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Artikel ; Online: Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA.

Kutz, Oliver / Drukewitz, Stephan / Krüger, Alexander / Aust, Daniela / William, Doreen / Oster, Sandra / Schröck, Evelin / Baretton, Gustavo / Link, Theresa / Wimberger, Pauline / Kuhlmann, Jan Dominik

Clinical chemistry and laboratory medicine

2024

Abstract: Objectives: We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer.: Methods: Targeted sequencing of 275 cancer-associated genes was performed in a primary tumor biopsy and in ctDNA of six longitudinal ... ...

Abstract	Objectives: We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer. Methods: Targeted sequencing of 275 cancer-associated genes was performed in a primary tumor biopsy and in ctDNA of six longitudinal plasma samples from 15 patients, using the Illumina platform. Results: While there was low overall concordance between the mutational spectrum of the primary tumor biopsies vs. ctDNA, TP53 variants were the most commonly shared somatic alterations. Up to three variant clusters were detected in each tumor biopsy, likely representing predominant clones of the primary tumor, most of them harbouring a TP53 variant. By tracing these clusters in ctDNA, we propose that liquid biopsy may allow to assess the contribution of ancestral clones of the tumor to relapsed abdominal masses, revealing two evolutionary patterns. In pattern#1, clusters detected in the primary tumor biopsy were likely relapse seeding clones, as they contributed a major share to ctDNA at relapse. In pattern#2, similar clusters were present in tumors and ctDNA; however, they were entirely cleared from liquid biopsy after chemotherapy and were undetectable at relapse. ctDNA private variants were present among both patterns, with some of them mirroring subclonal expansions after chemotherapy. Conclusions: We demonstrate that tracing the temporal heterogeneity of ctDNA, even below exome scale resolution, deciphers evolutionary trajectories in ovarian cancer. Furthermore, we describe two evolutionary patterns that may help to identify relapse seeding clones for targeted therapy.
Sprache	Englisch
Erscheinungsdatum	2024-04-05
Erscheinungsland	Germany
Dokumenttyp	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2023-1266
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Identification of novel snoRNA-based biomarkers for clear cell renal cell carcinoma from urine-derived extracellular vesicles.

Grützmann, Konrad / Salomo, Karsten / Krüger, Alexander / Lohse-Fischer, Andrea / Erdmann, Kati / Seifert, Michael / Baretton, Gustavo / Aust, Daniela / William, Doreen / Schröck, Evelin / Thomas, Christian / Füssel, Susanne

Biology direct

2024 Band 19, Heft 1, Seite(n) 38

Abstract: Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC with high rates of metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects ... ...

Abstract	Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC with high rates of metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects and tumor recurrence remain a challenge. As a result, ccRCC still have a high mortality rate. Early detection before metastasis has great potential to improve outcomes, but no suitable biomarker specific for ccRCC is available so far. Therefore, molecular biomarkers derived from body fluids have been investigated over the past decade. Among them, RNAs from urine-derived extracellular vesicles (EVs) are very promising. Methods: RNA was extracted from urine-derived EVs from a cohort of 78 subjects (54 ccRCC patients, 24 urolithiasis controls). RNA-seq was performed on the discovery cohort, a subset of the whole cohort (47 ccRCC, 16 urolithiasis). Reads were then mapped to the genome, and expression was quantified based on 100 nt long contiguous genomic regions. Cluster analysis and differential region expression analysis were performed with adjustment for age and gender. The candidate biomarkers were validated by qPCR in the entire cohort. Receiver operating characteristic, area under the curve and odds ratios were used to evaluate the diagnostic potential of the models. Results: An initial cluster analysis of RNA-seq expression data showed separation by the subjects' gender, but not by tumor status. Therefore, the following analyses were done, adjusting for gender and age. The regions differentially expressed between ccRCC and urolithiasis patients mainly overlapped with small nucleolar RNAs (snoRNAs). The differential expression of four snoRNAs (SNORD99, SNORD22, SNORD26, SNORA50C) was validated by quantitative PCR. Confounder-adjusted regression models were then used to classify the validation cohort into ccRCC and tumor-free subjects. Corresponding accuracies ranged from 0.654 to 0.744. Models combining multiple genes and the risk factors obesity and hypertension showed improved diagnostic performance with an accuracy of up to 0.811 for SNORD99 and SNORA50C (p = 0.0091). Conclusions: Our study uncovered four previously unrecognized snoRNA biomarkers from urine-derived EVs, advancing the search for a robust, easy-to-use ccRCC screening method.
Mesh-Begriff(e)	Humans ; Carcinoma, Renal Cell/urine ; Carcinoma, Renal Cell/genetics ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Biomarkers, Tumor/urine ; Biomarkers, Tumor/genetics ; Female ; Male ; Middle Aged ; Kidney Neoplasms/urine ; Kidney Neoplasms/genetics ; Aged ; RNA, Small Nucleolar/genetics ; Cohort Studies ; Adult
Chemische Substanzen	Biomarkers, Tumor ; RNA, Small Nucleolar
Sprache	Englisch
Erscheinungsdatum	2024-05-13
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2221028-3
ISSN	1745-6150 ; 1745-6150
ISSN (online)	1745-6150
ISSN	1745-6150
DOI	10.1186/s13062-024-00467-0
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model.

Clausing, Maximilian / William, Doreen / Preussler, Matthias / Biedermann, Julia / Grützmann, Konrad / Richter, Susan / Buchholz, Frank / Temme, Achim / Schröck, Evelin / Klink, Barbara

International journal of molecular sciences

2022 Band 23, Heft 10

Abstract: ... The ... ...

Abstract	The IDH1
Mesh-Begriff(e)	Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Cytokines/genetics ; Cytokines/metabolism ; Down-Regulation ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioma/genetics ; Glioma/metabolism ; Humans ; Isocitrate Dehydrogenase/genetics ; Isocitrate Dehydrogenase/metabolism ; NAD/metabolism ; NADP/metabolism ; Nicotinamide Phosphoribosyltransferase/genetics ; Nicotinamide Phosphoribosyltransferase/metabolism ; RNA Interference
Chemische Substanzen	Cytokines ; NAD (0U46U6E8UK) ; NADP (53-59-8) ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.) ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; nicotinamide phosphoribosyltransferase, human (EC 2.4.2.12)
Sprache	Englisch
Erscheinungsdatum	2022-05-21
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23105787
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The miR-183/96/182 cluster is upregulated in glioblastoma carrying EGFR amplification.

Schneider, Björn / William, Doreen / Lamp, Nora / Zimpfer, Annette / Henker, Christian / Classen, Carl Friedrich / Erbersdobler, Andreas

Molecular and cellular biochemistry

2022 Band 477, Heft 9, Seite(n) 2297–2307

Abstract: Glioblastoma (GBM) is one of the most frequent primary brain tumors. Limited therapeutic options and high recurrency rates lead to a dismal prognosis. One frequent, putative driver mutation is the genomic amplification of the oncogenic receptor tyrosine ... ...

Abstract	Glioblastoma (GBM) is one of the most frequent primary brain tumors. Limited therapeutic options and high recurrency rates lead to a dismal prognosis. One frequent, putative driver mutation is the genomic amplification of the oncogenic receptor tyrosine kinase EGFR. Often accompanied by variants like EGFRvIII, heterogenous expression and ligand independent signaling render this tumor subtype even more difficult to treat, as EGFR-directed therapeutics show only weak effects at best. So EGFR-amplified GBM is considered to have an even worse prognosis, and therefore, deeper understanding of molecular mechanisms and detection of potential targets for novel therapeutic strategies is urgently needed. In this study, we looked at the level of microRNAs (miRs), small non-coding RNAs frequently deregulated in cancer, both acting as oncogenes and tumor suppressors. Comparative analysis of GBM with and without EGFR amplification should give insight into the expression profiles of miRs, which are considered both as potential targets for directed therapies or as therapeutic reagents. Comparison of miR profiles of EGFR-amplified and EGFR-normal GBM revealed an upregulation of the miR-183/96/182 cluster, which is associated with oncogenic properties in several tumor entities. One prominent target of this miR cluster is FOXO1, a pro-apoptotic factor. By observing FOXO1 downregulation in EGFR-amplified tumors, we can see a significant correlation of EGFR amplification, miR-183/96/182 cluster upregulation, and repression of FOXO1. Although no significant difference in overall survival is shown, these data may contribute to the molecular understanding of this tumor subtype and offer potential targets for miR-based therapies.
Mesh-Begriff(e)	Brain Neoplasms/metabolism ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Glioblastoma/metabolism ; Humans ; MicroRNAs/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Signal Transduction
Chemische Substanzen	MIRN183 microRNA, human ; MicroRNAs ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Sprache	Englisch
Erscheinungsdatum	2022-04-29
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-022-04435-y
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Buch ; Online ; Dissertation / Habilitation: Etablierung und Analyse patientenindividueller Glioblastoma multiforme Modelle in vitro und in vivo

William, Doreen [Verfasser] / Classen, Carl Friedrich [Gutachter] / Schröder, Reinhard [Gutachter]

2018

Verfasserangabe	Doreen William ; Gutachter: Carl Friedrich Classen, Reinhard Schröder
Schlagwörter	Medizin, Gesundheit ; Medicine, Health
Thema/Rubrik (Code)	sg610
Sprache	Deutsch
Verlag	Universität Rostock
Erscheinungsort	Rostock
Dokumenttyp	Buch ; Online ; Dissertation / Habilitation
Datenquelle	Digitale Dissertationen im Internet

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Artikel ; Online: Treatment of Pheochromocytoma Cells with Recurrent Cycles of Hypoxia: A New Pseudohypoxic In Vitro Model.

Helm, Jana / Drukewitz, Stephan / Poser, Isabel / Richter, Susan / Friedemann, Markus / William, Doreen / Mohr, Hermine / Nölting, Svenja / Robledo, Mercedes / Bornstein, Stefan R / Eisenhofer, Graeme / Bechmann, Nicole

Cells

2022 Band 11, Heft 3

Abstract: Continuous activation of hypoxia pathways in pheochromocytomas and paragangliomas (PPGLs) is associated with higher disease aggressiveness, for which effective treatment strategies are still missing. Most of the commonly used in vitro models lack ... ...

Abstract	Continuous activation of hypoxia pathways in pheochromocytomas and paragangliomas (PPGLs) is associated with higher disease aggressiveness, for which effective treatment strategies are still missing. Most of the commonly used in vitro models lack characteristics of these pseudohypoxic tumors, including elevated expression of hypoxia-inducible factor (HIF) 2α. To address this shortcoming, we investigated whether recurrent hypoxia cycles lead to continuous activation of hypoxia pathways under normoxic conditions and whether this pseudohypoxia is associated with increased cellular aggressiveness. Rat pheochromocytoma cells (PC12) were incubated under hypoxia for 24 h every 3-4 days, up to 20 hypoxia-reoxygenation cycles, resulting in PC12 Z20 cells. PC12 Z20 control cells were obtained by synchronous cultivation under normoxia. RNA sequencing revealed upregulation of
Mesh-Begriff(e)	Adrenal Gland Neoplasms/pathology ; Adrenal Gland Neoplasms/therapy ; Animals ; Cell Hypoxia ; Cell Proliferation ; Disease Models, Animal ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Pheochromocytoma/pathology ; Pheochromocytoma/therapy ; Rats
Sprache	Englisch
Erscheinungsdatum	2022-02-05
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11030560
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids.

Naumann, Max / Czempiel, Tabea / Lößner, Anna Jana / Pape, Kristin / Beyreuther, Elke / Löck, Steffen / Drukewitz, Stephan / Hennig, Alexander / von Neubeck, Cläre / Klink, Barbara / Krause, Mechthild / William, Doreen / Stange, Daniel E / Bütof, Rebecca / Dietrich, Antje

Cancers

2022 Band 14, Heft 15

Abstract: To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT ...

Abstract	To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and proton irradiation and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and tumorigenicity was investigated in NMRI Foxn1
Sprache	Englisch
Erscheinungsdatum	2022-08-03
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14153781
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Temozolomide-induced increase of tumorigenicity can be diminished by targeting of mitochondria in in vitro models of patient individual glioblastoma.

William, Doreen / Walther, Madlin / Schneider, Björn / Linnebacher, Michael / Classen, Carl Friedrich

PloS one

2018 Band 13, Heft 1, Seite(n) e0191511

Abstract: Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential ... ...

Abstract	Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro. In this study, treatment of several primary GBM cell lines with clinically relevant doses of temozolomide increased their tumorigenicity as determined by colony formation assays in soft agar. Increased tumorigenicity is a known property of CSCs. Hence, therapy options that specifically target CSCs are under investigation. CSCs appear to be particularly dependent on mitochondria biogenesis which may represent a useful target for CSC elimination. Toxicity towards mitochondria is a known side effect of several antibiotics. Thus, addition of antibiotics like doxycycline may represent a useful tool to inhibit CSCs in GBM. Here, we show that combining temozolomide treatment of primary GBM cells with doxycycline could counteract the increase of tumorigenicity induced by temozolomide treatment.
Mesh-Begriff(e)	Anti-Bacterial Agents/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Agents, Alkylating/adverse effects ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; DNA Modification Methylases/genetics ; DNA Repair Enzymes/genetics ; Dacarbazine/administration & dosage ; Dacarbazine/adverse effects ; Dacarbazine/analogs & derivatives ; Doxycycline/administration & dosage ; Drug Resistance, Neoplasm ; Fucosyltransferases/metabolism ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Lewis X Antigen/metabolism ; Mitochondria/drug effects ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Nestin/metabolism ; Tumor Stem Cell Assay ; Tumor Suppressor Proteins/genetics
Chemische Substanzen	Anti-Bacterial Agents ; Antineoplastic Agents, Alkylating ; Biomarkers, Tumor ; Lewis X Antigen ; NES protein, human ; Nestin ; Tumor Suppressor Proteins ; Dacarbazine (7GR28W0FJI) ; DNA Modification Methylases (EC 2.1.1.-) ; MGMT protein, human (EC 2.1.1.63) ; FUT4 protein, human (EC 2.4.1.-) ; Fucosyltransferases (EC 2.4.1.-) ; DNA Repair Enzymes (EC 6.5.1.-) ; Doxycycline (N12000U13O) ; temozolomide (YF1K15M17Y)
Sprache	Englisch
Erscheinungsdatum	2018
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0191511
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Plasma extracellular vesicle messenger RNA profiling identifies prognostic EV signature for non-invasive risk stratification for survival prediction of patients with pancreatic ductal adenocarcinoma.

Journal of hematology & oncology

2023 Band 16, Heft 1, Seite(n) 7

Abstract: Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) is one of the most dismal of all cancers and the median survival of PDAC patients is only 6-8 months after diagnosis. While decades of research effort have been focused on early ... ...

Abstract	Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) is one of the most dismal of all cancers and the median survival of PDAC patients is only 6-8 months after diagnosis. While decades of research effort have been focused on early diagnosis and understanding of molecular mechanisms, few clinically useful markers have been universally applied. To improve the treatment and management of PDAC, it is equally relevant to identify prognostic factors for optimal therapeutic decision-making and patient survival. Compelling evidence have suggested the potential use of extracellular vesicles (EVs) as non-invasive biomarkers for PDAC. The aim of this study was thus to identify non-invasive plasma-based EV biomarkers for the prediction of PDAC patient survival after surgery. Methods: Plasma EVs were isolated from a total of 258 PDAC patients divided into three independent cohorts (discovery, training and validation). RNA sequencing was first employed to identify differentially-expressed EV mRNA candidates from the discovery cohort (n = 65) by DESeq2 tool. The candidates were tested in a training cohort (n = 91) by digital droplet polymerase chain reaction (ddPCR). Cox regression models and Kaplan-Meier analyses were used to build an EV signature which was subsequently validated on a multicenter cohort (n = 83) by ddPCR. Results: Transcriptomic profiling of plasma EVs revealed differentially-expressed mRNAs between long-term and short-term PDAC survivors, which led to 10 of the top-ranked candidate EV mRNAs being tested on an independent training cohort with ddPCR. The results of ddPCR enabled an establishment of a novel prognostic EV mRNA signature consisting of PPP1R12A, SCN7A and SGCD for risk stratification of PDAC patients. Based on the EV mRNA signature, PDAC patients with high risk displayed reduced overall survival (OS) rates compared to those with low risk in the training cohort (p = 0.014), which was successfully validated on another independent cohort (p = 0.024). Interestingly, the combination of our signature and tumour stage yielded a superior prognostic performance (p = 0.008) over the signature (p = 0.022) or tumour stage (p = 0.016) alone. It is noteworthy that the EV mRNA signature was demonstrated to be an independent unfavourable predictor for PDAC prognosis. Conclusion: This study provides a novel and non-invasive prognostic EV mRNA signature for risk stratification and survival prediction of PDAC patients.
Mesh-Begriff(e)	Humans ; Prognosis ; RNA, Messenger/genetics ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/diagnosis ; Carcinoma, Pancreatic Ductal/genetics ; Extracellular Vesicles/pathology ; Biomarkers, Tumor/genetics ; Risk Assessment ; Pancreatic Neoplasms
Chemische Substanzen	RNA, Messenger ; Biomarkers, Tumor
Sprache	Englisch
Erscheinungsdatum	2023-02-03
Erscheinungsland	England
Dokumenttyp	Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429631-4
ISSN	1756-8722 ; 1756-8722
ISSN (online)	1756-8722
ISSN	1756-8722
DOI	10.1186/s13045-023-01404-w
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Patient-Derived Organoids of Cholangiocarcinoma.

Maier, Christopher Fabian / Zhu, Lei / Nanduri, Lahiri Kanth / Kühn, Daniel / Kochall, Susan / Thepkaysone, May-Linn / William, Doreen / Grützmann, Konrad / Klink, Barbara / Betge, Johannes / Weitz, Jürgen / Rahbari, Nuh N / Reißfelder, Christoph / Schölch, Sebastian

International journal of molecular sciences

2021 Band 22, Heft 16

Abstract: Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient- ... ...

Abstract	Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient-derived organoid culture as well as a protocol for the transition of 3D organoid lines to 2D cell lines. Tissue samples of non-cancer bile duct and cholangiocarcinoma were obtained during surgical resection. Organoid lines were generated following a standardized protocol. 2D cell lines were generated from established organoid lines following a novel protocol. Subcutaneous and orthotopic patient-derived xenografts were generated from CC organoid lines, histologically examined, and treated using standard CC protocols. Therapeutic responses of organoids and 2D cell lines were examined using standard CC agents. Next-generation exome and RNA sequencing was performed on primary tumors and CC organoid lines. Patient-derived organoids closely recapitulated the original features of the primary tumors on multiple levels. Treatment experiments demonstrated that patient-derived organoids of cholangiocarcinoma and organoid-derived xenografts can be used for the evaluation of novel treatments and may therefore be used in personalized oncology approaches. In summary, this study establishes cholangiocarcinoma organoids and organoid-derived cell lines, thus expanding translational research resources of cholangiocarcinoma.
Mesh-Begriff(e)	Adult ; Aged ; Aged, 80 and over ; Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/pathology ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cholangiocarcinoma/drug therapy ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice ; Middle Aged ; Organ Culture Techniques/methods ; Organoids/cytology ; Organoids/drug effects ; Organoids/pathology ; Organoids/transplantation ; Precision Medicine ; Sequence Analysis, RNA ; Tumor Cells, Cultured ; Whole Exome Sequencing ; Xenograft Model Antitumor Assays
Chemische Substanzen	Antineoplastic Agents ; Biomarkers, Tumor
Sprache	Englisch
Erscheinungsdatum	2021-08-12
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22168675
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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