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| 1 | Hypoxia and cytokines regulate carbonic anhydrase 9 expression in hepatocellular carcinoma cells in vitro显示文摘AIM: To study the expression of carbonic anhydrase(CA) 9 in human hepatocellular carcinoma(HCC) cells.METHODS: We studied CA9 protein, CA9 m RNA and hypoxia-inducible factor-1 alpha(HIF-1α) protein levels in Hep3 B cells exposed in different parallel approaches. In one of these approaches, HCC cells were exposed to extreme in vitro hypoxia(24 h 0.1% O2) without or with interleukin(IL)-1, IL-6, tumor necrosis factoralpha(TNF-α) and transforming growth factor-beta(TGF-β) stimulation for the same hypoxic exposure time or exposed to normoxic oxygenation conditions without or with cytokine stimulation.RESULTS: The tumour cell line analysed showed a strong hypoxic CA9 m RNA expression pattern in response to prolonged severe hypoxia with cell-line specific patterns and a marked induction of CA9 protein in response to severe hypoxia. These results were paralleled by the results for HIF-1α protein under identical oxygenation conditions with a similar expression tendency to that displayed during the CA9 protein expression experimental series. Continuous stimulation with the cytokines, IL-1, IL-6, TNF-α and TGF-β, under normoxic conditions significantly increased the carbonic anhydrase 9 expression level at both the protein and m RNA level, almost doubling the CA9 m RNA and CA9 and HIF-1α protein expression levels found under hypoxia. The findings from these experiments indicated that hypoxia is a positive regulator of CA9 expression in HCC, and the four signal transduction pathways, IL-1, IL-6, TNF-α and TGF-β, positively influence CA9 expression under both normoxic and hypoxic conditions.CONCLUSION: These findings may potentially be considered in the design of anti- cancer therapeutic approaches involving hypoxia-induced or cytokine stimulatory effects on expression. In addition, they provideevidence of the stimulatory role of the examined cytokine families resulting in an increase in CA9 expression under different oxygenation conditions in human cancer, especially HCC, and on the role of the CA9 gene as a positive disease regulator in human cancer. | Feray Kockar Hatice Yildrim Rahsan Ilikci Sagkan Carsten Hagemann Yasemin Soysal Jelena Anacker Ahmed Ayad Hamza Dirk Vordermark Michael Flentje Harun M Said | 2012 | World Journal of Clinical Oncology2012，3，6： | 2 |
| 2 | Stereotactic radiotherapy of primary liver cancer and hepatic metastases显示文摘 | Joern Wulf Matthias Guckenberger Ulrich Haedinger Ulrich Oppitz Gerd Mueller Kurt Baier Michael Flentje | 2006 | Acta Oncologica2006，，7： | 2 |
| 3 | Magnitude and clinical relevance of translational and rotational patient setup errors: A cone-beam CT study显示文摘 | Matthias Guckenberger Juergen Meyer Dirk Vordermark Kurt Baier Juergen Wilbert Michael Flentje | 2006 | International Journal of Radiation Oncology, Biology, Physics2006，，： | 1 |
| 4 | Estimation of pneumonitis risk in three-dimensional treatment planning using dose-volume histogram analysis显示文摘 | Dieter Oetzel Peter Schraube Frank Hensley Gabriele Sroka-Pérez Markus Menke Michael Flentje | 1995 | International Journal of Radiation Oncology Biology Physics1995，，2： | 1 |
| 5 | Potential of Adaptive Radiotherapy to Escalate the Radiation Dose in Combined Radiochemotherapy for Locally Advanced Non–Small Cell Lung Cancer显示文摘 | Matthias Guckenberger Juergen Wilbert Anne Richter Kurt Baier Michael Flentje | 2011 | International Journal of Radiation Oncology, Biology, Physics2011，，： | 1 |
| 6 | Stereotactic radiotherapy of primary liver cancer and hepatic metastases显示文摘 | Joern Wulf Matthias Guckenberger Ulrich Haedinger Ulrich Oppitz Gerd Mueller Kurt Baier Michael Flentje | 2006 | Acta Oncologica2006，，7： | 1 |
| 7 | Influence of patient positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation:显示文摘 | Oliver Koelbl Susanne Richter Michael Flentje | 1999 | International Journal of Radiation Oncology Biology Physics1999，，5： | 1 |
| 8 | Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes?显示文摘 | Matthias Guckenberger Anne Richter Thomas Krieger Juergen Wilbert Kurt Baier Michael Flentje | 2009 | Radiotherapy and Oncology2009，，2： | 1 |
| 9 | Dose–response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy显示文摘 | Matthias Guckenberger Kurt Baier Buelent Polat Anne Richter Thomas Krieger Juergen Wilbert Gerd Mueller Michael Flentje | 2010 | Radiotherapy and Oncology2010，，1： | 1 |
| 10 | The Postoperative Adjuvant Radiation Therapy and Radiochemotherapy for UICC Stage II and III Rectal Cancer A Retrospective Analysis显示文摘 | Athanasios Bagatzounis Jochen Willner Ulrich Oppitz Michael Flentje | 2000 | Strahlentherapie und Onkologie2000，，3： | 1 |
| 11 | Pulmonary injury and tumor response after stereotactic body radiotherapy (SBRT): Results of a serial follow-up CT study显示文摘 | Matthias Guckenberger Katrin Heilman Joern Wulf Gerd Mueller Gabriele Beckmann Michael Flentje | 2007 | Radiotherapy and Oncology2007，，3： | 1 |
| 12 | Oxygen-dependent regulation of NDRG1 in human glioblastoma cells invitro and in vivo显示文摘 | Harun Said Susanne Stein Carsten Hagemann Buelent Polat Adrian Staab Jelena Anacker Beate Schoemig Matthias Theobald Michael Flentje Dirk Vordermark | 2009 | Oncology Reports2009，，1： | 1 |
| 13 | Magnitude and clinical relevance of translational and rotational patient setup errors: A cone-beam CT study显示文摘 | Matthias Guckenberger Juergen Meyer Dirk Vordermark Kurt Baier Juergen Wilbert Michael Flentje | 2006 | International Journal of Radiation Oncology Biology Physics2006，，3： | 1 |
| 14 | Dose–Response Relationship for Image-Guided Stereotactic Body Radiotherapy of Pulmonary Tumors: Relevance of 4D Dose Calculation显示文摘 | Matthias Guckenberger Joern Wulf Gerd Mueller Thomas Krieger Kurt Baier Manuela Gabor Anne Richter Juergen Wilbert Michael Flentje | 2009 | International Journal of Radiation Oncology, Biology, Physics2009，，1： | 1 |
| 15 | Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells显示文摘AIM: To study short ds RNA oligonucleotides(si RNA)as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1(NDRG1) gene induced under different physiological conditions(Normoxia and hypoxia) modulating NDRG1 transcription, m RNA stability and translation. METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 × 107 cells, nuclear extracts were prepared according to previous protocols. The p SUPERNDRG1 vectors were designed, two sequences were selected from the human NDRG1 c DNA(5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on β-actin and hypoxia-inducible factor(HIF)-1α m RNA sequences in Gen Bank. NDRG1 m RNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia(P < 0.05 was considered significant).RESULTS: si RNA- and iodoacetate(IAA)-mediated downregulation of NDRG1 m RNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results. CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it canrepresent a potential target for tumor treatment in human glioblastoma. The si RNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays. | Harun M Said Buelent Polat Susanne Stein Mathias Guckenberger Carsten Hagemann Adrian Staab Astrid Katzer Jelena Anacker Michael Flentje Dirk Vordermark | 2012 | World Journal of Clinical Oncology2012，3，7： | 0 |
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