Establishment, functional and genetic characterization of three novel patient-derived rectal cancer cell lines : = Establishment, functional and genetic characterization of three novel patient-derived rectal cancer cell lines
AIM To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens.METHODS Establishment of cell lines was conducted by direct in vitro culturing and in vivo xenografting with subsequent in vitro culturing. Cell lines were in-depth characterized concerning morphological features, invasive and migratory behavior, phenotype, molecular profile including mutational analysis, protein expression, and confirmation of origin by DNA fingerprint. Assessment of chemosensitivity towards an extensive range of current chemotherapeutic drugs and of radiosensitivity was performed including analysis of a combined radioand chemotherapeutic treatment. In addition, glucose metabolism was assessed with 18 F-fluorodeoxyglucose(FDG) and proliferation with 18 F-fluorothymidine.RESULTS We describe the establishment of ultra-low passage rectal cancer cell lines of three patients suffering from rectal cancer. Two cell lines(HROC126, HROC284 Met) were established directly from tumor specimens while HROC239 T0 M1 was established subsequent to xenografting of the tumor. Molecular analysis classified all three cell lines as CIMP-0/non-MSI-H(sporadic standard) type. Mutational analysis revealed following mutational profiles: HROC126: APC~(wt), TP53~(wt), KRAS~(wt), BRAF~(wt), PTEN~(wt); HROC239 T0 M1: APC~(mut), P53~(wt), KRAS~(mut), BRAF~(wt), PTEN~(mut) and HROC284 Met: APC~(wt), P53~(mut), KRAS~(mut), BRAF~(wt), PTEN~(mut). All cell lines could be characterized as epithelial(EpCAM+) tumor cells with equivalent morphologic features and comparable growth kinetics. The cell lines displayed a heterogeneous response toward chemotherapy, radiotherapy and their combined application. HROC126 showed a highly radio-resistant phenotype and HROC284 Met was more susceptible to a combined radiochemotherapy than HROC126 and HROC239 T0 M1. Analysis of 18 F-FDG uptake displayed a markedly reduced FDG uptake of all three cell lines after combined radiochemotherapy. CONCLUSION These newly established and in-depth characterized ultra-low passage rectal cancer cell lines provide a useful instrument for analysis of biological characteristics of rectal cancer..
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2018-11-21 2018 |
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Erschienen: |
2018-11-21 |
Enthalten in: |
Zur Gesamtaufnahme - year:2018 |
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Enthalten in: |
World journal of gastroenterology - (2018), 43 vom: 21. Nov., Seite 4880-4892 Original Letters: Enthalten in (DE-576)276271955 (DE-576)276271955 |
Reihe: |
China Academic Journals (CAJ), E, 医药卫生科技 = Medicine & Public Health |
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Sprache: |
Chinesisch |
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Weiterer Titel: |
Establishment, functional and genetic characterization of three novel patient-derived rectal cancer cell lines |
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Beteiligte Personen: |
Michael Gock [VerfasserIn] |
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Links: |
oversea.cnki.net [lizenzpflichtig] |
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Anmerkungen: |
Author info:Michael Gock;Christina S Mullins;Carina Bergner;Friedrich Prall;Robert Ramer;Anja G?der;Oliver H Kr?mer;Falko Lange;Bernd J Krause;Ernst Klar;Michael Linnebacher;Department of General Surgery, University Medical Center;Section of Molecular Oncology and Immunotherapy, University Medical Center;Department of Nuclear Medicine, University Medical Center;Institute of Pathology, University Medical Center;Institute of Pharmacology, University Medical Center;Institute of Toxicology, University Medical Center Mainz;Oscar-Langendorff-Institute of Physiology, University Medical Center |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
CAJ61027449X |
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245 | 1 | 0 | |a Establishment, functional and genetic characterization of three novel patient-derived rectal cancer cell lines |b = Establishment, functional and genetic characterization of three novel patient-derived rectal cancer cell lines |
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520 | |a AIM To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens.METHODS Establishment of cell lines was conducted by direct in vitro culturing and in vivo xenografting with subsequent in vitro culturing. Cell lines were in-depth characterized concerning morphological features, invasive and migratory behavior, phenotype, molecular profile including mutational analysis, protein expression, and confirmation of origin by DNA fingerprint. Assessment of chemosensitivity towards an extensive range of current chemotherapeutic drugs and of radiosensitivity was performed including analysis of a combined radioand chemotherapeutic treatment. In addition, glucose metabolism was assessed with 18 F-fluorodeoxyglucose(FDG) and proliferation with 18 F-fluorothymidine.RESULTS We describe the establishment of ultra-low passage rectal cancer cell lines of three patients suffering from rectal cancer. Two cell lines(HROC126, HROC284 Met) were established directly from tumor specimens while HROC239 T0 M1 was established subsequent to xenografting of the tumor. Molecular analysis classified all three cell lines as CIMP-0/non-MSI-H(sporadic standard) type. Mutational analysis revealed following mutational profiles: HROC126: APC~(wt), TP53~(wt), KRAS~(wt), BRAF~(wt), PTEN~(wt); HROC239 T0 M1: APC~(mut), P53~(wt), KRAS~(mut), BRAF~(wt), PTEN~(mut) and HROC284 Met: APC~(wt), P53~(mut), KRAS~(mut), BRAF~(wt), PTEN~(mut). All cell lines could be characterized as epithelial(EpCAM+) tumor cells with equivalent morphologic features and comparable growth kinetics. The cell lines displayed a heterogeneous response toward chemotherapy, radiotherapy and their combined application. HROC126 showed a highly radio-resistant phenotype and HROC284 Met was more susceptible to a combined radiochemotherapy than HROC126 and HROC239 T0 M1. Analysis of 18 F-FDG uptake displayed a markedly reduced FDG uptake of all three cell lines after combined radiochemotherapy. CONCLUSION These newly established and in-depth characterized ultra-low passage rectal cancer cell lines provide a useful instrument for analysis of biological characteristics of rectal cancer. | ||
610 | 2 | 4 | |a Department of General Surgery, University Medical Center,Rostock |
610 | 2 | 4 | |a Section of Molecular Oncology and Immunotherapy, University Medical Center,Rostock |
610 | 2 | 4 | |a Department of Nuclear Medicine, University Medical Center,Rostock |
610 | 2 | 4 | |a Institute of Pathology, University Medical Center,Rostock |
610 | 2 | 4 | |a Institute of Pharmacology, University Medical Center,Rostock |
610 | 2 | 4 | |a Institute of Toxicology, University Medical Center Mainz |
610 | 2 | 4 | |a Oscar-Langendorff-Institute of Physiology, University Medical Center,Rostock |
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