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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 | Fractionated radiosurgery for painful spinal metastases:DOSIS-a phase Ⅱ trial显示文摘 | Guckenberger M Hawkins M Flentje M | 2012 | BMC Cancer2012，12，： | 1 |
| 4 | Influence of patient positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation:a prospective study using a 3D planning system and a radiobiological model显示文摘 | Koelbl O Richter S Flentje M | 1999 | Int J Radiat Oncol Biol Phys1999，45，5： | 1 |
| 5 | Sequential chemora- diotherapy in non-small cell lung cancer 显示文摘 | Kotas M Willner J Flentje M | 2001 | Lung Cancer2001，33，1： | 1 |
| 6 | 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 |
| 7 | Fractionated radiosurgery for painful spinal metastases: DOSIS-a phase II trial 显示文摘 | Guekenberger M Hawkins M Flentje M | 2012 | BMC Cancer2012，12，： | 1 |
| 8 | Intensitymodulated radiotherapy (IMRT) of localized prostate cancer:a review and future perspectives 显示文摘 | GUCKENBERGER M FLENTJE M | 2007 | Strahlenther Onkol2007，183，2： | 1 |
| 9 | Rhizoctonia tip blight and stem rot ofpea显示文摘 | Flentje N T Hagedorn D J | 1964 | Phytopathology1964，54，7： | 1 |
| 10 | Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage Ⅲa or Ⅲb non - small - cell lung cancer:study CTRT99/97 by the Bronchial Carcinoma Therapy Group 显示文摘 | Huber RM Flentje M Schmidt M | 2006 | J Clin Oncol2006，24，27： | 1 |
| 11 | CT simulation in stereotactic brain radiotherapy-analysis of isocenter reproducibility with mask fixation显示文摘 | WILLNER J FLENTJE M BRATENGEIER K | 1997 | Radiother Oncol1997，45，1： | 1 |
| 12 | 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 |
| 13 | Influence of patient positioning on dose-volume histogram and normal tis- sue complication probability for small bowel and blad- der in patients receiving pelvic irradiation: a prospec- tive study using a 3D planning system and a radiobio- logical model显示文摘 | Koelbl O Richter S Flentje M | 1999 | Int J Radiat Oncol Biol Phys1999，45，5： | 1 |
| 14 | 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 |
| 15 | Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage Ⅲ A or Ⅲ B non-small-cell lung cancer: Study CTRT99/97 by the Bronchial Carcinoma Therapy Group显示文摘 | Huber RM Flentje M Schmidt M | 2006 | J Clin Oncol2006，24，27： | 1 |
| 16 | Influence of patient positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation: A prospective study using a 3D planning system and a radiobiological model 显示文摘 | Koelbl O Richter S Flentje M | 1999 | Int J Radiat Oncol Biol Phys1999，45，： | 1 |
| 17 | The bellyboard technic for the sparing of the small intestine studies on positioning accuracy taking into consideration conformational irradiation technics显示文摘 | Rudat V Flentje M Engenhart R | 1995 | Strahlenther Onkol1995，171，： | 1 |
| 18 | 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 |
| 19 | Influence of patients positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation:a prospective study using a 3D planning system and a radiological model显示文摘 | Koelbl O Richter S Flentje M | 1999 | Int J Radiat Oncol Biol Phys1999，45，5： | 1 |
| 20 | Stereotactic body radia- tion therapy in the re irradiation situation-a review显示文摘 | Mantel F Flentje M Guckenberger M | 2013 | Radiat 0neol2013，8，7： | 1 |
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