Cíle práce: Cílem této retrospektivní studie je zhodnotit naše zkušenosti s použitím jednobalónkového enteroskopu při diagnostické a terapeutické endoskopické retrográdní cholangiografii (ERC) u pacientů s Roux-Y hepatikojejunoanastomózou (HJA). Oproti standardní endoskopické retrográdní cholangiopankreatikografii (ERCP) je u takto výrazně pooperačně změněných anatomických poměrů provedení ERC podstatně náročnější. Soubor nemocných a metodika: Studium souboru probíhalo od ledna roku 2009 do září roku 2011. V práci bylo retrospektivně hodnoceno 14 pacientů s Roux-Y HJA, u kterých byly přítomny projevy biliární obstrukce. U těchto 14 pacientů s Roux-Y HJA bylo provedeno celkem 21 ERC, kdy byl ve všech případech použit jednobalónkový videoenteroskop Olympus SIF Q 180. Výsledky: Kanylačního úspěchu při diagnostické ERC bylo dosaženo u 11 pacientů ze 14 (79% úspěšnost diagnostické ERC). U 1 pacienta z 11 byl na ERC normální nález. U zbývajících 10 nemocných byl na ERC některý z patologických nálezů, který byl v 1 případě (cystická dilatace žlučovodu) řešen následně chirurgicky. U zbývajících 9 pacientů (4krát stenóza HJA, 2krát choledocholitiáza a 3krát současně přítomna stenóza HJA a choledocholitiáza) byla bezprostředně po diagnostické ERC zahájena endoskopická léčba, která byla úspěšná u 8 pacientů z 9 (89% úspěšnost terapeutické ERC). K provedeným endoskopickým terapeutickým výkonům patřily: balónková dilatace stenózy HJA – 9krát (u 6 pacientů), extrakce choledocholitiázy – 5krát (u 5 pacientů), zavedení biliárních plastových stentů – 5krát (u 3 pacientů), odstranění námi endoskopicky zavedených biliárních stentů – 5krát (u 3 pacientů). V našem souboru 14 pacientů se nevyskytly žádné komplikace. Závěry: ERC za použití jednobalónkového enteroskopu u pacientů s Roux-Y HJA je v důsledku odlišné pooperační anatomie podstatně obtížnější než standardní ERCP. V našem souboru pacientů jsme dosáhli 79% úspěšnosti diagnostické ERC a 89% úspěšnosti terapeutické ERC. Je třeba počítat s větším množství času na jednotlivé výkony, u kterých je navíc nezbytně nutná přítomnost anesteziologa (hluboká analgosedace). Jedná se o technicky velmi náročnou metodu, která je ale efektivní a bezpečná a významně rozšiřuje možnosti řešení biliární patologie u těchto stavů.
Aims of the study: The aim of this retrospective study was to evaluate our experience with using a single-balloon enetroscope for diagnostic and therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y hepatico jejunal anastomosis (HJA). Due to the considerably changed anatomic circumstances after the surgery, ERC is, in comparison to the standard endoscopic retrograde cholangiopancraeaticography (ERCP), significantly more difficult to perform. Patient sample and methodology: The sample was followed upFrom January 2009 to September 2011. The study retrospectively reviewed 14 patients with Roux-en-Y HJA with symptoms of biliary obstruction. A total of 21 ERCs were performed in these 14 Roux-en-Y HJA patients using the single-balloon videoenetroscope Olympus SIF Q 180. Results: Diagnostic ERC cannulation was successful in 11 of the 14 patients (79% success rate for the diagnostic ERC). One of the 11 patients had a normal finding on the ERC. The remaining 10 patients had a pathological finding on ERC that, in one patient (cystic dilatation of bile duct), was subsequently managed surgically. Endoscopic treatment was initiated in the remaining 9 patients (HJA stenosis in 4, choledocholithiasis in 2 and concurrent HJA stenosis and choledocholithiasis in 3) immediately after the diagnostic ERC; the surgery was successful in 8 of the 9 patients (89% success rate for the therapeutic ERC). The performed endoscopic therapeutic procedures included: balloon dilatation of HJA stenosis 9 times (6 patients), choledocholithiasis extraction – 5 times (5 patients), biliary plastic stent placement – 5 times (3 patients), removal of biliary stents placed by us – 5 times (3 patients). We did not observe any complications in our sample of 14 patients. Conclusions: ERC using a single-balloon enteroscope in patients with Roux-Y HJA is significantly more difficult than the standard ERCP due to different post-surgical anatomy. In our sample of patients, we achieved 79% success rate for the diagnostic ERC and 89% success rate for the therapeutic ERC. Additional time should be allowed for the individual procedures. Furthermore, the presence of an anaesthesiologist during these operations (deep analgosedation) is essential. This is a technically very demanding technique that, however, is effective and safe and importantly extends the options available for the management of biliary pathologies in these patients.
- Klíčová slova
- endoskopická léčba,
- MeSH
- cholangiopankreatografie endoskopická retrográdní metody přístrojové vybavení MeSH
- dospělí MeSH
- ductus hepaticus communis chirurgie MeSH
- jejunum chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci žlučových cest diagnóza MeSH
- Rouxova Y-anastomóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Transplantace krvetvorných buněk je život zachraňující výkon u celé řady hematologických nemocí. Rozvoj transplantací se datuje od začátku 70. let minulého století, po objevení HLA systému. V ÚHKT byl transplantační program zahájen v roce 1986 a do konce roku 2011 zde bylo provedeno 918 transplantací krvetvorných buněk pro různá hematologická onemocnění. Dlouhodobé přežití všech pacientů po transplantaci se pohybuje kolem 50 %, a to v rozmezí 20–90 % v závislosti na typu a pokročilosti onemocnění, na typu dárce a na věku pacienta.
Haematopoietic cell transplantation is a life-saving procedure in a number of haematological diseases. Development of transplantation dates back to 1970s, following discovery of the HLA system. The Institute of Haematology and Blood Transfusion in Prague had initiated its transplantation programme in 1986 and 918 haematopoietic cell transplantations were performed for various haematological diseases until 2011. Long-term survival of all patients after transplantation is around 50%, ranging from 20 to 90%, depending on the type of the disease and its stage, the type of a donor and the patient’s age.
- Klíčová slova
- transplantace pro těžkou aplastickou anémii, transplantace pro chronickou lymfatickou leukemii, transplantace pro myelofibrózu s myeloidní metaplazií, transplantace u non-Hodgkinských lymfomů, transplantace u akutní lymfatické leukemie, transplantace pro myelodysplastický syndrom, transplantace u chronické myeloidní leukemie, transplantace u akutní myeloidní leukemie, historie transplantace,
- MeSH
- akutní lymfatická leukemie terapie MeSH
- akutní myeloidní leukemie terapie MeSH
- analýza přežití * MeSH
- chronická lymfatická leukemie terapie MeSH
- chronická myeloidní leukemie terapie MeSH
- homologní transplantace statistika a číselné údaje MeSH
- lidé MeSH
- myelodysplastické syndromy terapie MeSH
- nehodgkinský lymfom terapie MeSH
- nemoci kostní dřeně * terapie MeSH
- primární myelofibróza terapie MeSH
- transplantace hematopoetických kmenových buněk trendy MeSH
- transplantace kostní dřeně * dějiny statistika a číselné údaje trendy MeSH
- Check Tag
- lidé MeSH
Recombinant plant nucleases R-TBN1 and R-HBN1 were isolated to homogeneity and examined for their antitumor effects and cytotoxicity. Although antiproliferative effects of both recombinant nucleases were not significant on the ML-2 cell culture in vitro, the nucleases were strongly cytostatic in vivo after their administration intravenously as stabilized conjugates with polyethylene glycol (PEG). Recombinant nucleases were as effective against melanoma tumors as previously studied pine pollen (PN) and mung bean nucleases and their effects were reached at about 10 times lower concentrations compared to the use of bovine seminal RNase (BS-RNase). Because the recombinant nucleases R-HBN1 and R-TBN1 share only 67.4% amino acid identity and showed only partial immunochemical cross-reactivity, their similar anticancerogenic effects can be mainly explained by their catalytical similarity. Both recombinant nucleases showed lower degree of aspermatogenesis compared to BS-RNAse and PN nuclease. Unlike BS-RNase, aspermatogenesis induced by both recombinant nucleases could not be prevented by the homologous antibody complexes. Owing to relatively low cytotoxicity on the one hand, and high efficiency at low protein levels on the other, recombinant plant nucleases R-HBN1 and R-TBN1 appear to be stable biochemical agents that can be targeted as potential antitumor cytostatics.
- MeSH
- endonukleasy farmakologie genetika MeSH
- glykosylace MeSH
- Humulus enzymologie MeSH
- lidé MeSH
- melanom enzymologie patologie prevence a kontrola MeSH
- myeloidní leukemie enzymologie patologie prevence a kontrola MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- proliferace buněk MeSH
- protinádorové látky farmakologie MeSH
- rekombinantní proteiny farmakologie genetika MeSH
- skot MeSH
- Solanum lycopersicum enzymologie MeSH
- spermatogeneze MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The antitumor effect of black pine (Pinus nigra) pollen nuclease (PN) tested in vitro was negligible in comparison with bovine seminal ribonuclease (BS-RNase). However, in the experiments in vivo a significant decrease of the human melanoma tumor size was observed in the mice treated with this nuclease and also with the animal RNases and DNase I. In nude mice injected intratumoraly with PN (10 microg/dose) the tumor size decreased from 100% in the control mice to 46% in treated mice whereas in counterparts treated with BS-RNase and DNase I the tumor growth was reduced a little more, however after ten times higher doses (100 and 80 microg per dose). Certain aspermatogenic and embryotoxic activity as an expression of side effects of PN and comparative enzymes also appeared, but it was lower compared to the effect of bovine seminal ribonuclease. Immunogenicity of PN was significantly weaker in comparison with BS-RNase. The antibodies against black pine nuclease produced in the injected mice did not inactivate the biological effects of this plant nuclease in vivo. In conclusion PN nuclease proved in vivo higher antitumor activity against human melanoma tumors growing in athymic mice in comparison with animal bovine seminal ribonuclease and DNase I.
- MeSH
- borovice enzymologie MeSH
- embryonální vývoj účinky léků MeSH
- endonukleasy farmakologie imunologie toxicita MeSH
- endoribonukleasy farmakologie MeSH
- financování organizované MeSH
- fytogenní protinádorové látky farmakologie MeSH
- lidé MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- pyl enzymologie MeSH
- spermatogeneze účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Polyspermine-ribonuclease A (PS-RNase A) and polyspermine-dimeric ribonuclease A (PS-dimeric RNase A) were prepared by cross-linking ribonuclease A or its covalently linked dimer to polyspermine (PS) using dimethyl suberimidate. The two RNase A derivatives were tested for a possible antitumor action. The in vitro and in vivo cytotoxic activity of PS-RNase A, although strong, is not higher than that known for free polyspermine. PS-dimeric RNase A, which was characterized by mass spectroscopy, titration of free amine groups, and enzymatic assays, proved instead to be a definitely more efficient antitumor agent, both in vitro and in vivo. This result could tentatively be explained in view of the importance of positive charges for ribonuclease activity, considering the higher basicity of PS-dimeric RNase A compared to that of PS-(monomeric)RNase A. It must be also taken into account that the dimeric RNase A moiety of PS-dimeric RNase A could evade the cytoplasmic ribonuclease inhibitor, which instead could trap the monomeric RNase A moiety of the other derivative. The two RNase A derivatives degrade poly(A).poly(U) under conditions where native RNase A is inactive. The results of this work demonstrate once again the importance of positive charges for the functions of mammalian pancreatic type ribonucleases in general, in particular for RNase A derivatives, and the potential therapeutic use of the ribonuclease A derivatives.
- MeSH
- dimerizace MeSH
- financování organizované MeSH
- gelová chromatografie MeSH
- kultivované buňky MeSH
- lidé MeSH
- molekulární struktura MeSH
- pankreatická ribonukleasa MeSH
- proliferace buněk účinky léků MeSH
- reagencia zkříženě vázaná chemie MeSH
- RNA metabolismus MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- spermin chemie MeSH
- Check Tag
- lidé MeSH
Growth-inhibitory and proapoptotic effects of the monoclonal antibody to CD34 molecule, clone 4H11, were tested in CD34+ leukemic cell lines (MOLM-9, JURL-MK1, HEL) and CD34- cell lines (PS-1, ML-2 and CTV-1). We have found that the monoclonal antibody to CD34 inhibited the proliferation and induced apoptosis of all CD34+ cell lines. We did not observe induction of differentiation by anti-CD34 antibody, but a growth arrest of cells in the G0/G1 phase of the cell cycle was detected in all the cell lines studied. Combinations of anti-CD34 antibody with both type I (alpha, beta) or type II (gamma) interferons did not enhance the effects on the cell growth or inhibition of cellular proliferation of the antibody alone. Our data suggest that the monoclonal antibody to CD34 molecule prepared from clone 4H11, after sufficient experimental and preclinical testing on laboratory animals, may provide a new basis for targeted antibody therapy of acute or chronic myeloid leukemia.
The antiproliferative and antitumor effect of wheat leaf ribonuclease was tested in vitro on the human ML-2 cell line and in vivo on athymic nude mice bearing human melanoma tumors. The antiproliferative activity of this plant ribonuclease was negligible in comparison with bovine seminal ribonuclease. In the experiments in vivo, a significant decrease of the tumor size, however, was observed in the mice treated with wheat leaf ribonuclease (27 kDa) compared with the control RNase A and polyethylene glycol. In nude mice injected intratumoraly with wheat leaf ribonuclease, the tumor size decreased from 100% in the control mice to 39% in treated mice. In the mice treated with polyethylene glycol-conjugated wheat leaf ribonuclease, the tumor reduction was observed from 100 to 28%, whereas in counterparts treated with polyethylene glycol-conjugated bovine seminal ribonuclease the tumor inhibition was reduced from 100 to 33%. Certain aspermatogenic and embryotoxic activity of wheat leaf ribonuclease and bovine seminal ribonuclease also appeared, but was lower in comparison with the effect of onconase. Mutual immunological cross-reactivity between wheat leaf ribonuclease antigens on one side and animal RNases (bovine seminal ribonuclease, RNase A, human HP-RNase and onconase) on the other side proved a certain structural similarity between animal and plant ribonucleases. Immunogenicity of wheat leaf ribonuclease was weaker in comparison with bovine seminal ribonuclease (titer of antibodies 160-320 against 1280-2560 in bovine seminal ribonuclease). Interestingly, immunosuppressive effect of wheat leaf ribonuclease tested on mixed lymphocyte culture-stimulated human lymphocytes reached the same level as that of bovine seminal RNase. The antibodies against wheat leaf ribonuclease produced in the injected mice did not inactivate the biological effect of this plant RNase in vivo. This is probably the first paper in which plant ribonuclease was used as antiproliferative and antitumor drug against animal and human normal and tumor cells and tissues in comparison with animal ribonucleases.
- MeSH
- embryo savčí účinky léků MeSH
- financování organizované MeSH
- fytogenní protinádorové látky izolace a purifikace terapeutické užití toxicita MeSH
- imunosupresiva MeSH
- injekce intraperitoneální MeSH
- lidé MeSH
- listy rostlin chemie MeSH
- lymfocyty imunologie účinky léků MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie terapie MeSH
- polyethylenglykoly MeSH
- proliferace buněk účinky léků MeSH
- pšenice enzymologie MeSH
- ribonukleasy MeSH
- spermatogeneze účinky léků MeSH
- těhotenství MeSH
- testis patologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Previously we have shown that monomeric RNase A has no significant biological activity, whereas its oligomers (dimer to tetramer) prepared by lyophilizing from 50% acetic acid solutions, show remarkable aspermatogenic and antitumor activities. Furthermore, conjugates prepared by chemical binding of native RNase A to polyethylene glycol (PEG) have shown a significant aspermatogenic and antitumor activities. In this work we show that the chemical conjugation of PEG to the RNase A C-dimer, and to the two RNase A trimers (NC-trimer and C- trimer) decreases the aspermatogenic activity of the oligomers while increasing their inhibitory activity on the growth of the human UB900518 amelanotic melanoma transplanted in athymic nude mice. Moreover, the PEG-conjugated RNaseA oligomers are devoid, like the free oligomers, of any embryotoxic activity.
- MeSH
- antispermatogenní látky farmakologie MeSH
- dimerizace MeSH
- embryo savčí účinky léků MeSH
- lidé MeSH
- melanom experimentální farmakoterapie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- pankreatická ribonukleasa farmakologie chemie MeSH
- peptidové fragmenty farmakologie chemie MeSH
- polyethylenglykoly farmakologie chemie MeSH
- protinádorové látky farmakologie chemie MeSH
- spermatogeneze účinky léků MeSH
- transplantace nádorů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- antispermatogenní látky farmakologie MeSH
- embryo savčí účinky léků MeSH
- endonukleasy specifické pro jednořetězcové nukleové kyseliny * farmakologie imunologie MeSH
- experimentální nádory * farmakoterapie MeSH
- fazol * enzymologie MeSH
- lidé MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- pankreatická ribonukleasa farmakologie imunologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie MeSH
- spermatogeneze účinky léků MeSH
- spermie účinky léků MeSH
- teratogeny farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
