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Biomedical subjects

M Dabrowska

Publications and source records attributed to M Dabrowska.

At least 19 recordsLinked to original sources
PubMed2002

Reactivity of alveolar macrophages in lung cancer patients and healthy subjects: surface ICAM-1 after INF-gamma stimulation in vitro.

The linearity of ICAM- I expression on alveolar macrophages (AM) before and after INF-gamma stimulation in healthy and lung cancer subjects were compared. AM were collected by bronchoalveolar lavage and incubated with/without INF-gamma according to standard procedures. The harvested cells were analyzed by flow cytometry using monoclonal antibodies against leucocytes and macrophages. Only viable cells were analyzed. Stimulation with INF-gamma revealed two AM subpopulations of similar size differentiated in the intensity of ICAM-1 expression. They were not distinctly marked in every studied case. Our preliminary results did not confirm the previously reported decreasing reactivity of AMs after INF-gamma stimulation in lung cancer patients.

Antineoplastic Agents↗
PubMed2002

Protein kinase C involvement in proliferation and survival of breast cancer cells.

Members of protein kinase C (PKC) family have been widely implicated in the regulation of cell proliferation, differentiation and survival. Increased protein C activity in malignant breast tissue and in most aggressive breast cancer cell lines suggests possible role of PKC in the development and progression of breast cancer. PKC may be therefore a target for breast cancer treatment. In our study we attempted to investigate the effect of: phorbol ester (PMA)-PKC activator, and bisindolylmaleimide II (GF II), a highly selective PKC inhibitor, on the proliferation as well as induction of apoptosis and necrosis in breast cancer cell line MDA-MB-231. Our results provide evidence for multidirectional effects of PKC on the proliferation of this type of breast cancer cells. The effects of both compounds were different after short time of exposition (1-3 h). PMA induced proliferation, while GF II showed an opposite effect. After 24 h, however, both compounds exhibited relatively high inhibitory effect on the proliferation and proved to be effective in induction of necrosis and apoptosis.

Apoptosis↗
PubMed2001

Potential role of beta 1 integrin and collagen biosynthesis in estrogen-dependent reduction of apoptosis in tamoxifen-treated breast cancer cells.

It was found that 10 microM tamoxifen induced apoptosis and a significant (approximately 50%) depletion of beta 1 integrin levels in human breast cancer cells. Estradiol-treated MCF-7 cells exhibited exceptional viability and adherence, high levels of beta 1 integrin and increased (by 100%) collagen biosynthesis. Pretreatment of MCF-7 cells with 1 nM estradiol prevented tamoxifen-induced cell death, loss of cell adherence and decrease in beta 1 integrin level. Tamoxifen and estradiol had an opposite effect on the beta 1 integrin level and adherence in breast cancer cells, suggesting that the decrease in the beta 1 integrin level may be an early event during tamoxifen-induced apoptosis in breast cancer cells.

Apoptosis↗
PubMed2001

13-cis retinoic acid and all-trans retinoic acid in the regulation of the proliferation and survival of human breast cancer cell line MCF-7.

Retinoids are a group of compounds which inhibit cell proliferation and induce cellular differentiation. The aim of this study was to compare the antiproliferative activity of various concentrations of 13-cis retinoic acid (isotretinoin) and all-trans retinoic acid (tretinoin) in a culture of the estrogen-sensitive human breast cancer cell line MCF-7. Evaluation was based on [3H]thymidine incorporation into the cancer cells and through immunocytochemical analysis of cell cycle-associated PCNA and Ki-67 protein expression. Both retinoids inhibited [3H]thymidine incorporation into the cancer cells most effectively at a concentration of 3x10(-3) M. Two basic substances used for line MCF-7 culture experiments, one stimulating - estradiol - and the other inhibiting - tamoxifen - were applied. Estradiol added to a culture containing decreasing concentrations of isotretinoin (from 3x10(-3) to 3x10(-8) M) caused a statistically significant reduction in the percentage of [3H]thymidine incorporation into the cancer cell line MCF-7, compared to the 17 beta estradiol group (189.25%+/-62.64, control=100%, p<0.05). In the group of decreasing tretinoin concentrations, statistically significant differences were found only at 3x10(-3), 3x10(-4) and 3x10(-8) M. Following culture supplementation with tamoxifen (1 microM), statistically significant differences were observed only at the highest concentrations of both retinoids (3x10(-3) and 3x10(-4) M). The evaluation of breast carcinoma cells with a positive immunocytochemical reaction to PCNA and Ki-67 has revealed that isotretinoin reduces their percentage in the most determined and statistically significant way (38.00%+/-2.58 and 39.25%+/-3.09), compared to the control group (86.50%+/-9.20 and 100%+/-3.87, p<0.001 and p<0.0001) and to the estradiol group (87.00%+/-6.79 and 86.10%+/-7.0, p<0.001). Apart from their blocking effect on the cell cycle, retinoids also induce the apoptotic pathway.

Antineoplastic Agents↗
PubMed2001

[Pseudolymphoma in patients with primary Sjogren's syndrome].

Sjögren's syndrome is an inflammatory autoimmune disease affecting primarily the exocrine glands. In the abscence of other autoimmune diseases it is classified as primary Sjögren's syndrome. Patients with primary syndrome have about 40 times higher relative risk of developing lymphoma then normal population, which offers a possibility to study malignant transformation's mechanisms in these patients. In the study we report a case of a woman with pseudolymphoma. The clinical diagnose used to be based on symptoms of proliferate disease, quetionnable histological evaluation and good response to steroids. Nowadays, applying advanced molecular techniques make it possible to diagnose lymphoma in labial salivary biopsy much earlier. It allows recognizing an incipient lymphoma in a group of patients with primary Sjögren's syndrome. Therefore so-called pseudolymphoma can usually be diagnosed as either benign or malignant lymphoproliferative lesions.

Adult↗
PubMed2001

[The routine coagulation tests along with activated protein C resistance (APC-R) in population of women applying for oral contraceptives].

The routine coagulation tests along with activated protein C resistance (APC-R) were studied in North-Eastern Poland women, applying for oral contraceptives. The APTT, PT and fibrinogen concentration were evaluated in 128 women, aged 20-40 years, by means of nephelometric method. For estimation of APC-R, Coatest APC Resistance V test was used. The abnormalities in routine coagulation test were found in 13.3% of studied women. The resistance to activated protein C was observed among 4.3% of women with normal results of routine coagulation tests. The thrombotic event occurred in one of five APC-R positive woman. There was no correlation between APC-V ratio and APTT, PT or fibrinogen values.

Activated Protein C Resistance↗
PubMed2000

Expression and purification of mammalian calreticulin in Pichia pastoris.

Calreticulin is a 46-kDa Ca(2+)-binding chaperone of the endoplasmic reticulum membranes. The protein binds Ca(2+) with high capacity, affects intracellular Ca(2+) homeostasis, and functions as a lectin-like chaperone. In this study, we describe expression and purification procedures for the isolation of recombinant rabbit calreticulin. The calreticulin was expressed in Pichia pastoris and purified to homogeneity by DEAE-Sepharose and Resource Q FPLC chromatography. The protein was not retained in the endoplasmic reticulum of Pichia pastoris but instead it was secreted into the external media. The purification procedures reported here for recombinant calreticulin yield homogeneous preparations of the protein by SDS-PAGE and mass spectroscopy analysis. Purified calreticulin was identified by its NH(2)-terminal amino acid sequences, by its Ca(2+) binding, and by its reactivity with anti-calreticulin antibodies. The protein contained one disulfide bond between (88)Cys and (120)Cys. CD spectral analysis and Ca(2+)-binding properties of the recombinant protein indicated that it was correctly folded.

Amino Acid Sequence↗
PubMed2000

Trichinella spiralis and Trichinella pseudospiralis: developmental patterns of enzymes involved in thymidylate biosynthesis and pyrimidine salvage.

Thymidylate synthase, dihydrofolate reductase and dUTPase specific activities were found to remain at a high and constant level in crude extracts from adult worms of Trichinella spiralis, as well as from muscle larvae of both Trichinella spiralis (isolated 1-24 months after infection) and Trichinella pseudospiralis (isolated 5.5-13 months after infection). The results obtained with Trichinella pseudospiralis muscle larvae isolated with the use of pepsin did not differ from those obtained when pepsin was not used. No thymidine kinase activity could be detected in muscle larvae of either species and thymidine phosphorylase could be found only in T. pseudospiralis larvae isolated without the use of pepsin. Muscle larvae of both species contained orotidylate phosphoribosyl transferase activity, pointing to a possibility of 5-fluorouracil activation. Uridine phosphorylase, another enzyme involved in 5-fluorouracil anabolism, was also present in T. pseudospiralis muscle larvae. Results of comparative studies on inhibition of purified T. spiralis and rat thymidylate synthases by substrate (4-thio-5-fluoro-dUMP, 2-thio-5-fluoro-dCMP and N4-hydroxy-dCMP) and cofactor (ZD 9331) analogues indicated only dUMP analogues to show feeble selectivity towards the parasite enzyme. A hypothesis is discussed, assuming high expression of thymidylate synthase in muscle larvae to be connected with their cells being arrested in the cell cycle.

Animals↗
PubMed2000

Reactive oxygen species activate mitogen-activated protein kinases in pancreatic acinar cells.

It has been recently reported that kinases that belong to the mitogen-activated protein kinase (MAPK) family are rapidly activated by cholecystokinin (CCK) in rat pancreas both in vitro and in vivo. It is known that reactive oxygen species (ROS) play an important role in the pathogenesis of acute pancreatitis induced by supraphysiologic stimulation with CCK analogue, cerulein. The aim of our study was to evaluate whether MAPKs are activated by ROS in pancreatic acini. The activity of MAPK, c-Jun amino-terminal kinase (JNK), and p38 MAPK was determined in isolated rat pancreatic acinar cells by means of Western blotting, with the use of specific antibody that recognizes active, dually phosphorylated kinases. Incubation of acini with ROS donors, hydrogen peroxide (H2O2) and/or menadione (MND), strongly activated all three kinases. Activation of these kinases by ROS, but not by CCK, was substantially inhibited by pretreatment of acini with antioxidant N-acetylo-L-cysteine (NAC). Whereas CCK-induced activation of MAPK or JNK was totally or partially blocked by protein kinase C (PKC) inhibitor GF-109203X, ROS-induced activation of MAPK, JNK, and p38 MAPK was PKC independent. In conclusion, ROS strongly activate MAPK, JNK, and p38 MAPK in pancreatic acinar cells. It may be of importance in acute pancreatitis, because ROS are involved in the pathogenesis of this disease.

Acetylcysteine↗
PubMed2000

[The phenotype characteristics of cord blood lymphocytes in premature neonates].

It has been observed high risk of infections in neonates as a result from lymphocytes immaturity. It is connected to phenotype differences of lymphocytes between neonates and adults. This high susceptibility to infections is especially high in premature neonates. With the use of flow cytometry we have evaluated the phenotype of cord blood lymphocytes in premature neonates. In comparison to results of healthy newborns we have observed significant decrease in CD7+, CD3+, CD4+, CD25+, CD57+ lymphocytes an increase in total number of CD8+ cells as well as alteration in CD4/CD8 ratio. Our results suggest deeply damage of cellular immunity in preterm infants.

Antibodies, Monoclonal↗
PubMed2000

alpha1-microglobulin as a marker of proximal tubular damage in urinary tract infection in children.

The urinary alpha1-microglobulin (alpha1-M) as a marker of proximal tubular damage was measured in 86 children, aged 3/12 to 12 years, with a diagnosis of urinary tract infection (UTI) and fever. All patients had normal glomerular filtration rates (GFR). They were divided into 2 groups: A: with UTI and etiological factor E. coli, B: with UTI and etiological factor Proteus sp. Similar measurements of alpha1-M were obtained for a control group of healthy children. An increased mean level serum alpha1-M was observed in patients with UTI and fever compared to control group (p < 0.001). Urinary alpha1-M as the alpha1-microglobulin/creatinine ratio was higher in both tested group of patients with UTI and fever. Those found in group A1 and B1 before treatment were the highest and statistically significantly elevated after treatment (group A2 and B2: p < 0.001). Our results indicate the usefulness of the urinary alpha-microglobulin/creatinine ratio as a marker of proximal kidney tubule damage in children with E. coli and Proteus sp. infections. Additionally, it seems to be associated with the humoral and cellular immune response.

Alpha-Globulins↗
PubMed2000

Influence of estrogen, antiestrogen and UV-light on the balance between proliferation and apoptosis in MCF-7 breast adenocarcinoma cells culture.

Studies of the mechanism of actions of estrogen, antiestrogen and physical factors may provide clues to an understanding of breast cancer growth and/or regression regulation and thus identify novel targets for therapeutic intervention. Defective control of apoptosis appears to play a central role in the pathogenesis of neoplasia. Conversely, cancer therapy and ionizing radiation can induce cancer cell death by apoptosis and/or necrosis. bcl-2 gene and p-53 gene products have been both linked to programmed cell death pathways. We have analyzed the effect of estradiol, tamoxifen and UV exposure on the induction of apoptosis, expression of p53 and bcl-2 gene products as well as the proliferative activity (expressed as [3H]thymidine incorporation and PCNA and MPM2 antigens involvement) in MCF7. It has been found that estradiol increases the speed of cell cycle in MCF7 and acts as antiapoptotic factor. Tamoxifen has multiple influence on the rate of growth of cancer cells: depends on estrogen receptor (ER), conducts reduction of proliferation rate; depends on ER and other mechanisms conducts to suppressions of Bcl-2 protein expression and induction of cell death through apoptotic pathway. Estradiol prevents the apoptotic influence of tamoxifen probably by enhancement of Bcl-2 protein expression and does not prevent the inhibition of proliferation rate. The irradiation with UV induces apoptosis by over-expression of p53 and down-regulation of bcl-2 gene.

Adenocarcinoma↗
PubMed2000

Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin--new carriers of alkylating elements.

A series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.

Alkylating Agents↗
PubMed2000

[Septic-toxic shock due to rhabdomyolysis in a patient treated with fenofibrate].

Lipid disorders have been treated with fibrates for many years. Rhabdomyolysis is one of the side effects of these drugs. We report a case of a septic-toxic shock due to rhabdomyolysis in a 75-year old patient, who had been treated with fenofibrate for 2 years. This case shows necessity of the standard monitoring of aminotransferase, phosphocreatine kinase and creatinine levels during treatment with fibrates.

Aged↗
PubMed2000

[Biochemical mechanism of raloxifen and tamoxifen action for the prevention of breast cancer. Studies in vitro].

Cancer growth follows fine balance disturbance between cell proliferation, differentiation and death. It has been shown that mutation of 4 to 5 genes controlling cellular proliferation events may be contributive to carcinogenesis. Estrogens play a central role in reproductive physiology. They are also a causative factors in the pathogenesis of neoplastic and non-neoplastic diseases, including breast cancer. The estrogen dependency of human breast cancer has been successfully exploited in the treatment of early and advanced diseases and provides a unique opportunity for chemoprevention of this common malignancy. The aim of present study was to examine the effects of tamoxifen and raloxifen on the induction of apoptosis and proliferative activity of human breast adenocarcinoma MCF-7 cells. It has been found that both tamoxifen and raloxifen decreased the speed of cell cycle in MCF-7 cells and acts as proapoptotic factors. It reduces viability of cancer cells and probability of neoplastic clone multiplification. This effect conducts to limitation of cancer expansion.

Adenocarcinoma↗
PubMed2000

[Levels of alpha-2-macroglobulin in blood serum of women giving birth to hypotrophic and eutrophic newborns].

We tested the concentration of alpha-2-macroglobulin in sera of 33 women bearing eutrophic newborns, 36 women bearing hypotrophic newborns and 30 healthy not pregnant women in reproductive age. The concentration of this inhibitor was measured using radial immunodiffusion method according to Mancini et al. We found distinct decrease of alpha-2-macroglobulin concentration in sera of bearing women. In women bearing eutrophic newborns we found 154 mg/dl, in women bearing hypo-trophic newborns 171 mg/dl whereas in controls 250 mg/dl. We have noted statistically significant differences between tested groups to controls and between investigated groups. Taking under consideration the role of alpha-2-macroglobulin as the modulator of immune system as well as the activity of several cytokins, therefore one can suppose that alpha-2-M may affect on cellular growth developed foetus in intrauterine.

Adult↗