- Publikační typ
- abstrakt z konference MeSH
Autoři popisují případ 22leté ženy kavkazské rasy s pátou a šestou recidivou prurigo pigmentosa v souvislosti s redukcí hmotnosti o 20 kg, které obě odezněly během tří týdnů po jednorázové intramuskulární aplikaci betametazonu. Klinickopatologická korelace obou atak je dokumentována. Současné poznatky o tomto onemocnění a o možnostech jeho léčby jsou uvedeny v přehledu. Jedná se o první popsaný případ v české literatuře.
The authors describe a case of a 22-year-old Caucasian patient who experienced the fifth and the sixth flare-ups of the skin rash diagnosed as prurigo pigmentosa which coincided with voluntary body weight loss of 20 kg. Both flare-ups subsided within three weeks after one-off intramuscular application of betamethasone. Clinicopathological correlation of these two attacks is documented. Current knowledge about this
- Klíčová slova
- prurigo pigmentosa,
- MeSH
- běloši MeSH
- betamethason terapeutické užití MeSH
- hmotnostní úbytek MeSH
- lidé MeSH
- mladý dospělý MeSH
- prurigo diagnóza farmakoterapie patofyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Among malignant diseases, chronic myeloid leukaemia (CML) is one of the best suited candidates for immunotherapy. For this purpose it is necessary to broaden the present knowledge on the immunology of this disease. As a part of such a project, the levels of kynurenine (KYN) and neopterin (NPT) were studied in 28 CML patients and in the same number of healthy subjects. At diagnosis, both KYN and NPT levels were found to be elevated in a significant portion of the patients and dependent on their leukocyte count. As in the case of KYN, increased NPT levels dropped after achieving remission. When correlating KYN and NPT levels with a selection of other markers tested, significant association was revealed only in the case of CRP and IL-6. However, there were several patients with increased KYN levels in whom NPT was not detected, and vice versa. The relapse of the disease observed in two patients was accompanied by an increased level of NPT in both cases, but by an increased level of KYN in only one of them. No significant correlation was found between KYN and NPT levels in sera taken at diagnosis. However, when the whole set of sera was taken into consideration, the association became statistically significant. Although the data obtained revealed a number of similarities between KYN and NPT production in CML patients, it also suggested a difference in the kinetics of these two biomarkers' production.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- chronická myeloidní leukemie krev MeSH
- dospělí MeSH
- interleukin-6 krev MeSH
- kynurenin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- mladý dospělý MeSH
- neopterin krev MeSH
- počet leukocytů MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tryptofan krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
1 svazek : ilustrace, tabulky ; 30 cm
Determination of the effects of chronic myeloid leukemia (CML) on immune profile of patient in dependence of its treatment modalities and the results of its treatment. Examination of leukemic cells, sampled prior to any therapy, for the presence of 15-20 selected antigens, determination of the cellular and humoral immunity to these antigens, and correlation of the findings with the clinical picture. An attempt to determine the optimal time for administering the anti-tumor vaccine-to-be using a mathematical model recently constructed.
Určení vlivu chronické myeloidní leukémie (CML) na imunitní profil pacienta v závislosti na způsobu a výsledků léčby. Stanovení antigenního složení leukemických buněk odebraných před zahájením terapie a určení buněčné a humorální imunity proti těmto antigenům a korelace nálezů s klinickým obrazem. Vytvoření matematického modelu pro určení optimální doby pro podání budoucí protinádorové vakcíny. Studie by měla objasnit komplex problémů, které se týkají dosud neznámých aspektů interakce mezi nádorovými buňkami a imunitním systémem pacientů s CML. Tyto poznatky by měly dále pootevřít dveře pro vývoj vakcíny k terapii této nemoci a snad i dalších myeloidních malignit. Znalost imunitního stavu jednotlivých pacientů umožní personalizovat jiné terapeutické postupy a tak přispěje k optimalizaci léčby.
Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-α, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.
- MeSH
- biologické markery krev MeSH
- chronická myeloidní leukemie * MeSH
- dospělí MeSH
- indolamin-2,3,-dioxygenasa MeSH
- kynurenin * krev MeSH
- kyselina močová * MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- tryptofan * krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
Although chronic myeloid leukemia is a rare malignancy, it has developed into a model system for the study of a variety of aspects of cancer biology and immunology. The introduction of tyrosine kinase inhibitors has resulted in a significant prolongation of the survival rates of chronic myeloid leukemia patients but has not resulted in a cure. There is a growing conviction that this aim can be achieved through immunotherapy. For this concept to be successful, a considerable increase in the present understanding of chronic myeloid leukemia immunology is required. The authors attempt to review and evaluate the current findings that demonstrate a number of immunological aberrations in patients prior to the start of any therapy and their normalization after achieving remission. They also discuss the recent clinical trials with experimental therapeutic vaccines and then present their own strategy on how to address the problem.
- MeSH
- chronická myeloidní leukemie imunologie terapie MeSH
- imunoterapie * MeSH
- indukce remise MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- protinádorové vakcíny * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In the recent past, it has repeatedly been reported that CD4 cells play an important role in the immunology of chronic myeloid leukaemia. It was therefore of interest to test their activity in an animal model using bcr-abl-transformed cells. BALB/c mice were four times immunized with a DNA vaccine carrying the bcr-abl fusion gene. Two weeks after the last vaccine dose, the animals were challenged with syngeneic bcr-abl-transformed 12B1 cells which form solid tumors after subcutaneous administration. At the time of challenge, animals were treated with antibodies against the CD8+ T cells or CD4+ T cells. The efficacy of the depletion was monitored and found highly effective. All nonimmunized animals developed tumors. All animals untreated with the antibodies as well as those in which CD8+ T cells had been depleted, were fully protected against the challenge. On the other hand, almost all mice treated with anti-CD4+ antibody developed tumors. These results strongly suggested that the CD4+ T cells acted as effectors in the present system.
- MeSH
- antigeny CD95 imunologie metabolismus MeSH
- bcr-abl fúzové proteiny genetika imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- CD8-pozitivní T-lymfocyty imunologie metabolismus MeSH
- DNA vakcíny imunologie MeSH
- histokompatibilita - antigeny třídy II imunologie metabolismus MeSH
- imunizace MeSH
- lidé MeSH
- ligand Fas metabolismus MeSH
- lymfocytární deplece MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorová transformace buněk genetika imunologie MeSH
- nádory genetika imunologie mortalita prevence a kontrola MeSH
- protinádorové vakcíny genetika imunologie MeSH
- slezina cytologie imunologie MeSH
- transformované buněčné linie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
B210 cells are murine (BALB/c) cells transformed by bcr-abl fusion gene. After intravenous administration they are capable of inducing leukaemia-like disease in syngeneic mice. From these cells a thymidine-kinase less subline was derived. It was significantly less pathogenic than the parental cells. However, a highly pathogenic clone denoted B210cTK-/cl-2 was isolated from its population. As determined by Western blotting, these cells produced more p210 protein than the parental B210 cells. To successfully transfect these cells a modified electroporation method was introduced. Bicistronic plasmids carrying gene for herpes simplex thymidine kinase (HSV TK) and the gene for either granulocyte-monocyte colony stimulation factor (GM-CSF), interleukin-2 (IL-2) or interleukin 12 (IL-12) were used for the transfection experiments. Gradually, cell lines producing these cytokines were isolated in media supplemented with hypoxantin, aminopterin and thymidine (HAT). All of them were highly sensitive to ganciclovir in vitro confirming that the cells produced HSV TK. The genetic modification of B210cTK-/cl-2 was associated neither with the alteration of p210 bcr-abl production nor with any changes in expression of MHC class I molecules. From populations of each of the three lines several cell clones were isolated and tested for the production of the respective cytokines. The original uncloned population and several clones differing in the cytokine production were administered intravenously into mice. All animals survived without symptoms of the disease suggesting that the gene-modification was associated with the loss of pathogenicity. Keywords: CML, Bcr-Abl, HSV TK, cytokines, gene-modified tumour cells, pathogenicity.
- MeSH
- adjuvancia imunologická genetika MeSH
- bcr-abl fúzové proteiny analýza MeSH
- cytokiny biosyntéza genetika MeSH
- ganciklovir terapeutické užití MeSH
- geny abl MeSH
- histokompatibilita - antigeny třídy I analýza MeSH
- histokompatibilita - antigeny třídy II analýza MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nádorová transformace buněk MeSH
- thymidinkináza genetika MeSH
- transfekce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
