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J Mattern

Publications and source records attributed to J Mattern.

At least 73 records · Page 4Linked to original sources
PubMed1991

Overexpression of P-glycoprotein in human lung carcinoma xenografts after fractionated irradiation in vivo.

In vivo exposure of a human epidermoid lung carcinoma xenograft to seven irradiation treatments of 10 Gy in consecutive passages resulted in expression of resistance to vincristine. This about threefold drug resistance was detectable with a single dose of 1 mg/kg vincristine. Characterization of the radiation-pretreated subline showed that overexpression of P-glycoprotein, as determined by immunofluorescence and Mabs C219 and 265/F4, occurred in this tumor. After six X-ray fractions, only single positive cells were observed, whereas seven fractions produced an intense immunofluorescent reaction with both antibodies. Southern blot analyses indicated that no gene amplification had occurred. This result shows that irradiation can influence expression of P-glycoprotein and in this way influences drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

[Reversal of multidrug resistance with (R)-verapamil in vitro and in vivo].

The clinical use of racemic (R/S)-verapamil (CAS 52-53-9) as resistance modifier is limited because of the cardiovascular activity of the substance. The stereoisomer (R)-verapamil shows significant less cardiovascular activity. Therefore we tested the resistance modifying abilities of (R)-verapamil and (R/S)-verapamil in murine multidrug-resistant L 1210 ascites-tumor-cells in vitro and in vivo. The present results demonstrate, that the (R)-isomer has the same resistance modifying effects as racemic verapamil. Both modifying substances have no effects in the parental (sensitive) and cytosine-arabinoside resistant L 1210 ascites-tumor-cells. Thus, (R/S)-verapamil and (R)-verapamil show their resistance modifying abilities only in multidrug-resistant tumor-cells.

Animals↗
PubMed1990

Overexpression of P-glycoprotein in rat hepatocellular carcinomas induced with N-nitrosomorpholine.

The most frequently reported alteration of multidrug resistance (MDR) is the overexpression of the 170 kd membrane glycoprotein. An increased expression of the MDR-gene in pre-neoplastic and neoplastic liver lesions produced experimentally by different carcinogens has been reported. As shown in rat liver by stop experiments, specific carcinogen-induced alterations can be separated from non-specific, toxic changes. Therefore, we induced rat hepatocellular carcinomas with N-nitrosomorpholine and investigated whether expression of the MDR-gene also takes place in hepatocellular carcinomas after withdrawal of the carcinogen. Using mAb C219 against P-glycoprotein, both normal liver and hepatocellular carcinomas show specific immunoreactivity by means of immunofluorescence and immunohistochemistry. In hepatocellular carcinomas, however, the reaction is increased if compared to normal liver of untreated control animals. These results were confirmed by immunoblotting. Using the cDNA probe 1.5, a significant increase in MDR-gene transcripts was found in hepatocellular carcinomas as compared to normal liver.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Detection of drug resistance and P-glycoprotein in human renal cell carcinomas.

Expression of the multidrug-resistance gene product P-glycoprotein (P-170) was screened in 21 untreated human renal cell carcinomas using monoclonal antibodies (265/F4, C219) and immunoperoxidase staining. The inherent drug resistance of the same samples against doxorubicin was established by a short-term chemoresistance test in order to investigate the association between the expression of P-170 and intrinsic drug resistance in kidney cancers. P-glycoprotein could be demonstrated in 10 cases. Using the short-term test for predicting resistance, 17 resistant and 4 sensitive cancers were found. In vitro 10 of 17 resistant tumors revealed an increase of P-glycoprotein. On the other hand, in the sensitive tumor in vitro, an expression of P-glycoprotein could not be demonstrated. This investigation reveals that intrinsic drug resistance exists in many renal cell carcinomas and it is associated at least in part with increased expression of P-glycoprotein. The immunohistochemical results suggest that the presence of the P-glycoprotein may be useful as a marker for screening the multidrug-resistant phenotype in renal cell carcinomas and as an indicator of the therapeutic efficacy of multidrug-resistant kidney cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Detection of P-glycoprotein in human leukemias using monoclonal antibodies.

Overexpression of a Mr 170,000 membrane glycoprotein (P-glycoprotein) is consistently associated with multidrug resistance in cell lines. Two monoclonal antibodies (Mab) against P-glycoprotein (265/F4 and C 219) were used to examine tumour samples from patients with leukemias for evidence of P-glycoprotein overexpression. High levels of P-glycoprotein (greater than 5% positive cells) were detected with both antibodies in samples from 3 out of 18 patients suggesting that a multidrug resistant phenotype may also occur in human leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein.

The aim of this study was to find out whether only resistant cells of the "multidrug-resistant" phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210dnr) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabino-side-resistant (L1210AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210ctx) (not multi-drug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210dox and L1210dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210AraC or L1210ctx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Detection of drug resistance in human ovarian carcinoma.

Drug-resistant cancer cells with the multidrug-resistance phenotype show overexpression of P-glycoprotein, and we therefore tested carcinoma tissue from five patients with stage III or IV ovarian cancer for P-glycoprotein using 265/F4 and C 219 monoclonal antibodies, prepared against membrane glycoproteins in colchicine-resistant CHO cells. Using immunofluorescence and immunoblotting techniques, one of the tumors showed a positive reaction. Using the pcDR 1.5 clone we found that the same cancer tissue had elevated expression of the genes responsible for multidrug resistance. The demonstration of elevated P-glycoprotein in ovarian carcinomas indicates that P-glycoprotein overexpression is not limited to experimental tumor models.

Carcinoma↗
PubMed1989

Detection of the multidrug resistant phenotype in human tumours by monoclonal antibodies and the streptavidin-biotinylated phycoerythrin complex method.

The aim of this study was to find out whether the membrane glycoprotein P-170 can be detected in human tumours with both acquired and intrinsic resistance to chemotherapeutic agents using monoclonal antibodies (265/F4 and C219) and the streptavidin-biotinylated phycoerythrin complex method. Pretreated leukaemia cells and untreated lung and ovarian carcinomas were analysed. Two plasmacytomas and one leukaemia expressed high levels of P-glycoprotein, whereas two leukaemias showed moderate, and three leukaemias no expression of this protein. The intrinsic resistance was analysed with a panel of four human epidermoid lung cancer xenografts grown in nude mice. The expression of P-glycoprotein could be correlated with the degree of resistance. In addition, one out of five ovarian carcinomas revealed a high level of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

P-glycoprotein expression in treated and untreated human breast cancer.

The expression of P-glycoprotein in primary and recurrent human breast cancer was investigated by means of immunohistochemistry, using a monoclonal antibody (C219) and the streptavidin-biotin-peroxidase method. Twelve patients received no chemotherapeutic treatment. The other 11 patients were treated with chemotherapy, and all developed clinical resistance to it. No or only minimal reactivity was found in specimens coming from the untreated patients (12 cases) or from patients treated with substances not involved in the multidrug resistance phenomenon (four cases). In contrast, three out of seven tumours from patients treated with multidrug resistance related substances showed clear reactivity (positive staining in more than 20% of the tumour cells). In one of these cases, where specimens of the tumour could be studied before and after treatment, an association between the latter and expression of P-glycoprotein was suggested. Finally, this marked expression of P-glycoprotein only took place in tumours treated over a longer space of time (five courses or more of multidrug resistance related chemotherapy).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Radiosensitivity of drug-resistant human tumour xenografts.

The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation.

Animals↗
PubMed1989

[Morphologic and tumor-marker studies of human planocellular carcinoma of the bronchi in xenografts].

Authors have studied the morphology of 10 human planocellular bronchus carcinoma xenografts parallel with that of the donor tumour. The expression of cytokeratin, epithelial membrane antigen and carcinoembryonic tumour markers was also studied and compared. The histological structure and marker expression of xenografts did not change as compared to the donor tissue. Tumour cells were characterized by cytokeratin rather than epithelial membrane antigen. Carcinoembryonic antigen positivity occurred mainly in well-differentiated tumours. The cellular heterogeneity of human planocellular bronchus carcinomas was found to occur also in xenograft tumours.

Antibodies, Monoclonal↗
PubMed1989

[Demonstration of independent cellular prognostic factors in squamous cell carcinoma of the lung].

The aim of this investigation was to find out whether a histopathologically homogeneous group of patients (similar in histology, grade, operation, and therapy) could be divided with respect to survival by determining cellular tumor factors. Therefore out a group of 100 patients 46 patients with previously untreated epidermoid lung carcinomas were selected. From these patients fresh surgical specimens of tumors were investigated by means of flow cytometry and the obtained data were correlated with five years survival. Patients with aneuploid tumors had significantly shorter survival times than did those with diploid tumors (p = 0.02). Seven of eleven patients with diploid tumors survived five years or more, whereas 25 of 35 patients with aneuploid tumors died within this period. Patients having tumors with a high proportion of G0/G1-phase cells survived significantly longer (p = 0.04) than patients having tumors with a lower proportion of G0/G1-phase cells. Within five years half of the patients with a high proportion of G0/G1-phase cells survived in contrast to 10% of patients in the other group. These data demonstrate that in addition to the well known clinical and histological factors independent cytometric prognostic factors in epidermoid carcinoma of the lung exist.

Aneuploidy↗
PubMed1989

Acquired drug resistance in human lung carcinoma xenografts.

The development of resistance to vincristine and dactinomycin has been investigated in a human epidermoid lung xenograft line grown in nude mice. With 1 mg/kg BW vincristine and 0.5 mg/kg BW dactinomycin per passage, resistance of the solid tumors was visible already at the second transplantation. The vincristine-resistant subline showed cross-resistance to dactinomycin and doxorubicin, and the dactinomycin-resistant subline only to vincristine. To determine whether multidrug resistance genes were overexpressed in the resistant sublines, slot blots were performed using the cDNA probe pcDR 1.5. Slightly elevated RNA levels could be detected in the vincristine-resistant subline and in the dactinomycin-resistant subline.

Animals↗