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Biomedical subjects

M Volm

Publications and source records attributed to M Volm.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Flow cytometric analysis of primary lung carcinomas and their lymph node metastases.

Specimens of primary lung carcinomas and lymph node metastases from the same 18 patients were investigated by means of flow cytometry. The number of DNA stemlines, DNA indices, the proportion of diploid cells in the tumors and the distribution of the cell cycle phases were compared. In 10 patients DNA stemlines and DNA indices were identical in primary tumors and metastases. In two cases the DNA indices were doubled in metastases. In 6 cases the primary tumors contained two abnormal DNA stemlines and their metastases contained only one aneuploid stemline. Gross differences between primary tumors and lymph node metastases with regard to the proportion of cell cycle phases could not be found. The large variation between primary tumors and lymph node metastases with regard to DNA stemlines indicates that flow cytometric analysis of lymph nodes gives only limited information about the primary tumors.

Adenocarcinoma↗
PubMedDate not supplied

Induced multidrug-resistance in murine sarcoma 180 cells grown in vitro and in vivo and associated changes in expression of multidrug-resistance DNA-sequences and membrane glycoproteins.

The aim of this investigation was to analyze the resistance to doxorubicin and daunorubicin of murine sarcoma 180 cells grown in vitro (monolayer) and in vivo (ascites form). The colchicine-resistant CHO cells were used as controls. A multidrug-resistant phenotype was found in all investigated cell lines. Multidrug resistant cells grown in tissue culture or as ascites tumor cells needed more time to accumulate rhodamine 123 than their sensitive parental cells. In order to evaluate whether the resistant cells show alterations in the plasma membranes, different methods were applied (immunocytochemistry, immunofluorescence, immunoblotting) using the monoclonal antibodies 265/F4 and C 219. These methods all revealed an increased expression of the glycoprotein Mr 170 kd in the multidrug-resistant cell lines. To determine whether multidrug DNA sequences were expressed in the resistant cell lines, slot blots and Northern blots with RNA of sensitive and resistant cells were performed using the clones pDR 7.8 and pcDR 1.5. Elevated RNA levels were detected in all resistant cell lines.

Animals↗
PubMedDate not supplied

Flow cytometry of epidermoid lung carcinomas: relationship of ploidy and cell cycle phases to survival. A five-year follow up study.

Surgical specimens of tumors of 105 patients with previously untreated epidermoid lung carcinomas were investigated by means of flow cytometry and the results compared with the survival of the patients. The aim of the present prospective study was to establish further the efficacy of cytometric analysis, independent of well known clinical factors. For determining prognosis, all patients had a minimum of 5 years follow-up. The present study clearly shows that, independent of clinical characteristics, cytometric DNA content analysis has prognostic importance in patients with epidermoid lung carcinomas. Patients with aneuploid tumors died significantly sooner than those who had tumors with DNA diploidy. Patients whose tumors had a high proliferative activity (proportion of Go/G1-phase-cells less than or equal to 78%, S-phase-cells greater than 8%, G2M-phase-cells greater than 14%) died significantly earlier than patients with tumors with lower proliferation activity. Comparisons within homogeneous groups of patients with respect to the clinical characteristics (T3, NM+, stage III, surgery, treatment) showed identical results. In addition to the univariate analyses, multivariate analyses (Cox-regression model) were used. The results of this study demonstrate two groups of independent prognostic factors for the survival of patients with epidermoid carcinomas: clinical factors and flow cytometric factors.

Carcinoma, Squamous Cell↗
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Clinical prognostic relevance of growth of human adenocarcinomas of the lung in nude mice.

Forty-nine adenocarcinomas of the lung were transplanted into nude mice in order to examine whether the growth of these tumors or the establishment of tumor lines might be of clinical prognostic value. Twenty-one of the tumors showed growth (= 43%) and 7 (= 14%) could be maintained by serial transplantation. There was no difference in the survival of patients whether their tumors showed growth in the first passage or not. On the other hand, the patients died significantly earlier if a tumor line by serial transplantation could be established (p less than 0.0001). Tumors which could be established had a higher proliferative activity in the primary tumor and in the xenografted tumor in the first passage. Therefore, the establishment of a tumor line might be an additional prognostic indicator for patients with adenocarcinomas of the lung.

Adenocarcinoma↗
PubMedDate not supplied

Optimum time sequence for the administration of cyclophosphamide and other drugs in vivo.

The significance of time interval for administration of a second drug after a first dose of cyclophosphamide (CTX) was studied for a human ovarian, lung, and colon carcinoma line growing as xenografts in nude mice. The effects of combination of two drugs were found to be dependent on the interval between the administration of each drug. The most effective chemotherapy schedules were those in which adriamycin (ADM) or CTX were sequenced to coincide with the time point where the tumour was regrowing from the single dose of CTX. The variation of the cell kinetic parameters, as estimated by flow cytometry analysis, could not be correlated with the antitumour action of the drug combination.

Animals↗
PubMedDate not supplied

Therapeutic response of human lung tumour xenografts to cyclophosphamide.

The effect of cyclophosphamide, given as a single i.p. injection (240 mg/kg) on 13 various fast growing human lung tumours, transplanted and passed serially in athymic nude mice, were studied. Cyclophosphamide showed activity against all tumours studied. The sensitivity of the different tumour lines tested varied considerably. The faster a tumor was growing, the more pronounced was the inhibitory effect of cyclophosphamide on growth, independent of the histological type. If different lung tumours were treated at the same size and site (8-10 mm, s.c. right anterior flank), growth rate was a factor of decisive importance for the sensitivity of a tumour to cyclophosphamide.

Animals↗
PubMedDate not supplied

Reversal of doxorubicin-resistance in solid tumors by clomipramine.

Resistance to cytotoxic treatment is a major obstacle to more successful cancer treatment, and approaches to overcome the drug resistance of tumors have received much attention in recent years. In the present in vivo study the psychotropic drug clomipramine was used as chemosensitizer in the doxorubicin (DOX)-resistant L 1210 cell line growing as solid tumors in mice. A significant reduction in the growth of DOX-resistant tumors was observed after treatment with clomipramine and DOX (p = 0.014, Kruskal Wallis-test; p = 0.006, Wilcoxon rank sum test). Thus, clomipramine might be useful in reversing DOX-resistance in solid tumors.

Animals↗
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p53 protein detected by two different antibodies: relationship to proliferation and prognosis in acute lymphoblastic leukemia.

The expression of p53 protein was examined in a series of 69 children with acute lymphoblastic leukemia with two different monoclonal antibodies (Mab 1801 and 240). p53 expression was detected with at least one antibody in 49 cases (71%), whereas only 19 cases (27%) were positive with both antibodies. Variability in the immunostaining could be observed depending on the antibody used. Mab 240 gave the highest rate of positive staining (58%), followed by 1801 with 39%. Positive staining with 1801 was significantly associated with decreased proliferation of tumor cells as measured by Ki-67 labelling, indicating that possibly the wild-type p53 protein is preferably stained with this antibody. However, neither of the two antibodies has prognostic value or is correlated with histopathological parameters.

Age Factors↗
PubMedDate not supplied

Associated expression of protein kinase C with resistance to doxorubicin in human lung cancer.

The expression of protein kinase C (PKC) in 83 untreated solid human non-small cell lung carcinomas was determined and its correlation with inherent resistance to doxorubicin, with the expression of P-glycoprotein (P-170), and with the expression of glutathione S-transferase-pi (GST-pi) was analysed. Doxorubicin resistance was measured using an in vitro short-term test. The expression of PKC, P-170 and GST-pi was assessed immunohistochemically. Twenty-three tumors (= 28%) were PKC-positive, whereas 60 tumors (= 72%) were PKC-negative. Nineteen tumors (= 23%) were classified as sensitive and 64 tumors (= 77%) as resistant to doxorubicin. Thirty-nine tumors (= 47%) were P-170-positive and 51 tumors (= 61%) GST-pi-positive. Out of the PKC-positive tumors, 21 were resistant to doxorubicin and 2 were sensitive. Of the same 23 tumors, 18 were P-170-positive and 19 were GST-pi-positive. The correlations between the expression of PKC and the resistance to doxorubicin, the expression of P-170 and the expression of GST-pi were statistically significant. Corresponding results were obtained comparing the results of all tumors with the results of a subgroup of tumors having the same histology (squamous cell carcinomas). This supports the hypothesis that PKC is involved in the inherent doxorubicin-resistance of human lung cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
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p53 expression and poor prognosis in childhood acute lymphoblastic leukemia.

Ninety-one children with untreated acute lymphoblastic leukemia (ALL) were analysed for expression of p53 using immunocytochemistry. p53 expression was found in 80% of the cases by Mab 421. Kaplan-Meier estimates show that patients with p53-positive leukemic cells had significantly shorter survival times under chemotherapy than those with p53-negative leukemic cells (p = 0.05, log-rank test). Statistical analysis revealed no correlation between p53 expression and patient's age, sex, immunotyping and initial peripheral blast cell count.

Antibodies, Monoclonal↗
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Detection of resistance proteins in matched primary lung tumors and lymph node metastases.

The expression of several resistance markers (P-glycoprotein, glutathione S-transferase-pi, thymidylate synthase, dihydrofolate reductase) was analyzed in matched primary tumors and lymph node metastases from 21 patients with lung cancer using immunohistochemistry. The analysis showed that expression of these resistance proteins is generally congruent in primary lung cancer and simultaneously resected lymph node metastases. This suggests that in general the resistance of a primary tumor predicts for the resistance of the metastases and vice versa.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Thymidylate synthase in childhood acute non-lymphoblastic leukemia.

Childhood acute nonlymphoblastic leukemias (ANLL) of untreated patients were analysed for expression of thymidylate synthase (TS) using immunocytochemistry. Only patients who achieved a complete remission were entered into the study (n = 21 patients). Of the 21 ANLL, 11 showed an overexpression of TS. There exists a strong correlation between the expression of TS and the relapse rate (p = 0.029, Fisher's exact test). Only 3 out of 11 cases of TS-negative patients with ANLL relapsed whereas 8 out of 10 TS-positive cases experienced relapses. The relapse-free intervals of the patients with TS-positive leukemic cells were significantly shorter than those of patients with TS-negative leukemic cells (p = 0.025, log rank test). There was a trend for shorter overall survival times of patients with TS-positive leukemic cells compared with patients with TS-negative leukemic cells (p = 0.12).

Adolescent↗
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Dihydrofolate-reductase and thymidylate-synthase in childhood acute lymphoblastic leukemia.

The expression of thymidylate-synthase (TS) and dihydrofolate-reductase (DHFR) was analysed immunohistochemically in 110 initial and 28 relapsed childhood acute lymphoblastic leukemia (ALL). Relapse-rates were not significantly higher in initial ALL with overexpression of TS- and DHFR than in ALL without overexpression of the proteins. In addition, the disease-free survival was not different for patients with TS or DHFR-negative and TS- or DHFR-positive ALL. No differences were found in the overall survival times of patients with relapsed ALL and with or without expression of TS or DHFR. Of the initial ALL 42% showed TS-overexpression, whereas of the relapsed ALL 64% of the cases were TS-positive (p = 0.03). The corresponding values for DHFR were 20% and 32% (p = 0.18). The results demonstrate clearly that expression of the proteins TS and DHFR has no importance for the resistance of ALL although the proteins increase during treatment.

Adolescent↗
PubMedDate not supplied

P-glycoprotein associated expression of c-fos and c-jun products in human lung carcinomas.

Surgical specimens of non-small cell lung carcinomas of 167 previously untreated patients were analyzed for expression of c-fos, c-jun, c-myc and c-neu products and for resistance to drugs. Because most of the patients were treated only by surgery, an in vitro test was used to determine the resistance. For the detection of the oncoproteins the streptavidin-biotin-peroxidase-complex method was used. An association between the resistance and c-fos and c-jun proteins was found (c-fos p = 0.01, c-jun p = 0.09), whereas a correlation between resistance and expression of c-neu and c-myc products was not observed. P-glycoprotein 170 was detected immunohistochemically in 91 tumors using the monoclonal antibody JSB-1. There was a significant correlation between the resistance measured by the in vitro test and P-glycoprotein 170 expression (p < 0.001). Also a significant correlation between the c-fos and c-jun proteins and the expression of P-glycoprotein was found (c-fos p = 0.017, c-jun p = 0.036). In contrast, no significant relationship was found between the expression of the c-neu or c-myc products and the expression of P-glycoprotein 170. Thus, there exists a significant relationship between resistance, P-glycoprotein 170, and c-fos and c-jun products in human non-small cell lung carcinomas. P-glycoprotein 170 may be regulated by the c-fos/c-jun protein complex, which binds specifically to AP-1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Reversal of inherent multidrug-resistance in primary human renal cell carcinoma cell cultures by S 9788.

In a panel of 14 primary cultures of human renal cell carcinomas the reversal of inherent multidrug-resistance by S 9788, a new triazinoaminopiperidine derivative, was analysed. In combination with doxorubicin S 9788 revealed an evident reversal of multidrug resistance in 12 cell cultures. Two cell cultures remained unaffected. An association between reversal and P-glycoprotein (P-170) expression suggests that S 9788 exerts its activity through P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Correlation between successful heterotransplantation of lung tumors in nude mice, poor prognosis of patients and expression of Fos, Jun, ErbB1, and Ras.

In order to examine whether the expression of the oncoproteins might be important for the malignancy of tumors, the relationship between the take rate of 88 human squamous cell lung carcinomas in nude mice and the expression of protooncogene products was analyzed. The expression of c-fos, c-jun, c-ras, c-erbB1, c-neu and c-myc at the protein level was investigated by immunohistochemistry. Tumor take was assumed if within three months growing nodules were detected and confirmed histologically. The take rate of squamous cell lung carcinomas in nude mice was 49%. Sixty-eight percent of the tumors were positive for Fos, 40% for Jun, 67% for Ras, 77% for ErbB1, 35% for Neu and 39% for Myc. Tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had a significantly higher take rate in nude mice than tumors without an (over)expression of the oncogene products. In contrast, the expression of the c-neu and the c-myc genes at the protein level had no influence on the take rate of the tumors in nude mice. Interestingly, only patients with tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had significantly shorter survival times than patients whose tumors did not show an (over) expression of the oncogene products. These results demonstrate that the aggressiveness of the tumors visible in the higher take rate of the tumors in nude mice and in the shorter survival times of patients can be detected by measurement of the expression of c-fos, c-jun, c-erbB1 and c-ras at the protein level.

Adult↗
PubMedDate not supplied

Interrelationships between microvessel density, expression of VEGF and resistance to doxorubicin of non-small lung cell carcinoma.

It has been shown that hypoxia can induce resistance to a number of antineoplastic agents. Since vessel density may be considered as an indirect measure of the oxygenation of tumours, in this study we analysed the relationship between tumour vascularity or vascular endothelial growth factor (VEGF) expression and drug resistance. Tumour specimens of 152 non-small cell lung carcinomas (NSCLC) of previously untreated patients were analysed for microvessel density by staining with factor VIII (von Willebrand factor) antibody and for expression of vascular endothelial growth factor (VEGF) using an anti-VEGF-antibody. Both proteins were determined by immunohistochemistry and the expression was compared with the resistance to doxorubicin measured in vitro. Microvessel density was significantly reduced in resistant tumours when compared with sensitive tumours. Of the 98 tumours with low microvessel density 83 (85%) were resistant; whereas of the 54 tumours with high microvessel density only 34 (63%) were resistant (p = 0.004). Expression of VEGF was significantly lower in resistant than in sensitive lung carcinomas. Of the 102 tumors with low expression of VEGF, 87 (85%) were resistant; whereas of the 50 tumors with high expression only 30 (60%) were resistant (p = 0.0009). Corresponding results were obtained when the analysis was restricted to squamous cell lung carcinomas or adenocarcinomas of the lung. Analysis of microvessel density or VEGF expression and clinical data (stage, histology, metastasis) revealed no significant interrelationships. These data show clearly that poor microvessel density (vascularisation) and reduced expression of VEGF are linked with resistance to doxorubicin.

Adult↗