0000000000353213
AUTHOR
Bernd Dr. Lecher
Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors
Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a…
Blood flow, oxygenation, metabolic and energetic status in different clonal subpopulations of a rat rhabdomyosarcoma.
Differentiation of a tumor plays an important role in terms of biological aggressiveness. The question arises as to whether this is reflected in differences in the metabolic and energetic status of solid tumors. The aim of this study was to analyze the influence of clonal tumor cell differentiation on the microenvironment of rat rhabdomyosarcomas. Two distinct lines of a rhabdomyosarcoma (BA-HAN-1) with different histomorphological properties were used (line F1, co-existence of mononuclear stellate cells and multinuclear myotube-like giant tumor cells; G8, polygonal, mononuclear tumor cells). Solid tumors were grown s.c. on the hind food dorsum of Lewis rats. Tumor oxygenation was measured …
IFN? expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein-accumulating transgenic livers
BACKGROUND/AIMS Interferon gamma (IFNgamma) controls hepatitis B virus replication. As systemic application may cause severe adverse effects, approaches of liver-directed IFNgamma gene therapy may represent an attractive alternative for treatment of chronic viral hepatitis B and thus needs testing in vivo in suitable animal models. METHODS We therefore crossbred Alb-1HBV transgenic mice overexpressing the large HBV surface protein (LHBs) in their livers and developing LHBs storage disease and ground glass hepatocyte appearance with SAP-IFNgamma transgenic animals previously shown to exhibit constitutive hepatic IFNgamma expression, and analyzed the resulting double-transgenic offspring. RES…
Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion.
Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca2+-channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100–140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 μg min−1 kg−1 BW). During constant-pressure isolated limb perfusion, nifedipine can signi…
Effect of Cell Line and Differentiation on the Oxygenation Status of Experimental Sarcomas
Since the measurement of tumor oxygenation status and the fraction of hypoxia within tumor tissue by computerized pO2-histography [10] has become increasingly im-portant in the clinical setting, many studies on tumor oxygenation in different experimental malignancies as well as in various human tumors have been carried out. Because pO2-histography is an invasive technique, this method has been used in humans mostly in superficial primary tumors and lymph node metastases [1,3,10] (for a review see [9]). Experimental studies in animals have been carried out on a wide range of isotransplanted rodent sarcomas or carcinomas [2,4,6–8,11] and of xenotransplanted human tumors [6]. The results obtai…
Decontamination of a barrier facility using microisolator cages and provisional partitioning
In 2000, the authors found endemic infections of mouse hepatitis virus, minute virus of mice, Syphacia obvelata, and Myobia musculi among mice in a large barrier facility at the University of Mainz. To eliminate the infections, they subdivided the facility into two distinct hygiene units. However, architectural constraints made it impossible to completely separate the HVAC systems of both hygiene units and to establish adequate personnel locks. To compensate for these suboptimal barrier conditions of the two newly established units, the authors replaced the open-top caging and open-servicing system with filter-top cages that were manipulated in cage-changing stations. The authors then depop…
Synthesis of 131I-labeled glucose-conjugated inhibitors of O6-methylguanine-DNA methyltransferase (MGMT) and comparison with nonconjugated inhibitors as potential tools for in vivo MGMT imaging.
O 6 -Substituted guanine derivatives are powerful agents used for tumor cell sensitization by inhibition of the DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT). To provide targeted accumulation of MGMT inhibitors in tumor tissue as well as tools for in vivo imaging, we synthesized iodinated C 8 -alkyl-linked glucose conjugates of 2-amino-6-(5-iodothenyl)-9H-purine (O 6 -(5-iodothenyl) guanine, ITG) and 2-amino-6-(3-iodobenzyloxy)-9H-purine (O 6 -(5-iodobenzyl) guanine, IBG). These compounds have MGMT inhibitor constants (IC 5 0 values) of 0.8 and 0.45 μM for ITGG and IBGG, respectively, as determined in HeLa S3 cells after 2-h incubation with inhibitor. To substantiate tha…
Quantitative changes of metabolic and bioenergetic parameters in experimental tumors during fractionated irradiation.
Abstract Purpose: Previous studies with rat rhabdomyosarcomas indicate that during fractionated irradiation profound alterations of the tumor microvasculature and the oxygenation status occur when the total dose exceeds 45 Gy. At this dose a destruction which included all structures of the vessels and a significant worsening in tumor oxygenation were found. The aim of the present study was to analyze whether these effects of fractionated irradiation on the microvasculature and on tumor oxygenation also induce changes in the bioenergetic and metabolic status in the tumors during radiation treatment. Methods and Materials: R1H rhabdomyosarcomas of the rat implanted into the flank were irradia…