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Paweł Surowiak

Publications and source records attributed to Paweł Surowiak.

At least 19 recordsLinked to original sources
PubMed2007

Taxol-resistance-associated gene-3 (TRAG-3/CSAG2) expression is predictive for clinical outcome in ovarian carcinoma patients.

An obstacle in chemotherapy of ovarian cancer is the development of drug resistance. Taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) was found to be overexpressed in a paclitaxel-resistant ovarian carcinoma cell line. However, clinical impact of TRAG-3 in ovarian carcinoma has not been demonstrated previously. For demonstration of potential clinical impact of TRAG-3, immunohistochemistry was applied to determine TRAG-3 protein expression in specimens obtained from ovarian carcinoma patients (n=37) who received a paclitaxel-based chemotherapy at two different time points, initial laparotomy before chemotherapy, and secondary cytoreduction after chemotherapy. The TRAG-3-specific immunohistochemical staining was correlated with clinical outcome. In ovarian carcinoma specimens obtained at the initial laparotomy, an advantage in overall (P < 0.001) and progression-free (P = 0.003) survival for patients with weak TRAG-3 expression could be demonstrated. Tumor specimens excised at secondary cytoreduction procedure were not predictive for clinical outcome. In summary, TRAG-3 was found to be a prognostic factor for the prediction of clinical outcome after the application of paclitaxel-based chemotherapy.

Adult↗
PubMed2006

Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations.

Cancer patients with tumors of similar grading, staging and histogenesis can have markedly different treatment responses to different chemotherapy agents. So far, individual markers have failed to correctly predict resistance against anticancer agents. We tested 30 cancer cell lines for sensitivity to 5-fluorouracil, cisplatin, cyclophosphamide, doxorubicin, etoposide, methotrexate, mitomycin C, mitoxantrone, paclitaxel, topotecan and vinblastine at drug concentrations that can be systemically achieved in patients. The resistance index was determined to designate the cell lines as sensitive or resistant, and then, the subset of resistant vs. sensitive cell lines for each drug was compared. Gene expression signatures for all cell lines were obtained by interrogating Affymetrix U133A arrays. Prediction Analysis of Microarrays was applied for feature selection. An individual prediction profile for the resistance against each chemotherapy agent was constructed, containing 42-297 genes. The overall accuracy of the predictions in a leave-one-out cross validation was 86%. A list of the top 67 multidrug resistance candidate genes that were associated with the resistance against at least 4 anticancer agents was identified. Moreover, the differential expressions of 46 selected genes were also measured by quantitative RT-PCR using a TaqMan micro fluidic card system. As a single gene can be correlated with resistance against several agents, associations with resistance were detected all together for 76 genes and resistance phenotypes, respectively. This study focuses on the resistance at the in vivo concentrations, making future clinical cancer response prediction feasible. The TaqMan-validated gene expression patterns provide new gene candidates for multidrug resistance.

Antineoplastic Agents↗
PubMed2006

Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers.

It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA) in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02). Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis.

Actins↗
PubMed2005

Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients.

Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.

Antineoplastic Agents↗
PubMed2005

Significance of cyclooxygenase 2 and MDR1/P-glycoprotein coexpression in ovarian cancers.

Immunohistochemical analysis of prognostic significance of COX-2 and P-gp expression in ovarian cancers was performed on samples originating from 73 tumors. COX-2-positive cases were shown to demonstrate higher expression of P-gp. The studies demonstrated also that, higher P-gp expression was typical for cases which responded poorly to chemotherapy and for cases with shorter progression-free time. Expression of COX-2 predisposed to a more rapid disease progression. The study documented a relationship between COX-2 and P-gp suggesting that COX-2 inhibitors might investigated in clinical trials as a treatment supplementary to chemotherapy of ovarian cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Differences in oestrogen and progesterone receptors, HER-2, p53 expression and proliferation in ductal breast cancers in relation to histopathological grade.

In case of breast cancer the grade of differentiation and expression of oestrogen and progesterone receptors falls within the first category of prognostic factors according to the College of American Pathologists. HER-2, p53 and Ki67 belong to the second category and their significance still awaits confirmation. The aim of the present study was to examine the relationship between the intensity of expression of oestrogen receptors (ER), progesterone receptors (PgR), HER-2, p53 and Ki67 in cells of ductal breast cancer of G1, G2 or G3 differentiation grade. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunocytochemical reactions were performed to detect the expression of ER, PgR, HER-2, p53 and Ki67. Following a semi-quantitative appraisal of the preparations under examination, appropriate statistical tests were used to document significant relationships. We noted significant positive correlations between ER and PgR (the entire group studied, G1-3, and the G1 group), HER-2 and p53 (G2) and between p53 and Ki67 expression (G2). Significant negative correlations were found between ER and p53 (G1-3), PgR and p53 (G1-3, G1, G3) and between PgR and Ki67 (G1-3, G2). The studies performed demonstrated distinct relationships between the expression intensity of various proteins in tumour cells in relation to the grade of differentiation of the tumour. We also showed that a parallel determination of ER, PgR and p53 expression may carry high predictive value as to response to tamoxifen treatment.

Biomarkers, Tumor↗
PubMed2005

[The relationship of the expression of proliferetron--related antigens Ki67 and PCNA in the cells of ductal breast cancer with the differentiation grade].

OBJECTIVES: Ki67 and PCNA proteins are characteristic for cells in mitotic cycle and represent unfavourable prognostic indices. Intensity of the proteins expression directly correlates with grade of tumour differentiation. They belong to the second category of prognostic factors in breast cancer according to the College of American Pathologists. DESIGN: Present study aimed at examining the relationship between intensity of expression of proliferation-related antigens--Ki67 and PCNA in cells of ductal breast cancer of G1, G2 or G3 differentiation grade. MATERIALS AND METHODS: In paraffin sections of 60 ductal breast cancers, immunocytochemical reactions were performed to detect expression of Ki67 and PCNA. Following semiquantitative appraisal of studied preparations, appropriate statistical tests were used to document statistical relationships. RESULTS: Intensity of Ki67 expression was most pronounced in G3 group and least pronounced in G1 group (ANOVA rang Kruskal-Wallis, p=0.00001). In the case of PCNA we did not show any differences. Only in the G1 we showed a positive correlation between expression intensity of studied antigens (Spearmans rang correlation, r=0.67, p=0.024). CONCLUSIONS: The study showed that Ki67 and not PCNA correlates with morphologic features of proliferation.

Analysis of Variance↗
PubMed2005

Prognostic value of immunohistochemical estimation of CD24 and Ki67 expression in cisplatin and paclitaxel treated ovarian carcinoma patients.

CD24 is a small membranous protein which may participate in invasion of tumor cells. Present study aimed at evaluation of prognostic significance linked to immunohistochemical demonstration of CD24 expression and the proliferation index, Ki67 expression in ovarian cancers. The immunohistochemical reactions with monoclonal CD24- and Ki67-specific antibodies were performed in paraffin sections originating from 30 patients with ovarian cancer treated using cisplatin and paclitaxel. Results of the reactions and analysis of the clinical course of the patients were subjected to statistical analysis. Cases with cytoplasmic-membranous expression of CD24 (CD24c-m) were found to exhibit significantly shorter overall survival time (P = 0.0002) and progression-free period (P = 0.0005). Cases with membranous expression of CD24 (CD24m) manifested a longer overall survival time (P = 0.022). No relationship was disclosed between expression of Ki67 on the one hand and survival time and CD24 expression on the other. As documented using chi square test, expression of CD24c-m predisposed to relapses (P = 0.012), progression (P = 0.0362) and to death (P = 0.0034). Deaths were encountered significantly less frequently in cases with CD24m expression (P = 0.0465). The studies demonstrated that CD24c-m represented a strongly unfavorable prognostic indicator. The antigen represents an interesting target in the search for novel therapeutic methods. The more aggressive course of cases with CD24c-m expression was not linked to more intense proliferation of the tumor cells.

Antigens, CD↗
PubMed2005

[Classical and novel molecular prognostic factors in ovarian cancers].

Development of molecular biology techniques allows at present for a more rapid and more reliable diagnosis of ovarian cancers. Present paper describes genetic alterations which predispose to development of ovarian cancer and mutations which play principal role in pathogenesis of sporadic cases of the disease. Prognostic significance has also been outlined of expression of cyclooxygenase 2, ligands of P-selectin and inhibitors of complement in cells of ovarian cancer as well as their potential therapeutic significance. A separate chapter has been devoted to the potential and achievements gained using DNA microarray techniques.

CD24 Antigen↗
PubMed2004

Steroid receptor status, proliferation and metallothionein expression in primary invasive ductal breast cancers.

The most important immunocytochemical prognostic and predictive factors in cases of breast cancer include estrogen receptor alpha (ER) and progesterone receptor (PgR). The present study aimed at examining the relationship between the manifestation intensity of proliferation markers (Ki-67 and nucleolar organizer regions--AgNORs) on one hand, and expression of ER and PgR on the other in a uniform group of invasive ductal breast cancers of G2 grade. Moreover, the study aimed at examining the relationship between the above mentioned markers and expression of metallothionein (MT). The studies were performed on samples of invasive ductal breast cancers of G2 grade, originating from 60 females. In paraffin sections originating from the studied cases immunocytochemical reactions were performed using monoclonal antibodies to ER, PgR, Ki-67 and MT, and silver staining was conducted to localize AgNORs. The obtained results were subjected to statistical analysis using Statistica software. Results indicate that manifestation of AgNORs does not correlate with any of the studied antigens (ER, PgR, Ki-67, MT) (p>0.05). Moreover, no relationship could be demonstrated between the intensity of MT expression and proliferation markers or steroid receptor status (p>0.05). A negative correlation was shown between the expression of ER and Ki-67 (p=0.0009). The most intense proliferative activity was demonstrated in cases of breast cancer showing PgR expression but no ER expression (p=0.015), while the lowest proliferative activity was detected in breast cancers with expression of both ER and PgR (p<0.05).

Biomarkers, Tumor↗
PubMed2004

Lack of relationship between metallothionein (MT) expression and proliferation exponents in cells of primary ductal breast cancer of G2 grade of differentiation.

BACKGROUND: The metallothioneins (MTs) are a group of proteins which, due to their unique structure, fulfil numerous functions in the cell. They participate in growth, differentiation, and reparative processes, protect cells against free radicals, and are responsible for heavy metal homeostasis. Their involvement has been reported in the multidrug resistance to cytostatic drugs. Numerous reports document MT presence in cells of various tumors, including breast cancer. Augmented expression of MTs has been reported in less differentiated tumors. MT expression used to be linked to higher proliferative activity of tumor cells, shorter survival of the patients, and tamoxifen-resistance. The present study aimed at examining the relation between MT expression and the manifestation of proliferation exponents (Ki67, nucleolar organizers--AgNORs) in cells of ductal breast cancer of G2 grade of malignancy. MATERIAL/METHODS: Reactions were performed to detect MTs (clone E9), Ki67 (clone MIB-1) (immunocytochemistry), and AgNORs (silver impregnation) in paraffin sections of breast cancers in G2 grade originating from 60 females. Results of the reactions were subjected to statistical analysis using Statistica 98 PL software. RESULTS: Statistical analysis (Spearman's rank correlation) demonstrated no relationships between the studied markers (p>0.05). CONCLUSIONS: There is no correlation between metallothionein expression and proliferation and between Ki67 and AgNORs in ductal breast cancers of G2 grade of differentiation.

Breast Neoplasms↗
PubMed2004

Expression of metallothionein (MT) and gluthatione s-transferase pi (SGTP) in the bone marrow of patients with myeloproliferative disorders (MPD).

Overexpression of SGTP and/or MT may contribute to various carcinogenic processes and to resistance to anticancer treatment. The importance of these proteins, although clearly established in solid tumours, has not been fully understood in haematopoietic neoplasm. The aim of this study was to determine the expression of MT and SGTP in the bone marrow of patients with MPD. Twenty paraffin-embedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated -- osteomyelofibrosis (OMF), n = 9 and chronic myelocytic leukaemia (CML), n = 11. We demonstrate increased SGTP and MT expression in the bone marrow of MPD patients. In our study levels of MT in OMF patients were higher than in CML. This suggests that MT expression may correlate with bone marrow fibrosis. These data, although based on a relatively small number of patients, raise the possibility that SGTP and MT may play a role in the pathogenesis of MPD. The clinical significance of this phenomenon needs further investigation.

Bone Marrow↗
PubMed2003

Prognostic value of immunocytochemical determination of parathyroid hormone-related peptide expression in cells of mammary ductal carcinoma. Analysis of 7 years of the disease course.

Parathyroid hormone-related peptide (PTHrP) participates in the development of humoral hypercalcaemia of malignancy. The peptide is thought to affect growth and differentiation of normal and neoplastic cells. The present study aimed at evaluation of the relationship between survival time and development of distant metastases in patients with ductal mammary carcinoma on the one hand and PTHrP expression on the other. Immunocytochemical reactions using mouse monoclonal (clone 212-10.7) anti-PTHrP (38-64) antibodies were performed in paraffin sections originating from 47 patients with ductal mammary carcinoma. Expression of the protein was quantified employing a scale, considering the number of positive cells and intensity of the reaction (immunoreactive score, IRS). Survival time of the patients, determined during the course of a 7-year observation was also analysed. The obtained results demonstrated a relationship between intensity of PTHrP expression and the survival time. Patients with high expression of PTHrP (IRS>6) manifested longer survival than patients with lower PTHrP expression (IRS< or =6; Cox'es F test, P<0.05). Moreover, in the group with the lower PTHrP expression, a negative relationship was detected between expression of the protein and the survival time (Cox'es model, P<0.05). No relationship was detected between PTHrP expression and the development of distant metastases.

Adult↗
PubMed2003

Melatonin stimulates the activity of protective antioxidative enzymes in myocardial cells of rats in the course of doxorubicin intoxication.

The study aimed at determining the effect of melatonin on the activity of protective antioxidative enzymes in the heart and of lipid peroxidation products in the course of intoxication with doxorubicin (DOX). The rats were categorized into four groups, receiving: 0.9% NaCl i.p. (NaCl control); melatonin [20 mg/kg body weight (b.w.)] s.c. (control Mel); DOX (2.5 mg/kg b.w.) i.p.; melatonin plus DOX in doses as above. All the substances were administered once in a week for four consecutive weeks. Homogenates of heart tissue were examined for activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), levels of reduced glutathione (GSH) and of lipid peroxidation indices (MDA + 4-HDA). Administration of melatonin alone did not induce alterations in levels of MDA + 4-HDA, GSH, or in activity of GPx, SOD or CAT, as compared to the group receiving 0.9% NaCl. GSH levels decreased following DOX but remained at normal levels following DOX and melatonin. The level of MDA + 4-HDA increased following DOX, as compared with the control, a change prevented by the combination of DOX + melatonin. Activities of GPx, SOD and CAT were higher in groups receiving DOX and/or DOX plus melatonin than in control groups. Activity of CAT and the level of GSH in the group receiving DOX plus melatonin were significantly higher than in the group intoxicated with DOX alone. The obtained results demonstrate that, when given in parallel with DOX, melatonin protects cardiomyocytes from damaging effects of the cytostatic drug (reflected by the levels of MDA + 4-HDA). The protective effect resulted, in part from the augmented levels of GSH and from stimulation of CAT activity by melatonin in cardiomyocytes subjected to the action of DOX.

Animals↗
PubMed2003

Localisation of exogenous surfactants in cell membranes in the air-blood barrier: rat model.

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier.

Animals↗
PubMed2003

Evaluation of transfection effectiveness using fluorescein-labelled oligonucleotides and various liposomes.

Silencing of genes using siRNA represents a generally used technique aimed at inhibiting expression of proteins in cells. Results have frequently not met expectations and this has posed problems in association with this technique. The phenomenon might reflect an incorrect sequence of RNAi, poor penetration of the cells by the nucleotides or insufficient knowledge of the protein in question. The present study is aimed at evaluating the effectiveness of the transfection of selected cell lines using various liposomes. The studies were performed using 9 cell lines: EPG 257/85 RNOV, EPG 257/85 RDB, W 181/A17, A 2780P, A 2780 RCIS, MEWO CIS, 181 RDB, 181 P and MCF-7/MX. The lines were transfected with fluorescently labelled oligonucleotides. Two parallel experiments were performed. In one oligofectamin and in the other DMRI were used as oligonucleotide carriers. The studies demonstrated that in every case nucleotides penetrated more than 90% of the cells. In 4 cell lines the signal was stronger when oligofectamin was used, in 4 cell lines when DMRI was employed and in one case the signal strength was comparable using any carrier. The studies showed that various liposomes demonstrated distinct transfection efficiency, depending on the cell line used, and that application of fluorescently labelled nucleotides may be helpful in the optimisation of transfection conditions.

Cell Line↗
PubMed2003

The expression of metallothionein (MT) and proliferation intensity in ovarian cancers treated with cisplatin and paclitaxel.

Metallothioneins (MT) represent low molecular weight proteins that are supposed to fulfil several functions. They participate in the cell cycle, protect cells from oxidative stress, control levels of heavy metals and participate in multidrug resistance processes, particularly in cases of alkylating drugs. The present study aimed at evaluation of proliferation intensity (Ki67, PCNA) in ovarian cancers treated using cisplatin and paclitaxel, as related to expression of MT. The experiments were performed on samples originating from 10 patients operated on due to ovarian cancer. The material originated from the first operations or second-look operations. All the patients were treated with cisplatin and paclitaxel. Immunocytochemical reactions using antibodies to MT, Ki67 and PCNA were performed in paraffin sections originating from the cases studied. Statistical analysis was performed using Statistica software. The studies demonstrated no relation between expression of MT on the one hand and intensity of proliferation before or after chemotherapy on the other hand (gamma correlation, p > 0.05). The results indicate that expression of MT is not related to resistance to treatment using cisplatin and paclitaxel.

Adenocarcinoma↗