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M Adamek

Publications and source records attributed to M Adamek.

10 recordsLinked to original sources

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.

Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.

Animals↗

Photodynamic therapy of premalignant lesions and local recurrence of laryngeal and hypopharyngeal cancers.

The main advantage of photodynamic therapy (PDT) in laryngology seems to be its non-invasiveness and the possibility of using it despite previous application of conventional methods. In the study, we gave PDT to two separate groups of patients, i.e. five patients with advanced tumour (four of them with local recurrence (squamous cell carcinoma) after surgery and radiotherapy and one with a primary hypopharyngeal tumour) and five patients with leucoplakia. In the first group delta-aminolaevulinic acid (ALA) was administered orally (dose 3 g), while in the second, an ointment containing 10% ALA was applied locally. In both groups prior to irradiation, the tissue level of protoporphyrin IX was verified using an adapted Xillix Life instrument. All treated lesions were irradiated with an argon-pumped dye laser (dose range 100-250 J/cm2, wavelength 635 nm). In the first group, partial response was obtained. In these advanced cases, diminution of cancerous ulcerations was observed. In the leucoplakia group, complete response was achieved in four out of five treated patients. On the basis of our preliminary results, PDT may be useful in eradicating premalignant lesions of the oral cavity and in the palliation of advanced lesions of the oropharynx and larynx.

Aminolevulinic Acid↗

Does trimetazidine exert cytoprotective activity on astrocytes subjected to hypoxia in vitro?

The aim of the present study was to establish whether trimetazidine (TMZ) is capable of protecting astrocytes against hypoxic injury. Using the model of astrocyte cell culture we tried to observe the cells treated with TMZ before, during and after hypoxia simulated in vitro. Cell viability was determined by Live/Dead (viability/cytotoxicity) Assay Kit and MTT conversion test. Apoptotic cell death was distinguished by a method using fluorescence microscopy with Hoechst 33342. The effect of the drug on the DNA synthesis was evaluated by measuring the incorporation of [3H]thymidine into DNA of astrocytes. TMZ stimulates the proliferation of astrocytes most significant one when the astrocytes are exposed to the drug in normoxia, hypoxia and/or re-oxygenation. Adding TMZ into cultures during re-oxygenation and hypoxial re-oxygenation significantly decreases the number of dead and apoptotic cells. Our experiment has proved that TMZ exerts the most significantly cytoprotective effect on astrocytes in vitro when added during hypoxia and/or re-oxygenation. We may conclude that the protective effect of TMZ depends on the sequence of drug adding and hypoxia/ re-oxygenation onset.

Animals↗

Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response.

Aqueous extracts from leaves of the European mistletoe (Viscum album L.) are postulated to exert an anticancer efficacy by cytotoxic and/or immunological mechanisms of action. Although popular as an unconventional therapy modality, no controlled randomized clinical trials are available, reliably documenting a clinically beneficial antineoplastic potential of the various commercial mistletoe preparations. Since previous investigations have focused on the purified galactoside-specific lectin (Viscum album L. agglutinin, VAA) as major biological response modifier in the low-dose range, the objective of the present experimental study was to examine its effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced carcinogenesis in the urinary bladder of rats, a suitable animal model for human disease. The carcinogen was fed by gavage in three fractionated low doses (150 mg/kg body weight each) to obtain low-grade and low-stage transitional cell carcinomas. From the onset of the experiment VAA was injected subcutaneously twice a week (1 ng/kg body weight) continuously for either 6 or 15 months. Following an experimental period of 6 months the incidence of bladder carcinomas was 10.2% in rats given exclusively BBN and 6.7% in those additionally treated with VAA. After an experimental time of 15 months 25.8% of the rats fed BBN only and 19.7% of the animals additionally receiving VAA had developed urothelial carcinomas. The differences of the tumor incidences did not reach the level of statistical significance, neither after an experimental duration of 6 (P = 0.88) nor of 15 months (P = 0.71). A difference was found in the size of the transitional cell carcinomas. They proved to be significantly larger (P = 0.02) in the rats additionally treated with VAA for 15 months (mean maximum diameter: 3.31 mm) than in those without lectin treatment (mean maximum diameter: 1.88 mm). Quantitative immunocytochemistry analyzing a panel of immune cells yielded no evidence for the ability of the lectin to provoke a substantial, biologically relevant local cellular immune response in the wall of tumor-free and tumor-bearing bladders. From the current experiment it is obvious that galactoside-specific mistletoe lectin failed to protect against, inhibit, delay or reduce development of chemically induced urothelial carcinomas of the urinary bladder even after long-term administration in the clinically recommended schedule. It seems highly unlikely that adjuvant treatment with mistletoe extracts or VAA might favorably influence bladder cancer in patients by immunological effector mechanisms.

Animals↗

Mitochondrial localization and photodamage during photodynamic therapy with tetraphenylporphines.

The subcellular localization sites of TPPS4 and TPPS1 and the subsequent cellular site damage during photodynamic therapy were investigated in CT-26 colon carcinoma cells using spectroscopic and electron microscopy techniques. The association of both porphyrins with the mitochondria was investigated and the implications of this association on cellular functions were determined. Spectrofluorescence measurements showed that TPPS4 favors an aqueous environment, while TPPS1 interacts with lipophilic complexes. The subcellular localization sites of each sensitizer were determined using spectral imaging. Mitochondrial-CFP transfected cells treated with porphyrins revealed localization of TPPS1 in the peri-nuclear region, while TPPS4 localized in the mitochondria, inducing structural damage and swelling upon irradiation, as shown by transmission electron microscopy. TPPS4 fluorescence was detected in isolated mitochondria following irradiation. The photodamage induced a 38% reduction in mitochondrial activity, a 30% decrease in cellular ATP and a reduction in Na(+)/K(+)-ATPase activity. As a result, cytosolic concentrations of Na(+) and Ca(2+) increased, and the level of K(+) decreased. In contrast, the lipophilic TPPS1 did not affect mitochondrial structure or function and ATP content remained unchanged. We conclude that TPPS4 induces mitochondrial structural and functional photodamage resulting in an altered cytoplasmic ion concentration, while TPPS1 has no effect on the mitochondria.

Adenocarcinoma↗

[Chaotic dynamics in medicine].

It has turned out that almost all laws of nature (especially in biology and medicine) are nonlinear. This means that within the mathematical formulation of a law of nature some systems variables are coupled nonlinearly. The field, describing these nonlinear formulation, is referred to as dynamical systems theory or chaos theory. Analytical techniques derived from the field of chaos theory can be useful in characterising stability and complexity of homeostasis parameters (blood pressure, renal vascular, heart rate). It seems, that nonlinear characteristics may play an important role in prediction of some illnesses of the nervous and cardiovascular system.

Cardiovascular Diseases↗

[Personal experience in clinical use of low power laser therapy].

The results of our own clinical trials regarding therapeutical effects of low power lasers in the treatment of some diseases of motional system, skin and lesions of peripheral circulation were presented in the paper. The laser therapy was used in over 320 patients in period of last 3 years. The infra-red laser (wave-length 904 nm, mean power 4 mW) was used. The procedures were performed daily, for 5 days a week in 2 stages: the scan of sore region (3-min.) and the irradiation of trigger points (2-3 min. each). As a result of 10-25 procedures a significant clinical improvement in 65-90% patients was obtained. On the base of obtained results one can conclude that low-power laser therapy could make a useful supplementary method of treatment of overloading syndrome of motional system, postthrombotic syndrome, lymphatic edema and trophic lesions of skin.

Adolescent↗

Delay of diethylnitrosamine-induced hepatoma in rats by carrot feeding.

Carcinogenesis and death caused by diethylnitrosamine(DENA)-induced hepatomas in Sprague Dawley rats can be significantly delayed by feeding only carrots for several days a week. As this result is not obtained by supplementing food with even higher concentrations of synthetic beta-carotene, there must be several other factors which--together with the carotenoid--contribute to the positive effect. Several other possibilities such as effects of fasting, direct interactions with the carcinogen, resorption, vitamin A storage in the liver, etc., are proposed and discussed.

Animals↗

[Use of magnetic field in treatment of trophic leg ulcers].

Theoretical basis and favourable therapeutical application of magnetic field in case of trophic ulcerations of the lower limbs are discussed. As a clinical example of such action a case of a 39-year old female patient with trophic ulceration of the leg is presented. Practical advantages of magnetotherapy in similar to the described case patients are suggested.

Adult↗