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Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 microg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of downregulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.

To create cytotoxic hybrid analogs of somatostatin (SST), octapeptides RC-160 (D-Phe-Cys-Tyr-D-Trp- Lys-Val-Cys-Trp-NH2) and RC-121 (D-Phe-Cys-Tyr-D-Trp- Lys-Val-Cys-Thr-NH2) were linked to doxorubicin (DOX) or its superactive derivative, 2-pyrrolino-DOX (AN-201). The conjugation was performed by coupling N-9-fluorenylmethoxycarbonyl (N-Fmoc)-DOX-14-O-hemiglutarate or 2-pyrrolino-DOX-14-O-hemiglutarate to the amino terminus of [Lys(Fmoc)5]RC-160 yielding AN-163 and AN-258, respectively, after deprotection. The respective cytotoxic conjugates of RC-121 (AN-162 and AN-238) were prepared similarly. In vitro tests on human cancer cell lines-MKN-45 gastric cancer, MDA-MB-231 breast cancer, PC-3 prostate cancer, and MIA PaCa-2 pancreatic cancer-demonstrated that the antiproliferative activity of the cytotoxic radicals in these conjugates was virtually retained. In H-345 human small cell lung carcinoma cell line, conjugates of RC-121 preserved the cytotoxic activity of their radicals, but the hybrids with RC-160 showed approximately 10 times lower activity. The ability of the carriers and the hybrids to inhibit the binding of 125I-labeled RC-160 to receptors for SST on rat pituitary membrane preparation was also determined. The cytotoxic conjugates inhibited 50% of the specific binding of the radioligand in the nanomolar concentration range (IC50 < 80 nM). When SST-like activities of AN-238 and its carrier, RC-121, were compared in the rat pituitary superfusion system, both compounds were found to suppress a stimulated growth hormone release at nanomolar concentrations. Preliminary studies in animal models of breast and prostate cancers showed that AN-238 is less toxic than AN-201 and more potent in inhibiting tumor growth. These highly active cytotoxic analogs of SST have been designed as targeted antitumor agents for the treatment of various cancers expressing receptors for SST octapeptides.

A 3-mm strumal carcinoid was found incidentally in a mature ovarian cystic teratoma of a 38-year-old woman followed up for more than 9 years. Although the thyroid component disclosed a typical normal light microscopic appearance, no thyroglobulin and thyroxine were detected immunohistochemically. Immunoreactive calcitonin was demonstrated within the tumour cells. The close relationship between functionally imperfect thyroid tissue and a neuroendocrine marker-secreting tumour seems to be concordant with the theory of the existence of a pluripotential stem cell capable of differentiating multidirectionally.

The authors present the case of a 74-year-old man in whom bladder tumor was detected the reason for haematuria. The histological investigation of transurethral resected pattern showed lymphocytic lymphoma. In possession of the histological finding detailed haematological examination has been carried out, the patient was without evidence of lymphoma dissemination. He received multichemotherapy (6 courses) and locoregional cytostatic therapy and complete clinical remission was detected. The authors report our experience with extranodal bladder lymphoma included diagnostic and therapeutical notes as well as a review of the relevant literature.

Rhizoplast or striated rootlet is a rarely described cytoplasmic organelle in non-ciliated mammalian cells. We observed the centrosome related rhizoplast like structures relatively often in the human renal glomerular cells. Of 226 kidney biopsies striated microfilament bundles (SMF) have been found in 41 cases in a total of 64 cells. More than half of these organelles were found in podocytes, about a quarter in endothelial cells, fewer in mesangial cells and they rarely occurred in the parietal epithelium. The majority of SMF are connected with the centrosome, but not in direct connection with the centriole. The longer bundles have often been located near the Golgi complex. The thickness of the SMF varies, their cross striation has a periodicity of 88 +/- 13.4 nm. The occurrence of SMF does not show any connection with the age of the patients, the type of disease, the morphological changes or therapy. It is difficult to say whether they are normal or pathological organelles. Their presence can be regarded as a metaplastic process in functionally overloaded cells.

The hepatoprotective effect and the possible mechanism of action of AICA-phosphate (AIP) were studied. Both the morphological and biochemical data proved the protective i.e. the connective tissue reducing effect of AIP in cirrhotic rat liver. Labelled AIP incorporated very intensively into microsomal RNA, suggesting that the compound may take part in the de novo purine synthesis. The increased rate of protein synthesis can be the consequence of the incorporation into RNA, promoting the regenerative processes in injured cells.