Neurochirugie je zásadní pro získání histologických vzorků, provádění správných chirurgických výkonů, pro indikace k výkonům a následné pooperační sledování. V posledních letech došlo jak ke zpřesnění indikací neurochirurgických intervencí, tak ke snížení komplikací. Zásadní je použití moderních zobrazovacích, navigačních a elektrofyziologických technik. Péče o pacienty s nádory je však multioborová, proto je nezbytná kooperace s dalšími odbornostmi.
Neurosurgery plays a crutial role in obtaining histological samples, in performance of adequate surgical procedures, in decision about surgical procedures and postoperative follow-up. Indications of neurosurgical procedures has been refined as well as the rate of complications has been reduced. Modern imaging, navigation and eletrophysiological techniques are of utmost importance. Care has to be multidisciplinar, thus cooperation between key care givers is vital.
- MeSH
- astrocytom chirurgie diagnóza patologie MeSH
- chemoradioterapie metody MeSH
- ependymom chirurgie diagnóza patologie MeSH
- glioblastom diagnóza patologie terapie MeSH
- gliom diagnóza klasifikace terapie MeSH
- kraniofaryngeom chirurgie diagnóza MeSH
- lidé MeSH
- lymfom diagnóza patologie terapie MeSH
- meningeom chirurgie diagnóza patologie MeSH
- metastázy nádorů diagnóza terapie MeSH
- nádory centrálního nervového systému * diagnóza klasifikace terapie MeSH
- nádory hypofýzy chirurgie diagnóza patologie MeSH
- nádory míchy diagnóza terapie MeSH
- neurochirurgické výkony metody MeSH
- stupeň nádoru MeSH
- vestibulární schwannom chirurgie diagnóza MeSH
- Check Tag
- lidé MeSH
Myeloid/lymphoid neoplasms with eosinophilia (M/LN-eo) and tyrosine kinase (TK) gene fusions are a rare group of haematopoietic neoplasms with a broad range of clinical and morphological presentations. Paediatric cases have increasingly been recognised. Importantly, not all appear as a chronic myeloid neoplasm and eosinophilia is not always present. In addition, standard cytogenetic and molecular methods may not be sufficient to diagnose M/LN-eo due to cytogenetically cryptic aberrations. Therefore, additional evaluation with fluorescence in-situ hybridisation and other molecular genetic techniques (array-based comparative genomic hybridisation, RNA sequencing) are recommended for the identification of specific TK gene fusions. M/LN-eo with JAK2 and FLT3-rearrangements and ETV6::ABL1 fusion were recently added as a formal member to this category in the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO-HAEM5). In addition, other less common defined genetic alterations involving TK genes have been described. This study is an update on M/LN-eo with TK gene fusions with focus on novel entities, as illustrated by cases submitted to the Bone Marrow Workshop, organised by the European Bone Marrow Working Group (EBMWG) within the frame of the 21st European Association for Haematopathology congress (EAHP-SH) in Florence 2022. A literature review was performed including paediatric cases of M/LN-eo with TK gene fusions.
- MeSH
- dítě MeSH
- eozinofilie * genetika patologie MeSH
- fúzní onkogenní proteiny genetika MeSH
- hematologické nádory * patologie MeSH
- kostní dřeň patologie MeSH
- lidé MeSH
- lymfom * patologie MeSH
- myeloproliferativní poruchy * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- anemie diagnóza etiologie terapie MeSH
- hemoragické poruchy diagnóza etiologie terapie MeSH
- hypochromní anemie diagnóza etiologie terapie MeSH
- komorbidita MeSH
- krevní nemoci * diagnóza etiologie terapie MeSH
- leukemie diagnóza terapie MeSH
- lidé MeSH
- lymfoidní leukemie diagnóza farmakoterapie patologie MeSH
- lymfom diagnóza patologie terapie MeSH
- makrocytární anemie diagnóza etiologie terapie MeSH
- polycytemie diagnóza etiologie terapie MeSH
- trombofilie diagnóza etiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
- MeSH
- hematologické nádory * MeSH
- lidé MeSH
- lymfom * patologie MeSH
- Světová zdravotnická organizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- anemie klasifikace komplikace patofyziologie MeSH
- diferenciální diagnóza MeSH
- koagulopatie diagnóza klasifikace patofyziologie patologie MeSH
- leukemie diagnóza klasifikace komplikace patofyziologie MeSH
- lidé MeSH
- lymfom diagnóza klasifikace patofyziologie patologie MeSH
- mnohočetný myelom diagnóza klasifikace komplikace MeSH
- nemoci retiny diagnostické zobrazování patofyziologie terapie MeSH
- nitrooční lymfom diagnostické zobrazování klasifikace komplikace MeSH
- oční symptomy * MeSH
- přední segment oční diagnostické zobrazování patofyziologie patologie MeSH
- retinální krvácení diagnostické zobrazování etiologie terapie MeSH
- snížené vidění diagnostické zobrazování etiologie MeSH
- zadní segment oční diagnostické zobrazování patofyziologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L1)2] (1) and [Pt(ox)(L2)2] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- cisplatina škodlivé účinky MeSH
- lidé MeSH
- lymfom patologie MeSH
- myši inbrední DBA MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny chemie MeSH
- oxaláty chemie MeSH
- roskovitin chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- imunoglobuliny aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- lymfom * farmakoterapie komplikace patologie MeSH
- monoklonální protilátky terapeutické užití MeSH
- rituximab škodlivé účinky terapeutické užití MeSH
- syndromy imunologické nedostatečnosti * chemicky indukované farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) form the family of immunomodulatory drugs (IMiDs). Lenalidomide (CC5013, Revlimid®) was approved by the US FDA and the EMA for the treatment of multiple myeloma (MM) patients, low or intermediate-1 risk transfusion-dependent myelodysplastic syndrome (MDS) with chromosome 5q deletion [del(5q)] and relapsed and/or refractory mantle cell lymphoma following bortezomib. Lenalidomide has also been studied in clinical trials and has shown promising activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Lenalidomide has anti-inflammatory effects and inhibits angiogenesis. Pomalidomide (CC4047, Imnovid® [EU], Pomalyst® [USA]) was approved for advanced MM insensitive to bortezomib and lenalidomide. Other IMiDs are in phases 1 and 2 of clinical trials. Cereblon (CRBN) seems to have an important role in IMiDs action in both lymphoid and myeloid hematological malignancies. Cereblon acts as the substrate receptor of a cullin-4 really interesting new gene (RING) E3 ubiquitin ligase CRL4CRBN. This E3 ubiquitin ligase in the absence of lenalidomide ubiquitinates CRBN itself and the other components of CRL4CRBN complex. Presence of lenalidomide changes specificity of CRL4CRBN which ubiquitinates two transcription factors, IKZF1 (Ikaros) and IKZF3 (Aiolos), and casein kinase 1α (CK1α) and marks them for degradation in proteasomes. Both these transcription factors (IKZF1 and IKZF3) stimulate proliferation of MM cells and inhibit T cells. Low CRBN level was connected with insensitivity of MM cells to lenalidomide. Lenalidomide decreases expression of protein argonaute-2, which binds to cereblon. Argonaute-2 seems to be an important drug target against IMiDs resistance in MM cells. Lenalidomide decreases also basigin and monocarboxylate transporter 1 in MM cells. MM cells with low expression of Ikaros, Aiolos and basigin are more sensitive to lenalidomide treatment. The CK1α gene (CSNK1A1) is located on 5q32 in commonly deleted region (CDR) in del(5q) MDS. Inhibition of CK1α sensitizes del(5q) MDS cells to lenalidomide. CK1α mediates also survival of malignant plasma cells in MM. Though, inhibition of CK1α is a potential novel therapy not only in del(5q) MDS but also in MM. High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide. While transfusion independence (TI) after lenalidomide treatment is more than 60% in MDS patients with del(5q), only 25% TI and substantially shorter duration of response with occurrence of neutropenia and thrombocytopenia were achieved in lower risk MDS patients with normal karyotype treated with lenalidomide. Shortage of the biomarkers for lenalidomide response in these MDS patients is the main problem up to now.
- MeSH
- imunomodulace účinky léků MeSH
- lidé MeSH
- lymfom farmakoterapie patologie MeSH
- myelodysplastické syndromy farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In this study, we report the in vivo anti-lymphoma efficacy and diagnostic potential of newly designed near-infrared fluorescent dye containing polymer-doxorubicin conjugates using murine models of malignant lymphomas including one cell line-derived xenograft (RAJI) and two patient-derived lymphoma xenografts (VFN-D1 and VFN-M2). Two types of passively targeted conjugates differing in architecture of the polymer backbone were synthesized. One of the conjugates was designed using a single linear polymer chain, and the second was more sophisticated with a star-shaped high-molecular-weight (HMW) polymer employing a dendrimer core. The linear HPMA copolymers were linked to the dendrimer core via a one-point attachment, thus forming a hydrophilic polymer shell. Both polymer-doxorubicin conjugates were long-circulating with reduced side effects. Both polymer prodrugs were designed as stimuli-sensitive systems in which the anti-cancer drug doxorubicin was attached to the hydrophilic copolymers via a pH-labile hydrazone linkage. Such polymer prodrugs were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acid environments at pH 5-6.5 by hydrolysis of the hydrazone bonds. In addition, polymers were labelled with near-infrared fluorescent dye enabling long term in vivo visualization. Malignant lymphomas represent the most common type of haematological malignancies. Therapy for the majority of malignant lymphomas consists of multi-agent chemotherapy based on an anthracycline doxorubicin, the most prominent side effect of which is cardiotoxicity. We have demonstrated significant anti-lymphoma efficacy of the polymer-doxorubicin conjugates when compared to equally toxic doses of conventional (unbound) doxorubicin in all tested models. Favourable pharmacokinetics for carried drug and labelled polymer carrier was observed, showing predominant uptake of the drug and polymer itself in the tumour mass. In addition, we have observed a promising diagnostic potential of fluorescently labelled polymer prodrugs. Dynamically analyzed fluorescence intensity over subcutaneously xenografted lymphomas closely corresponded to changes in the lymphoma tumour volumes, thereby enabling a non-invasive assessment of treatment efficacy.
- MeSH
- akrylamidy chemie MeSH
- antitumorózní látky chemie terapeutické užití MeSH
- dendrimery chemie MeSH
- doxorubicin chemie terapeutické užití MeSH
- fluorescenční barviva chemie MeSH
- heterografty MeSH
- hydrazony chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lymfom diagnostické zobrazování farmakoterapie patologie MeSH
- methakryláty chemie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nanokapsle chemie MeSH
- polymerizace MeSH
- polymery chemie MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
