Wyniki wyszukiwania - Biblioteka Nauki

1

Modelling tumour-immunity interactions with different stimulation functions

100%

Zhivkov P. , Waniewski J.

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nr 3

307-315

EN

Tumour immunotherapy is aimed at the stimulation of the otherwise inactive immune system to remove, or at least to restrict, the growth of the original tumour and its metastases. The tumour-immune system interactions involve the stimulation of the immune response by tumour antigens, but also the tumour induced death of lymphocytes. A system of two non-linear ordinary differential equations was used to describe the dynamic process of interaction between the immune system and the tumour. Three different types of stimulation functions were considered: (a) Lotka-Volterra interactions, (b) switching functions dependent on the tumour size in the Michaelis-Menten form, and (c) Michaelis-Menten switching functions dependent on the ratio of the tumour size to the immune capacity. The linear analysis of equilibrium points yielded several different types of asymptotic behaviour of the system: unrestricted tumour growth, elimination of tumour or stabilization of the tumour size if the initial tumour size is relatively small, otherwise unrestricted tumour growth, global stabilization of the tumour size, and global elimination of the tumour. Models with switching functions dependent on the tumour size and the tumour to the immune capacity ratio exhibited qualitatively similar asymptotic behaviour.

2

In vitro co-stimulation of anti-tumor activity by soluble B7 molecules

100%

He W. , Hu Z.-B. , Liu F. , Feng X.-Q. , Zou P.

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nr 4

807-813

EN

In order to investigate the anti-tumor activity of a soluble B7-1/immunoglobulin G fusion protein and explore an effective method to eliminate immune escape of tumor cells, a recombinant vector encoding this fusion protein was constructed and constitutively expressed in Chinese hamster ovary cells. After purification with protein G affinity chromatography, the soluble fusion protein was tested for bioactivity. Results showed that the fusion protein could significantly increase the density of B7-1 molecules on WEHI-3 cells, a mouse leukemia cell line. Through allogeneic mixed lymphocyte tumor cultures, it was demonstrated that, with the presence of the first signal, it could also significantly enhance T cell activation and killing activity against WEHI-3 cells and interleukin-2 secretion by activated mouse T lymphocytes. The conclusion can be drawn that the soluble B7-IgG fusion protein has a potent capacity to generate or enhance anti-tumor immune response in vitro, and its clinical value deserves further investigation.

3

Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes

100%

Łuczyński W. , Wawrusiewicz-Kurylonek N. , Stasiak-Barmuta A. , Urban R. , Iłendo E. , Urban M. , Hryszko M. , Krętowski A. , Górska M.

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nr 2

361-370

EN

Diabetes mellitus is one of the most common chronic diseases in children. T regulatory cells (Tregs) modulate response to autoantigens and probably play a role in pathogenesis of type 1 diabetes (T1DM). The aim of the present study was the assessment of T regulatory cells including their percentages and expression of critical genes in these cells in children with newly diagnosed type 1 diabetes. The examined group consisted of 50 children with T1DM. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD4, anti-CD25 and anti-CD127 (=IL-7R). Additionally, T regulatory cells were isolated for assessment of mRNA levels for chosen genes with the real-time RT-PCR technique. The percentages of CD4+CD25highCD127dim/- were very low and did not differ between T1DM and control children. We did not observe any statistically significant differences between healthy and diabetic children in mRNA expression for FoxP3, IL-7R (CD127), IL-8RA, IL-10RA, IL-12A, IL-2RA (CD25), IL-21, STAT1, STAT3, SOCS2, SOCS3, TGF-β1-R1, TGF-β-R2 and TBX-21 genes. Interestingly the mRNA level for CTLA-4, ICOS1, IL-23, IL-27, SMAD3 and GITR were lower in Treg cells of children with diabetes compared to the control patients. No disturbances in the percentages of T regulatory cells in patients with diabetes but diminished expression of some elements important in Treg function could be the result of an immunologic imbalance accompanying the onset of the diabetes. The results of our study should be used in future research in the field of immunotherapy in pediatric diabetes.

4

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

88%

Łuczyński W. , Stasiak-Barmuta A. , Iłendo E. , Krawczuk-Rybak M. , Malinowska I. , Mitura-Lesiuk M. , Parfieńczyk A. , Szymański M.

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nr 2

377-382

EN

Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4. Results: 1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [3H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.

5

Salmonella and cancer: from pathogens to therapeutics

75%

Chorobik P. , Czaplicki D. , Ossysek K. , Bereta J.

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nr 3

285-297

EN

Bacterial cancer therapy is a concept more than 100 years old - yet, all things considered, it is still in early development. While the use of many passive therapeutics is hindered by the complexity of tumor biology, bacteria offer unique features that can overcome these limitations. Microbial metabolism, motility and sensitivity can lead to site-specific treatment, highly focused on the tumor and safe to other tissues. Activation of tumor-specific immunity is another important mechanism of such therapies. Several bacterial strains have been evaluated as cancer therapeutics so far, Salmonella Typhimurium being one of the most promising. S. Typhimurium and its derivatives have been used both as direct tumoricidal agents and as cancer vaccine vectors. VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.

6

Immunologiczne aspekty choroby Alzheimera

75%

Wojtera M. , Kłoszewska I. , Sobów T. , Liberski P. P.

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nr 2

108-115

EN

Alzheimer’s disease (AD) is an incurable neurodegenerative disease, which is accompanied by chronic inflammation. The immune system has an important role in the process of the disease. The deposition of amyloid β (Aβ) protein is a key pathological feature in Alzheimer’s disease. This article reviews immunotherapeutic strategies against AD. In murine models of AD, both active and passive immunization against Aβ induces a marked reduction in an amyloid brain burden and an improvement in cognitive functions. The findings from murine studies lead to clinical studies. One Phase II clinical trial of active immunization against Aβ was discontinued after 18 patients developed meningoencephalitis. After this lesson learned, new immunotherapeutic strategies, including both active and passive immunization, are investigated in clinical centers.

PL

Choroba Alzheimera (AD) jest nieuleczalną chorobą neurodegeneracyjną, której towarzyszy przewlekły proces zapalny. Układ immunologiczny może mieć istotny wpływ na przebieg procesu chorobowego. Głównym patologicznym wyznacznikiem choroby Alzheimera jest gromadzenie w obrębie mózgu złogów β-amyloidu. W obecnym artykule przedstawiono informacje na temat możliwości zastosowania immunoterapii w leczeniu choroby Alzheimera. Metody immunoterapeutyczne, mające usuwać amyloid β z chorych mózgów, dały bardzo pozytywne rezultaty w badaniach na zwierzętach. Zarówno metody aktywnej, jak i biernej immunizacji powodowały wyraźne zmniejszenie zawartości amyloidu w mózgach myszy transgenicznych oraz poprawę ich funkcji poznawczych. Bardzo dobre wyniki na modelach zwierzęcych pozwoliły przeprowadzić wstępne badania kliniczne. Ich wyniki są również obiecujące, choć obarczone ryzykiem zapalenia mózgu. Jedyne dotychczas badanie II Fazy z zastosowaniem szczepionki przeciwko Aβ zostało przerwane z powodu rozwoju u 18 pacjentów zapalenia opon mózgowych i mózgu. Obecnie ośrodkach badawczych pojawiają się nowe rodzaje technik immunoterapeutycznych.

7

Cardiovascular complications of selected antibodies used in oncological immunotherapy

75%

Kufel-Grabowska J.

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nr 2

78-82

EN

Immunotherapy supports other therapeutic methods and is an important element in the fight against cancer. Its main tasks include stimulation and guidance of the immune system to fight cancer, inhibition of the mechanisms that block the immune system, and direct destruction of neoplastic cells. Different from chemotherapy or hormonal therapy, its mechanism of action is associated with a different profile of adverse events. HER2 receptor inhibitors may cause symptoms of heart failure, which usually recede, once the treatment has been discontinued. Bevacizumab, an anti-VEGF antibody, induces numerous cardiovascular complications, including arterial hypertension, arterial embolism, haemorrhage and haemoptysis as well as venous thromboembolism.

8

High efficacy of methotrexate in patients with recurrent idiopathic acute anterior uveitis: a prospective study

75%

Bachta A. , Kisiel B. , Tlustochowicz M. , Raczkiewicz A. , Rekas M. , Tlustochowicz W.

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nr 1

9

Cancer immunogene therapy

75%

Yoshizawa H. , Kagamu H. , Gejyo F.

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2001

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tom 49

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nr 5

10

Immunotherapy in Gram-negative bacterial infections

75%

Lugowski C.

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nr 1

EN

Endotoxins are responsible for initiation of septic shock which increases the number of fatalities in Gram-negative bacteremia among hospital patients. The morality from septic shock is still high despite recent developments in antibiotic therapy because antibiotics are unable to decrease the level of free lipopolysaccharide in the blood stream. Another approach to the treatment and prevention of septicaemia involves stimulation of an immune response against LPS. It was found that immunization with the core structures of endotoxin conjugated with proteins protected animals against infections and endotoxic shock. Anticonjugate sera are of great interest because they are directed against conserved parts of LPS and therefore could have cross-reactive and cross-protective properties with respect to many Gram-negative rods.

11

GK1 improves the immune response induced by dendritic cells of BALB/c mice infected with Leishmania mexicana promastigotes

63%

Gutierrez-Kobeh L. , Wilkins-Rodriguez A. A.

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nr 1

12

Reestablishing T cell tolerance by antibody-based therapy in type 1 diabetes

63%

Morillon Y. M. , Martin A. , Gojanovich G. , Wang B. , Tisch R.

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nr 4

13

Rebalancing immune specificity and function in cancer by T-cell receptor gene therapy

63%

Udyavar A. , Geiger T. L.

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nr 5

335-346

14

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

63%

Zhong W. , Fei M. , Zhu Y. , Zhang X.

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nr 4

587-608

EN

Dendritic cells (DC) are professional antigen-presenting cells capable of initiating primary immune responses. They have been intensively studied and are used in both basic immunology research and clinical immunotherapy. However, the genetic pathways leading to DC differentiation and maturation remain poorly understood. Using focused microarrays with oligonucletotide probes for 120 genes encoding co-stimulatory molecules, chemokines, chemokine receptors, cytokines, cytokine receptors, TLRs, and several other related molecules, we analyzed the kinetics of gene expression for the overall differentiation process of monocytes into mature DC. In parallel, we compared the transcriptional profiles in DC maturation in the presence of LPS, TNF-α or trimeric CD40L. We found similar transcriptional profiles for early immature DC and immature DC, respectively generated by culturing monocytes with GM-CSF and IL-4 for three or six days. We identified sets of common and stimuli-specific genes, the expression of which changed following stimulation with LPS, TNF-α or CD40L. A dynamic analysis of the entire DC differentiation and maturation process showed that some important inflammatory and constitutive chemokines are transcribed in both immature and mature DC. The correlative expression kinetics of the gene pairs IL1R1/IL1R2, IL15/IL15RA, DC-SIGN/ICAM-2 and DC-SIGN/ICAM-3 imply that they all play crucial roles in mediating DC functions. Thus, our analysis with focused microarrays shed light on the transcriptional kinetics of DC differentiation and maturation, and this method may also prove useful for identifying novel marker genes involved in DC functions.

15

Nonviral transfection of human umbilical cord blood dendritic cells is feasible, but the yield of dentritic cells with transgene expression limits the application of this method in cancer immunotherapy

63%

Markowicz S. , Niedzielska J. , Kruszewski M. , Oldak T. , Gajkowska A. , Machaj E. K. , Skurzak H. , Pojda Z.

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nr 1

EN

Dendritic cells (DC) generated from human umbilical cord blood might replace patients' DC in attempts to elicit tumor-specific immune response in cancer patients. We studied the efficiency of transfection of human cord blood DC with plasmid DNA carrying the enhanced version of green fluorescent protein (EGFP) as a reporter gene, to test if nonviral gene transfer would be a method to load DC with protein antigens for immunotherapy purposes. Cord blood mononuclear cells were cultured in serum-free medium in the presence of granulocyte-monocyte colony stimulating factor (GM-CSF), stem cell factor (SCF) and Flt-3 ligand (FL), to generate DC from their precursors, and thereafter transfected by electroporation. Maturation of DC was induced by stimulation with GM-CSF, SCF, FL and phorbol myristate acetate (PMA). Transfected DC strongly expressed EGFP, but transfection efficiency of DC, defined as HLA-DR+ cells lacking lineage-specific markers, did not exceed 2.5%. Expression of the reporter gene was also demonstrated in the DC generated from transfected, purified CD34+ cord blood cells, by stimulation with GM-CSF, SCF, FL, and tumor necrosis factor α (TNF-α). Transfection of CD34+ cells was very efficient, but proliferation of the transfected cells was much reduced as compared to the untransfected cells. Therefore, the yield of transgene-expressing DC was relatively low. In conclusion, nonviral transfection of cord blood DC proved feasible, but considering the requirements for immunotherapy in cancer patients, transfection of differentiated DC or generation of DC from transfected hematopoietic stem cells provide only a limited number of DC expressing the transgene.

16

Cancer immunotherapy using cells modified with cytokine genes

63%

Kowalczyk D. W. , Wysocki P. J. , Mackiewicz A.

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tom 50

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nr 3

EN

The ability of various cytokines to hamper tumor growth or to induce anti-tumor immune response has resulted in their study as antitumor agents in gene therapy approaches. In this review we will concentrate on the costimulation of antitumor immune responses using modification of various cell types by cytokine genes. Several strategies have emerged such as (i) modification of tumor cells with cytokine genes ex vivo (whole tumor cell vaccines), (ii) ex vivo modification of other cell types for cytokine gene delivery, (iii) delivery of cytokine genes into tumor microenvironment in vivo, (iv) modification of dendritic cells with cytokine genes ex vivo. Originally single cytokine genes were used. Subsequently, multiple cytokine genes were applied simultaneously, or in combination with other factors such as chemokines, membrane bound co-stimulatory molecules, or tumor associated antigens. In this review we discuss these strategies and their use in cancer treatment as well as the promises and limitations of cytokine based cancer gene therapy. Clinical trials, including our own experience, employing the above strategies are discussed.

17

CD3plus/CD16plusCD56plus cell numbers in peripheral blood are correlated with higher tumor burden in patients with diffuse large B-cell lymphoma

51%

Hus I. , Staroslawska E. , Bojarska-Junak A. , Dobrzynska-Rutkowska A. , Surdacka A. , Wdowiak P. , Wasiak M. , Kusz M. , Twardosz A. , Dmoszynska A. , Rolinski J.

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tom 49

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nr 1

18

Expanding and converting regulatory T cells: a horizon for immunotherapy

51%

Khattar M. , Chen W. , Stepkowski S. M.

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nr 3

199-204

19

Prostate cancer and immunoproteome: awakening and reprogramming the Guardian Angels

51%

Farooqi A. A. , Fayyaz S. , Qureshi M. Z. , Rashid S.

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nr 3