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Biomedical subjects

M Dietel

Publications and source records attributed to M Dietel.

At least 163 records · Page 9Linked to original sources
PubMed1990

Immunocytochemical differential diagnosis of adrenocortical neoplasms using the monoclonal antibody D11.

The monoclonal antibody D11 is a valuable aid in the accurate typing of adrenal tumours as, in formalin-fixed, paraffin-embedding material, strong nuclear D11 positivity was observed only in adrenocortical cells in 190 neoplasms (including 100 adrenal tumours). This pattern was demonstrated for all zona glomerulosa cells in 27 normal adrenals and for the neoplastic cells of 15 adrenocortical adenomas derived from that zone, as judged from clinically evident hyperaldosteronism. Normal cells of zona fasciculata and reticularis also showed strong diffuse D11 immunostaining and the same nuclear plus cytoplasmic D11 reactivity was evident in 15 benign and malignant adrenocortical neoplasms derived from these zones, documented by hypercortisolism. Cytoplasmic and/or nuclear D11 staining made topohistogenetic typing possible in 15 non-functioning cortical tumours. D11 immunostaining gave negative results in 50 specimens containing normal, hyperplastic and neoplastic adrenomedullary cells. In addition, absence of D11 reactivity was recorded in 4 adrenal metastases of extra-adrenal carcinomas, 5 paragangliomas, 25 primary renal carcinomas and 59 of 60 primary thyroid carcinomas. D11 immunocytochemistry allows the accurate typing of benign and malignant adrenocortical neoplasms, irrespective of histology and function. With this method, primary adrenocortical tumours can be separated from carcinomas metastatic to the adrenal gland, including secondary tumours of similar phenotype (such as renal carcinomas). By exclusion, D11 negativity provides evidence of the medullary origin of primary adrenal tumours even in the absence of clinical, structural, histochemical and conventional immunohistochemical indicators of phaeochromocytoma.

Adenoma↗
PubMed1990

Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries.

Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n = 74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.

Adolescent↗
PubMed1990

Prognostic factors for adenoid cystic carcinoma of the head and neck: a retrospective evaluation of 96 cases.

Cases of adenoid cystic carcinomas of the salivary (n = 90) and lacrimal glands (n = 6) from the years 1965-1980 were evaluated retrospectively with regard to clinical, epidemiologic and histomorphologic parameters, and in 52 cases, nuclear DNA content was assessed using a single cell scanning cytophotometry procedure in order to determine prognostic factors. Clinical courses were poor with a high incidence of recurrences, hematogenous metastases and deaths from tumor. Histology was related to prognosis, glandular tumors showing a better prognosis than solid ones. Tumor size greater than 4 cm was correlated with an unfavorable clinical course in all cases. Cytophotometry yielded various types of histograms (7 diploid, 10 proliferative, 14 triploid, 19 atypical, 2 tetraploid). Significant correlations were found as to the time of survival, tumors with diploid histograms showing the longest intervals and those with atypical ones the shortest. Although the prognosis of adenoid cystic carcinoma remains poor, cytophotometry can offer additional prognostic information in the individual case.

Adult↗
PubMed1990

Chemotherapy of metastatic soft tissue sarcoma with a combination of adriamycin and DTIC or adriamycin and ifosfamide.

Between 1982 and 1986, 38 patients with soft tissue sarcomas were treated with a combination of ADM/DTIC (group A), another 45 (group B) received ADM/IFO between 1986 and 1990. Clinical characteristics were comparable in both groups. Remission rate was 34% in group A and 43% in group B. Duration of remission was 10 months and median survival 13 months in both groups. Toxicity, especially myelotoxicity, was severe without marked differences between both groups. We conclude that adriamycin/DTIC and adriamycin/ifosfamide are both active regimens in metastatic soft tissue sarcomas, nevertheless, overall prognosis remains poor.

Adolescent↗
PubMed1990

Elevated expression of v-mos is correlated with altered differentiation of carcinoma cells.

Permanent alterations of the epithelial differentiation pattern were investigated after infection of HH-16 cl. 4 adenocarcinoma cells with Moloney murine sarcoma virus (MoMuSV). Transformed cell clones with fibroblastoid morphology were isolated and compared with clones of unchanged epithelioid phenotype. Southern blot analyses showed intact MoMuSV proviral genomes in copy numbers between 4 and 9 in the DNA of the morphologically transformed cell clones as well as in the clones with unaltered morphology. The fibroblastoid cells produced sarcomas after inoculation of newborn rats, whereas MoMuSV-infected cell clones with unaltered epithelioid morphology yielded adenocarcinomas. Immunocytochemical analyses revealed that morphological transformation into the fibroblastoid phenotype was accompanied by loss of cytokeratin expression and appearance of the mesenchymal marker protein vimentin. Proviral DNA was transcribed in the infected cell clones irrespective of their phenotype; however, transcription was significantly higher in cells with fibroblastoid morphology than in epithelioid cells.

Adenocarcinoma↗
PubMed1989

[Individualization of chemotherapy through in vitro predictive determination of the cytostatic sensitivity of malignant tumors].

An in-vitro test was developed for predicting the efficacy of anti-tumour chemotherapy. Cell cultures were grown from freshly removed tumours and it was then demonstrated by DNA cytophotometry and immuno-cyto-chemistry whether the growing tumour cells corresponded to those of the original tumour cells. Several cytostatic agents were then tested for their efficacy of inhibiting growth at clinically customary dosage. Growing cell cultures were established in 306 of 413 submitted tumours (74%). They responded quite differently to the various drugs that were tried. The clinical course in 94 cases was observed for minimally four and a mean of eight months to obtain an in-vitro to in-vivo correlation of response, with 178 individual correlations. A discrepancy was recorded in 16% of cases, a false-positive in-vitro sensitivity result was 3.6 times more frequently associated with an in vivo resistance than the reverse. Concordance between test results and clinical tumour response occurred in 84%. The monolayer proliferation assay correctly indicated resistance in 93.8%, sensitivity in 72.8%.

Antineoplastic Agents↗
PubMed1989

Effect of continuous vs intermittent application of 3-OH-tamoxifen or tamoxifen on the proliferation of the human breast cancer cell line MCF-7 M1.

The antiproliferative potency of 5 x 10(-7) M tamoxifen (TAM) and 3-hydroxytamoxifen (3-OH-TAM) was investigated during continuous (8 days) or intermittent (2 h every 2nd or 3rd day, respectively) application to the oestrogen-receptor-positive, estradiol-sensitive human mammary carcinoma cell line MCF-7 M1, a variant of MCF-7 wild type. Growth modulation was evaluated in parallel by counting cells and by measuring DNA content. Continuous incubation resulted in a growth inhibition to 21.8 +/- 3.2% by 3-OH-TAM and to 39.5 +/- 4.8% by TAM when compared with control cultures defined as 100%. Intermittent addition induced a growth reduction to 23.0 +/- 2.1% by 3-OH-TAM and to 41.2 +/- 2.4% by TAM in relation to 100% controls. Addition of 3-OH-TAM for 2 h only at day 1 resulted in an inhibition to 70.3 +/- 3.2%, again in relation to 100% controls. When TAM was administered once for 2 h at day 1 it induced an inhibition to 79.0 +/- 4.9% at day 8. The in vitro results indicate that (a) at 5 x 10(-7) M 3-OH-TAM has a better antiproliferative effectiveness than TAM, (b) the intermittent application is as effective as continuous application (no significant difference), and (c) the addition once a week reveals only a slight growth reduction after 8 days of culture. Application of the long-living TAM results in continuously high serum concentrations, which have been shown to create resistant cell clones. Compared to TAM the 3-OH metabolite has a considerably shorter half-life and its application in vivo reveals rise and fall of its serum concentrations. Since the presented data demonstrate that 3-OH-TAM is more potent than TAM and that the intermittent application is as effective as the continuous form, interval therapy with 3-OH-TAM may slow down the process of acquiring resistance to antioestrogens.

Breast Neoplasms↗
PubMed1989

Cytokines and pancreatic cancer. The effect of rIFN-gamma, HuLeIFN, rTNF-alpha, and LAK-cells on pancreatic and other gastrointestinal tumors in vitro.

A panel of 10 digestive tract carcinoma cell lines (6 pancreatic carcinomas) was assayed for their sensitivity to HuLeIFN, human rIFN-gamma, rTNF-alpha and allogeneic human LAK-cells in vitro. In addition, a combination of rIFN-gamma + rTNF-alpha was tested on 3 pancreatic carcinoma cell lines. Whereas 6/7 cell lines were completely resistant to HuLeIFN, rIFN-gamma and rTNF-alpha did inhibit growth of some carcinomas tested. The individual sensitivity was heterogenous as is already known from cytostatics. Response to rIFN-gamma tended to increase with increment of cell doubling time. Only high concentrations (greater than 1000 U/ml) of rIFN-gamma displayed cytotoxicity on sensitive tumors. The antitumoral effect of rIFN-gamma was stimulated by rTNF-alpha. As revealed by isobole analysis this interaction was synergistic in all pancreatic carcinomas tested. In comparison to rIFN-gamma or rTNF-alpha the response to LAK-cells was slightly superior at high effector target ratios, even though heterogenous.

Biological Factors↗
PubMed1989

Cytokines and pancreatic cancer. Sensitivity of xenotransplants of predominantly pancreatic carcinomas to rIFN-gamma and rTFN-alpha in nude mice.

Ten xenotransplants of human gastrointestinal carcinomas (eight human pancreatic carcinomas) were assayed for their sensitivity to human rIFN-gamma and human rTNF-alpha in nude mice. Both substances demonstrated a dose and route dependent antitumoral activity in principle. However, the extent of response varied distinctly between the tested xenografts. rTNF-alpha was clearly superior to rIFN-gamma at systemic application of comparable doses (0.8 mg/kg/d). Intramural administration of both cytokines could cause cytotoxic effects and was significantly more effective than systemic administration that predominantly resulted in antiproliferation. Growth inhibition of rIFN-gamma or rTNF-alpha alone could be clearly enhanced by combining both cytokines. In addition, the results suggest: the possibility to enhance the effects of rIFN-gamma alone also by combination with nIL 2, as well as a decrease of the effects of rTNF-alpha with time of therapy.

Animals↗
PubMed1988

Effectiveness of mitoxantrone on the proliferation of cell cultures derived from malignant mesenchymal tumors of human origin.

The antiproliferative potency of mitoxantrone (MITOX) has predominantly been established for epithelial and hematologic neoplasias. In this study the effectiveness of MITOX was investigated in vitro for 6 sarcomatous human cell lines derived from 2 synovial sarcomas, a malignant schwannoma, a malignant histiocytoma, a leiomyosarcoma, and a chondrosarcoma. The examination was performed using a proliferation assay with monolayer cell cultures. The effect of MITOX was compared with that of adriamycin (ADR) and cisplatin (CDDP). For each drug at least 3 concentrations were tested which covered the therapeutically achievable range, i.e., for MITOX 0.2-0.002 micrograms/ml, for ADR 0.5-0.005 micrograms/ml, and for CDDP 5.0-0.05 micrograms/ml. Test incubations were performed for 3 days. Antiproliferative potency of the cytostatic drugs was assessed by counting the number of cells at the start and the end of the test period with and without drug addition. Furthermore the dose inhibiting cell growth to 50% of controls (ID50) was determined for MITOX. For comparison 4 cell lines from carcinomatous lesions were included in the study. MITOX inhibited proliferation rates of 4 sarcomatous tumor cell lines more intensively than ADR, and was less effective in 2 cell lines. However, these differences were not significant. In all mesenchymal cell lines tested the antiproliferative potency of MITOX was more pronounced than that of CDDP. In carcinomatous cell lines the MITOX-induced growth inhibition was similar to that found in response to administration of ADR and CDDP confirming the described effect on epithelial tumors. The study suggests that MITOX possesses a growth inhibitory potency for malignant soft tissue tumors in vitro. From these data it may be worthwhile to initiate clinical trials testing the treatment of sarcomatous lesions with MITOX.

Adolescent↗
PubMed1988

DNA cytophotometry in malignant thyroid tumors--use of different evaluation schemes for prognostic statements.

Quantitative evaluation of nuclear DNA has been found to provide information on diagnosis and prognosis in a number of malignant tumours and borderline lesions. Using 53 carcinomas of the thyroid with varying differentiation we examined the prognostic information obtained by DNA cytophotometry with respect to clinical outcome, applying three different evaluation schemes. DNA cytophotometry allowed the discrimination of euploid carcinomas with good prognosis from aneuploid tumours with bad prognosis and a generally shortened life span. However, the encapsulated variants of follicular and papillary thyroid carcinomas, with their generally excellent prognosis, exhibited DNA histograms similar to those of their widely invasive counterparts. Thus, the favourable prognosis of these minimal invasive subtypes may primarily be related to the tumours' encapsulation and cannot be ascribed to a particular DNA content. We conclude that DNA cytophotometry can provide additional prognostic information for the individual patient suffering from thyroid carcinoma and may probably lead to an individualization of the therapeutic strategies.

Adenocarcinoma↗
PubMed1988

What's new in the importance of receptors in pathology?

Highly organized multicellular organisms require a complex system of intercellular communication to coordinate the great variety of physiological functions. Major components of this system are the (i) signalling substances delivering the information and (ii) the corresponding cellular receptors recognizing the information and translating them to special intracellular organelles of the target cell. For the process of signal binding and transmission various types of receptor proteins are known playing a key role in the mutual understanding between cells. The present paper comprehends lectures on functions and deficiencies of the different types of cell receptors given during the Symposion on "Receptors in Pathology" during the 11th European Congress of Pathology. Each section is written under the personal responsibility of the author indicated.

Breast Diseases↗
PubMed1988

A novel method to demonstrate parathyroid hormone binding on unfixed living target cells in culture.

We present a rapid and specific procedure that enables one to identify living target cells of peptide hormones within heterogeneous cell populations by means of morphological demonstration of ligand-receptor binding. This is exemplified using a biotinylated parathyroid hormone (PTH) analogue (biotinyl-b-PTH 1-84) which reacts with avidin-fluorescein (avidin-FITC) as a histochemical marker. The experiments revealed a fine dot-like distribution pattern of binding after 1-5 min of incubation at room temperature, changing to a more clustered pattern after 10 min of incubation. Competition of labeled and unlabeled PTH exhibited lack of staining if unlabeled PTH was applied in excess. The results suggest that the demonstrated binding sites represent specific receptors for PTH on living target cells.

Animals↗