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M Mirowski

Publications and source records attributed to M Mirowski.

At least 19 recordsLinked to original sources
PubMed2005

Cyclin D1 protein and CCND1 gene expression in colorectal cancer.

AIMS: To report the expression of cyclin D1 protein and its gene in a series of colorectal adenocarcinoma. METHODS: One hundred and eleven specimens of colorectal carcinomas and adjacent normal colorectal mucosa were investigated by staining with a monoclonal antibody against cyclin D1 and by RT-PCR. RESULTS: Expression of CCND1 gene was found in 54 out of 111 cases of colorectal cancers, while in normal mucosa the expression of this gene was not observed. Cyclin D1 protein expression was checked in the same group of adenocarcinoma cases. Presence of this protein was observed in 69 cases and for 43 of them also expression of its gene was found. Dependence between the presence of protein and the gene expression was statistically significant (p=0.0002). In the group of cases where CCND1 gene expression was detected, high level of its protein expression was found in 20 cases. The CCND1 gene expression was associated with metastases to lymph nodes (p=0.0181) and also with distant metastasis (p=0.0204). CONCLUSIONS: The combined measurement of both the gene and its protein product, is an important contribution to the study of molecular markers in histological material.

Adenocarcinoma↗
PubMed2005

Binding of endomorphin-2 to mu-opioid receptors in experimental mouse mammary adenocarcinoma.

Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) binds with high affinity and selectivity to the mu-opioid receptor. In the present study, [125I]endomorphin-2 has been used to characterize mu-opioid-binding sites on transplantable mouse mammary adenocarcinoma cells. Cold saturation experiments performed with [125I]endomorphin-2 (1 nM) show biphasic binding curves in Scatchard coordinates. One component represents high affinity and low capacity (K(d) = 18.79 +/- 1.13 nM, B(max) = 635 +/- 24 fmol/mg protein) and the other shows low affinity and higher capacity (K(d) = 7.67 +/- 0.81 microM, B(max) = 157 +/- 13 pmol/mg protein) binding sites. The rank order of agonists competing for the [125I]endomorphin-2 binding site was [d-1-Nal3]morphiceptin > endomorphin-2 >> [d-Phe3]morphiceptin > morphiceptin > [d-1-Nal3]endomorphin-2, indicating binding of these peptides to mu-opioid receptors. The uptake of 131I-labeled peptides administered intraperitoneally to tumor-bearing mice was also investigated. The highest accumulation in the tumor was observed for [d-1-Nal3)morphiceptin, which reached the value of 8.19 +/- 1.14% dose/g tissue.

Adenocarcinoma↗
PubMed2005

Expression of the P65 gene in gastric cancer and in tissues with or without Helicobacter pylori infection.

A 65-kDa tumor-associated protein (P65) is a potential non- specific tumor marker expressed by many types of tumor cells. Our recent studies indicate that P65 gene expression is connected with poor prognosis for the patients with colorectal cancer. In the present study P65 gene expression was determined by means of RT-PCR in the group of 22 gastric cancer and adjacent normal gastric mucosa. Its presence was correlated with some parameters of clinical staging. P65 gene expression was also determined in 102 tissue antral gastric endoscopic biopsy specimens from the patients suspected of H. pylori infection. The presence of H. pylori infection was determined by urease test. We found that in the group of gastric cancers, similarly to colorectal cancer, P65 gene expression was connected with poor clinicopathological parameters as T3, lymph nodes and distant metastases. There was no dependence between P65 gene expression and H. pylori infection. However, more often P65 gene expression was detected in the group of infected men than women. There was also a statistically significant dependence between age and P65 gene expression in the group of people above 60 years old. It could be then postulated that P65 gene expression is connected with poor prognosis for the patients suffering from gastric cancer and that this expression does not depend on H. pylori infection.

Adult↗
PubMed2004

HMGI(Y) gene expression as a potential marker of thyroid follicular carcinoma.

BACKGROUND: We assessed HMGI(Y) gene expression in thyroid tumors, control thyroid tissue and in the blood of patients diagnosed with papillary and follicular thyroid cancers to try to differentiate between malignant and benign disease. METHODS: HMGI(Y) gene expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 60 cases of thyroid tumors. Among this number 11 were diagnosed as papillary carcinoma, 37 as follicular carcinoma, and 12 as follicular adenoma. All carcinoma cases selected for this study were classified according to the tumor, lymph node metastases, distant metastases (TNM) classification. RESULTS: HMGI(Y) gene expression was detected only in follicular carcinomas, whereas in papillary carcinomas, follicular adenomas and control tissues there was no positive reaction. In follicular carcinomas the percentage of positive cases (number of samples with presence of HMGI(Y) gene transcript) was the highest and reached approximately 84. There was no statistical dependence between the presence of HMGI(Y) gene expression and tumor size or the presence of lymph node and distant metastases. HMGI(Y) gene expression was also analyzed in whole blood taken from a selected group of patients diagnosed with papillary or follicular carcinomas. Among follicular carcinomas there were 83% of positive cases, whereas among papillary carcinomas there were only 6%. CONCLUSIONS: On the basis of our study, we conclude that HMGI(Y) gene expression analysis could be helpful in differentiation between follicular carcinoma and adenoma.

Adenocarcinoma, Follicular↗
PubMed2004

Expression of the p65 gene in patients with colorectal cancer: comparison with some histological typing, grading and clinical staging.

AIMS: P65 protein/gene is a potential, non-specific tumour marker expressed by different types of neoplasms. In this study p65 gene expression was estimated in a group of colorectal cancers and compared with some histological features, grading and clinical staging of the neoplasms to assess its role as a prognostic marker for colorectal cancer. METHODS: 109 pairs of frozen samples of colorectal carcinomas and adjacent normal colorectal mucosa and four samples of tissue from patients without neoplastic diseases were analysed by means of RT-PCR. RESULTS: Expression of p65 gene was found in 51 out of 109 cases of colorectal cancers. For 19 of them expression of examined gene was observed both in cancer and corresponding healthy mucosa. p65 Gene expression was associated with more advanced tumours (T3, T4; p=0.0003) with metastases to lymph nodes (N1, N2; p=0.0003) and distant metastases (p=0.0005). We did not find association between the age, gender, tumour localization, histological type and p65 gene expression. CONCLUSIONS: p65 Gene expression in primary tumour tissue is associated with poor prognosis for the patients with colorectal cancer in this series.

Aged↗
PubMed2004

Uptake of radiolabeled morphiceptin and its analogs by experimental mammary adenocarcinoma: in vitro and in vivo studies.

Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) and its analogs modified at position 3: [D-Phe(3)]morphiceptin, [D-ClPhe(3)]morphiceptin and [D-Cl(2)Phe(3)]morphiceptin were synthesized and labeled with [(125)I] or [(131)I]. Their binding to membranes isolated from experimental adenocarcinoma was examined in vitro with the use of a cross-linking assay followed by the Western blot technique. The radioactive complex had molecular weight of about 65 kDa and was detectable by anti-mu-opioid receptor polyclonal antibody. Expression of the mu-opioid receptor in mouse mammary adenocarcinoma was confirmed by reverse transcriptase-polymerase chain reaction. The binding studies showed the highest affinity and capacity for [D-Phe(3)]morphiceptin (K(d) 0.39 and B(max) 1112) and [D-ClPhe(3)]morphiceptin (K(d) 1.8 and B(max) 220). Morphiceptin and its D-Cl(2)Phe analog had significantly lower B(max) values (131 and 83, respectively). Biodistribution experiments in tumor-bearing C3H/Bi mice with the use of the (131)I-labeled peptides confirmed the results of our in vitro studies. The highest accumulation of radioactive peptides in the tumor tissue was also found for peptides with D-Phe and D-ClPhe.

Adenocarcinoma↗
PubMed2004

Usefulness of polyclonal antibodies raised against P65 oncofetal protein in immunohistochemical diagnosis of ductal breast cancer.

Paraffin-embedded infiltrating ductal breast cancer tissue slides (135) were analyzed by immunohistochemistry with the use of rabbit polyclonal anti-P65 oncofetal protein and mouse monoclonal anti-estrogen/progesterone receptor (ER, PR) antibodies. Analysis with anti-P65 antibody revealed the positive cytoplasmic reaction in 83 cases, 98 showed the nucleic reaction and 3 were immunologically negative. Among the analyzed cases 49 revealed both cytoplasmic and nucleic reactions. For the whole group of cancers the correlation was found between ER or PR level and P65 cytoplasmic reaction (r = 0.77 and 0.66, respectively) and low inverse correlation with nucleic localization of P65 protein. The percentage of positive cells with cytoplasmic expression of P65 was significantly higher in more histologically differentiated cancers (grade I and II according to Bloom and Richardson) than in grade III. Opposite tendency was observed for the nucleic expression of P65 protein. The percentage of immunopositive nuclei grew with the advance of the disease and was the highest in poorly-differentiated (grade III) tumors. The tumors with P65 cytoplasmic reaction were mainly small (T1, T2), without metastases to lymph nodes (N0) and distant metastases (M0). The dependence between P65 protein localization and clinical stage of disease (TNM classification) was evaluated statistically. The straight dependence existed between P65 nucleic reaction and tumor size (p = 0.0002), metastases to lymph nodes (p = 0.0032) and distant metastases (p = 0.0006). The obtained results suggest that the transfer of P65 protein from cytoplasm to nuclei of the breast cancer cells is connected with more clinically advanced stages and worse prognosis for the patients.

Adult↗
PubMed2004

Expression of p65 gene in experimental colon cancer under the influence of 5-fluorouracil given alone and in combination with hormonal modulation.

The effect of tamoxifen (TAM), lanreotide (LAN) and 5-fluorouracil (5-FU), given separately or together, on p65 gene expression in murine Colon 38 cancer was investigated by RT-PCR method. The findings were compared with cell proliferation determined by bromodeoxyuridine (BrdU) labeling index, apoptosis visualized by TUNEL method and tumor mass. It was found that in the control group (mice bearing colon cancer without treatment) the expression of p65 gene was present in 57% of investigated samples. In the groups treated with TAM or LAN p65 gene expression was detected in 87.5% and 83.3% of analyzed cases, respectively. Both these substances increased apoptotic index in Colon 38 cancer and LAN also decreased the proliferation index. After a combined treatment with TAM and LAN a percentage of p65 positive cases was similar to that of the control group and equaled approximately 60%. This treatment did not increase proapoptotic effects of these drugs, and even reduced the antiproliferogenic effect of LAN. In the group treated with 5-FU and LAN p65 gene expression was also close to the control value (about 66%). Similarly in this group the combined treatment with these two drugs did not cause any favorable effect on proliferation and apoptosis. Moreover, in this group even reduced antiproliferogenic effect of LAN was observed. In the group with 5-FU alone the expression of p65 was present in about 80% of samples. The treatment with 5-FU increased apoptotic index and did not change proliferation. In the group treated with a combination of TAM and 5-FU all analyzed cases showed the presence of p65 gene expression. Previously, we observed in this group the most pronounced and synergistic effect of these substances on the inhibition of cell proliferation and tumor mass reduction. Based on these findings we conclude that p65 gene expression in murine Colon 38 cancer tissues can be modulated via chemotherapy (5-FU) and also via hormonal modulation (TAM and LAN).

Animals↗
PubMed2003

Synthesis of novel morphiceptin analogues modified in position 3 and their binding to mu-opioid receptors in experimental mammary adenocarcinoma.

Binding of the (125)I-labeled mu-opioid receptor selective ligands, morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) and [D-Phe(3)]morphiceptin, to membranes isolated from experimental mouse mammary adenocarcinoma was examined in vitro using a cross-linking assay followed by a Western blot technique. The radioactive complex had a molecular weight of about 65 kDa and was detectable by anti-mu-opioid receptor antibody, indicating the presence of mu-opioid receptors in tumor membranes. A series of new morphiceptin analogues, modified at the pharmacophoric position 3, was synthesized in order to find the correlation between the lipophilicity, electronic and steric properties of the amino acid in this position and the in vitro affinity of new analogues for mu-opioid receptors on mouse brain and tumor membranes. In in vivo studies the uptake of (131)I-labeled analogues by experimental mammary adenocarcinoma was estimated. The highest affinity for mu-opioid receptors in both, in vitro and in vivo experiments was observed for [D-Phe(3)]morphiceptin and [D-ClPhe(3)]-morphiceptin.

Adenocarcinoma↗
PubMed2003

HMGI(Y) gene expression in colorectal cancer: comparison with some histological typing, grading, and clinical staging.

We investigated HMGI(Y) gene expression in 81 pairs of frozen samples obtained from colorectal carcinomas and adjacent normal colorectal mucosas and in four samples from colorectal mucosa from patients without neoplastic diseases. In this group, HMGI(Y)-positive/-negative expression was compared with some histological features, grading, and clinical staging of neoplasms investigated to assess its potential role as a prognostic marker for colorectal cancer. Expression of HMGI(Y) gene was found in 51 of 81 cases of colorectal cancers, while, in normal mucosa, expression of this gene was not observed. HMGI(Y) gene expression was associated with more advanced tumors (T3, T4) and metastases to lymph nodes (N1, N2). The most interesting finding was that expression of this gene correlated with distant metastases. HMGI(Y) gene expression was detected in all cases classified as M1 (n = 19, p = 0.0008). We did not find any association between age, gender, tumor localization, histological type and this gene expression.

Adenocarcinoma↗
PubMed2003

Uptake of radiolabelled alpha-fetoprotein by experimental mammary adenocarcinoma and adenoma: in vivo and in vitro studies.

The biodistribution of iodine-labelled alpha-fetoprotein ( I-AFP) in experimental mammary tumours was studied. C3H mice with subcutaneously transplanted mammary adenocarcinoma and Sprague-Dawley rats treated with -methyl- -nitrosourea for mammary adenoma induction were used as animal models. The accumulation of labelled I-AFP in mouse mammary adenocarcinoma was significantly higher than that in rat mammary adenoma. The tumour/muscle radioactivity ratios increased with time and, 48 h after intravenous injection, were estimated as 23.4 and 6.7, respectively. For experiments, extracts from both mammary tumours were prepared. The extracts were subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), transferred to polyvinylidene difluoride (PVDF) membranes and incubated with I-AFP. A single major AFP-binding protein with a molecular weight of about 30 kDa was detected in both extracts. The amount of AFP-binding protein was clearly higher for adenocarcinoma than for adenoma. In the presence of cross-linking reagent, I-AFP formed a complex (about 100 kDa) with adenocarcinoma proteins.

Adenocarcinoma↗
PubMed2003

Expression of C-ERBB2 and P65 genes and their protein products in follicular neoplasms of thyroid gland.

C-ERBB2 and P65 gene expression was investigated by reverse transcriptase polymerase chain reaction method (RT-PCR) in thirty follicular thyroid cancers and twenty follicular adenomas. Additionally, the cancers and adenomas were stained by immunohistochemistry for the expression of their protein products. We did not observe P65 gene expression in any of the analyzed follicular cancers (n=30) but it was observed in 13 out of 20 (65%) follicular adenomas. The presence of C-ERBB2 gene expression was found in 18 (90%) follicular adenomas but not in cancers. There were 10 (50%) adenomas and 11 (36.7%) cancers with positive staining for C-ERBB2 protein and 15 (75%) adenomas and 2 (6.7%) cancers with positive staining for P65 protein. We conclude that expression of C-ERBB2 and P65 genes is associated with follicular adenoma but not with cancer of thyroid gland.

Adenocarcinoma, Follicular↗
PubMed2003

Expression of p65, DD3 and c-erbB2 genes in prostate cancer.

The expression of p65, DD3 and c-erbB2 genes was analyzed in 39 histologically verified human prostate cancers. The expression of p65 and DD3 genes was observed in significant percentage in well- and moderately-differentiated tumors. Both genes expression was lower in poorly differentiated tumors. On the contrary, c-erbB2 gene expression increased with advanced histological grading and reached the highest percentage in poorly-differentiated cancers. In the all investigated groups straight dependence between p65 and DD3 genes expression occurred. Opposite dependence was noticed in expression of p65/DD3 and c-erbB2 genes.

Carrier Proteins↗
PubMed2003

p65 and c-erbB2 genes expression in breast tumors: comparison with some histological typing, grading and clinical staging.

Using PCR technique we have analyzed p65 and c-erbB2 genes expression in 47 frozen tissue slides taken from patients diagnosed as ductal and lobular breast cancer, classified as G3, and in a limited panel of proliferative breast disease cases. Expression of p65 was generally connected with small tumor size and with absence of metastases in regional lymph nodes. We have found interdependence between p65 gene expression and negative states of lymph nodes. On the contrary, c-erbB2 expression was observed in patients with large tumors and with metastases to the regional lymph nodes. Between both genes (p65 and c-erbB2) opposite interdependence was found. No statistical dependence between estrogen/progesterone receptor levels and p65 or c-erbB2 expression were noticed. The presence of p65 expression appeared in the group of proliferating breast disease cases which were connected with higher risk of breast cancer. Lack of p65 expression accompanied cases which were classified as fibroadenoma.

Biomarkers, Tumor↗
PubMed2002

Expression of gene encoding P65 oncofetal protein in acute and chronic leukemias.

In this study we have established conditions for p65 gene expression analysis by reverse transcriptase polymerase chain reaction (RT-PCR). On the basis of this technique we analyzed p65 gene expression in various types of leukemia: acute myeloblastic leukemia (AML) (n=26); acute lymphoblastic leukemia (ALL) (n=26) and chronic lymphocytic leukemia (CLL) (n=40). The highest frequency of p65 gene expression was found in the patients with CLL (66%). No relationship between the expression of p65 gene and clinical stage of leukemia was observed. The lower percentage of positivity (presence of gene transcript) was seen in patients with ALL (42%) and AML (46%).

Adolescent↗
PubMed2000

Immunohistochemical analysis of expression of a 65 kDa oncofetal protein (p65), epidermal growth factor receptor (EGFR), oncogene c-erb B2 and tumor suppressor gene p53 protein products in breast cancer patients.

Paraffin-embedded tissue slides from 88 infiltrating ductal breast carcinoma were examined by immunohistochemistry technique with the use of monoclonal antibody against human p65 antigen and polyclonal antibody against p65-like protein present in fetal bovine serum. Immunohistochemical analysis of expression of growth factor receptors (EGFR), protein product of oncogene c-erb B2 as well as protein product of mutated anti-oncogene p53 was also done. It was established that there is no correlation between p65 and c-erbB2, EGFR or p53 expression. In low differentiated tumors (grade III) high p53 index and high EGFR and c-erbB2 expression was connected with low p65 expression. The lack of c-erbB2 and EGFR and low p53 expression was combined usually with high p65 oncoprotein levels.

Antibodies, Monoclonal↗
PubMed2000

Some oncogene and tumour suppressor gene protein products expression in B-cell chronic lymphocytic leukaemia.

The expression of Bcl-2, P53 proteins and known markers of proliferation, namely proliferating cell nuclear antigen (PCNA) and Ki67, in 29 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was investigated. All leukaemic patients were classified, and immunophenotyped by the two-colour immunofluorescence method with the use of fluorocytometry. B-CLL was heterogeneous in the range of biological parameters of tumour cells. B-CLL patients manifested 34% positive Ki67 and 61% PCNA expression, whereas Bcl-2 and P53 positivity was 81% and 42%, respectively. The level of intracellular expression of Bcl-2 and P53 proteins did not depend on the stage of disease estimated by routine methods. Ki67 and PCNA expression was significantly higher in B-CLL patients with more advanced stages of the disease. A statistically significant correlation was established between their mutual expression.

Aged↗