Granulocyte colony-stimulating factor (G-CSF) receptor gene expression of ovarian carcinoma does not correlate with G-CSF caused cell proliferation.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a growth factor commonly used to avoid leukopenia after chemotherapy. Endogenous G-CSF is produced by macrophages and granulocytes that infiltrate tumors. It has been reported that rhG-CSF stimulates the proliferation of several cell lines as well as bladder carcinoma cells. Conversely, in some hematopoietic cell lines such as U-937, WEHI-3B, and K-562 no effect or in some cases a differentiation pattern was found. Moreover, the role of rhG-CSF on the proliferation of solid tumors is not well understood. METHODS: In this study, 10 ovarian carcinoma biopsies were characterized for the presence of G-CSF and G-CSF receptor by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Proliferation was analyzed by ATP viability assays. RESULTS: Performing RT-PCR, these biopsies and four ovarian carcinoma cell lines were analyzed for endogenous G-CSF production, which was found in some biopsies and in all cell lines. Despite the presence of the G-CSF receptor in all biopsies and cell lines, no proliferation was found after rhG-CSF incubation of the cell lines or the tumor samples for 3 and for 6 days, respectively. CONCLUSIONS: Summarizing the authors' in vitro studies, rhG-CSF does not affect the proliferation of ovarian carcinoma cells in vitro.

G-CSF receptor expression in ovarian cancer.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is clinically used to overcome neutropenic periods during chemotherapy. In vitro studies using cell lines as a model system have recently suggested that G-CSF can promote ovarian cancer growth. The objective of this work is to determine whether tumor cells express G-CSF-receptors (G-CSFR). A set of ovarian tumor biopsies and ovarian cancer cell lines was analyzed by RT-PCR, immunohistochemistry and immunofluorescence. The presence of a 276 bp-amplicon (exon 8-10) obtained by RT-PCR showed that 12 out of 16 ovarian tumor biopsies and two out of four ovarian cancer cell lines expressed G-CSFR-mRNA. G-CSFR-protein was detected in tumor cells of the 12 biopsies that also contained G-CSFR-mRNA. A second 409 bp-amplicon (exon 17) obtained by RT-PCR from the variable C-terminal cytoplasmic region of G-CSFR could be amplified only in four out of 16 biopsies and in none of the ovarian cancer cell lines studied. The results presented here indicate that G-CSFR is frequently expressed in ovarian cancer cells. Moreover, the failure of RT-PCR amplification of the 409 bp-amplicon in samples that express G-CSFR-mRNA suggests that C-terminal truncated receptor forms are also expressed.

[Neodymium YAG laser effects on the cornea]. / Neodym-YAG-Laser Effekte an der Hornhaut.

With the Nd:YAG laser it is possible to produce epithelial defects, fractures of Bowman's membrane or ulcer-like defects of the anterior stroma, depending on the distance, intensity, and number of optical breakdowns in front of the cornea. The histologic picture is similar to the well-known changes on the posterior surface of the cornea. The possibility of therapeutic application of the Nd:YAG laser in corneal disease is discussed.

Halothane hepatotoxicity in glutathione depleted rats.

Experimental models for halothane hepatotoxicity require microsomal enzyme induction by phenobarbital or triiodo-thyronine pretreatment and hypoxic conditions. The role of GSH in the metabolism of halothane, however, is still unclear. We therefore pretreated male rats with phorone to deplete hepatic GSH, phenobarbital as a microsomal enzyme inducer and exposed them to halothane 1% for 4 h under hypoxia (10% O2). Increases in serum enzyme activities of alanine aminotransferase (GPT) and sorbitol dehydrogenase (SDH) were observed 24 and 48 h later. Histomorphological examinations showed centrilobular hepatic necrosis. In GSH-depleted rats the increments of serum enzyme activities and histomorphological alterations were significantly aggravated as compared with controls. In this model (+)-catechin protected against halothane-induced hepatotoxicity as evidenced by reduced serum enzyme elevations and morphological alterations whereas diethyldithiocarbamate failed to exert any protective effects. Free fluoride concentrations in plasma was used as an index of the non-oxidative defluorination of halothane. Increased plasma fluoride levels were observed under conditions which evoked hepatotoxicity but did not correlate with the protective effect of (+)-catechin. Our experimental data indicate that glutathione might be involved in the non-oxidative metabolic pathways of halothane. Furthermore, (+)-catechin seems capable of protecting against the direct toxic effect of halothane metabolites resulting from the reductive pathways.

[Concretions in the nasolacrimal duct and lacrimal sac]. / Konkremente im Tränennasengang und Tränensack.

Report on six patients with concretions in the lacrimal sac and the nasolacrimal duct. It was possible to remove the concretions in four patients by irrigation of the nasolacrimal sac with cortisone solutions. In one patient a dacryocystostomy was necessary.

[Cast metal spongioid bone implants in animal experiments]. / Gegossene spongiösmetallische Implantate im Tierversuch.

Spongyimplant cubes produced out of an alloying DIN 58800 are driven in an artificial produced split in the ileosacral articulation of sheeps. The animals were killed after a period of 70 til 181 days. All the implants are enclosed by bone and so bring about an ankylosis of the ileosacral articulation. In different degree the porous slices of the implant are grown through by bone. By producing spongyimplants with more porous slices the transfer of the animal experiment to human beings is justified, for example for special problems in osteosynthesis of in the arrange of the surface from artificial implants. The produced spongy implants out of metal are characterized specially by its primary stability.

Studies on the oxygen radical mechanism involved in the small intestinal reperfusion damage.

Characteristic mucosal lesions develop in the small intestine during ischaemia and hypotension. This tissue damage can be further aggravated in the immediate reperfusion phase, presumably secondary to the generation of oxygen free radicals which have been proposed to be generated in this situation through the hypoxanthine-xanthine oxidase system. This was further investigated in the cat small intestine using a standardized regional intestinal hypotension model in which the effects of allopurinol (a xanthine oxidase inhibitor) were compared to those of an exogenous supply of inosine. The grade of mucosal damage, the nucleotide levels, the concentrations of hypoxanthine, total and oxidized glutathione, and of conjugated dienes were measured in the intestinal tissue. The results indicate that oxygen radicals generated by xanthine oxidase are very important, but not the only significant factor in the small intestinal reperfusion damage.

[Grading of epithelial ovarian cancers]. / Grading epithelialer Ovarialkarzinome.

UNLABELLED: Tissue slides of 230 epithelial ovarian cancers were examined by two different pathologic teams to determine the following details: histological pattern, grade of polymorphy, mitotic index, density of chromatin, presence of nuclei and macronuclei, lymphocytic infiltration, psammoma bodies, and necrosis. For statistical evaluations the data were presented together with stage, age and survival times in form of an information vector for each of the 230 patients and analysed using hazard-models (Cox 1972, Carter 1983) and contingency tables. RESULTS: The agreement between the 2 pathologic teams was good. There were many interrelated histological concomitants, such as polymorphy and chromatin density, and as nuclei and macronuclei. Necrosis was relatively independent. Significant effects on prognosis could be demonstrated for polymorphy, chromatin density, mitotic index, histologic pattern, (macro)nuclei. Polymorphy was the best histological prognostic indicator and, together with necrosis, produced the best prognostic grading system.

The prognostic value of age for patients with common epithelial ovarian cancer.

For 230 patients with common epithelial ovarian cancer, the prognostic impact of age was examined. Statistical analysis was done using proportional hazard models, 3- and 5-year survival rates and median survival of stratified groups, and the Kaplan-Meier mean. Taking the age-adjusted mortality into account, the prognosis of the older patients was significantly worse. This effect depended primarily on early mortality (survival time less than 2 months). A comparative analysis was made of the prognostic factors age, grade, and stage, taking into account the correlation between factors. This analysis showed that, for our series, age was of lesser prognostic significance than grading, and both of these were of much less prognostic importance than staging.

[Recent aspects in the diagnosis and therapy of inflammatory aneurysms of the abdominal aorta]. / Neurere Aspekte zur Diagnostik und Therapie des inflammatorischen Bauchaortenaneurysmas.

The so-called inflammatory infrarenal abdominal aneurysm is characterized by huge perianeurysmal retroperitoneal fibrosis, which may achieve a size of more than 1 to 2 cm. It impeats the surgical proceeding enormously. By means of computed tomography a diagnosis of this kind of aneurysm can already be given before the operation. A therapy of the fibrosis resp. the hereby caused complications especially in the urinary system is not an essential in the first place due to the fact that these complications tend to vanish spontaneously after the resection of the aneurysm.

Posthypotensive generation of superoxide free radicals--possible role in the pathogenesis of the intestinal mucosal damage.

Graded small intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery. Specimens from the small intestine were studied at the end of the hypotensive period, 10 min and 60 min posthypotensively . Specimens obtained late during hypotension revealed characteristic mucosal damage in all cases. However, the intestinal mucosal damage was more pronounced in the specimens taken posthypotensively . This aggravation was prevented if the cats were given superoxide dismutase (SOD) during the hypotensive period. Further, the intestinal tissue concentration of total glutathione was reduced posthypotensively . It is suggested that the posthypotensive aggravation of the intestinal mucosal damage is caused by generation of cytotoxic oxygen free radicals. Data favouring the suggestion that the glutathione-glutathione peroxidase system is an important generator of free radicals in intestinal ischemia is presented.

[Tumour immunology (author's transl)]. / Tumorimmunologie.

The anti-tumour immune mechanism as it operates in vivo and in vitro is reviewed. Tumour-specific antigens on the surface of the tumour cell induce cellular (lymphocytes, macrophages) and humoral (antibodies, mediators) reactions which are capable of destroying the tumour cell. The combined operation of these mechanisms is described in detail, e.g. opsonization of tumour cells, enhancement, escape mechanism, specific versus unspecific reactions, potentiation. Analyses of tumour-specific cell-mediated reactions gain more and more importance as attempts to influence the function and differentiation of individual cells become more and more successful.