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Biomedical subjects

F Hofstaedter

Publications and source records attributed to F Hofstaedter.

51 records · Page 3Linked to original sources
PubMed1992

The effect of retinoic acid on chemosensitivity of PA-1 human teratocarcinoma cells and its modulation by an activated N-ras oncogene.

Combination of chemotherapeutic drugs with agents that induce cell differentiation is a possible means of improving cancer chemotherapy. To explore this approach we used 4 cell lines established from the human teratocarcinoma-derived cell line PA-1; 2 retinoic acid (RA)-sensitive lines compared to 2 RA-resistant lines transformed by an activated N-ras oncogene. Equal numbers of colony-forming cells were exposed for 72 hr to 10(-6)M RA and subsequently to a range of concentrations of cisplatinum, etoposide or bleomycin. Enhanced cytotoxicity of cisplatin and etoposide (3- to 5-fold) was observed in the N-ras-transformed cell lines compared to the non-transformed lines. Treatment with RA caused an increase in the cytotoxicity of all 3 drugs to the 2 RA-sensitive cell lines. In contrast, a reduction of cytotoxicity was observed in the 2 N-ras-transformed lines. Our results indicate that sensitivity to cytotoxic agents can be increased by RA in RA-sensitive cells, but the opposite effect is seen in N-ras transformed, RA-resistant cells. Therefore, a general rationale for combination therapy with RA and cytotoxic drugs cannot be inferred.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Characterization of the new bladder cancer cell line HOK-1: expression of transitional, squamous and glandular differentiation patterns.

The new continuous cell line HOK-1 derived from a grade-III transitional-cell bladder carcinoma with foci of squamous and glandular differentiation was shown to retain this phenotypical heterogeneity for more than 45 passages in vitro. Electron microscopy revealed transitional as well as a considerable proportion of squamous carcinoma and adenocarcinoma cells. PAS-positive mucus was detected in numerous cells. These features were principally maintained when grown as multicellular spheroids and in nude mice. More pronounced signs of differentiation (i.e., expression of cytokeratins 10 and 11, formation of glandular structures) were found in xenograft tumours. Independently, cytokeratins 13, 18 and 19 were detected in vitro and in vivo, reflecting the urothelial origin. The line forms distinct colonies in soft agar, expresses Lewis-x and Lewis-y antigens and reacts with monoclonal antibodies (MAbs) against CEA, beta-HCG and URO-5. Cytogenetic analysis revealed several related clones with a rearrangement at chromosome 1 and loss of one X chromosome as common karyotypic changes in all clones. DNA content, as quantified by image analysis, showed a DNA stemline close to 2c. The new cell line HOK-1 can be used as an in vitro model to study the mechanisms of heterogeneous differentiation patterns in bladder cancer.

Aged↗
PubMed1990

Magnetic resonance imaging of acute and long-term alterations following extracorporeal shock wave lithotripsy in rats.

The kidneys of 30 rats were treated by extracorporeal shock wave lithotripsy (ESWL) with different doses of extracorporeal shock waves: 500, 1,000 and 2,000. The animals were sacrificed after 24 h, 7, 14 or 35 days. Magnetic resonance (MR) imaging at 1.5T was used to evaluate the effects of ESWL on T1- and T2-weighted (spin echo 600/22, 1,600-2,000/90) images compared to histology and macroscopy. The severity of pathologic changes correlated dose dependently with the number of shock waves given (500-2,000). The MR findings following ESWL in 50 kidneys included diffuse loss of the corticomedullary junction (n = 20), perirenal and subcapsular fluid (n = 23), intrarenal foci of increased (n = 16) or decreased (n = 8) signal intensity, and loss of distinction between renal, splenic or hepatic contours (n = 7), detected macroscopically as adhesions. Subcapsular and intrarenal findings corresponded to acute hematomas and organized fibrotic tissue morphologically. In long-term groups MR revealed fibrotic shrinkage of the renal convexity as indentation of the kidney surface (n = 12). MR imaging is a sensitive method for the detection of specific alterations following ESWL, especially intrarenal changes, which are important for possible long-term lesions after ESWL.

Animals↗
PubMed1990

Differentiation patterns in two- and three-dimensional culture systems of human squamous carcinoma cell lines.

Relative quantification of the pattern of differentiation of two squamous carcinoma cell lines of the female genital tract, A431 and CaSki, was studied in various experimental tissue culture states that are frequently used to evaluate drug and radiation effects on human tumors. Two- and three-dimensional in vitro cultures, ie, monolayers and multicellular tumor spheroids (MCTS), and nude mice-xenograft tumors as in vivo tumor models were compared. In addition, epidermal growth factor (EGF) was used comparatively in the in vitro studies. Morphologic signs of epithelial differentiation could be recognized in both cell lines gradually increasing from monolayers to MCTS to xenograft tumors. Cytokeratin (CK) expression is described as stable in A431 cells. Using immunohistochemistry, however, partial masking of CK antigens was found when applying the antibody 8.12 on monolayer cells and could be quantified by flow cytometric measurements. Fundamental cellular changes were found in a CaSki xenograft tumor, which showed newly established features of a keratinizing carcinoma after late onset of tumor growth. Epidermal growth factor caused reduction of both intercellular contacts and later onset of necrosis in MCTS, leading to an increased viability of the spheroids. Significant differences in differentiation of the tumor model systems indicates that the characterization of differentiation with immunohistochemistry and flow cytometry is necessary to assist interpretation of data obtained with these different tumor models.

Antibodies, Monoclonal↗
PubMed1990

[Proliferation-associated antigens PCNA and Ki-67 in two- and three-dimensional experimental systems of human squamous epithelial carcinomas].

Multiparameter-flow-cytometry was used to compare the levels of two proliferation-associated antigens, proliferating cell nuclear antigen (PCNA) and the Ki-67-related antigen, in squamous carcinoma cells grown as monolayers, multicellular spheroids (MCTS), and xenograft tumors. While the level of Ki-67-positive cells decreased with time of culture, the percentage of PCNA-positive cells stayed high in all experimental states investigated (up to 5 weeks of growth). The reduction of the mean fluorescence of PCNA/cell indicated a different way of regulation of this antigen in squamous carcinoma cells in comparison to other cell types.

Animals↗
PubMed1985

Multiple intracranial metastases from a prolactin secreting pituitary tumour.

A 28 year old man presented with partial hypopituitarism and signs of a pituitary tumour. A chromophobe adenoma was partially removed by right frontal craniotomy. Seven years later complete hypopituitarism and hyperprolactinaemia were documented, at which time there was no evidence of tumour recurrence of CT scan. The patient was treated with bromocriptine but the pituitary tumour redeveloped a year later. Nine years after the original operation the first metastasis was demonstrated together with very high prolactin levels. The intracranial metastasis, and the pituitary tumour were removed at a second craniotomy following which the prolactin concentration fell. Further metastases developed subsequently and the patient died 12 years after the initial diagnosis. At autopsy multiple metastases were found in the brain, tumour cells were present in the subarachnoid space and in cerebral veins. The pituitary tumour and secondaries were shown by immunocytochemistry to contain prolactin but not ACTH or growth hormone. This appears to be the third well documented case of a metastasizing, prolactin secreting pituitary tumour.

Adenoma, Chromophobe↗
PubMed1985

Extraction of cells from paraffin-embedded tissue sections for single-cell DNA cytophotometry.

A simple technique is presented for the isolation of cells from paraffin-embedded tissues for Feulgen DNA cytophotometric investigations. Tissue fragments from paraffin blocks were deparaffinized in xylene, rehydrated and refixed in a formalin solution and incubated in a solution of 0.5 pepsin in 0.25% hydrochloric acid. After filtration through a 70 micron mesh and centrifugation, the cells were smeared upon a glass slide. Comparison between the results obtained with freshly prepared imprints and with pepsin-extracted cells of the same tumor showed that the extraction technique does not influence the Feulgen reaction or the DNA distribution pattern. Investigations carried out on bladder and embryonal carcinomas have demonstrated that the method permits an analysis of histologically or histochemically identified tumor cells within individual tissue areas.

Cell Separation↗
PubMed1984

Gastric stump carcinoma following Billroth II resection for peptic ulcer disease. Comparison with cancer in non-operated stomach.

40 gastric stump carcinomas have been investigated. The results are compared with 72 gastric carcinomas without preceding Billroth II resection. The aim of this study was to contribute to our knowledge about the pathogenesis of gastric stump carcinoma. The mean age of patients with gastric stump carcinoma and with carcinoma without preceding Billroth II resection is identical. The age distribution, too, is similar in both groups. Furthermore the time of the Billroth II resection for benign peptic ulcer shows no correlation with the appearance of the gastric stump carcinoma, which suggests that there is no constant time lag between Billroth II resection and stump carcinoma. The histological investigation of the tumor-free gastric mucosa shows similar alterations in the two groups compared. Intestinal metaplasia and cystic dilatation seems to be more common in the gastric mucosa after Billroth II resection as compared with the non-tumorous mucosa of patients without preceding Billroth II resection. But the grade of nuclear atypia in non-tumorous mucosa is identical in both groups. Interestingly enough, the frequency of the main types of gastric cancer, intestinal carcinoma and diffusely infiltrating carcinoma is very similar. Thus, both the epidemiological and histological data seem to indicate that the pathogenesis of gastric carcinoma is very similar to that of gastric carcinoma without preceding gastric surgery. The Billroth II resection does not seem to be a main factor in pathogenesis, but may have co-factorial significance.

Adult↗
PubMed1984

Biological behaviour and DNA cytophotometry of urothelial bladder carcinoma.

In this prospective study, primary urothelial bladder tumour specimens from 64 patients were investigated by means of DNA Feulgen cytophotometry. The patients were followed clinically for at least 7 years. The objective cytophotometric parameters correlated well with the histopathological grading and the cytochemical data were of considerable prognostic value. They were closely correlated with the stage of the tumour, 5- and 7-year survival rates and the probability of tumour recurrence. It is concluded that DNA cytophotometry can serve as a method for the standardisation of histological grading and can give more objective and more detailed prognostic information than conventional histopathology.

Adult↗
PubMed1983

Primary hepatocellular carcinoma with hepatitis B virus infection in a 16-year-old noncirrhotic patient.

Primary hepatocellular carcinoma metastasizing to abdominal lymph nodes and to the left lung was observed in a 16-year-old male patient. No clinically apparent chronic liver disease preceded the carcinoma and no signs of cirrhosis were detectable in the nonneoplastic liver. Hepatitis B surface antigen, hepatitis B e antigen and antibody to hepatitis B core antigen were found to be positive in the serum. By immunohistochemistry (peroxidase-antiperoxidase technique) hepatitis B surface antigen could be demonstrated in the nontumorous liver parenchyma, but not in the primary hepatocellular carcinoma itself. Serum alpha-fetoprotein was only moderately elevated (75 ng/ml), but immunohistochemically primary hepatocellular carcinoma revealed a considerable number of alpha-fetoprotein-containing cells, whereas nontumorous parenchyma did not. Carcinoembryonic antigen could be demonstrated immunohistochemically in some tumor cells of a lymph node metastasis, but not in the primary tumor or in the nontumorous liver parenchyma. We propose that primary hepatocellular carcinoma developed in this case in a symptomless hepatitis B virus carrier without preceding cirrhosis, an we exclude a simultaneous acute hepatitis B.

Adolescent↗
PubMedDate not supplied

Techniques for studies on growth characteristics of human prostatic cancer cells.

The methods described in this article seem to be useful for studies on the growth characteristics of malignant epithelial prostate cells which are still under the influence of healthy cells. Before establishing primary cultures, pieces of tissue were sectioned in such a way that they could be unfolded to obtain a large surface. These pieces were treated enzymatically and then incubated for at least 4-6 weeks. In this time, cells grew or migrated out of the tissue and spread over the surface of the culture flasks. The viable single cells harvested from these primary cultures were characterized flow cytometrically, fractionated by countercurrent centrifugal elutriation, or further incubated above agarose so that they formed three-dimensional spheroids. Cytometric determinations of cellular cytokeratin, vimentin, and DNA were performed before and after incubation. They suggested that the percentages of cytokeratin-positive (epithelial) cells, vimentin-positive cells (fibroblasts), and aneuploid cells remained at levels (in vitro) similar to those within the pieces of tissue used for the culturing experiments, respectively. Since our culture technique allows the propagation of human epithelial prostate cells in vitro as they would grow in vivo under the control of the surrounding tissue, the method should help to investigate which particular treatment of the cells influences the growth of the malignant cells, while they are still surrounded by other cells of the same prostatic organ.

Antigens, Neoplasm↗
PubMedDate not supplied

Ultrastructural telepathology--remote EM-diagnostic via Internet.

New collaboratory opportunities in ultrastructural research and diagnostics are now available on the Internet through the combination of digital image acquisition, remote operation of modern digitally controlled and automated electron microscopes, and the development of software specifically tailored for collaboratory needs. Remote experts can examine samples directly, and unique instruments can be utilized from anywhere. In the case of diagnostic dilemmas, the second-opinion expert is no longer constrained by problems inherent in the interpretation of preselected images. The remote examiner can independently choose the area of interest on the sample as well as select the appropriate magnification for an accurate diagnosis. With these capabilities and together with teleconferencing tools and securely accessible databases on-line, telepathology can provide increased effectiveness and support for diagnostics, research, and teaching in many areas. The authors report their experience with remote electron microscope diagnoses of pathological samples using two different dynamic imaging systems and discuss the main technical issues encountered. It appears that only minor technical issues need to be resolved before ultrastructural telepathology can be promoted for routine use in areas with high-speed Internet access.

Dementia, Multi-Infarct↗
PubMedDate not supplied

Effects of lithotripsy on rat kidney: evaluation with MR imaging, histology, and electron microscopy.

Magnetic resonance (MR) imaging at 1.5 T was used to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) in 30 rats and the findings on T1- and T2-weighted (spin echo 600/22, 1,600-2,000/90) images were compared with histology and scanning microscopy. The observed pathologic changes increased in severity with the number of shock waves given (500-5,000 15 kV). Post-ESWL MR findings in 54 kidneys included perirenal and subcapsular fluid (n = 30), diffuse loss of corticomedullary junction definition (n = 28), intrarenal foci of increased (n = 7) or decreased (n = 6) signal intensity, focal indentation of the renal contour (n = 5), and loss of distinction between the renal, splenic, or hepatic contour (n = 7). The subcapsular and intrarenal findings corresponded pathologically to areas of hemorrhage and hematoma formation--the contour changes to foci of renal scarring or perirenal adhesions. Electron microscopy demonstrated marked alterations of the renal tubules and vasculature. The study shows the feasibility of assessing the nature and chronology of renal damage post-ESWL in a rat model by MR.

Animals↗