HPMA copolymer-anticancer drug-OV-TL16 antibody conjugates. 3. The effect of free and polymer-bound adriamycin on the expression of some genes in the OVCAR-3 human ovarian carcinoma cell line.

The effect of an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-Adriamycin-OV-TLl6 antibody conjugate [P(GFLG)-ADR-Ab] on OVCAR-3 human ovarian carcinoma cells was studied. A nontargeted HPMA copolymer-ADR conjugate (P(GFLG)-ADR) and free ADR were the controls. The IC(50) doses were 0.65, 3.0, and 65 microM for free ADR, targeted P(GFLG)-ADR-Ab conjugate, and nontargeted P(GFLG)-ADR conjugate, respectively. These differences reflect the different mechanisms of cell entry of the compounds evaluated. Free ADR and HPMA copolymer-ADR conjugates had different impacts on the expression of MDR1, MRP, c-fos, c-jun, and bcl-2 genes which encode the P-glycoprotein (MDR1) and the multidrug resistance-associated protein (MRP) efflux pumps, and play an important role in cell death signaling pathways (c-fos, c-jun, and bcl-2). Whereas high doses of free ADR induced MDR1 gene expression, HPMA copolymer-bound ADR appeared to be without effect. On the contrary, expression of the MRP gene was not influenced by free ADR, whereas HPMA copolymer-ADR conjugates seemed to suppress the gene expression in a concentration-dependent manner. There were differences in the expression of c-fos, c-jun, and bcl-2 genes after the incubation of OVCAR-3 cells with free and HPMA copolymer-bound ADR indicating differences in activation of cell death signaling pathways.

[Significance of parathyroid hormone (PTH) within the scope of central nervous system disorders in hemodialysis patients]. / Die Bedeutung von Parathormon (PTH) im Rahmen zentral-nervöser Störungen bei Hämodialysepatienten.

The role of PTH as possible uraemic toxin within the scope of disturbances of the central nervous system (progressive dialysis encephalopathy, PDE) was investigated in 88 patients undergoing haemodialysis. A radioimmunoassay covering the C-terminal PTH fragment was used. Patients undergoing haemodialysis with a PDE showed the highest values with 2,015.4 +/- 457.9 pg/ml, and also in the preclinical stage of a PDE the PTH values with 1,845.7 +/- 663.1 pg/ml lay significantly above those ones of the patients undergoing haemodialysis without PDE (794.8 +/- 364.7 pg/ml). The findings speak for the importance of PTH in the development of complications of the central nervous system within the scope of the uraemia syndrome.

[Autopsy-statistical analysis of multiple myeloma (author's transl)]. / Sektionsstatistische Analyse der Plasmozytome.

150 autopsies with multiple meyeloma were analysed. In about one third of the cases the multiple myeloma was diagnosed only at autopsy. Two thirds of the carriers of multiple myeloma were between 60 and 70 years old when they deceased. The osseous foci of multiple myeloma extended predominantly to the central parts of the skeletal system. In 120 patients the multiple myeloma was the cause of death. In half of these cases infections, particularly of the lung, had caused death. The second frequent cause of death was uraemia. 63 of the 150 multiple myeloma have been immunologically classified. The cases in question are 10 IgA-, 2 IgD-, and 42 IgG-multiple myeloma. Extraosseous foci of multiple myeloma appeared significantly more frequent in IgA-than in IgG-multiple myeloma. A haemorrhagic diathesis existed more frequent in IgA-multiple myeloma. Venous thromboses were more frequently to be found in IgG-multiple myeloma. Amyloid deposits and changes of the kidneys characteristic for the multiple myeloma appeared nearly in the same frequency in both types of multiple myeloma.