BACKGROUND: The outcome of children with refractory/relapsed malignancies remains poor and novel therapies are urgently required. One of the promising approaches is metronomic chemotherapy. We present the clinical results of 74 children with advanced solid tumors treated according to treatment recommendation with data registry in three European pediatric centers. METHODS: COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) included low-dose daily temozolomide, etoposide, celecoxib, vitamin D, fenofibrate and retinoic acid. From 2004 to 2010, 74 children were enrolled. RESULTS: The 2-year overall survival (OS) was 43.1% (median 15.4, range 1.3-69.9 months). Of the 74 patients, 50 patients (68%) died and 24 are alive: 6 (8%) with progressive disease, 7 (9%) with stable disease/partial response and 11 (15%) in complete response. Median time to response was 6 months. Of 62 patients with initially measurable disease, 25 (40%) had radiological response or stable disease. Fourteen of 25 showing clinical benefit responded within the first 6 months. The treatment was well tolerated on an outpatient basis. Regarding non-hematological toxicity of grade ≥2, hepatotoxicity of grade 3 occurred in 8 children and grade 3 cheilitis in 16 children. CONCLUSION: COMBAT is a feasible and effective treatment option for patients with relapsing/refractory malignancies. The treatment is well tolerated with a low acute toxicity profile.
- MeSH
- dakarbazin aplikace a dávkování analogy a deriváty MeSH
- dítě MeSH
- dospělí MeSH
- etoposid aplikace a dávkování MeSH
- fenofibrát aplikace a dávkování MeSH
- inhibitory angiogeneze aplikace a dávkování MeSH
- isotretinoin aplikace a dávkování MeSH
- kojenec MeSH
- lidé MeSH
- metronomické podávání léků MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory farmakoterapie MeSH
- předškolní dítě MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování MeSH
- pyrazoly aplikace a dávkování MeSH
- registrace MeSH
- studie proveditelnosti MeSH
- sulfonamidy aplikace a dávkování MeSH
- vitamin D aplikace a dávkování MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Caspases are key enzymatic components of the intracellular apoptotic machinery, and their role in mammalian systems is often studied using fluoromethylketone (FMK) inhibitors. Despite many advantages of such approach, efficiency of the inhibitor and membrane permeability speed are often questioned. This work therefore focuses on an exact evaluation of caspase-3 FMK inhibition dynamics in camptothecin-induced mesenchymal micromasses. Two parameters of caspase-3 FMK inhibitor were investigated: first, the stability of the inhibitory potential in the time course of cultivation and, simultaneously, the dynamics of caspase-3 FMK inhibition after camptothecin-induced apoptosis peak. A photon-counting chemiluminescence approach was applied for quantification of active caspase-3. The sensitivity of the photon-counting method allowed for evaluation of active caspase-3 concentration in femtogram amounts per cell. The inhibitor penetrated the cells within the first minute after its application, and the peak of caspase-3 started to decline to the blank level after 30 min. The inhibitory effect of the FMK inhibitor was unchanged during the entire 48 h of cultivation.
- MeSH
- apoptóza účinky léků MeSH
- inbrední kmeny myší MeSH
- inhibitory kaspas farmakologie MeSH
- kamptothecin farmakologie MeSH
- kaspasa 3 metabolismus fyziologie MeSH
- kultivované buňky MeSH
- luminiscenční měření metody MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Laser capture microdissection (LCM) uniquely allows the selection of specific cell populations from histological sections. These selected cells are then catapulted into a test tube without any contamination from surrounding tissues. During the last ten years, many significant results have been achieved, particularly at the level of DNA and RNA where amplification techniques are available. However, where amplification procedures are difficult, the benefits of LCM diminish. To overcome such difficulties, a novel approach, combining laser capture microdissection and flow cytometry, has been tested here for detection of apoptosis and proliferation in tissue bound cell populations without any amplification steps. The mouse cap stage molar tooth germ was used as a model. At the centre of the inner enamel epithelium, the primary enamel knot is a clearly defined apoptotic population with minimal proliferation, flanked by the highly proliferative cervical loops on each side. Thus within the tooth germ epithelium at this stage, two distinct populations of cells are found side by side. These populations were selected by laser capture microdissection and then analysed by flow cytometry for apoptosis and proliferation. Flow cytometric results correlated well with immunohistochemical findings, demonstrating the success and sensitivity of this combined procedure.
- MeSH
- apoptóza fyziologie MeSH
- epitelové buňky cytologie MeSH
- gestační stáří MeSH
- imunohistochemie MeSH
- koncové značení zlomů DNA in situ MeSH
- kryoprezervace MeSH
- laserová terapie metody MeSH
- mikrodisekce metody MeSH
- moláry embryologie MeSH
- myši MeSH
- orgán skloviny cytologie MeSH
- počet buněk MeSH
- proliferace buněk MeSH
- proliferační antigen buněčného jádra analýza MeSH
- průtoková cytometrie MeSH
- senzitivita a specificita MeSH
- zubní krček cytologie embryologie MeSH
- zubní zárodek cytologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
