Nanostructured titanium(IV) oxide was used for the destructive adsorption and photocatalytic degradation of mitoxantrone (MTX), a cytostatic drug from the group of anthracycline antibiotics. During adsorption on a titania dioxide surface, four degradation products of MTX, mitoxantrone dicarboxylic acid, 1,4-dihydroxy-5-((2-((2-hydroxyethyl)amino)ethyl)amino)-8-((2-(methylamino)ethyl)amino)anthracene-9,10-dione, 1,4-dihydroxy-5,8-diiminoanthracene-9,10(5H,8H)-dione and 1,4-dihydroxy-5-imino-8-(methyleneamino)anthracene-9,10(5H,8H)-dione, were identified. In the case of photocatalytic degradation, only one degradation product after 15 min at m/z 472 was identified. This degradation product corresponded to mitoxantrone dicarboxylic acid, and complete mineralization was attained in one hour. Destructive adsorbent manganese(IV) oxide, MnO2, was used only for the destructive adsorption of MTX. Destructive adsorption occurred only for one degradation product, mitoxantrone dicarboxylic acid, against anatase TiO2.
IntroductionMacrocrystalline oxides of alkaline earth metals (Mg and Ca) or light metals (Al and Ti) can respond to standard warfare agents such as sulfur mustard, soman, or agent VX. In this paper, we compared the decontamination ability of sodium hydroxide (NaOH) and sodium hypochlorite (NaClO) for nitrogen mustards (cyclophosphamide [CP] and ifosfamide [IFOS]) with a new procedure using a destructive sorbent based on nanocrystalline and nanodispersive titanium dioxide (TiO2) as a new efficient and cheap material for complete decontamination of surfaces.MethodsTitanium (IV) dioxide nanoparticles were prepared by the homogeneous hydrolysis of titanium(IV) oxysulfate (TiOSO4) with urea. The as-prepared TiO2 nanoparticles were used for the fast and safe decontamination of cytostatics from the nitrogen mustard family (CP and IFOS) in water. The adsorption–degradation process of cytostatics in the presence of TiO2 was compared with decontamination agents (0.01 M solution of sodium hydroxide and 5% solution of sodium hypochlorite). The mechanism of the decontamination process and the degradation efficiency were determined by high-performance liquid chromatography with mass spectrometry.ResultsIt was demonstrated that a 0.01 M solution of sodium hydroxide (NaOH) decomposes CP to 3-((amino(bis(2-chloroethyl)amino)phosphoryl)oxy)propanoic acid and sodium hypochlorite formed two reaction products, namely, IFOS and 4-hydroxy-cyclophosphamide. IFOS is cytotoxic, and 4-hydroxy-cyclophosphamide is a known metabolite of CP after its partial metabolism by CYP/CYP450. IFOS degrades in the pres¬ence of NaOH to toxic IFOS mustard. Titanium(IV) dioxide nanoparticles adsorbed on its surface CP after 5 minutes and on IFOS after 10 minutes. The adsorption–degradation process of CP in water and in the presence of TiO2 led to 4-hydroxy-cyclophosphamide and IFOS, respectively, which decayed to oxidation product 4-hydroxy-ifosfamide.ConclusionNanodispersive TiO2 is an effective degradation agent for decontamination of surfaces from cytostatics in medical facilities.
Unnafected female carriers of BRCA1 and BRCA2 pathogenic/likely pathogenic variants (P/LPVs) are at higher risk of breast cancer (BC) and ovarian cancer (OC). In the retrospective single-institution study in the Czech Republic, we analyzed the rate, longitudinal trends, and effectiveness of prophylactic risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) on the incidence of BC and OC in BRCA1/2 carriers diagnosed between years (y) 2000 to 2020. The study included 496 healthy female BRCA1/2 carriers. The median follow-up was 6.0 years. RRM was performed in 156 (31.5%, mean age 39.3 y, range 22–61 y) and RRSO in 234 (47.2%, mean age 43.2 y, range 28–64 y) BRCA1/2 carriers. A statistically significant increase of RRM (from 12% to 29%) and RRSO (from 31% to 42%) was observed when comparing periods 2005–2012 and 2013–2020 (p < 0.001). BC developed in 15.9% of BRCA1/2 carriers without RRM vs. 0.6% of BRCA1/2 carriers after RRM (HR 20.18, 95% CI 2.78- 146.02; p < 0.001). OC was diagnosed in 4.3% vs. 0% of BRCA1/2 carriers without vs. after RRSO (HR not defined due to 0% occurrence in the RRSO group, p < 0.001). Study results demonstrate a significant increase in the rate of prophylactic surgeries in BRCA1/2 healthy carriers after 2013 and the effectiveness of RRM and RRSO on the incidence of BC and OC in these populations.
Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (NSCLC) in recent five years. Even though we can reach long-term response to this treatment in approximately 20% of patients with NSCLC, we are still not able to identify this cohort of patients based on predictive biomarkers. In our study we have focused on tumor mutation burden (TMB), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to TMB quantification and ununiform threshold. We determined the value of TMB in tumor tissue (tTMB) and blood (bTMB) in 20 patients with early stage NSCLC using original custom gene panel LMB_TMB1. We evaluated various possibilities of TMB calculation and concluded that TMB should be counted from both somatic non-synonymous and synonymous mutations. Considering various factors, we established cut-offs of tTMB in/excluding HLA genes as ≥22 mut/Mb and 12 mut/Mb respectively, and cut-offs of bTMB were defined as ≥21 mut/Mb and ≥5 mut/Mb, respectively. We also observed trend in correlation of somatic mutations in HLA genes with overall survival of patients.
Východiska: Hypertermická izolovaná perfuze končetiny využívá terapeutických účinků hypertermie v ohraničeném kompartmentu končetiny spolu s působením mnohonásobně vyšší koncentrace cytostatika, než by bylo možné dosáhnout v rámci systémové chemoterapie. Zlatým standardem se stal melfalan (Alkeran) v kombinaci s tasonerminem (Beromun, tumor nekrotizující faktor alfa). Účinnost této kombinace byla prokázána u sarkomů měkkých tkání končetin a u pacientů s tzv. bulky disease postižením končetiny maligním melanomem. Případ: Popisujeme případ 65leté pacientky s nediferencovaným vřetenobuněčným sarkomem levého lýtka léčené multidisciplinárním týmem na II. chirurgické klinice kardiovaskulární chirurgie a na Onkologické klinice VFN v Praze a na Ortopedické klinice Nemocnice na Bulovce s cílem zachování končetiny i přes vstupně pokročilé onemocnění. Pacientce byla provedena hypertermická izolovaná perfuze končetiny s tasonerminem a melfalanem s částečnou odpovědí dle vyšetření magnetickou rezonancí. Následně byla provedena široká excize s nálezem kompletní patologické remise dle histologického vyšetření se současným zachováním plně funkční končetiny. Pacientka je dále dispenzarizovaná bez známek recidivy. Závěr: Hypertermická izolovaná perfuze končetiny s tasonerminem a melfalanem představuje důležitou součást multimodálního přístupu v léčbě končetinových sarkomů s vysokým procentem odpovědí, které zvyšují procento končetinu zachovávajících resekcí. Tato možnost by měla být multidisciplinárním týmem zvažována vždy u pacientů s lokalizovanými končetinovými sarkomy a měla by být prováděna ve specializovaných centrech se zkušenostmi s tímto postupem. Klíčová slova hypertermická izolovaná perfuze-sarkom měkkých tkání-dolní končetina-kompletní remise-tasonermin Tato práce byla podpořena projektem Progres Q28-LF1. This work was supported by project Progres Q28-LF1. Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.
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