BACKGROUND: Investigation remains incomplete regarding potential variations in the effect of androgen receptor pathway inhibitors, including apalutamide, based on baseline tumor burden in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: The authors analyzed individual participant-level data from 1052 patients with mCSPC who were randomized in the TITAN trial (apalutamide vs. placebo, both with androgen-deprivation therapy). Outcomes included radiographic progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Multivariable Cox proportional hazards regression models, with and without restricted cubic splines, were used to determine the association between apalutamide benefit and bone metastasis count or visceral metastasis. Subgroup treatment effects were quantified based on inverse probability of treatment weighting-adjusted hazard ratios (HRs). RESULTS: Analysis using restricted cubic splines indicated that apalutamide provided less benefit for PFS2 and OS in patients with fewer bone metastases. The authors also found evidence of a heterogeneous effect of apalutamide on PFS2 and OS between patients with two or less bone metastases and those with three or more bone metastases. In patients who had two or less bone metastases, there was no evidence of a benefit from apalutamide for radiographic PFS (HR, 0.65; 95% confidence interval [CI], 0.35-1.22), PFS2 (HR, 1.18; 95% CI, 0.66-2.12), or OS (HR, 1.05; 95% CI, 0.60-1.83). No evidence of an association was noted between visceral metastasis and apalutamide benefit. CONCLUSIONS: The addition of apalutamide to androgen-deprivation therapy may provide less benefit in patients with mCSPC who have fewer bone metastases. Counting baseline bone metastases may help identify optimal candidates for apalutamide treatment of mCSPC. CLINICAL TRIALS REGISTRATION: NCT02489318 PLAIN LANGUAGE SUMMARY: In an analysis of individual participant data from a trial (the TITAN trial) in patients with metastatic (spreading) castration-sensitive prostate cancer, treatment intensification based on the addition new drugs to standard androgen-deprivation therapy (ADT) was analyzed and compared with the effects in patients who received only standard ADT. Compared with ADT alone, the survival benefit of adding the new drug apalutamide to standard ADT varied according to the number of bone metastases, but no association was observed between the spread of cancer to soft tissues and organs and a survival benefit from adding apalutamide. The results indicate that counting the number of bone metastases may help identify which patients with metastatic castration-sensitive prostate cancer are optimal candidates for treatment intensification with the addition of apalutamide to standard ADT.
- Klíčová slova
- apalutamide, castration‐sensitive prostate cancer, heterogeneity in treatment effect, prostate cancer,
- MeSH
- antagonisté androgenních receptorů * terapeutické užití MeSH
- antagonisté androgenů terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory kostí * sekundární farmakoterapie MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie patologie mortalita MeSH
- senioři MeSH
- thiohydantoiny * terapeutické užití aplikace a dávkování MeSH
- tumor burden * účinky léků MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- antagonisté androgenních receptorů * MeSH
- antagonisté androgenů MeSH
- apalutamide MeSH Prohlížeč
- thiohydantoiny * MeSH
- MeSH
- kortikální kost chirurgie MeSH
- kyretáž * metody MeSH
- lidé MeSH
- nádory kostí * chirurgie patologie sekundární MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Uveal melanoma is a rare cancer, in which metastases occur in approximately one half of cases. In metastatic disease, the prognosis is unfavorable and the median of survival does not exceed 6 months. Effective treatment options were very limited up to date. Tebentafusp is a bispecific fusion protein, which as the first drug proved efficacy in uveal melanoma. CASE: The patient was referred for suspected uveal melanoma of the left eye. She was treated for Hodgkin's disease in the past. Primarily, the tumor was treated by radiosurgery with radiotherapy of a small lesion of the vertebral body. However, later the patient had to undergo bulbus enucleation with confirmation of a large tumor category pT4b. PET/CT revealed metastases of the bones and the liver; simultaneously, haplotype A*02: 01 was confirmed. The patient underwent radiotherapy of the sternum and later, after confirmation of payment from the health insurance company, she started treatment with tebentafusp. The first three doses were administered during admission to the hospital, with a need to treat cytokine release syndrome by corticosteroids. Later, the administration was performed in an out-patient regimen, without complications, except for a transient elevation of transaminases. The first CT restaging confirmed stable disease; however, the second restaging confirmed a new osteolytic lesion in the processus of Th11. Because of progression, the treatment with tebentafusp was withdrawn after 6 months. Unfortunately, the lesion could not be treated by radiotherapy. Two months later, the patient was urgently admitted to the hospital because of right-sided hemiplegia; MRI revealed bleeding metastatic lesion in the brain stem. CONCLUSION: In this case report, we present the case of the first patient treated with this drug in the Czech Republic.
- Klíčová slova
- tebentafusp, treatment, type 2 diabetes, uveal melanoma,
- MeSH
- lidé MeSH
- melanom * sekundární terapie MeSH
- nádory jater sekundární terapie MeSH
- nádory kostí sekundární terapie MeSH
- nádory uvey * patologie terapie MeSH
- protinádorové látky terapeutické užití MeSH
- rekombinantní fúzní proteiny terapeutické užití MeSH
- uveální melanom MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- protinádorové látky MeSH
- rekombinantní fúzní proteiny MeSH
PURPOSE OF THE STUDY The increasing prevalance of patients with metastatic bone cancer and their improved survival puts more emphasis on the quality of treatment of bone metastases. Although most pelvic lesions are treated non-operatively, extensive destruction of the acetabular segment poses a therapeutic challenge. A potential treatment option may be the modified Harrington procedure. MATERIAL AND METHODS At our department, this surgical procedure has been opted for in 14 patients (5 men and 9 women) since 2018. The mean age at the time of surgery was 59 years (range 42 to 73). Twelve patients suffered from metastatic cancer, one patient had a fibrosarcoma metastasis and one female patient presented with aggressive pseudotumor. Radiological and clinical followup of the patients was performed. Pain was assessed using the Visual Analogue Scale, and the Harris Hip Score and the MSTS score were used to evaluate the functional outcome. The paired samples Wilcoxon test was used to analyze the statistical significance of the difference. RESULTS The mean follow-up period was 25 months. At the time of assessment, ten patients were alive with the mean follow-up of 29 months (range 2 to 54 months) and four patients had died of cancer progression, with the mean follow-up being 16 months. No perioperative death or mechanical failure were reported. One female patient developed a hematogenous infection during febrile neutropenia, which was successfully managed with early revision and implant preservation. Statistically, a significant improvement in the MSTS (median 23) and HHS (median 86) functional scores compared to the preoperative values (MSTS median 2, p<0.01, r-effect size = 0.6; HHS preop median 0, p<0.005, r-effect size = -0.7) was observed. There was also a statistically significant reduction in pain (VAS postoperative median 1, VAS preoperative median 8, p<0.01, r-effect size = -0.6). All patients were capable of independent ambulation after the surgery, nine patients walked without support. DISCUSSION There are not many alternatives to this surgical procedure. Apart from non-operative palliative treatment, the options include ice cream cone prostheses or customized 3D implants which are, impractical in terms of time and cost. Our results are comparable to other studies, confirming the reproducibility and reliability of the method. CONCLUSIONS The Harrington procedure is an efective method for management of large acetabular tumor defects with good functional outcomes, an acceptable perioperative risk and a low risk of failure in the medium term, thus suitable also for patients with good cancer prognosis. Key words: umor, metastasis, acetabulum, pelvis, Harrington, reconstruction.
- MeSH
- acetabulum * patologie chirurgie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorová bolest * chirurgie MeSH
- nádory kostí * sekundární chirurgie MeSH
- reprodukovatelnost výsledků MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- zákroky plastické chirurgie * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
PURPOSE: To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate. METHODS: We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians. RESULTS: After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p < 0.001). In OCM adjusted multivariable analyses, Asian race/ethnicity was associated with lower CSM (HR 0.66, CI 0.52-0.83, p < 0.001). Conversely, African-American and Hispanic/Latino race/ethnicity did not affect CSM. OCM rates were comparable between examined races/ethnicities. CONCLUSION: In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients.
- Klíčová slova
- Cancer-specific mortality, External beam radiotherapy, Metastatic prostate cancer, Other-cause mortality, Race/ethnicity,
- MeSH
- Američané asijského původu statistika a číselné údaje MeSH
- běloši statistika a číselné údaje MeSH
- černoši nebo Afroameričané statistika a číselné údaje MeSH
- Hispánci a Latinoameričané statistika a číselné údaje MeSH
- karcinom etnologie mortalita radioterapie sekundární MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mortalita etnologie MeSH
- nádory kostí etnologie mortalita sekundární MeSH
- nádory prostaty etnologie mortalita patologie radioterapie MeSH
- program SEER MeSH
- radioterapie * MeSH
- senioři MeSH
- tendenční skóre MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: With regards to the anatomical relationships in the mouth, oral squamous cell carcinoma can invade the maxilla or the mandible. According to the TNM system, tumours that invade through cortical bone are classified as T4a, stage IVA. Bone invasion by oral squamous cell carcinoma most often occurs in tumours close to the bone or in larger and more advanced tumours. It is considered an adverse prognostic factor and it is often a diagnostic and therapeutic problem. Destruction of the bone tissue is mediated by activated osteoclasts rather than directly by carcinoma. Tumor necrosis factors - receptor activator of NF-kB (RANK), receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) - play an important role in osteoclastogenesis. According to histological point of view, there are three patterns of bone invasion - erosive, mixed and infiltrative. The most commonly used imaging techniques when evaluating bone invasion by oral squamous cell carcinoma include CT and MRI. PURPOSE: This review is focused on the cellular and molecular mechanisms, histological patterns and detection methods of bone invasion caused by oral squamous cell carcinoma.
- Klíčová slova
- bone invasion, oral squamous cell carcinoma, osteoclast,
- MeSH
- lidé MeSH
- mandibula MeSH
- nádory kostí sekundární MeSH
- nádory úst * patologie MeSH
- spinocelulární karcinom * patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Like other malignancies, prostate tumors are thought to contain cancer stem-like cells (CSCs) that are responsible for growth, metastasis, and therapy resistance. ΔNp63 (also called p40) is a regulator of normal prostate stem/progenitor cell activities and a marker of normal basal epithelial cells. The levels of ΔNp63 are reduced in prostate adenocarcinomas, although there is also evidence that ΔNp63 is involved in CSC regulation and drives metastasis to the bone. We studied metastatic deposits of prostate cancers with isoform-specific ΔNp63 and TAp63 antibodies. We identified p63-positive cells in only 3 of 42 metastatic prostate tumors (7%), including 2/38 (5.3%) "usual-type" adenocarcinomas. ΔNp63 and TAp63 isoforms were present in the nuclei of a small subpopulation (< 1%) of tumor cells in these metastases. ΔNp63-positive cells showed a basal-like cell phenotype (cytokeratin 8- and androgen receptor-negative, high molecular weight cytokeratin- and cytokeratin 19-positive), distinct from the tumor bulk. TAp63-positive cells were similar but were sometimes cytokeratin 8-positive. A subset of ΔNp63-positive tumor cells were CD44-positive, a marker of "basal" CSCs but were not positive for the "epithelial" CSC marker ALDH1. TAp63 was not associated with either of these CSC markers. None of the tumors containing p63-positive cells showed evidence of bone metastasis, compared with 28% of the p63-negative tumors. These data show that both ΔNp63 and TAp63 are present in only a small proportion of prostate adenocarcinomas and do not associate with metastasis. The data suggest heterogeneity of CSCs in prostate cancer, similar to other cancer types.
- Klíčová slova
- CD44, Cancer stem cells, Metastasis, Prostate cancer, p40, p63,
- MeSH
- adenokarcinom metabolismus sekundární MeSH
- dospělí MeSH
- fenotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové kmenové buňky metabolismus patologie MeSH
- nádorové supresorové proteiny metabolismus MeSH
- nádory kostí metabolismus sekundární MeSH
- nádory prostaty metabolismus patologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- transkripční faktory metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
- nádorové supresorové proteiny MeSH
- TP63 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
BACKGROUND: Current standard treatments for patients with metastatic renal cell carcinoma (mRCC) involve tyrosine kinase inhibitors (TKI) that inhibit angiogenesis. Cabozantinib is a multi TKI used for the treatment of mRCC in the first- and second-line setting. PURPOSE: The aim of this study was the final analysis of treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib after previous targeted therapy. PATIENTS AND METHODS: A total of 54 patients with mRCC from four oncology centers in the Czech Republic were evaluated retrospectively; the median follow-up was 18.5 months. Cabozantinib was administered in a dose of 60mg/day, a subset of patients received an initial dose of 40mg/day. The treatment was administered until the progression. The Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by regression analysis. All statistics were evaluated at the significance level α = 0.05. RESULTS: The median PFS in all patients was 9.3 months (95% CI 7.2 - 11.4). The median OS in all patients was 21.9 months (95% CI 15.5 - 28.4). The median PFS in patients with bone metastases was not statistically significantly different compared with patients without bone metastases (9.3 vs 8.7 months, P = 0.53). The median OS in patients with bone metastases was statistically significantly shorter compared with patients without bone metastases (17.7 vs 26.8 months, P = 0.021). A treatment response was observed in 40.7 % of cases, including one complete remission. The regression analysis demonstrated a significant effect on OS in patients with the presence of subsequent treatment (P = 0.001), patients with treatment duration of first line therapy 6 months (P = 0.019) and 12 months (P = 0.003) and in patients without bone metastases (P = 0.021). CONCLUSION: Our final analysis of patients with mRCC treated with cabozantinib after previous targeted therapy confirmed its effectiveness.
- Klíčová slova
- cabozantinib, metastases, molecular targeted therapy, neoplasm metastasis, renal carcinoma, targeted treatment, treatment results,
- MeSH
- analýza dat MeSH
- anilidy terapeutické užití MeSH
- dospělí MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- karcinom z renálních buněk farmakoterapie mortalita patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory kostí farmakoterapie mortalita sekundární MeSH
- nádory ledvin farmakoterapie mortalita patologie MeSH
- onkologická péče - zařízení MeSH
- protinádorové látky terapeutické užití MeSH
- pyridiny terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři 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
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- anilidy MeSH
- cabozantinib MeSH Prohlížeč
- inhibitory proteinkinas MeSH
- protinádorové látky MeSH
- pyridiny MeSH
PURPOSE: In the integrated analysis of phase III head-to-head trials in patients with advanced solid tumors, denosumab demonstrated superiority over zoledronic acid in preventing skeletal-related events (SREs). Regular and continued drug use (persistence) is a precondition of clinical efficacy; persistence in real-life is yet undetermined for denosumab. METHODS: This was a single-arm, prospective, observational, non-interventional study in 598 patients with bone metastases from breast, prostate, lung, or other solid tumors treated with denosumab every four weeks in real-world clinical practice in Austria, Czech Republic, Hungary, Slovakia, and Bulgaria. Persistence was defined as denosumab administration at ≤ 35-day intervals over 24 or 48 weeks, respectively. RESULTS: Previous SREs were found in 10.9% of patients. 62.6% were persistent over 24 weeks and 40.1% over 48 weeks. The Kaplan-Meier median (95% CI) time to non-persistence was 274.0 days (232.0, 316.0). The most frequent reason for non-persistence was delayed administration. There was a trend towards weaker analgesics over time, with approximately 60% of patients not requiring any analgesics. Serum calcium remained within the normal range throughout the study. Adjudicated osteonecrosis of the jaw was documented in three patients with an incidence per patient-year (95% CI) of 0.012 (0.004, 0.029). CONCLUSIONS: Most patients received denosumab regularly once every four weeks over 24 weeks of treatment. Non-persistence was mainly due to delayed administration. The incidence of adverse drug reactions, especially of osteonecrosis of the jaw, was in line with expectations from previous studies.
- Klíčová slova
- Bone metastases, Denosumab, Observational study, Persistence, Solid tumors,
- MeSH
- denosumab aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- inhibitory kostní resorpce aplikace a dávkování škodlivé účinky MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory kostí farmakoterapie sekundární MeSH
- nádory farmakoterapie patologie MeSH
- osteonekróza chemicky indukované MeSH
- prospektivní studie MeSH
- rozvrh dávkování léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Názvy látek
- denosumab MeSH
- inhibitory kostní resorpce MeSH
INTRODUCTION: In an earlier report of the ASCEND-8 study (open-label, phase I, three-arm study, treatment-naive patients and pre-treated patients with advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted. METHODS: Here, we report efficacy and updated safety data from primary efficacy analysis of the ASCEND-8 study. Key secondary endpoints were overall response rate and duration of response, assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: In total, 306 patients were randomized to ceritinib 450-mg fed (n = 108) or 600-mg fed (n = 87) or 750-mg fasted (n = 111), of which 304 patients were included in safety analysis and 198 treatment-naive patients (ALK receptor tyrosine kinase [ALK]-positive by immunohistochemistry) were included in the efficacy analysis (450-mg fed [n = 73], 600-mg fed [n = 51], and 750-mg fasted [n = 74]). The BIRC-assessed overall response rate was 78.1% (95% confidence interval [CI]: 66.9-86.9), 72.5% (95% CI: 58.3-84.1), and 75.7% (95% CI: 64.3-84.9), respectively; and the median duration of response (months) by BIRC was not estimable (NE) (95% CI: 11.2-NE), 20.7 (95% CI: 15.8-NE), and 15.4 (95% CI: 8.3-NE), respectively. Based on the safety analysis (n = 304), the 450-mg fed arm showed the highest median relative dose intensity (100% versus 78.5% versus 83.7%), lowest proportion of patients with dose reductions (24.1% versus 65.1% versus 60.9%), and lowest proportion of patients with gastrointestinal toxicities (75.9% versus 82.6% versus 91.8%). CONCLUSION: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity.
- Klíčová slova
- ALK receptor tyrosine kinase, Ceritinib, Food effect, NSCLC,
- MeSH
- anaplastická lymfomová kináza genetika MeSH
- dospělí MeSH
- genová přestavba MeSH
- kritéria léčebné odpovědi MeSH
- lidé středního věku MeSH
- lidé MeSH
- maximální tolerovaná dávka MeSH
- mladý dospělý MeSH
- nádory jater farmakoterapie genetika sekundární MeSH
- nádory kostí farmakoterapie genetika sekundární MeSH
- nádory mozku farmakoterapie genetika sekundární MeSH
- nádory plic farmakoterapie genetika patologie MeSH
- následné studie MeSH
- nemalobuněčný karcinom plic farmakoterapie genetika patologie MeSH
- omezení příjmu potravy * MeSH
- potraviny * MeSH
- prognóza MeSH
- protinádorové látky terapeutické užití MeSH
- pyrimidiny terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sulfony terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- ALK protein, human MeSH Prohlížeč
- anaplastická lymfomová kináza MeSH
- ceritinib MeSH Prohlížeč
- protinádorové látky MeSH
- pyrimidiny MeSH
- sulfony MeSH