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The preparation and characterization of polymeric, enzymatically cleavable carriers for cancerostatic drugs
Zelený, Jan ; Etrych, Tomáš (advisor) ; Ječmen, Tomáš (referee)
As the development of cancerostatic drugs progresses it is becoming necessary to contemplate the question of how to deliver these drugs, which themselves tend to exhibit carcinogenic properties, effectively and accurately to the affected tissues and thus to circumvent their destructive effects upon the healthy parts of the organism. One approach to delivering drugs selectively to cancerous tissues is to make use of some of the specific properties which these tissues tend to possess, one of which being the so-called enhanced permeability and retention effect (EPR effect). This effect, which will be further discussed within this thesis, allows for macromolecules that are too massive to pass from the bloodstream into healthy tissue, to exit the blood vessels of cancerous tissue and to accumulate there. Therefore, a drug molecule can specifically enter cancerous tissue along with a suitable macromolecule, to which it is conveniently attached. If, moreover, the given drug is connected to the carrier molecule via an enzymatically cleavable spacer, it is possible to make use of lysosomal proteases (such as cathepsin B, which is overexpressed in some cancer cells) in order to attain its detachment from the carrier molecule and its subsequent activation. This bachelor thesis focuses on describing the...
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The preparation and characterization of polymeric, enzymatically cleavable carriers for cancerostatic drugs
Zelený, Jan ; Etrych, Tomáš (advisor) ; Ječmen, Tomáš (referee)
As the development of cancerostatic drugs progresses it is becoming necessary to contemplate the question of how to deliver these drugs, which themselves tend to exhibit carcinogenic properties, effectively and accurately to the affected tissues and thus to circumvent their destructive effects upon the healthy parts of the organism. One approach to delivering drugs selectively to cancerous tissues is to make use of some of the specific properties which these tissues tend to possess, one of which being the so-called enhanced permeability and retention effect (EPR effect). This effect, which will be further discussed within this thesis, allows for macromolecules that are too massive to pass from the bloodstream into healthy tissue, to exit the blood vessels of cancerous tissue and to accumulate there. Therefore, a drug molecule can specifically enter cancerous tissue along with a suitable macromolecule, to which it is conveniently attached. If, moreover, the given drug is connected to the carrier molecule via an enzymatically cleavable spacer, it is possible to make use of lysosomal proteases (such as cathepsin B, which is overexpressed in some cancer cells) in order to attain its detachment from the carrier molecule and its subsequent activation. This bachelor thesis focuses on describing the...
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Immunochemical determination of active and inactive form of cathepsin B in patients with bladder cancer
Urban, Tomáš ; Bosáková, Zuzana (advisor) ; Klapková, Eva (referee)
This thesis is focused on immunochemical determination of concentration of active and inactive form of cathepsin B in patients with bladder cancer in order to compare diagnostic efficiency of methods for their possible use for routine diagnosis. Cathepsin B and procathepsin B were measured in serum and urine in 82 patients with bladder cancer (47 men and 35 women), with the average age of 66.5 year. The control group contain of 72 healthy subjects (31 men and 41 women), with the average age of 58.5 year. The concentration of cathepsin B and procathepsin B in the urine were corrected to creatinine, which was determined by the enzymatic creatinase method. The concentrations of cathepsin B in urine were singnificantly elevated in patients than in control group (median = 3.5 µg/l vs. 0.9 µg/l, P = 0.01), similarly the results of the cathepsin B/creatinine ratio were elevated (median = 0.4 µg/mmol vs. 0.1 µg/mmol, P = 0.01). There were no significant difference in concentration in serum between patients and control group (median = 4.8 µg/l vs. 4.2 µg/l, P = 0.8). The concentration values of procathepsin B were significantly higher in patients compare to control group both in urine (median = 3.9 µg/l vs. 1.4 µg/l, P < 0.0001), in serum (median = 73.3 µg/l vs. 58.7 µg/l, P = 0.0005) and similarly in...
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Role of glial cells in the immune response of mice infected by neurotropic fluke Trichobilharzia regenti
Macháček, Tomáš ; Panská, Lucie (advisor) ; Kopecký, Jan (referee)
A central nervous system (CNS) can be invaded by plenty of parasites, including parasitic helminths. Host's immune response during such infections includes not only participation of peripheral lymphocytes, but also astrocytes and microglia, resident glial cells present in the CNS. Activation of astrocytes and microglia has been recently demonstrated also in mice infected by neurotropic avian trematode Trichobilharzia regenti (Digenea: Schistosomatidae) for which mammals represent accidental hosts. The parasite does not mature in them and elicits development of inflammatory reaction in the CNS which may take part in parasite's destruction. Employing in vitro experiments, this thesis aimed at evaluation of the possible role of astrocytes and microglia in murine immune response to T. regenti. For this purpose, primary astrocyte and microglia culture preparations were established and the cells were then stimulated by antigens of T. regenti (homogenate of transformed cercariae, recombinant cathepsins B1.1 and B2). After that, production of nitric oxide and proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) was measured. The results revealed that in vitro stimulated astrocytes and microglia increase production of nitric oxide, IL-6 and TNF-alpha. Such response to parasite's antigens could influence...
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Potentials and limits of RNA interference in the tick \kur{Ixodes ricinus}
MUSIL, František
The function of chitin binding protein (CBP) and two isoforms of cathepsin B (cathB1, cathB2) were tested by using RNA interference in the tick I. ricinus. Two different methods have been used to deliver dsRNA for RNAi in ticks {--} injection and capillary feeding. The synthesized dsRNA was used to find out the impact of RNAi in the tick tissues, which were tested by RT-PCR and Western blot. The expression of CBP was successfully silenced by RNAi in the salivary glands. The silencing of cathB1 and cathB2 in the gut was less effective, but still limited tick`s ability to feed.
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