Disruption of the thyroid hormone (TH) system is connected with diverse adverse health outcomes in wildlife and humans. It is crucial to develop and validate suitable in vitro assays capable of measuring the disruption of the thyroid hormone (TH) system. These assays are also essential to comply with the 3R principles, aiming to replace the ex vivo tests often utilised in the chemical assessment. We compared the two commonly used assays applicable for high throughput screening [Luminol and Amplex UltraRed (AUR)] for the assessment of inhibition of thyroid peroxidase (TPO, a crucial enzyme in TH synthesis) using several cell lines and 21 compounds from different use categories. As the investigated cell lines derived from human and rat thyroid showed low or undetectable TPO expression, we developed a series of novel cell lines overexpressing human TPO protein. The HEK-TPOA7 model was prioritised for further research based on the high and stable TPO gene and protein expression. Notably, the Luminol assay detected significant peroxidase activity and signal inhibition even in Nthy-ori 3-1 and HEK293T cell lines without TPO expression, revealing its lack of specificity. Conversely, the AUR assay was specific to TPO activity. Nevertheless, despite the different specificity, both assays identified similar peroxidation inhibitors. Over half of the tested chemicals with diverse structures and from different use groups caused TPO inhibition, including some widespread environmental contaminants suggesting a potential impact of environmental chemicals on TH synthesis. Furthermore, in silico SeqAPASS analysis confirmed the high similarity of human TPO across mammals and other vertebrate classes, suggesting the applicability of HEK-TPOA7 model findings to other vertebrates.

• Klíčová slova
• Amplex UltraRed, Cross-species, In vitro, Luminol, Peroxidation, Thyroid,
• MeSH
• autoantigeny metabolismus   MeSH
• buněčné linie MeSH
• endokrinní disruptory toxicita   MeSH
• HEK293 buňky MeSH
• jodidperoxidasa * antagonisté a inhibitory   metabolismus   genetika   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• luminol MeSH
• oxaziny MeSH
• proteiny vázající železo metabolismus   MeSH
• rychlé screeningové testy metody   MeSH
• štítná žláza účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• Amplex Red MeSH Prohlížeč
• autoantigeny MeSH
• endokrinní disruptory MeSH
• jodidperoxidasa * MeSH
• luminol MeSH
• oxaziny MeSH
• proteiny vázající železo MeSH
• TPO protein, human MeSH Prohlížeč

• MeSH
• bcr-abl fúzové proteiny genetika   MeSH
• blastická krize * genetika   farmakoterapie   patologie   MeSH
• chronická myeloidní leukemie * farmakoterapie   genetika   patologie   MeSH
• imidazoly * terapeutické užití   aplikace a dávkování   MeSH
• inhibitory proteinkinas terapeutické užití   farmakologie   MeSH
• lidé MeSH
• mutace * MeSH
• myši MeSH
• niacinamid analogy a deriváty   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• pyrazoly MeSH
• pyridaziny * terapeutické užití   aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• asciminib MeSH Prohlížeč
• bcr-abl fúzové proteiny MeSH
• imidazoly * MeSH
• inhibitory proteinkinas MeSH
• niacinamid MeSH
• ponatinib MeSH Prohlížeč
• pyrazoly MeSH
• pyridaziny * MeSH

FLT3 kinase is a potential drug target in acute myeloid leukemia (AML). Patients with FLT3 mutations typically have higher relapse rates and worse outcomes than patients without FLT3 mutations. In this study, we investigated the suitability of various heterocycles as central cores of FLT3 inhibitors, including thieno[3,2-d]pyrimidine, pyrazolo[1,5-a]pyrimidine, imidazo[4,5-b]pyridine, pyrido[4,3-d]pyrimidine, and imidazo[1,2-b]pyridazine. Our assays revealed a series of imidazo[1,2-b]pyridazines with high potency against FLT3. Compound 34f showed nanomolar inhibitory activity against recombinant FLT3-ITD and FLT3-D835Y (IC50 values 4 and 1 nM, respectively) as well as in the FLT3-ITD-positive AML cell lines MV4-11, MOLM-13, and MOLM-13 expressing the FLT3-ITD-D835Y mutant (GI50 values of 7, 9, and 4 nM, respectively). In contrast, FLT3-independent cell lines were much less sensitive. In vitro experiments confirmed suppression of FLT3 downstream signaling pathways. Finally, the treatment of MV4-11 xenograft-bearing mice with 34f at doses of 5 and 10 mg/kg markedly blocked tumor growth without any adverse effects.

• MeSH
• akutní myeloidní leukemie * patologie   MeSH
• antitumorózní látky * farmakologie   terapeutické užití   MeSH
• apoptóza MeSH
• inhibitory proteinkinas farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pyridaziny * farmakologie   terapeutické užití   MeSH
• pyrimidiny farmakologie   MeSH
• tyrosinkinasa 3 podobná fms genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky * MeSH
• FLT3 protein, human MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• pyridazine MeSH Prohlížeč
• pyridaziny * MeSH
• pyrimidiny MeSH
• tyrosinkinasa 3 podobná fms MeSH

BACKGROUND: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. METHODS: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. RESULTS: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. CONCLUSIONS: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.

• Klíčová slova
• BRCA mutation, HRR, Maintenance, Olaparib, Ovarian cancer,
• MeSH
• antitumorózní látky * terapeutické užití   MeSH
• epiteliální ovariální karcinom farmakoterapie   genetika   MeSH
• ftalaziny škodlivé účinky   MeSH
• kvalita života MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   genetika   MeSH
• mutace MeSH
• nádory vaječníků * farmakoterapie   genetika   patologie   MeSH
• prospektivní studie MeSH
• rekombinační oprava DNA MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky * MeSH
• ftalaziny MeSH
• olaparib MeSH Prohlížeč

A highly efficient and versatile synthetic approach for the synthesis of 4-(pyren-1-ylmethyl)-1-(d-glycosyloxy) phthalazine nucleosides 11a,b, 13, β-S-nucleosides 16, 18, 20, and acyclo C-nucleosides 23a,b, 24, 25 and 27a-f was described and fully characterized. Furthermore, a series of desired new nucleoside analogues containing Se of 4-(pyren-1-ylmethyl) phthalazine-1(2H)-selenone 28-33 were synthesized. The structures of all reported compounds were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. All compounds have been screened for their antibacterial and antifungal activities. Maximum activity was shown by 20 and 33a comparable to the standard drugs with lower toxicity. The cytotoxicity of the selected compound was measured and evaluated. The energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital was calculated using theoretical computations to reflect the chemical reactivity and kinetic stability of the synthesized compounds. Using density functional theory (DFT), electronic parameters such as the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) and the molecular electrostatic potential (MEPS) were calculated. On the basis of different studied structures, these properties were computed in order to elucidate the chemical reactivity and the kinetic stability. Obviously, the band gap energy (Eg) of structures studied reveals that the lowest band gap obtained for the structure 16-a indicates that it has the highest chemical reactivity and lowest kinetic stability.

• Klíčová slova
• S-nucleosides, antibacterial, biocompatibility, mono/disaccharides, nucleoside analogues, quantum calculations,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• ftalaziny farmakologie   MeSH
• kvantová teorie MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární modely MeSH
• nukleosidy * farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• ftalaziny MeSH
• nukleosidy * MeSH

BACKGROUND: Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL). METHODS: This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (≤50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients. FINDINGS: Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15·9 months (IQR 8·1-25·5) in the olaparib plus abiraterone group and 24·5 months (8·1-27·6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43-100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was -0·10 (95% CI -2·50 to 2·71) in the olaparib plus abiraterone group and -1·20 (-4·15 to 1·74) in the placebo plus abiraterone group (difference 1·30, 95% CI -2·70 to 5·30; p=0·52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0·90 [95% CI 0·62-1·32], p=0·30; worst bone pain HR 0·85 [0·59-1·22], p=0·18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group. INTERPRETATION: In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results. FUNDING: AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

• MeSH
• androgeny MeSH
• androsteny MeSH
• antagonisté androgenů terapeutické užití   MeSH
• bolest chemicky indukované   MeSH
• docetaxel škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• ftalaziny MeSH
• hodnocení výsledků péče pacientem MeSH
• kvalita života MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• piperaziny MeSH
• prednisolon MeSH
• prednison MeSH
• prostatický specifický antigen * terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• testosteron MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• androgeny MeSH
• androsteny MeSH
• antagonisté androgenů MeSH
• docetaxel MeSH
• ftalaziny MeSH
• olaparib MeSH Prohlížeč
• piperaziny MeSH
• prednisolon MeSH
• prednison MeSH
• prostatický specifický antigen * MeSH
• testosteron MeSH

BACKGROUND: Preclinical studies and results of a phase 2 trial of abiraterone and olaparib suggest a combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor olaparib is combined with next-generation hormonal agent abiraterone to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. HRRm status was determined following enrollment by tumor tissue and circulating tumor DNA tests. Patients were randomly assigned (1:1) to receive abiraterone (1000 mg once daily) plus prednisone or prednisolone with either olaparib (300 mg twice daily) or placebo. The primary end point was imaging-based progression-free survival (ibPFS) by investigator assessment. Overall survival was among the secondary end points. RESULTS: At this planned primary analysis at the first data cutoff, median ibPFS was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs. 16.6 months; hazard ratio, 0.66; 95% confidence interval [CI], 0.54 to 0.81; P<0.001) and was consistent with blinded independent central review (hazard ratio, 0.61; 95% CI, 0.49 to 0.74). At this data cutoff, overall survival data were immature (28.6% maturity; hazard ratio, 0.86; 95% CI, 0.66 to 1.12; P=0.29). The safety profile of olaparib and abiraterone was consistent with the known safety profiles of the individual drugs. The most common adverse events in the abiraterone and olaparib arm were anemia, fatigue/asthenia, and nausea. CONCLUSIONS: At primary analysis at this first data cutoff, abiraterone combined with olaparib significantly prolonged ibPFS compared with abiraterone and placebo as first-line treatment for patients with mCRPC enrolled irrespective of HRRm status. (Funded by AstraZeneca and Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; ClinicalTrials.gov number, NCT03732820.)

• MeSH
• androsteny MeSH
• ftalaziny * MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   MeSH
• piperaziny * MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• androsteny MeSH
• ftalaziny * MeSH
• olaparib MeSH Prohlížeč
• piperaziny * MeSH

INTRODUCTION: The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors. PATIENTS AND METHODS: Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial. RESULTS: Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks. CONCLUSION: Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population.

• Klíčová slova
• Adverse event, Edema, MET inhibitor, Nausea, Non–small cell lung cancer,
• MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• exony genetika   MeSH
• hypoalbuminemie farmakoterapie   MeSH
• inhibitory proteinkinas * škodlivé účinky   MeSH
• klinické zkoušky, fáze II jako téma MeSH
• kreatinin terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * farmakoterapie   genetika   MeSH
• nauzea chemicky indukované   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   MeSH
• piperidiny škodlivé účinky   MeSH
• pleurální výpotek MeSH
• průjem MeSH
• pyridaziny škodlivé účinky   MeSH
• pyrimidiny škodlivé účinky   MeSH
• senioři MeSH
• zvracení chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory proteinkinas * MeSH
• kreatinin MeSH
• piperidiny MeSH
• pyridaziny MeSH
• pyrimidiny MeSH
• tepotinib MeSH Prohlížeč

We present chemical kinetics measurements of the luminol oxidation chemiluminescence (CL) reaction at the interface between two aqueous solutions, using liquid jet technology. Free-flowing liquid microjets are a relatively recent development that have found their way into a growing number of applications in spectroscopy and dynamics. A variant thereof, called flat-jet, is obtained when two cylindrical jets of a liquid are crossed, leading to a chain of planar leaf-shaped structures of the flowing liquid. We here show that in the first leaf of this chain, the fluids do not exhibit turbulent mixing, providing a clean interface between the liquids from the impinging jets. We also show, using the example of the luminol CL reaction, how this setup can be used to obtain kinetics information from friction-less flow and by circumventing the requirement for rapid mixing by intentionally suppressing all turbulent mixing and instead relying on diffusion.

• MeSH
• difuze MeSH
• kinetika MeSH
• luminol * MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• luminol * MeSH
• voda * MeSH

OBJECTIVE: The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. METHODS: In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose. RESULTS: Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6-10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. CONCLUSION: Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals.

• Klíčová slova
• BRCA, Maintenance, Olaparib, Ovarian cancer,
• MeSH
• epiteliální ovariální karcinom farmakoterapie   genetika   MeSH
• ftalaziny * škodlivé účinky   MeSH
• lidé MeSH
• lokální recidiva nádoru * farmakoterapie   genetika   MeSH
• mutace MeSH
• nádory vaječníků * farmakoterapie   genetika   MeSH
• piperaziny * škodlivé účinky   MeSH
• platina terapeutické užití   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• udržovací chemoterapie MeSH
• zárodečné buňky MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BRCA1 protein, human MeSH Prohlížeč
• BRCA2 protein, human MeSH Prohlížeč
• ftalaziny * MeSH
• olaparib MeSH Prohlížeč
• piperaziny * MeSH
• platina MeSH
• protein BRCA1 MeSH
• protein BRCA2 MeSH