National Repository of Grey Literature 43 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Gradual Molecular Changes in Primary Porcine Cells Expressing Mutated Huntingtin
Šmatlíková, Petra ; Motlík, Jan (advisor) ; Trejbalová, Kateřina (referee) ; Reiniš, Milan (referee)
Huntington's disease (HD) is inherited fatal disorder caused by CAG triplet expansions in the huntingtin gene resulting in the expression of mutated huntingtin protein (mtHtt). The main symptoms of HD are neurodegeneration, osteoporosis, testicular degeneration, loss of muscle tissue and heart muscle malfunction, weight loss, metabolic changes, and sleeping disturbances. Since huntingtin protein (Htt) has a role in several biological processes, many molecular mechanisms, like oxidative stress, mitochondrial dysfunction, DNA-damage, and others, are affected by mtHtt. However, its exact pathogenic mechanisms in HD are still not well understood. Transgenic minipig model of HD (TgHD) serves an opportunity to isolate unlimited number of primary cells and unlike primary cells obtained from HD patients, often in the late stages of the disease, the TgHD minipig model allows to monitor molecular changes occurring gradually with age and progression of the disease. Thus, TgHD minipig model and primary cells isolated from it play an important role in investigating and understanding the underlying mechanistic cause of HD. We focused on molecular and cellular changes in primary cells isolated from TgHD minipigs and their wild type (WT) controls at different ages (24, 36, and 48 months). In mesenchymal stem cells...
Molecular mechanisms of apoptosis induction by taxanes in breast cancer cells
Jelínek, Michael ; Kovář, Jan (advisor) ; Brábek, Jan (referee) ; Reiniš, Milan (referee)
Taxanes are cytostatic routinely used for the treatment of solid breast, ovarian, prostate, head and neck tumors and other types of tumors. Resistance of tumor cells to the effect of taxanes represents serious obstacle for the employment of taxanes in the treatment of tumors. This resistance can be associated, among other things, with lower rate of apoptosis induction in cancer cells or also with increased level of transporters transporting taxanes out of the cell. In this PhD thesis we tried: (1) to contribute to elucidation of the role of molecular mechanisms of apoptosis induction by taxanes in cells of human breast cancer. Specifically, it meant to contribute to elucidation of the role of initiator caspase -8 a - 9 and mainly of initiator caspase-2. Next, to contribute to elucidation of the role of executioner caspase -3 - 6, and -7 and selected proteins of the Bcl-2 family. (2) To contribute to elucidation of molecular mechanisms of resistance of human breast cancer cells to taxanes. Specifically, it meant to describe the role of selected functional groups in taxane structure in bringing about and overcoming resistance to taxane and next to contribute to elucidation of the role of P-glycoprotein (ABCB1 transporter) in the resistance to individual taxanes. 1) We found that caspase-2 represents...
Development of therapeutic vaccine against HPV-16 induced tumor- influence of E7 antigen modification on cell madiated immune response
Macková, Jana ; Němečková, Šárka (advisor) ; Eckschlager, Tomáš (referee) ; Reiniš, Milan (referee)
Conclusions We constructed the vaccines carrying IIPV-16 E7 antigen based on .B. pertussisCyaA toxin We introduced ELISPOT and MHC-I totaÍner assays for testing of cell-mediarcdimmrmeresponsein themousemodel We tested cell-mediated immune response following immunization with differentkinds of thevaccinescarryingthemodifiedHPV-16 E7 antigen: o Recombinantadenylďe cyclase toxoid CyaA336IE7 is able to induce E7 specific CDE- cellular immuneresponsein mice and proteď them againstTC-l firmorgrowth o Some DNA vaccines carying the E7 genefusď to anothergeneare able to induoe betteranti-tumorimmuneresponsethan non-modified E7 genein mice @NA vaccinesevďuated accordingto themagpitude of CTL responseinduced: ETCTGG.GUS > ETGGGHSP, ETHSP >> cP-E7 >E7) o Fusion of E7 with W hemagglutininleadsto cell-surfaceexpressionof E7 and following vaccinďion with W.E7.HA it induces Th-2 polarized immuner€spons€ type ďong with the absenceof anti.tumor Th-l response o Co-expression of IL-12 from double recombinant vaccinia virus (W.IL-l2-sig/E7|LAI\D) reducesCD8- cellular immuniý inducedby Sig/E7lLAMP o Immunization with dendritic cells transducedby rW improves the efficacy of rW vaccination o Combined immunization increases vaccination effectiveness (CyaA336/E7+MVA- Sig/E7lLAMP, DNA-SigETGGG/LAMP+cellular vaccine) I7
Epigenetic regulation of HLA class II genes and their role in autoimmune diseases
Čepek, Pavel ; Černá, Marie (advisor) ; Štechová, Kateřina (referee) ; Reiniš, Milan (referee)
(EN) Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with HLA (human leukocyte antigen) class II genes, including HLA-DQA1 gene. Our aim was to investigate DNA methylation of HLA-DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA-DQA1 allele expression of T1D patients and healthy controls. DNA methylation is one of the epigenetic modifications, that regulate gene expression and is known to be shaped by the environment. 61 T1D patients and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulfite and HLA-DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA-DQA1 promoter alleles was analyzed. Individual mRNA HLA-DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA-DQA1 allele 02:01 expression (PPIA normalization, Pcorr=0.041; DRA normalization, Pcorr=0.052) between healthy controls and T1D patients. The complete methylation profile of the HLA-DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in T1D patients and healthy...

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