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R Wierzbicki

Publications and source records attributed to R Wierzbicki.

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↗
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↗
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↗
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↗
PubMed1998

A 65 kDa oncofetal protein (p65), proliferating cell nuclear antigen (PCNA) and Ki67 expression in breast cancer patients.

Paraffin-embedded tissue slides from 89 infiltrating ductal breast carcinoma, 10 fibrocystic disease and 10 fibroadenoma were assessed immunohistochemically using monoclonal antibodies against human p65 antigen and polyclonal antibodies against p65-like protein present in fetal bovine serum. We did not find any evident differences in p65 detection by polyclonal and monoclonal antibodies, however, monoclonal antibody seems to be more specific. This factor is not induced by cellular proliferation associated with nonneoplastic diseases what was confirmed by immunohistochemical analysis of expression of p65 protein and well know markers of proliferation (proliferating cell nuclear antigen--PCNA and Ki67). It was established that there is no correlation between p65 and PCNA or Ki67 expression. High proliferating indexes (PI) for PCNA (PI-PCNA) or Ki67 (PI-Ki67) may help in selection of tumors with high proliferating activity independently from histological grade of malignancy established by routine methods. The estimation of p65 protein may be useful in the selection of precancerous changes and more differentiated ductal cancer of the breast what raises the possibility that p65 antigen may be helpful in the screening examination of women with high risk for cancer development.

Animals↗
PubMed1997

Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup.

BACKGROUND: A previous trial by the European Osteosarcoma Intergroup (EOI) suggested that a short intensive chemotherapy regimen with doxorubicin and cisplatin might produce survival of operable, non-metastatic osteosarcoma similar to that obtained with complex and longer-duration drug regimens based on the widely used T10 multi-drug protocol. We undertook a randomised multicentre trial to compare these two approaches. METHODS: 407 patients with operable, non-metastatic osteosarcoma were randomly assigned the two-drug regimen (six cycles [18 weeks] of doxorubicin 25 mg/m2 on days 1-3 and cisplatin 100 mg/m2 on day 1) or a multi-drug regimen (preoperatively vincristine, high-dose methotrexate, and doxorubicin; postoperatively bleomycin, cyclophosphamide, dactinomycin, vincristine, methotrexate, doxorubicin, and cisplatin; this protocol took 44 weeks). Surgery was scheduled for week 9 for the two-drug group and week 7 for the multi-drug group. Analyses of survival and progression-free survival were by intention to treat. FINDINGS: Of 407 randomised patients, 391 were eligible and have been followed up for at least 4 years (median 5-6 years). Toxic effects were qualitatively similar with the two regimens. However, 188 (94%) of 199 patients completed the six cycles of two-drug treatment, whereas only 97 (51%) of 192 completed 18 or more of the 20 cycles of the multi-drug regimen. The proportion showing a good histopathological response (> 90% tumour necrosis) to preoperative chemotherapy was about 29% with both regimens and was strongly predictive of survival. Overall survival was 65% at 3 years and 55% at 5 years in both groups (hazard ratio 0.94 [95% CI 0.69-1.27]). Progression-free survival at 5 years was 44% in both groups (hazard ratio 1.01 [0.77-1.33]). INTERPRETATION: We found no difference in survival between the two-drug and multi-drug regimens in operable, non-metastatic osteosarcoma. The two-drug regimen is shorter in duration and better tolerated, and is therefore the preferred treatment. However, 5-year survival is still unsatisfactory and new approaches to treatment, such as dose intensification, are needed to improve results.

Adolescent↗
PubMed1997

Expression of 65-kDa oncofetal protein in experimental hepatoma after anticancer therapy.

We have tested the expression of a 65-kDa oncofetal protein (p65) after combined treatment with menadione and methotrexate in hamsters transplanted with Kirkman-Robins hepatoma. The treatment of tumor-bearing animals with these compounds significantly inhibited both the tumor development and the expression of p65. This inhibition in tumor tissue was calculated from densitograms of Western blots. The inhibition of p65 expression was also confirmed in the serum of hepatoma bearing animals by using solid-phase radioimmunoassay (RIA) to quantify the specificity of polyclonal antibodies to fetal p65 molecules. Additionally, p65 was shown to localize both in cytoplasm and in the nuclear extracts prepared from hepatoma tissue.

Animals↗
PubMed1994

VP-16, ifosfamide and cisplatin (VIP) for extensive small cell lung cancer.

Thirty-seven extensive disease SCLC patients were treated with ifosfamide 1.0 g/m2 (maximum 1.75 g), VP-16 (etoposide) 75 mg/m2 and cisplatin 20 mg/m2 (VIP) daily for 5 days in hospital. Mesna was given as a continuous infusion until 12 h after the last ifosfamide dose. Treatment was reduced to 4 days after the first 8 patients experienced serious myelotoxicity. 30 patients were evaluable for response. 8 (27%) achieved a complete response and 60% had a partial response. The median duration of response was 23 weeks. The median survival of all 37 patients was 41 weeks, and 47 weeks for the 30 evaluable patients. Fifty per cent and 26% of the evaluable treatment courses were associated with grade 4 and 3 granulocytopenia, respectively. There were eight febrile events including four treatment-related deaths from sepsis on the 5-day regimen. Although the response to VIP was generally rapid, the proportion achieving complete response (27% of evaluable patients) and the median survival is similar to standard chemotherapy regimens which are less toxic and less complex to administer.

Adult↗
PubMed1993

[Specific inhibitors of plasminogen activators].

The article contains a survey of the recent papers on the fibrinolytic inhibitors which regulate the process of plasminogen activation--PAI-1 and PAI-2. Both of them belong to serine protease inhibitors family and are specific for tPA as well as uPA, forming stable complexes in molar ratio 1:1 with them. PAI-1, secreted mainly by endothelial cells and platelets, is the main plasmic inhibitor of plasminogen activation. PAI-2, originated essentially from placenta, appears in blood during pregnancy.

Animals↗
PubMed1992

Vulvar sarcoma: a report of four cases.

The clinical profiles of four patients with primary vulvar sarcomas are presented. Two patients had leiomyosarcoma in association with pregnancy, a third patient had a leiomyosarcoma with epithelioid elements, and a fourth had alveolar rhabdomyosarcoma. The natural history of the disease in the three leiomyosarcomas (including the case with epithelioid elements) was characterized by an indolent protracted course and frequent local recurrence, followed by distant fatal metastases. The patient with alveolar rhabdomyosarcoma is alive-with-disease. Surgery, chemotherapy, and radiotherapy achieved palliation rather than cure. Pregnancy did not seem to influence the prognosis.

Adolescent↗
PubMed1992

A phase II study of recombinant tumor necrosis factor in renal cell carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group.

The National Cancer Institute (NCI) Canada Clinical Trials Group conducted a phase II study of recombinant tumor necrosis factor (rTNF) given intravenously daily for 5 days every other week, in measurable metastatic renal cell carcinoma. Two of 26 patients responded with responses lasting greater than 200 days. Toxicity was severe including rigors, fever, headache, fatigue, hypotension, and localized pain. We conclude that rTNF, given as described, has only modest antitumor activity in renal cell carcinoma and produces considerable toxicity. We plan no further studies of rTNF in this disease.

Adult↗
PubMed1992

Phase I-II study of high-dose epirubicin in advanced non-small-cell lung cancer.

PURPOSE: A phase I multicenter trial was performed to determine the maximum-tolerated dose (MTD) of epirubicin, given on 3 consecutive days every 3 weeks to previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: After appropriate staging and a baseline multiple-gated angiogram (MUGA) scan, at least four patients were entered at each dose level, starting at 35 mg/m2 of epirubicin given intravenously (IV) daily for 3 days (105 mg/m2) and escalating by 5 mg/m2 per injection in each dose level (15 mg/m2 per course). Epirubicin was administered up to a maximum dose of 60 mg/m2/d for 3 days (180 mg/m2). The MTD was determined to be 55 mg/m2/d for 3 days (165 mg/m2) after treating a total of 35 (33 assessable) patients. Nadir granulocyte counts and associated febrile episodes comprised the dose-limiting toxicity, but there were no treatment-related deaths. A phase II trial was performed using a dose of 50 mg/m2/d for 3 days (150 mg/m2) every 3 weeks with no dose escalation, but with dose reduction for toxicity as required. A total of 30 patients were entered onto this phase of the study. RESULTS: The major toxicity, as in the phase I trial, was neutropenia with five febrile episodes, again with no treatment-related deaths. An overall response rate of 12 of 63 (19%) was noted in the combined patient population of the phase I-II trial, with 95% confidence intervals of 10% to 31%. When the response rate was analyzed by histology, only one of 17 (6%) patients with squamous histology, as compared with 11 of 46 (24%) with non-squamous histology, responded, but this did not reach statistical significance (P = .15). CONCLUSIONS: High-dose epirubicin is tolerable and is an active single agent in NSCLC. It should be combined with relatively nonmyelosuppressive agents such as cisplatin to try to obtain higher response rates and extend the survival in this disease.

Adult↗
PubMed1991

Phase II study of 2'-deoxycoformycin in patients with renal cell carcinoma. A National Cancer Institute of Canada Clinical Trials Group study.

The National Cancer Institute of Canada Clinical Trials Group undertook a phase II study of 2'-deoxycoformycin in patients with metastatic renal cell carcinoma. When 2'-deoxycoformycin 4 mg/m2 was administered intravenously weekly for three weeks then every two weeks no significant antitumor activity was noted in 19 evaluable patients. Toxic effects experienced were as expected, consisting primarily of nausea/vomiting, anorexia, and lethargy. It is concluded that 2'-deoxycoformycin at this dose and schedule has no clinical activity in the treatment of metastatic renal cell carcinoma.

Adult↗