtOx-b-PCL). The effects of the critical formulation parameters (the amount of copolymer, the concentration of poly(vinyl alcohol) (PVA) as a stabilizing agent in the inner aqueous phase, and volume of the inner phase) are evaluated to achieve optimal nanoparticle (NP) properties using Central Composite Design. The optimized NPs demonstrated a desirable size distribution (167.8 ± 1.4 nm) with a negative surface charge (-19.9 ± 0.4) and a suitable loading capacity for CPS (70.80 ± 0.05%). The CPS & N-GQD NPs are found to have remarkable toxicity on human breast adenocarcinoma cell line (MCF-7). The solid fluorescent signal is acquired from cells containing multifunctional NPs, according to the confocal microscope imaging results, confirming the significant cellular uptake. This research illustrates the enormous potential for cellular imaging and enhanced cancer therapy offered by multifunctional nanocarriers that combine drug substances with the novel fluorescent agents.

• MeSH
• dusík * chemie   MeSH
• fluorescenční barviva chemie   MeSH
• grafit * chemie   MeSH
• kapsaicin * chemie   farmakologie   MeSH
• kvantové tečky * chemie   terapeutické užití   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• teranostická nanomedicína * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

• MeSH
• cystektomie * metody   MeSH
• lidé MeSH
• nádory močového měchýře * farmakoterapie   chirurgie   MeSH
• neoadjuvantní terapie metody   MeSH
• nomogramy MeSH
• retrospektivní studie MeSH
• svaly patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Východiska: U metastatického karcinomu prostaty (metastatic prostate cancer – mPCa) je standardem léčby systémová léčba v podobě androgen deprivační terapie (ADT), příp. v kombinaci s novými preparáty, tzv. androgen receptor targeting agents (ARTA), nebo docetaxelem. Léčba samotné prostaty u mPCa představuje nové paradigma u tzv. oligometastatického karcinomu prostaty (OMPCa), který je považován za jakýsi mezistupeň mezi lokalizovaným onemocněním a rozsáhlým metastatickým onemocněním. Díky novým diagnostickým metodám je OMPCa stále častěji diagnostikovaným stadiem mPCa. Agresivní lokální terapie by mohla pacientům přinést kromě zlepšení lokální kontroly onemocnění zkrácení ADT i zlepšení přežití. Radioterapie již prokázala onkologický benefit u OMPCa v randomizované studii a nyní je součástí guidelines k léčbě tzv. low volume de novo mPCa. Cytoredukční prostatektomie (CP) zatím na výsledky randomizovaných studií čeká, nicméně již existují retrospektivní data podporující tuto léčebnou modalitu. Bylo publikováno několik populačních studií, které prokázaly benefit CP. Menší retrospektivní práce prokázaly bezpečnost provedení CP v klinické praxi. V současné době probíhá několik prospektivních randomizovaných studií zkoumajících tuto léčebnou modalitu. Celý koncept CP u OMPCa je však stále opředen mnoha nevyřešenými otázkami, jako je definování vhodného pacienta a role další formy lokální terapie cílené na metastázy. Cíl: Záměrem tohoto sdělení je podat přehled klíčových publikovaných nebo probíhajících studií týkajících se CP ve vztahu nejen k funkčním a onkologickým výsledkům, ale i indikačním kritériím a designu jednotlivých studií.

Background: In metastatic prostate cancer (mPCa), the standard treatment involves systemic treatment including androgen deprivation therapy (ADT), possibly in combination with new drugs called androgen receptor targeting agents (ARTA) or docetaxel. The treatment of the prostate itself in mPCa represents a new paradigm in the so-called oligometastatic prostate cancer (OMPCa), which is considered to be a kind of intermediate stage between localized disease and extensive metastatic disease. Thanks to new diagnostic methods, OMPCa is an increasingly frequently diagnosed stage of mPCa. In addition to improving local control of the disease, aggressive local therapy could lower the need for ADT, or improve survival. Radiotherapy has already demonstrated the oncological benefit of OMPCa in a randomized study and is now part of the guidelines for the treatment of low volume de novo mPCa. Cytoreductive prostatectomy (CP) is still awaiting the results of randomized trials; however, retrospective data already exist to support this treatment modality. Several population-based studies have been published that have demonstrated the benefit of CP. Minor retrospective works have demonstrated the safety of CP in clinical practice. Several prospective randomized trials investigating this treatment modality are currently underway. However, the whole concept of CP in OMPCa is still shrouded in many unresolved issues such as the definition of a suitable patient and the role of another form of local therapy targeted to metastases. Purpose: This article aims to provide an overview of key published or ongoing studies related to CP in relation not only to functional and oncological results but also to the indication criteria and design of individual studies.

• MeSH
• antagonisté androgenů * farmakologie   terapeutické užití   MeSH
• cytoredukční chirurgie * metody   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory prostaty * chirurgie   patologie   MeSH
• prospektivní studie MeSH
• prostata chirurgie   patologie   MeSH
• prostatektomie metody   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• přehledy MeSH

PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

• MeSH
• cystektomie MeSH
• invazivní růst nádoru MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory močového měchýře farmakoterapie   mortalita   patologie   chirurgie   MeSH
• neoadjuvantní terapie statistika a číselné údaje   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVES: To investigate the relationship of dual-phase dual-energy CT (DE-CT) and tumour size in the evaluation of the response to anti-EGFR therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Dual-phase DE-CT was performed in 31 patients with NSCLC before the onset of anti-EGFR (erlotinib) therapy and as follow-up (mean 8 weeks). Iodine uptake (IU; mg/mL) was quantified using prototype software in arterial and venous phases; arterial enhancement fraction (AEF) was calculated. The change of IU before and after therapy onset was compared with anatomical evaluation in maximal transverse diameter and volume (responders vs. non-responders). RESULTS: A significant decrease of IU in venous phase was proved in responders according to all anatomical parameters (p=0.002-0.016). In groups of non-responders, a significant change of IU was not proved with variable trends of development. The most significant change was observed using the anatomical parameter of volume (cut-off 73 %). A significant difference of percentage change in AEF was proved between responding and non-responders (p=0.019-0.043). CONCLUSION: Dual-phase DE-CT with iodine uptake quantification is a feasible method with potential benefit in advanced assessment of anti-EGFR therapy response. We demonstrated a decrease in vascularization in the responding primary tumours and non-significant variable development of vascularization in non-responding tumours. KEY POINTS: • Dual-phase DE-CT is feasible for vascularization assessment of NSCLC with anti-EGFR therapy. • There was a significant decrease of iodine uptake in responding tumours. • There was a non-significant and variable development in non-responding tumours. • There was significant difference of AEF percentage change between responders and non-responders.

• MeSH
• erlotinib terapeutické užití   MeSH
• jod MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• lymfatické uzliny diagnostické zobrazování   MeSH
• nádory plic farmakoterapie   patologie   MeSH
• nemalobuněčný karcinom plic diagnóza   farmakoterapie   sekundární   MeSH
• počítačová rentgenová tomografie metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• protinádorové látky terapeutické užití   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• staging nádorů * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in ABCC3, CPS1, and TRIP6 gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients' poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• chemorezistence genetika   MeSH
• down regulace účinky léků   genetika   MeSH
• epiteliální ovariální karcinom farmakoterapie   genetika   MeSH
• karbamoylfosfátsynthasa (amoniak) genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myši nahé MeSH
• myši MeSH
• nádorové biomarkery genetika   MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků farmakoterapie   genetika   MeSH
• paclitaxel terapeutické užití   MeSH
• proteiny s doménou LIM genetika   MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům genetika   MeSH
• taxoidy terapeutické užití   MeSH
• transkripční faktory genetika   MeSH
• viabilita buněk účinky léků   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH