Biomedical subjects

U Lauer

Publications and source records attributed to U Lauer.

23 records · Page 2Linked to original sources

PubMed1990

The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator.

Hepatitis B virus (HBV) is regarded as the main aetiologic factor in the development of human hepatocellular carcinoma (HCC), one of the most frequent fatal malignancies worldwide. Detection of integrated HBV sequences in the cellular DNA of almost all HCCs studied, and the recent finding that the integrated HBV open reading frame (orf) X encodes a transactivating activity, supports the notion that integrated HBV DNA could contribute to liver carcinogenesis by activation of cellular genes in trans. But not all HCCs seem to harbour a functional orf X. We report here that 3'-truncated preS2/S sequences in integrated HBV DNA of liver cell carcinomas encode a so far unidentified transcriptional trans-activation activity. This activity is also produced by an artificially 3'-truncated preS2/S gene of the wild-type HBV genome. Besides the simian virus 40 promoter of the reporter plasmid pSV2CAT, the promoter of the human c-myc oncogene can also be activated. These results, taken together with the fact that preS/S is the only HBV gene found to be integrated in almost every HBV-related HCC analysed so far, indicate that trans-activation by integrated preS2/S sequences is a possible mechanism for HBV-associated oncogenesis.

Amino Acid Sequence↗

PubMed1990

A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA.

The X gene of wild-type hepatitis B virus or integrated DNA has recently been shown to stimulate transcription of a variety of enhancers and promoters. To further delineate the viral sequences responsible for trans-activation in hepatomas, we cloned the single hepatitis B virus insert from human hepatocellular carcinoma DNA M1. The plasmid pM1 contains 2004 base pairs of hepatitis B virus DNA subtype adr, including truncated preS/S sequences and the enhancer element. The X promoter and 422 nucleotides of the X coding region are present. The entire preC/C gene is deleted. In transient cotransfection assays using Chang liver cells (CCL 13), pM1 DNA exerts a 6- to 10-fold trans-activating effect on the expression of the pSV2CAT reporter plasmid. The trans-activation occurs by stimulation of transcription and is dependent on the simian virus 40 enhancer in the reporter plasmid. Deletion analysis of pM1 subclones reveals that the trans-activator is encoded by preS/S and not by X sequences. A frameshift mutation within the preS2 open reading frame shows that this portion is indispensable for the trans-activating function. Initiation of transcription has been mapped to the S1 promoter. A comparable trans-activating effect is also observed with cloned wild-type hepatitis B virus sequences similarly truncated. These results show that a transcriptional trans-activator function not present in the intact gene is generated by 3' truncation of integrated hepatitis B virus DNA preS/S sequences.

Carcinoma, Hepatocellular↗

PubMed1989

Antibiotics from basidiomycetes. XXXI. Aleurodiscal: an antifungal sesterterpenoid from Aleurodiscus mirabilis (Berk. & Curt.) Höhn.

Aleurodiscal, an antifungal antibiotic has been isolated from mycelial cultures of Aleurodiscus mirabilis (Berk. & Curt.) Höhn. It causes abnormal apical branchings of Mucor miehei hyphae at very low concentrations. The structure and absolute configuration of the antibiotic has been determined by a single crystal X-ray analysis and hydrolysis to D-(+)-xylose. Aleurodiscal is a hydroxysesterterpene aldehyde beta-D-xyloside with a novel carbon skeleton.

Aminoglycosides↗

PubMedDate not supplied

Growth characteristics and imaging properties of the morris hepatoma 3924A in ACI rats: a suitable model for transarterial chemoembolization.

PURPOSE: For experimental studies investigating modalities and efficacy of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) an animal model resembling the human situation as closely as possible would be appropriate. Specifically, reproducible tumor growth characteristics with the capability for appropriate in vivo imaging to monitor treatment efficacy are required. METHODS: Morris hepatoma 3924A was implanted into the liver of 30 ACI rats. Tumor growth was followed by angiography (n = 10), ultrasound (US, n = 30), native computed tomography (CT, n = 16), and native magnetic resonance imaging (MRI, n = 30) between day 8 and day 36 after implantation. The radiological morphological characteristics were compared with the macroscopic and microscopic histological findings of the explanted tumors. RESULTS: In all 30 animals a solitary liver tumor was found and macroscopically no signs of metastases, ascites, or peritoneal tumor were visible. On histopathological examination tumor sizes ranged between 27 +/- 3 mm(3) (day 8) and 3468 +/- 79 mm(3) (day 36). The first signs of tumor necrosis occurred at day 16. US allowed tumor visualization from day 8, MRI from day 8, angiography from day 10, and CT from day 14. CONCLUSIONS: The tumor model has the potential to be used for the visualization of tumor growth by MRI and US. The potential for monitoring therapeutic effects of TACE needs to be investigated.

Angiography↗

PubMedDate not supplied

The hepatitis B virus transactivator HBx causes elevation of diacylglycerol and activation of protein kinase C.

Chronic infection with hepatitis B virus (HBV) is accompanied by an increasing risk of developing hepatocellular carcinoma. There are indications that the HBx protein of HBV is involved in the process of tumour formation. HBx also transactivates several transcription factor binding sites. Recently, we reported that HBx can use a tumour promotor pathway for transactivation. In particular, we found that transactivation of the binding motif for transcription factor AP-1 (JUN/FOS) by HBx is dependent on functional protein kinase C (PKC), as indicated by abolition of the transcriptional stimulation following downregulation or inhibition of the enzyme. Moreover, HBx activates PKC, probably via increasing the endogenous PKC activator sn-1,2-diacylglycerol (DAG). Here we extend these data and report on the time course of PKC activation. We found that activation of PKC by HBx is transient and differs from activation of PKC by the ras oncogene product or phorbol ester in that it does not lead to rapid downregulation of the enzyme subsequent to the activation. Moreover, we provide evidence that an increase in cellular DAG is observable not only as an early event in response to HBx but also in cell lines transformed after transfection with HBV DNA and stably expressing HBx. Besides its important role in the regulation of cellular genes, PKC is also the intracellular receptor for tumour-promoting agents and an activator of proto-oncogenes, suggesting that our observations might provide an explanation for the oncogenic properties of HBx.

3T3 Cells↗