[Receptor mediated modification of cell growth in vitro--kinetics and description of the morphological receptor].
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Biomedical subjects
Publications and source records attributed to H Arps.
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The presence of the blood group substances A, B, AB, Lea, and Leb and of CEA was demonstrated by peroxidase-antiperoxidase or fluorescein immunohistochemistry in histological sections of normal ovarian tissue and ovarian tumors of varying differentiation. In surface cells of normal ovaries and of benign tumors, blood group substances (BGS) were found in patterns corresponding to the serum blood group type of the patients. BGS were localized exclusively at the apical border of normal cells. CEA was almost always absent. In borderline lesions the presence of BGS was reduced by approximately 13%. The polar differentiation was often lost, and the BGS were unevenly distributed in the cytoplasm. The percentage of CEA-specific staining increased from less than 5% in normal tissue and benign tumors to 15% in mucinous and 10% in serous borderline tumors. Malignant tumors contained altered distribution patterns of BGS and CEA. In contrast to normal ovarian epithelia, BGS positivity was diminished distinctly; the decrease was particularly evident for Leb presence by reduction from 75 to 10%. CEA was observed in nearly 50% of the carcinomas (more often in mucinous than in serous carcinomas). Our study revealed that expression of blood group antigens was related to benign lesions, whereas its loss was associated with a greater malignant potential. Inverse correlations were found for CEA. Thus, immunohistological determination of these marker substances may be applied to tumor prognosis.
Epithelial tumours of the ovary with a tumour status between benign and malignant are classified as borderline tumours (BOT). They are particularly frequent in women between 30 and 40 years of age, emphasising the need for effecting a therapy directed at preserving fertility. To keep the risk of this therapy at a minimum it is imperative to effect accurate determination of the prognosis on the basis of an examination of the histological preparation. Conventional histology is insufficient for this purpose, thus requiring the use of additional morphological methods. In the present study the DNA of the cell nucleus was determined via quantitative cytophotometry and also via several tumour or differentiating markers by immunohistology, in healthy ovaries, 10 benign and 20 malignant ovarian tumours and in 20 borderline tumours (BOT). The DNA histograms of the tumours classified histologically as BOT, yielded distribution patterns pointing towards a benign, proliferative or malignant potency of the tumours without a correlation to conventional histology being present in each case. Immunohistological identification of the carcinoembryonal antigen (CEA) and of the blood group substances (A, B, Lewis, Lewis) produced characteristic distribution patterns which correlated with the tendency to proliferation in DNA cytophotometry. To achieve relevant determination of prognosis of BOT in individual cases, conventional histology should be complemented by additional examinations using DNA cytophotometry and immunhistology as diagnostic tools.
Antigens A, B, Lea, Leb, CA 12-5, CA 19-9 and CEA were prepared immunohistologically, a DNA-cytophotometry was carried out and the value of a new in vitro proliferation assay to test cytostatic drugs investigated. Material was as follows: 20 normal ovaries and 105 ovarian tumors. Blood group antigens were expressed at a high percentage from well-differentiated epithelial cells, CEA in 50% and CA 12-5 in 70% of the ovarian carcinoma. Predictions about the dignity of borderline tumors can be made with DNA-cytophotometry. The efficacy of 6 different cytostatic agents was investigated in a new in vitro proliferation assay.
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In a retrospective study of 86 follicular carcinomas of the thyroid gland, 35 lesions were classified as encapsulated carcinomas (40.7%). In two of these, lymph node metastases were detected initially. Another patient presented with distant metastases. The biological behaviour of these 35 tumours was studied over a long-term follow-up period (0.4-19.1 years, mean 10.3 years) which featured three cases of death from thyroid carcinoma 0.4-5.0 years after thyroidectomy. Another patient suffered from local recurrence of a follicular carcinoma 13.9 years later. The morphological and clinical findings of those five patients who initially presented with metastases and/or whose follow-up registered the local recurrence of thyroid cancer or death as a result of it, were compared with the remaining 30 cases which were of a benign clinical course. Statistical analysis showed that the prognosis of encapsulated follicular carcinoma is more serious when tumours occur in patients older than 65 years of age and when the tumour diameter is 5.0 cm or more. There was a tendency towards poorer prognosis in those tumours exclusively composed of oxyphilic epithelium.
In vitro parathyroid hormone secretion of normal (n = 10) and adenomatous (n = 20) human parathyroid glands was compared in response to different calcium (Ca++) concentrations. The glands, prepared for tissue culture immediately after surgical removal, were incubated under identical conditions for 6 h. The medium was changed hourly and analyzed for PTH and cAMP using radioimmunoassay. During the first 2 h of the experiment, the Ca++ concentrations of all preparations was kept constant at 1.2 mM equivalent to the normal Ca++ level of the intercellular space. The PTH level of the 2nd h was defined as reference value corresponding to 100%. After the 2nd h of incubation the Ca++ concentration in the medium was shifted either to low (0.9 or 0.6 mM) or to high (1.9 or 2.6 mM) values. In low Ca++ concentrations (0.6 mM) the normal parathyroid glands responded by stimulation of the PTH release up to 310% in relation to the reference value, whereas the adenomas enhanced the PTH release to 160% only. The incubations in 0.9 mM Ca++ resulted in a slightly lower degree of stimulation. During the incubation in high Ca++ the PTH secretion was reduced to 28% by normal glands and to 52% by adenomatous parathyroid glands. Movements of cAMP measurements paralleled PTH values. The study provides evidence for an abnormally low responsiveness of parathyroid adenomas to Ca++ when compared with normal glands. The reduction in Ca++ responsiveness of adenomatous cells appears to have a fundamental role in primary hyperparathyroidism since the tumour cells may obviously recognize normal Ca++ levels as 'hypocalcaemic' and react by a stimulated PTH secretion.
29 non-endocrine tumors with clinical suspicion of paraneoplastic hypercalcemia were examined using immunohistochemistry specific for PTH and CT. In 19 of these cases intracellular immunoprecipitates have been demonstrable thus showing the paraneoplastic production of peptide hormones (18 PTH, 1 CT). Four of these tumors have been tested in tissue culture for in vitro production of endocrine active substances. In all cases the incubation medium yielded a positive reaction for PTH. The use of immunocytochemistry in the differential diagnosis of hypercalcemia in tumor patients is discussed.
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BACKGROUND: Rats are susceptible to irradiation and can develop benign and malignant tumors either spontaneously or in the field of irradiation. In the head and neck region, there are no reports available on the type of tumor after fractionated irradiation using a human therapy protocol. MATERIAL AND METHODS: We analyzed 19 tumors, in 19 rats, which developed after external X-irradiation of the left neck area in Wistar rats (2 Gy/day, monofractions, 5 days/week, total dosage 60 Gy) and compared the findings with tumors in untreated rats of the same strain. RESULTS: Tumors in the irradiation field proved to be squamous cell carcinoma or adenoid cystic carcinoma (ACC), not sarcoma. These entities were sporadically found in non-irradiated rats at a higher age. CONCLUSIONS: ACC has rarely been reported in the literature on laboratory rats. The development of this highly aggressive malignant tumor can be expected 3 months to 1 year after completion of irradiation.
The aim of this study was to investigate the expression of intermediate filaments (cytokeratin, vimentin), epithelial membrane antigen (EMA) and the presence of Epstein-Barr virus (EBV) DNA in undifferentiated nasopharyngeal carcinoma (NPC). A high incidence of nuclear signals in NPC was found in primaries and regional lymph node metastases (70%), using 35S-labelled probes of EBV plasmids for in-situ hybridization. Keratinizing squamous cell carcinomas were EBV-negative. All carcinomas were immuno-reactive for cytokeratin (KL-1). 45% of the carcinomas were positive for vimentin. The expression of epithelial membrane antigen was restricted to epithelial cells and reduced in NPC as compared to the distribution pattern of cytokeratin. Both EBV DNA and vimentin in NPC were present in 9 cases. However, in 5 cases NPC were harboring EBV but were not immunoreactive for anti-vimentin antibodies. In no case was a vimentin-positive NPC also EBV-negative. The identification of cytokeratin subtypes revealed no specific cytokeratin pattern in NPC. The expression of vimentin in NPC is not specific for EBV, but seems to reflect the loss of inter-epithelial contact in anaplastic carcinomas.
OBJECTIVE: While radiation-induced sarcomas or carcinomas following chemical carcinogens are well-documented in rats, radiation-induced carcinomas, especially adenoid-cystic carcinomas (ACC) and adenocarcinomas, originating from the head and neck region, including the major salivary glands (SG) are rarely reported. Because in human ACC of the SG structural changes of the basement membrane (BM) with positive correlation of tumor differentiation loss and BM thinning have been described, this study set out to analyze collagen distribution in malignant rat tumors (TM) developing inside the radiation field (RF) and spontaneously. The TM arose in the course of studies on other questions regarding radiation effects following fractionated radiation (2 Gy/day, 5 times a week; total dose 60 Gy). METHODS: We investigated 22 TM (14 malignant, 8 benign) of 22 female Wistar rats. The RF comprised the left head and neck area. Besides assessment of hematoxylin-eosin (HE)-stained sections collagens (C; types III and IV) were investigated using immunohistochemical methods. RESULTS: Nine malignant TM originated from the SG, a further three from the milk line and two from the maxilla. Two ACC, two cystadenocarcinomas, one microcystic adenocarcinoma and four squamous cell carcinomas (SCC) arising from the SG (one SCC was observed in the maxilla) developed in the RF. One microcystic adenocarcinoma, one ACC and one adenocarcinoma with sebaceous differentiation arising from the milk line and one SCC arising from the maxilla were found in non-irradiated animals. As typical results, in the ACC (glandular subtype), C III was detected in the interstitium with sometimes stronger staining surrounding myoepithelial cells (MC) and excretory duct structures (ECD). Weak C IV staining in a string-like fashion was found in ECD and MC. In larger pseudocysts the lumen contained substances reacting with C IV antibodies. In the cystadenocarcinomas and the microcystic adenocarcinomas reactions at variable levels after anti-C III incubation were found close to modified MC and ECD with transition to the interstitium. C IV was more intensely stained in these entities, in part continuously and with broadening around MC and ECD. However, especially in more anaplastic parts of the tumor, fragments, interruptions or loss of the BM were noted. Focal interstitial immunoreactivity, e.g. conglomerates, was also identified. CONCLUSION: In rat carcinomas collagen detection was partially of a continuous layer, even with BM thickening and more extended deposition. In contrast, BM fragmentation or loss was displayed more often in anaplastic parts of the tumor. Also, the interstitium showed conglomerated collagen formations. Therefore, the increasing loss of BM in rat SG tumors is similar to that in humans and in both species is a sign of dedifferentiation.
OBJECTIVE: Laboratory rats can develop benign or malignant tumors (TM) spontaneously or following various carcinogenic processes, e.g. irradiation. The effects of irradiation vary according to the irradiation field (RF), the dosage and the strain of rat. Radiation-induced malignant TM in rats are predominantly sarcomas. Carcinomas, especially adenoid-cystic carcinomas (ACC) and adenocarcinomas of the head and neck region, are rarely reported in rats. The aim of this study was to add to the knowledge on ACC and adenocarcinomas in rats developing inside the RF and spontaneously. The TM arose in the course of studies on other questions of radiation effects following fractionated irradiation (2 Gy/day, 5 times a week up to a total dose of 60 Gy). METHODS: We investigated 22 TM (14 malignant, 8 benign) of 22 female Wistar rats. Ten malignant TM developed in the RF and 4 outside of the left head and neck area. The RF comprised the left neck, extending from left auricle to left clavicle and included the midline organs of the neck. Besides assessment of hematoxylin-eosin (HE)-stained sections, epithelial differentiation was investigated using cytokeratin (CK) antibodies against CK 5/6, CK 7, CK 8/18, CK 13/15/16, CK 17 and CK 20 and the LSAB-2 detection system. RESULTS: Nine malignant TM originated from the major salivary glands (SG), a further three from the milk line and two from the maxilla. Using HE staining the pattern of rat malignant TM differed from that found in humans and was difficult to interpret. Two ACC, two cystadenocarcinomas, one microcystic adenocarcinoma and four squamous cell carcinomas (SCC) arising from the SG (one SCC was observed in the maxilla) developed in the RF. One microcystic adenocarcinoma, one ACC and one adenocarcinoma with sebaceous differentiation arising from the milk line and one SCC arising from the maxilla were found in non-irradiated animals. As typical results, in the ACC CK 17 was distinctly immunoreactive in excretory duct structures (ECD). CK 5/6 and CK 13/15/16 were marked at variable levels in myoepithelial cells (MC) and in basal cells of ECD. In the cystadenocarcinomas the ECD were clearly identified with CK 17 and CK 8/18 antibodies. MC and basal cells of ECD were positive for CK 5/6 and CK 13/15/16 antibodies. CONCLUSION: The CK expression profile of these rare and aggressive TM in rats differed according to the entity and SG structure. The differentiation markers were predominantly found in ECD and in modified MC. Concerning the growth pattern of the TM, the variation in size of the cysts and pseudocysts was remarkable. The unusual tumor features reduced the comparability with humans. The differentiation pattern did not differ noticeably between TM originating inside or outside the RF. Identification of CK subtypes in rat tumors facilitates their differential diagnosis.