Biomedical subjects

J Mattern

Publications and source records attributed to J Mattern.

178 records · Page 10Linked to original sources

PubMedDate not supplied

Relevance of DNA-fluorimetry and short-term resistance testing for adjuvant treatment of non-small cell lung carcinomas.

In a clinical study 127 patients with previously untreated stage III non-small cell lung carcinomas (NSCLC) were investigated using flow cytometry and an in vitro short-term test for predicting resistance to cytostatic agents. Patients with aneuploid tumors and tumors with high proliferative activity had significantly shorter survival times than those with diploid or low proliferating tumors. The aim of this study was to find out whether groups of patients classified according to the additionally observed prognostic factors, experience an advantage or disadvantage from particular modalities of treatment. Seventy-nine patients had surgery alone, 18 patients were treated additionally with chemotherapy, and 30 patients with radiation. Patients with aneuploid, low proliferating and in vitro resistant tumors showed no different survival rates after treatment with chemo- and radiotherapy adjuvant to surgery. In contrast, patients with high proliferating tumors died earlier under adjuvant chemotherapy and radiation. Patients with in vitro chemosensitive tumors had shorter survival times after irradiation than patients who had surgery alone or who were treated with adjuvant chemotherapy.

Adult↗

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↗

PubMedDate not supplied

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

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

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

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↗

PubMedDate not supplied

Up-regulation of heat shock protein 70 in adenocarcinomas of the lung in smokers.

Tumour samples of smokers (n = 32) and non-smokers (n = 21) with previously untreated adenocarcinomas of the lung were analysed, immunohistochemically, for expression of the heat shock protein 70 (hsp70). A correlation between smoking habits and expression of hsp70 was found. Of the tumours from the 21 non-smokers 12 (57%) and of the 32 smokers 24 tumours (75%) showed high hsp70 expression. The expression of hsp70 depended on the number of cigarettes smoked daily. Of the patients who smoked more than 20 cigarettes, 16 out of 18 had tumours with a high hsp70 expression (89%; p = 0.028).

Adenocarcinoma↗

PubMedDate not supplied

Association of vascular endothelial growth factor expression with tumor cell proliferation in ovarian carcinoma.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that may also function as an autocrine growth regulator. Thirty-one ovarian carcinomas were investigated for mRNA expression of VEGF and of a proliferation-dependent gene (histone H3) using slot-blot analysis. Tumor vascularity was assessed by immunohistochemistry and factor VIII. All tumors were demonstrated to express VEGF and histone H3, though to various degrees. There was a good correlation between VEGF mRNA values and histone H3 mRNA values (r = 0.71, p < 0.05). No correlation was found between tumor cell proliferation and tumor vascularity. There was no significant difference in relapse-free interval or overall survival between tumors with low and high VEGF expression. The close correlation of VEGF expression with tumor cell proliferation in this study raises the possibility of autocrine stimulation of ovarian carcinoma.

Adolescent↗

PubMedDate not supplied

Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships to drug response in vitro.

Tumor specimens of non-small cell lung carcinomas (NSCLC) from previously untreated patients (n = 153) were analysed immunohistochemically for expression of vascular endothelial growth factor (VEGF), VEGF-receptor (Flt-1), basic fibroblast growth factor (bFGF) and FGF-receptor (FGFR-1, (Flg). Expression of the proteins was compared with the in vitro response of the tumors against doxorubicin. The data clearly demonstrate that a significant relationship exists between VEGF (p < 0.001) and Flt-1 expression (p < 0.01) and drug response. The expression of VEGF and Flt-1 was lower in resistant than in sensitive tumors. In contrast, no significant interrelationship was found between expression of bFGF and response to doxorubicin. However, there exists a significant correlation between the expression of FGF-receptor (FGFR-1) and the response of the carcinomas to doxorubicin (p < 0.05). Expression of FGFR-1 was more frequently negative or weak in resistant and more frequently moderate or high in sensitive NSCLC. The data from this investigation clearly demonstrate that a significant interrelationship exists between the expression of VEGF, VEGF-receptor Flt-1 and FGF-receptor, FGFR-1 and the response of NSCLC to doxorubicin in vitro.

Carcinoma, Non-Small-Cell Lung↗

PubMedDate not supplied

Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density.

Tumor specimens from 84 patients with untreated epidermoid lung carcinomas were analysed immunohistochemically for the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor cell proliferation (PCNA index) and tumor vascularity (vessel density). The purpose of this study was to find out whether differences in tumor cell proliferation and tumor vascularity might be associated with differential angiogenic growth factor expression. The present results indicate that the proliferation of the tumors is closely related to their expression of VEGF, but not for bFGF. The PCNA labelling index in VEGF positive tumors (VEGF+/bFGF- or VEGF+/bFGF+) was significantly higher than that in VEGF negative tumors (VEGF-/bFGF- or VEGF-/bFGF+; Wilcaxon rank sum test, p < 0.0001). To investigate whether VEGF or bFGF is involved in lung tumor angiogenesis, the data of VEGF and bFGF expression were correlated with vessel density. It was found that the expression of VEGF and bFGF were associated with increment of vessel density, however, vessel density was significantly increased only when VEGF and bFGF were coexpressed (p < 0.02). It is suggested that VEGF and bFGF might act cooperatively in the neovascularization of human epidermoid lung carcinomas.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Prognostic value of p16INK4A expression in lung adenocarcinoma.

The analysis attempted to determine whether the expression of p16INK4A has prognostic relevance for patients with lung adenocarcinomas. For this purpose, immunohistochemistry was used to analyze 58 adenocarcinomas. Of the tumors investigated, 20 did not express p16INK4A, while 38 yielded a positive staining result. Median survival time was shorter for patients with p16INK4A negative carcinomas than for those with p16INK4A positive tumors (47 vs. 79 weeks, P = 0.11). The relative risk for patients with p16INK4A negative tumors was increased by a factor of 1.6 in comparison to positively stained tumors. There exists a direct correlation between the proportion of G0/G1 phase cells and the p16INK4A expression. Additionally, there is an inverse relationship between S phases and p16INK4A expression. Furthermore, p16INK4A negative adenocarcinomas show more frequent growth in nude mice than p16INK4A positive carcinomas.

Adenocarcinoma↗