Biomedical subjects

J Mattern

Publications and source records attributed to J Mattern.

At least 37 records · Page 2Linked to original sources

PubMed1998

Expression of platelet-derived endothelial cell growth factor in non-small cell lung carcinomas: relationship to various biological factors.

The expression of platelet-derived endothelial cell growth factor (PD-ECGF) was determined immunohistochemically in 143 non-small cell lung carcinomas. Staining was observed in 48% of the cases. A relationship between histology, stage, erbB-1, erbB-2, ras and PD-ECGF expression was not found. A relationship of borderline significance was observed between PD-ECGF and p53 expression. There was also no relationship between PD-ECGF expression and proliferative activity (G1 phases, S phases, cyclin A). In contrast, a correlation between PD-ECGF- and VEGF-expression was detectable (p=0.009). Furthermore, PD-ECGF expression was related to the response of lung carcinomas to doxorubicin (p=0.0004). Of 35 sensitive tumors, 26 carcinomas were PD-ECGF-positive (74%) while of 108 resistant carcinomas only 43 tumors (40%) exhibited PD-ECGF expression.

Antineoplastic Agents↗

PubMed1998

Spontaneous apoptosis in ovarian cancer: an unfavorable prognostic factor.

Apoptosis and cell proliferation play important roles in the cellular response to chemotherapy, and may have prognostic value. The percentage of apoptotic cells [apoptotic index (AI)] was evaluated in ovarian carcinomas of 25 patients by the terminal desoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) technique. All patients were surgically treated and received postoperatively chemotherapy consisting of cytoxan and cisplatin or carboplatin. As a marker of proliferation the mRNA expression of histone H3 in tumor tissue was determined. In addition, tumor vascularity was assessed by immunohistochemistry and factor VIII. Patients with high AI had significantly shorter survival times (p=0. 0001) or recurrence-free intervals (p=0.004) than patients with low AI. No significant relationship was found between AI and histone H3 mRNA expression, however, an inverse correlation of AI with microvessel density was detected. Tumors with high AI had significantly lower microvessel count than tumors with low AI (p=0. 002). The obtained data suggest that AI can be predictive of treatment outcome in ovarian cancer.

Antineoplastic Agents↗

PubMed1997

Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer.

Tumor specimens from 109 patients with previously untreated squamous cell lung carcinomas were analyzed immunohistologically for the expression of vascular endothelial growth factor (VEGF) and its receptor Flt-1. Our analysis attempted to determine whether these factors have additional prognostic value for the patients' survival. VEGF staining was seen in 59% and Flt-1 staining in 68% of the cases. No significant correlations were detected between VEGF or Flt-1 expression and stage or metastasis. Patients with VEGF-stained tumors had significantly lower survival times than patients with negative tumors. Expression of Flt-1 showed no significant correlation with survival. Combining VEGF and Flt-1 expressions did not improve the prognostic value. Multivariate analysis showed that metastasis and VEGF expression are significant and independent prognostic factors for the survival of patients with squamous cell lung carcinomas.

Adult↗

PubMed1997

Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas.

Tumour specimens of 206 patients with untreated non-small cell lung carcinomas (NSCLC) were analysed immunohistochemically for the expression of the basic fibroblast growth factor (bFGF) and for its receptor (FGFR-1, Flg). Seventy of the tumours showed weak expression, 109 moderate and 27 high expression of bFGF. Thirty-eight tumours had low expression of FGFR-1, 116 had moderate and 52 cases high expression. Patients with high FGFR-1 expression had significantly shorter survival times than patients with weak or moderate expressions (P < 0.05), but there was no significant correlation between bFGF expression and patient survival. The results of the multivariate analysis demonstrated that FGFR-1 in the presence of stage is not an independent prognostic factor.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Cyclin A is associated with an unfavourable outcome in patients with non-small-cell lung carcinomas.

Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Of the 187 NSCLCs, 141 cases (75%) showed expression of cyclin A. Patients with cyclin A-positive carcinomas had significantly shorter median survival times than patients with cyclin A-negative carcinomas (79 vs 129 weeks, P = 0.045). Similar results were obtained with more homogeneous groups of patients: patients with only T3 tumours, patients with epidermoid carcinomas and patients with lymph node involvement. The clinical parameters (age, stage, histology, extent of tumour size, lymph node involvement) had no influence on expression of cyclin A. A direct correlation between cyclin A and the proportion of S-phase cells (P = 0.08) and an inverse relationship between cyclin A and the proportion of G0/G1-phase cells (P = 0.04) were found. Furthermore, a significant correlation between the expression of cyclin A and the response of NSCLC to doxorubicin in vitro was detected (P = 0.026).

Adenocarcinoma↗

PubMed1997

Expression of lung resistance-related protein (LRP) in non-small cell lung carcinomas of smokers and non-smokers and its predictive value for doxorubicin resistance.

Immunohistochemical methods were used to determine the expression of the lung resistance-related protein (LRP) in 87 cases of untreated non-small cell lung carcinoma. LRP expression was detected in 39 patients (45%). A significant correlation between LRP expression and tumor resistance to doxorubicin was found (p=0.03, Fisher's exact test). An inter-relationship between LRP expression and gender, age, stage, lymph node status and survival times was not observed. Furthermore, a relationship between LRP expression and proliferation (cell cycle phases, take rate of lung tumors in nude mice and cyclin A expression) was not detectable. However, a correlation of borderline significance was noticed between LRP expression and the patients' smoking habits. Carcinomas in heavy smokers (more than 30 cigarettes daily) were more frequently LRP-positive than carcinomas found in non-smokers (p=0.09, Fisher's exact test).

Animals↗

PubMed1996

Expression of resistance-related proteins in tumoral and peritumoral tissues of patients with lung cancer.

Twenty tumoral and peritumoral tissues from patients with lung cancer were analyzed immunohistochemically for the drug resistance-related proteins P-glycoprotein (P-170), topoisomerase II (Topo-II), glutathione S-transferase-pi (GST-pi), metallothionein (MT), heat shock protein-70 (HSP-70) and the putative regulators of resistance (ErbB1, Fos and Jun). Protein expression of Topo-II, GST-pi, MT, HSP-70, ErbB1, Fos and Jun was elevated in tumor tissue in comparison to normal tissue. The different expression of the proteins between tumoral and normal tissues was statistically significant for Topo-II (P = 0.05), MT (P = 0.03), and HSP-70 (P = 0.01), whereas ErbB1 showed a borderline significance. The expression of the proteins was frequently increased in smokers in comparison to non-smokers. In general, the increase of the proteins of smokers corresponded in tumoral and non-tumoral tissue. Different expression was only found with MT and HSP-70 which were higher in tissues of smokers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Association of resistance-related protein expression with poor vascularization and low levels of oxygen in human rectal cancer.

Rectal carcinomas of previously untreated patients were analyzed for oxygen status using a computerized polarographic needle electrode histograph. Microvessel density and expression of c-jun, vascular endothelial growth factor (VEGF) and several resistance-related proteins (glutathione S-transferase-pi, GST; thymidylate synthase, TS; metallothioneine, MT) were determined using immunohistochemistry. To examine whether a relationship exists between intratumoral vessel density and tumor oxygenation, microvessel counts were determined in a 400x field using factor-VIII-related antigen and were correlated with the corresponding pO2 values. Linear regression analysis revealed a significant relationship between vessel density and oxygenation status of the tumors. Expression of c-jun, VEGF and resistance-related proteins was correlated with microvessel counts and pO2 values. Significantly lower vessel counts were found in GST- and MT-positive tumors and in tumors with overexpression of c-jun and VEGF than in negative tumors. In addition, significantly lower pO2 values were found in c-jun- and VEGF-positive tumors as well as a tendency for pO2 values to be lower in tumors where MT, GST and TS were expressed. These data show that expression of c-jun, VEGF, and resistance-related proteins is linked with poor vascularization and low oxygenation status in rectal cancer.

Glutathione Transferase↗

PubMed1996

[Vascular thickness and cytostatic-resistant bronchial carcinoma].

BACKGROUND AND OBJECTIVE: A new way of treatment of malignant tumours was suggested by blocking angiogenesis and thus creating subpopulations of cells which, due to their decreased oxygen content, react differently to treatment. The relationship between angiogenesis (vessel density) and resistance to cytostatic drugs was investigated. PATIENTS AND METHODS: Results were analysed retrospectively for 83 untreated patients (73 men, 10 women; mean age 60 [37-75] years) with non-small cell bronchial carcinoma. Vessel density and resistance proteins were determined immunohistochemically. Radioactive incorporation of nucleic acid precursors with and without doxorubicin was measured with the in vitro short-term test. RESULTS: There were significant differences between vessel density and various resistance proteins. With low vessel density (less than mean value) glutathione-S-transferase pi (P < 0.01), thymidylate synthase (P < 0.05) and metallothioneine (P < 0.05) were significantly increased. P-glycoprotein showed a corresponding relationship, but it was not statistically significant, while there was no relationship with topoisomerase II. Bronchial carcinoma with low vessel density was more frequently resistant in vitro to doxorubicin than carcinomas with higher vessel density (P < 0.05). CONCLUSIONS: Non-small cell bronchial carcinoma with low vessel density more frequently expresses resistance proteins and is more commonly resistant to doxorubicin. Blocking angiogenesis to improve the results of treatment is therefore problematic.

Adult↗

PubMed1996

Microvessel density, expression of proto-oncogenes, resistance-related proteins and incidence of metastases in primary ovarian carcinomas.

Relationships between the incidence of metastatic spread and microvessel density, expression of proto-oncogene products, or expression of resistance-related proteins were investigated in human ovarian carcinomas by immunohistochemistry. Ovarian carcinomas with a high microvessel density showed a significantly increased formation of metastases (P = 0.005). Tumors with positive immunoreactivity of c-jun and c-myc products had a higher metastatic spread; however, these results were not statistically significant. A marginally significant correlation existed between the expression of erbB1 (EGFR) and metastatic spread (P = 0.05). No significant relationship was found between the expression of the resistance-related proteins P-glycoprotein or glutathione S-transferase-pi and the incidence of metastases. Furthermore, no correlation was detected between expression of the heat shock protein 70 and the occurrence of metastases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma.

Vascular endothelial growth factor (VEGF) expression, vascularisation and tumour cell proliferation were analysed in 91 human epidermoid lung carcinomas using immunohistochemistry. A polyclonal anti-VEGF antibody was used for VEGF expression, a polyclonal antibody directed against human von Willebrand factor (factor VIII) to identify blood vessels and the proliferating cell nuclear antigen (PCNA) as a marker for proliferating cells. Positive staining for VEGF was obtained in 54 out of 91 cases (59%), the number of blood vessels varied from zero to 64 counts (mean 9.4) and the proportion of PCNA-positive cells varied from 1.3% to 72.1% (mean 25.2%). The mean PCNA labelling index and mean microvessel count in VEGF-positive tumours were significantly higher than those in VEGF-negative tumours (Wilcoxon rank sum test, P<0.0001; p<0.05). In addition, PCNA labelling index significantly increased with increasing VEGF expression (Jonckheere test, P<0.0001). In contrast, no association was found between PCNA labelling index and tumour vascularity (r=0.07, P=0.48). The close correlation of VEGF expression with tumour cell proliferation and microvessel density suggests that VEGF acts both as an autocrine growth factor and as stimulator for angiogenesis. However, tumour cell proliferation and microvessel growth and/or density may be regulated by separate mechanisms.

Adult↗

PubMed1996

Resistance mechanisms and their regulation in lung cancer.

Data obtained from multiple sources indicate that no single mechanism can explain the drug resistance and the poor prognosis of patients with lung cancer. The resistance-related proteins P-glycoprotein, glutathione-dependent enzymes, topoisomerase II, metallothioneins, O-6-alkylguanine-DNA alkyltransferase, thymidylate synthase, dihydrofolate reductase and heat shock proteins have been found in lung carcinomas, but these alone cannot explain the drug-resistant phenotype. Cell cycle-related proteins, angiogenic factors, protooncogenes, and tumor suppressor genes also play a role in the phenotype that is resistant lung cancer. A key future challenge involves determining the relative quantitative contributions of each of these mechanisms to overall resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Messenger RNA expression of resistance factors in human tumor cell lines after single exposure to radiation.

Resistance of tumor cells to chemotherapeutic drugs can not only be caused by treatment with antineoplastic agents but also by radiotherapy. The aim of this study was to analyze whether ionizing radiation can influence the mRNA expression of proteins which have been found to be involved in drug resistance of tumor cells. Human tumor cell lines (MCF-7, LXF and Sk-Mel) were treated with single doses of irradiation (5, 10 and 20 Gy). The expression of the resistance related proteins glutathione S-transferase-pi (GST-pi), topoisomerase II alpha (Topo II), thymidylate synthase (TS), O6-methylguanine-DNA-methyltransferase (MGMT), P-glycoprotein (Pgp), glutathione peroxidase (GPX) multidrug resistance-associated protein (MRP) and also of the heat-shock protein 70 (HSP 70) were determined at the mRNA level during the time interval from 1.5 to 72 h post-irradiation and compared with their corresponding controls. We also examined whether a relationship exists between these proteins and the proliferative activity (histone 3, Ki-67, statin) of the cells. We found that exposure of MCF-7, LXF and Sk-Mel cells to ionizing radiation increases the expression of the mRNA of GST-pi. Topo II, TS, HSP 70 and proliferation markers were also altered by exposure to ionizing radiation, but there was no common response of the three cell lines. No significant changes were observed in the expression of MGMT, Pgp, GPX and MRP after radiation treatment. Drug resistance tests revealed that irradiated MCF 7 cells were less sensitive to doxorubicin than non-irradiated control cells. Our results indicate that ionizing irradiation modifies the expression of some proteins involved in drug resistance and the response of MCF 7 cells to doxorubicin and may, therefore, play a role in clinical drug response.

Blotting, Northern↗

PubMed1995

Expression of resistance-related proteins in nephroblastoma after chemotherapy.

Tumor tissues of untreated and cytostatic-agent-treated patients with nephroblastomas were investigated for expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty-three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no preoperative chemotherapy. In untreated patients, no expression of P-glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P-glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S-transferase-pi, we found significant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione-peroxidase-mRNA content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P-glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase-II expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Heat shock (hsp70) and resistance proteins in non-small cell lung carcinomas.

The aim of the study was to prove whether or not an association exists between the heat shock protein 70 (hsp70) and drug resistance. Tumor samples of 90 patients with previously untreated non-small lung carcinomas were investigated immunohistochemically for expression of resistance related proteins. Additionally, resistance to doxorubicin was determined using a short term test. No association between resistance related proteins. Additionally, resistance to doxorubicin was determined using a short term test. No association between resistance to doxorubicin and hsp70 was found. Of 63 resistant tumors, 33 showed low and 30 high hsp70 expression. Of the 26 sensitive tumors, 11 had low and 16 had high hsp70 expression. No relationship could be found between P-glycoprotein which is related to multidrug resistance and hsp70 expression or between hsp70 expression and expression of topoisomerase II, thymidylate synthase and metallothionein. On the other hand, a trend was noted for tumors with high glutathione S-transferase-pi expression to show high hsp70 expression. In addition, there was a significant relationship between hsp70 and catalase positivity. These data indicate that heat shock and stress promote intracellular oxidative damage and catalase is necessary for protection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Predictive value of statin, a G0-associated cell cycle protein, in childhood acute lymphoblastic leukemia.

Blast cells of 71 children with newly diagnosed acute lymphoblastic leukemia (ALL) were examined with a novel monoclonal antibody (MAb), S-44, immunoreactive to statin, a nuclear protein specifically expressed in non-proliferating cells. The statin labeling index (LI) varied greatly from case to case and ranged from 0.3% to 86%, with a mean value of 10%. The degree of statin LI correlated inversely with the expression of Ki-67. When patients were subdivided according to whether the statin LI was higher or lower than the mean value, patients with higher statin LI did not respond to chemotherapy and survived for a shorter period of time. Our results suggest that labeling of statin with the S-44 MAb is a useful prognostic marker of the cytotoxic effects of anti-cancer drugs in patients with ALL.

Adolescent↗

PubMed1995

Effects of single doses of irradiation on the expression of resistance-related proteins in murine NIH 3T3 and human lung carcinoma cells.

In this report the effects of single doses of ionizing radiation on the mRNA expression of several proteins involved in multiple drug resistance were analyzed. Murine NIH 3T3 cells treated with single doses of 5, 10 and 20 Gy during the time interval from 1.5 to 72 h after irradiation were compared with their corresponding controls at the same points of time. The glutathione S-transferase-pi (GST pi) level was elevated in cells treated with 10 or 20 Gy from 24 to 72 h after irradiation compared with the control. Topoisomerase II alpha and thymidylate synthase were decreased in irradiated cells 24-72 h after exposure. These down-regulations were associated with cellular proliferation, determined by mRNA expression of the proliferation marker histone 3. Irradiated cells exhibited no alteration in the P-glycoprotein or glutathione peroxidase mRNA content. The finding that GST pi mRNA was overexpressed after irradiation was validated by investigations on a human lung carcinoma cell line (LXF 289) on the mRNA and protein level. Thus, our results indicate that irradiation alters the expression of proteins involved in multidrug resistance and may, therefore, play a role in clinical drug response.

3T3 Cells↗

PubMed1995

Up-regulation of resistance-related proteins in human lung tumors with poor vascularization.

Microvessel density was investigated by immunostaining endothelial cells for factor VIII antigen in 84 non-small cell lung carcinomas and compared with the expression of several resistance-related proteins. Glutathione S-transferase-pi, thymidylate synthase, metallothionein and, with limitations, P-glycoprotein were overexpressed in tumors with poor vascularization.

ATP Binding Cassette Transporter, Subfamily B, Mem↗