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J Mattern

Publications and source records attributed to J Mattern.

At least 91 records · Page 5Linked to original sources
PubMed1988

Five-year follow-up study of independent clinical and flow cytometric prognostic factors for the survival of patients with non-small cell lung carcinoma.

Fresh surgical specimens of tumors of 187 patients with previously untreated non-small cell lung carcinomas were investigated by means of flow cytometry. The aim of the study was to look for cellular prognostic indicators for survival times of these patients in addition to the well-known clinical prognostic factors. All patients had a minimum of 5 years follow-up. Patients with aneuploid tumors had significantly shorter survival times than did those with diploid tumors (P less than or equal to 0.001). Identical results are obtained when the analysis is restricted to just those patients with T3 tumors or to patients with metastatic tumors at time of surgery or who were classified as Stage III (P less than or equal to 0.01). These data indicate that DNA ploidy is a strong and independent prognostic factor in patients with non-small cell lung carcinoma. Patients having tumors with a high proliferative activity died significantly (P less than 0.05) earlier than patients having tumors with lower proliferative activity. As with tumor ploidy, survival time in patients with high or low proliferative tumor activities was independent of whether the patients had T3-tumors, metastases, or were in Stage III. Univariate and multivariate analyses of the data in this study demonstrate two groups of independent prognostic factors for the survival of patients with non-small cell lung carcinoma: a group of clinical factors and a group of flow cytometric factors.

Adult↗
PubMed1988

DNA and S-phase distribution and incidence of metastasis in human primary lung carcinoma.

The aim of the study was to investigate the relationship between DNA and S-phase distribution in primary non-small-cell lung carcinomas with the incidence of metastasis. Patients with non-small-cell lung carcinomas were divided into two groups depending on whether at time of surgery there were metastases or not, and these groups were correlated with the data obtained by flow cytometry or autoradiography. As expected from other studies, survival time was significantly longer for those patients without metastases at time of surgery (P = .0002) and the incidence of metastasis was significantly higher when the primary tumor was greater than or equal to 70 cm3 (P = .026). In this study, a total of 185 fresh specimens of lung carcinomas were investigated by flow cytometry. Patients with aneuploid tumors had a higher tendency to have metastases (P = .016). Patients with tumors with a higher proportion of S-phase cells measured by either flow cytometry or autoradiography demonstrated significant increase in the formation of metastases (P = .02 and P = .05). We feel that these results warrant further investigation with other primary tumors. A comparison of primary tumors that are known to rapidly metastasize vs. those that either slowly or rarely metastasize may prove to yield valuable insight into the important factors associated with metastatic potential.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Disposition of the aldose reductase inhibitor AL01576 in rats.

The disposition of the aldose reductase inhibitor AL01576 was studied in rats following intravenous and oral dosing. Single 4-mg/kg intravenous bolus and oral doses of [14C] AL01576 were administered and levels of radioactivity in blood, excreta, and various tissues were determined over a 168-h period. The decline of radioactivity in blood was quite similar for the two routes of administration, with an apparent half-life of approximately 30 h. At 120 to 144 h, a second, slower elimination phase began that was not fully characterized in the 168-h duration of the study. The HPLC analysis of plasma samples revealed intact AL01576 as the only compound in plasma. The mean plasma parent and radioactivity concentrations are in agreement; suggesting the absence of or an insignificant amount of metabolite in the plasma. The urinary and fecal excretion rate data showed a kinetic pattern similar to that of blood radioactivity. Fecal excretion was the primary route of elimination following both intravenous and oral dosing, accounting for 59% of the administered intravenous dose and 61% of the oral dose. Urinary excretion accounted for 32% of the intravenous dose and 29% of the oral dose. Negligible amounts of radioactivity were recovered as expired 14CO2. Experiments with bile-duct cannulated rats confirmed that the major route of elimination of the drug is biliary excretion. The pattern of distribution of [14C] AL01576 in tissues was quite similar following the two routes of administration. Tissue radioactivity concentration peaked at 4 h (the first sampling time) following both routes of administration in all tissues except the GI tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1988

Human tumor xenografts as model for drug testing.

This paper reviews the history of xenografts, the endpoints commonly used to evaluate response and chemotherapeutic results obtained with serially maintained human tumor xenografts from different laboratories, and discusses the potential clinical relevance of the heterotransplant model for cancer chemotherapy. Specifically, an attempt is made to correlate the published xenograft data with the clinical data. Drug testing with different types of xenotransplanted tumors has shown that the response of xenografts obtained in immune-deficient animals is comparable to that in clinical practice. In addition, xenografts of a particular tumor type are able to identify agents of known clinical activity against that disease.

Animals↗
PubMed1988

Development of drug resistance in a human epidermoid lung carcinoma xenograft line.

The development of resistance to vincristine, actinomycin D and cisplatin has been examined in a human epidermoid lung carcinoma xenograft line (HXL 55) growing in nude mice. Treatment of HXL 55 with 1 mg kg-1 vincristine or 0.5 mg kg-1 actinomycin D once in each in vivo passage resulted in a rapid reduction in tumour responsiveness to these drugs. A partial resistance was already acquired at the 2nd transplant generation. In contrast, a gradual decrease in therapeutic response was observed with 10 mg kg-1 cisplatin. Irradiation with a local dose of 10 Gy induced no resistance. The three induced drug-resistant sublines were characterized in terms of the time course of development of resistance, the degree of induced resistance, cross-resistance, growth rate and stability of the phenotype.

Animals↗
PubMed1988

Intrinsic drug resistance in a human lung carcinoma xenograft is associated with overexpression of multidrug-resistance DNA-sequences and of plasma membrane glycoproteins.

The purpose of this study was to examine whether multidrug resistance can be detected in human lung tumors not previously treated with chemotherapy. Therefore, the intrinsic sensitivity or resistance of 8 human epidermoid lung cancer xenografts grown in nude mice has been examined. The tumor lines responded differently to vincristine and the other cytostatic agents. When the effects of vincristine on the 8 tumor lines are correlated with the effect of dactinomycin (actinomycin D), a close relationship could be found (r = 0.96). These results demonstrate that xenografts derived from human lung tumors not previously treated with chemotherapy exhibited a similar pattern of cross-resistance as is observed in sublines of murine and human tumors which were resistant to various drugs following repeated exposure of the cells to a sublethal concentration of these drugs. The resistant lung tumor HXL 54 also shows an overexpression of the P170-membrane glycoprotein (detected by Mab 265/F4). To determine whether multidrug genes were expressed in resistant lung tumors, slot blots and Northern blots were performed using the probes pDR 7.8 and pcDR 1.5. The level of expression can be correlated with the degree of drug resistance.

Animals↗
PubMed1987

Occurrence of a multidrug-resistant phenotype in human lung xenografts.

The intrinsic sensitivity of a panel of 8 human epidermoid lung cancer xenografts to vincristine and actinomycin D has been examined and the cross-resistance patterns of the most vincristine-resistant and vincristine-sensitive tumour line were tested to a variety of other drugs, including radiation. The results demonstrate that xenograft lines derived from human lung tumours not previously treated with chemotherapy exhibit a similar general pattern of cross-resistance to the drugs vincristine, actinomycin D and adriamycin as is observed in human cell lines and in animal models selected for resistance to these drugs. It is also shown that intrinsic resistance to vincristine can be partially overcome by verapamil. This may indicate a potential role of this substance in circumventing clinically observed drug resistance.

Animals↗
PubMed1987

Flow cytometry as a tool for the prognostic assessment of patients with lung and ovarian carcinomas.

In two cooperative studies surgical specimens of 187 tumors of patients with non-small cell lung carcinomas (NSCLC) and 37 tumors of patients with ovarian carcinomas (OC) were investigated by means of flow cytometry (ICP-22). From NSCLC30 cases were classified as tumors with DNA diploidy, 119 as tumors with DNA aneuploidy containing one abnormal DNA stemline, and 38 as tumors with DNA aneuploidy containing more than one abnormal DNA stemline. Seven tumors of patients with OC were classified as tumors with DNA diploidy, and 31 as tumors with DNA aneuploidy (three cases had more than one abnormal DNA stemline). The DNA index values of NSCLC range from 0.7 to 4.5 and the values of OC from 0.8 to 2.7 (DNA diploid = 1). A relationship between DNA content and distribution of the cell cycle phases was observed. The results of DNA content analysis have prognostic importance with regard to the length of survival time. Patients with aneuploid and high proliferative tumors had shorter survival times than did those with diploid or near diploid tumors and tumors with low proliferative activity.

Aged↗
PubMed1985

Prognostic significance of DNA patterns and resistance-predictive tests in non-small cell lung carcinoma.

In a cooperative study, 240 surgical specimens of patients with non-small cell lung carcinomas (NSCLC) were investigated by means of flow cytometry, xenotransplantation to athymic mice and, an in vitro short-term test for predicting resistance. Aneuploidy was found in 83% of the tumors, and 20% showed more than one aneuploid DNA stemline. Patients with both aneuploid tumors and tumors with more than one DNA stemline had a significantly shorter survival rate than those with only diploid or only one DNA stemline. Patients whose tumors showed a low G0/G1-cell proportion or a high proliferation pool (S and G2/M-cell proportion) died earlier. A relationship could not be discerned between growth of tumors in nude mice or establishment of cell lines and the prognosis for the patients. Patients with in vitro-resistant tumors died earlier under chemotherapy than those with in vitro-sensitive tumors. Patients treated by radiation survived longer if the tumors were resistant in vitro. Thus, DNA patterns and in vitro short-term tests for predicting resistance represent useful tools for prognostic evaluation of patients with NSCLC.

Adult↗
PubMed1985

DNA distribution in non-small-cell lung carcinomas and its relationship to clinical behavior.

A study of 187 surgical specimens of tumors of patients with non-small-cell lung carcinomas was carried out by means of flow cytometry. Eighty-four percent of the tumors were classified as tumors with abnormal DNA stemlines (DNA aneuploidy). Patients with tumors demonstrating DNA aneuploidy had significantly shorter survival times than those with tumors demonstrating DNA diploidy (p = .009). Cell cycle analysis was possible in 122 tumors. Patients whose tumors had 0-8% S-phase cells died later than patients whose tumors had 9-16% S-phase cells (p = .018). In addition, patients with tumors with a low fraction of labeled S-phase cells (autoradiography) had a better prognosis than patients with tumors with a high proportion of labeled S-phase cells (p = .041).

Adenocarcinoma↗
PubMed1985

Use of gene transfer and a novel cosmid rescue strategy to isolate transforming sequences.

Mouse Lewis Lung tumor DNA was ligated to a cosmid containing a geneticin (G418)/kanamycin resistance gene and transferred into NIH3T3 cells. Recipient cells were first selected for geneticin resistance and subsequently for their ability to grow as a tumour when injected into nude mice. By repeating this transfection procedure with DNA from resultant tumours, geneticin-resistant NIH3T3 cells were obtained which were tumorigenic and contained approximately 1-5 copies of the transferred cosmid. The functional oncogene was cloned by preparing cosmid libraries of third round tumour DNAs, using a cosmid which does not contain a kanamycin resistance gene. Due to the original linkage of the oncogene with the cosmid containing the kanamycin resistance gene, a series of kanamycin-resistant cosmids were isolated, five of which contained an active oncogene. Subsequent analysis showed that the oncogene present was highly related to the human N-ras gene. Using a DNA probe from the MLL N-ras gene, a non-transforming counterpart was isolated from mouse liver DNA. A comparison between the two N-ras genes showed that a mutation at the amino acid position corresponding to 61 in the human gene is responsible for transforming activity of the rescued gene.

Animals↗
PubMed1985

Sequential methotrexate (MTX) and 5-fluorouracil (FU) in human tumor xenografts.

Human and animal tumor-lines heterotransplanted in nude mice were treated with MTX and FU sequentially. In order to investigate the relationship between tumor response and drug toxicity sequence, time and dose of both MTX and FU were varied. Pretreatment with MTX followed by FU with intervals of 3 or 24 h produced superior therapeutic results when compared to single administration of MTX or FU, simultaneous treatment, or the reverse sequence. In the MTX followed by FU regimen, dose reduction of either MTX or FU tended to decrease the anti-tumor effect. To investigate the toxic effects of different regimens, tumor-free nude mice were treated with MTX and FU the same way as the tumor-bearing animals. In this case, toxicity (weight loss, leukopenia) was more pronounced in those schedules with the best therapeutic results. However, toxicity appears to be more clearly related to the applied FU-dose.

Animals↗
PubMed1985

Inhibition of the hydro-osmotic response to vasopressin and hypertonicity by phenothiazines and W7, calmodulin antagonists.

Phenothiazines and W7, calmodulin antagonists, inhibit the water flow response produced by ADH, exogenous cyclic AMP, phosphodiesterase inhibition and serosal hypertonicity. Calmodulin antagonists had no effect on osmotic water movement in the absence of hormone. Calmodulin was isolated and localized by immunofluorescence in bladder epithelial cells. Phenothiazines inhibited toad bladder calmodulin activation of phosphodiesterase and prevented fluorescent antibody recognition. The results suggest that the calcium-calmodulin process plays a role in the hydro-osmotic response to ADH and that produced by serosal hypertonicity. The calmodulin common site occurs subsequent to cyclic AMP formation, perhaps on the microtubule-microfilament system.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Growth of human bronchial carcinomas in nude mice.

Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large cell and small cell carcinoma had a lower success rate (38% for both). The average volume doubling times in the first passage in nude mice ranged from 8.2 in large cell carcinomas to 18.9 days in adenocarcinomas. In subsequent passages an increase in growth rate was found, the overall average doubling time falling from 14.5 days in the first passage to 7.1 days in the second passage. In a study with 171 non-small cell lung carcinomas (NSCLC), the growth data in nude mice were correlated with the clinical data of the corresponding patients. A relationship between the growth parameters in nude mice and prognosis of patients could not be found.

Adenocarcinoma↗
PubMed1985

Influence of hormone therapy on human lung tumors transplanted into nude mice.

Specific estrogen, progesterone, androgen and glucocorticoid receptors were determined in 8 lung tumor lines transplanted into athymic nude mice. It was found that the receptor content for estrogen, progesterone or androgen was very low for all tumor lines tested, whereas the glucocorticoid receptor content was high in all cases except 1. The growth inhibition of lung carcinomas on nude mice by glucocorticoid or antiglucocorticoid treatment suggests that lung cancer may also be influenced by hormonal therapy.

Animals↗