@misc{Steinberg2018, author = {Steinberg, Pablo}, title = {Only one Component of a holistic Nutrition Policy}, series = {Fleischwirtschaft}, volume = {98}, journal = {Fleischwirtschaft}, number = {11}, publisher = {Deutscher Fachverlag GmbH}, address = {Frankfurt am Main}, issn = {0015-363X}, pages = {8 -- 9}, year = {2018}, language = {de} } @article{ThierbachFlorianWolfrumetal.2012, author = {Thierbach, Rene and Florian, Simone and Wolfrum, Katharina and Voigt, Anja and Drewes, Gunnar and Blume, Urte and Bannasch, Peter and Ristow, Michael and Steinberg, Pablo}, title = {Specific alterations of carbohydrate metabolism are associated with hepatocarcinogenesis in mitochondrially impaired mice}, series = {Human molecular genetics}, volume = {21}, journal = {Human molecular genetics}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0964-6906}, doi = {10.1093/hmg/ddr499}, pages = {656 -- 663}, year = {2012}, abstract = {Friedreich's ataxia is an inherited neurodegenerative disease caused by the reduced expression of the mitochondrially active protein frataxin. We have previously shown that mice with a hepatocyte-specific frataxin knockout (AlbFxn(-/-)) develop multiple hepatic tumors in later life. In the present study, hepatic carbohydrate metabolism in AlbFxn(-/-) mice at an early and late life stage was analyzed. In young (5-week-old) AlbFxn(-/-) mice hepatic ATP, glucose-6-phosphate and glycogen levels were found to be reduced by similar to 74, 80 and 88\%, respectively, when compared with control animals. This pronounced ATP, G6P and glycogen depletion in the livers of young mice reverted in older animals: while half of the mice die before 30 weeks of age, the other half reaches 17 months of age and exhibits glycogen, G6P and ATP levels similar to those in age-matched controls. A key event in this respect seems to be the up-regulation of GLUT1, the predominant glucose transporter in fetal liver parenchyma, which became evident in AlbFxn(-/-) mice being 5-12 weeks of age. The most significant histological findings in animals being 17 or 22 months of age were the appearance of multiple clear cell, mixed cell and basophilic foci throughout the liver parenchyma as well as the development of hepatocellular adenomas and carcinomas. The hepatocarcinogenic process in AlbFxn 2/2 mice shows remarkable differences regarding carbohydrate metabolism alterations when compared with all other chemically and virally driven liver cancer models described up to now.}, language = {en} } @article{MuellerUllmannSteinberg2011, author = {M{\"u}ller, Carsten and Ullmann, Kristina and Steinberg, Pablo}, title = {The grapevine-shoot extract Vineatrol30 Inhibits the chemically induced malignant transformation of BALB/c-3T3 Cells}, series = {Journal of medicinal food}, volume = {14}, journal = {Journal of medicinal food}, number = {1-2}, publisher = {Liebert}, address = {New Rochelle}, issn = {1096-620X}, doi = {10.1089/jmf.2010.0022}, pages = {34 -- 39}, year = {2011}, abstract = {Vineatrol (R) 30 (developed and produced jointly by Breko GmbH [Bremen, Germany] and Actichem [Montauban, France]) is a grapevine-shoot extract that contains resveratrol as well as considerable amounts of resveratrol oligomers. In the present study it is shown that Vineatrol30 at a noncytotoxic concentration of 2.3 mu g/mL significantly reduced the number of malignantly transformed foci induced by a sequential treatment of BALB/c-3T3 cells with 3-methylcholanthrene and 12-O-tetradecanoylphorbol 13-acetate in the so-called BALB/c-3T3 cell transformation assay. At a higher concentration Vineatrol30 drastically decreased the relative plating efficiency of the cells. Furthermore, the results suggest that the resveratrol oligomers present in Vineatrol30, independently from resveratrol itself, were indeed able to inhibit the formation of malignantly transformed BALB/c-3T3 foci.}, language = {en} } @article{ThierbachDrewesFusseretal.2010, author = {Thierbach, Ren{\´e} and Drewes, Gunnar and Fusser, Markus and Voigt, Anja and Kuhlow, Doreen and Blume, Urte and Schulz, Tim Julius and Reiche, Carina and Glatt, Hansruedi and Epe, Bernd and Steinberg, Pablo and Ristow, Michael}, title = {The Friedreich's ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals}, issn = {0264-6021}, doi = {10.1042/Bj20101116}, year = {2010}, abstract = {DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron-sulfur clusters). The nuclear-encoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte- specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frataxin deficiency in murine liver is associated with increased basal levels of oxidative DNA base damage. Accordingly, eukaryotic V79 fibroblasts overexpressing human frataxin show decreased basal levels of these modifications, while prokaryotic Salmonella enterica serotype Typhimurium TA 104 strains transformed with human frataxin show decreased mutation rates. The repair rates of oxidative DNA base modifications in V79 cells overexpressing frataxin were significantly higher than in control cells. Lastly, cleavage activity related to the ISC-independent repair enzyme 8-oxoguanine glycosylase was found to be unaltered by frataxin overexpression. These findings indicate that frataxin modulates DNA-repair mechanisms probably due to its impact on ISC-dependent repair proteins, linking mitochondrial dysfunction to DNA repair and tumour initiation.}, language = {en} } @article{ThierbachBlumeWolfrumetal.2010, author = {Thierbach, Ren{\´e} and Blume, Urte and Wolfrum, K. and Drewes, Gunnar and Voigt, Anja and Ristow, Michael and Steinberg, Pablo}, title = {Altered carbohydrate metabolism in a tumour developing knock-out mice model}, issn = {0028-1298}, doi = {10.1007/s00210-010-0508-7}, year = {2010}, language = {en} } @misc{ScholtkaSchneiderMelcheretal.2009, author = {Scholtka, Bettina and Schneider, Mandy and Melcher, Ralph and Katzenberger, Tiemo and Friedrich, Daniela and Berghof-J{\"a}ger, Kornelia and Scheppach, Wolfgang and Steinberg, Pablo}, title = {A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80\% of early (UICC I) colon cancer stages in humans}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-44587}, year = {2009}, abstract = {Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243-1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80\% of early stage CRC (UICC stages I and II) and over 90\% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80-90\% of human sporadic CRC samples analyzed.}, language = {en} } @article{MuellerUllmannWilkensetal.2009, author = {Mueller, Carsten and Ullmann, Kristina and Wilkens, Andrea and Winterhalter, Peter and Toyokuni, Shinya and Steinberg, Pablo}, title = {Potent antioxidative activity of vineatrol (R) 30 grapevine-shoot extract}, issn = {0916-8451}, doi = {10.1271/Bbb.90213}, year = {2009}, abstract = {The health promoting effects of a grapevine-shoot extract named Vineatrol (R) 30, which contains resveratrol (Resv) as well as considerable amounts of Resv oligomers, have recently been investigated. In the present study, we analyzed the free radical scavenging capacity, the ability to inhibit lipid peroxidation, and the capacity to enhance the human glutathione peroxidase 1 (GPx) and the human superoxide dismutase 1 (SOD) gene promoter activities of Vineatrol (R) 30. Vineatrol (R) 30 was able to scavenge the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical cation and led to concentration-dependent inhibition of lipid peroxidation, Vineatrol (R) 30 not being superior to Resv alone in both cases. Vineatrol (R) 30 also enhanced the gene promoter activities of human GPx and SOD expressed in V79 cells, whereas this effect could not be demonstrated for Resv. In summary, the results presented in this study show that the Vineatrol (R) 30 grapevine-shoot extract is a free radical scavenger and potent antioxidant at non- eytotoxic concentrations.}, language = {en} } @article{ThierbachDrewesFusseretal.2009, author = {Thierbach, Ren{\´e} and Drewes, Gunnar and Fusser, Markus and Wolfrum, Kathrin and Epe, Bernd and Ristow, Michael and Steinberg, Pablo}, title = {A role for iron-sulfur cluster proteins in DNA repair}, issn = {0028-1298}, doi = {10.1007/s00210-009-0404-1}, year = {2009}, language = {en} } @misc{ScholtkaKuehnelTaugneretal.2009, author = {Scholtka, Bettina and K{\"u}hnel, Dana and Taugner, Felicitas and Steinberg, Pablo}, title = {Inflammation does not precede or accompany the induction of perneoplastic lesions in the colon of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-fed rats}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-44570}, year = {2009}, abstract = {Heterocyclic aromatic amines (HCAs) are formed in meat cooked at high temperatures for a long time or over an open flame. In this context 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant HCA in cooked meat, has been suggested to be involved in colon and prostate carcinogenesis. In the latter case it has been reported that: (1) roughly 50\% of Fischer F344 male rats treated with PhIP develop carcinomas in the ventral prostate lobe at 1 year of age; (2) inflammation precedes prostatic intraepithelial neoplasia in PhIP-fed rats; (3) inflammation specifically occurs in the ventral prostate lobe of PhIP-fed rats. To test whether PhIP by itself leads to inflammation in the colon and whether a human-relevant concentration of PhIP is able to induce preneoplastic lesions in the colon, male F344 rats were fed 0.1 or 100 ppm PhIP for up to 10 months and thereafter the colon tissue was analyzed histochemically. In none of the experimental groups signs of acute or chronic colonic inflammation were observed. 0.1 ppm PhIP leads to the development of hyperplastic and dysplastic lesions in the colon of single animals, but the incidence of these lesions does not reach a statistical significance. In contrast, in rats fed 100 ppm PhIP for 10 months hyperplastic and dysplastic colonic lesions were induced in a statistically significant number of animals. It is concluded that: (1) the induction of preneoplastic lesions in rat colon by PhIP is not preceded or accompanied by an inflammatory process; (2) a human-relevant concentration of PhIP alone is not sufficient to initiate colon carcinogenesis in rats.}, language = {en} } @article{SinghDaniSharmaetal.2006, author = {Singh, Jasbir and Dani, Harinder M. and Sharma, Reeta and Steinberg, Pablo}, title = {Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B-1 can disrupt protein targeting}, series = {Cell biochemistry and function}, volume = {24}, journal = {Cell biochemistry and function}, publisher = {Wiley}, address = {Chichester}, issn = {0263-6484}, doi = {10.1027/cbf.1285}, pages = {507 -- 510}, year = {2006}, abstract = {Cell culture and western blotting studies revealed that aflatoxin B-1 (AFB(1)) inhibits the biosynthesis of two of the constituent polypeptides of signal recognition particle (SRP) (SRP54 and 72). SRP escorts polyribosomes carrying signal peptides from free form in the cytosol to the bound form on endoplasmic reticulum (ER) membrane during protein targeting. These effects of AFB(1) on SRP biosynthesis may inhibit the formation of functional SRP Our experiments have further shown that AFB(1) also inhibits the biosynthesis/translocation of a secretory protein, preprolactin, which fails to appear in the lumen of ER consequent to the treatment with this hepatocarcinogen. The results of the experiments presented in this article therefore enable us to infer for the first time that aflatoxin B-1 may inhibit the functioning of SRP as an escort and deplete the ER of polyribosomes for secretory protein synthesis. As these secretory proteins are important components of the plasma membrane, gap junctions and intercellular matrix, their absence from these locations could disturb cell to cell communication leading to tumorigenesis.}, language = {en} }