@article{ThongDoegeWeisseretal.2023,
  author    = {Thong, Melissa S. Y. and Doege, Daniela and Weißer, Linda and Koch-Gallenkamp, Lena and Jansen, Lina and Bertram, Heike and Eberle, Andrea and Holleczek, Bernd and Nennecke, Alice and Waldmann, Annika and Zeissig, Sylke Ruth and Brenner, Hermann and Arndt, Volker},
  title     = {Persisting deficits in health-related quality of life of colorectal cancer survivors 14-24 years post-diagnosis: a population-based study},
  series = {Current Oncology},
  volume    = {30},
  journal   = {Current Oncology},
  number    = {3},
  issn      = {1718-7729},
  doi       = {10.3390/curroncol30030257},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311084},
  pages     = {3373 -- 3390},
  year      = {2023},
  abstract  = {(1) Background: The health-related quality of life (HRQOL) of colorectal cancer (CRC) survivors >10 years post-diagnosis is understudied. We aimed to compare the HRQOL of CRC survivors 14-24 years post-diagnosis to that of age- and sex-matched non-cancer controls, stratified by demographic and clinical factors. (2) Methods: We used data from 506 long-term CRC survivors and 1489 controls recruited from German population-based multi-regional studies. HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire. We estimated differences in the HRQOL of CRC survivors and controls with multiple regression, adjusted for age at survey, sex, and education, where appropriate. (3) Results: CRC survivors reported poorer social functioning but better health status/QOL than controls. CRC survivors, in general, had higher levels of symptom burden, and in particular diarrhea and constipation, regardless of demographic or clinical factors. In stratified analyses, HRQOL differed by age, sex, cancer type, and having a permanent stoma. (4) Conclusions: Although CRC survivors may have a comparable health status/QOL to controls 14-24 years after diagnosis, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Healthcare providers should provide timely and adapted follow-up care to ameliorate potential long-term suffering.},
  language  = {en}
}
@article{KlementAbbasiSengerAdebahretal.2019,
  author    = {Klement, Rainer J. and Abbasi-Senger, N. and Adebahr, S. and Alheid, H. and Allgaeuer, M. and Becker, G. and Blanck, O. and Boda-Heggemann, J. and Brunner, T. and Duma, M. and Eble, M. J. and Ernst, I. and Gerum, S. and Habermehl, D. and Hass, P. and Henkenberens, C. and Hildebrandt, G. and Imhoff, D. and Kahl, H. and Klass, N. D. and Krempien, R. and Lewitzki, V. and Lohaus, F. and Ostheimer, C. and Papachristofilou, A. and Petersen, C. and Rieber, J. and Schneider, T. and Schrade, E. and Semrau, R. and Wachter, S. and Wittig, A. and Guckenberger, M. and Andratschke, N.},
  title     = {The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases},
  series = {BMC Cancer},
  volume    = {19},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-019-5362-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325877},
  year      = {2019},
  abstract  = {Background The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.},
  language  = {en}
}
@article{DiersBaumLehmannetal.2022,
  author    = {Diers, Johannes and Baum, Philip and Lehmann, Kai and Uttinger, Konstatin and Baumann, Nikolas and Pietryga, Sebastian and Hankir, Mohammed and Matthes, Niels and Lock, Johann F. and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study},
  series = {Cancer Medicine},
  volume    = {11},
  journal   = {Cancer Medicine},
  number    = {22},
  doi       = {10.1002/cam4.4784},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312858},
  pages     = {4256-4264},
  year      = {2022},
  abstract  = {Background Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in-hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications. Methods All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in-hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses. Results Three lakh twenty-eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In-hospital mortality following colorectal cancer surgery was 4.9\% but geriatric patients displayed a significantly higher postoperative in-hospital mortality of 10.6\%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3\% for SSI and 29.9\% mortality for patients with AI, both p < 0.001). Logistic regression analysis adjusting for confounders showed that geriatric patients had almost five-times higher odds for death after surgery than the baseline age group below 60 (OR 4.86; 95\%CI [4.45-5.53], p < 0.001). Conclusion Geriatric patients have higher mortality after colorectal cancer surgery. This may be partly due to higher frailty and disproportionately higher rates of failure to rescue arising from postoperative complications.},
  language  = {en}
}
@article{MuellerKoehlerHendricksetal.2021,
  author    = {M{\"u}ller, Sophie and K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and B{\"o}rner, Kevin and Diers, Johannes and Lock, Johan F. and Petritsch, Bernhard and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Brain metastases from colorectal cancer: a systematic review of the literature and meta-analysis to establish a guideline for daily treatment},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {4},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13040900},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228883},
  year      = {2021},
  abstract  = {Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words "brain", "metastas*", "tumor", "colorectal", "cancer", and "malignancy". In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1\% and 11.5\%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8\% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.},
  language  = {en}
}
@article{SchmidtDenkWiegering2020,
  author    = {Schmidt, Stefanie and Denk, Sarah and Wiegering, Armin},
  title     = {Targeting protein synthesis in colorectal cancer},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {5},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12051298},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206014},
  year      = {2020},
  abstract  = {Under physiological conditions, protein synthesis controls cell growth and survival and is strictly regulated. Deregulation of protein synthesis is a frequent event in cancer. The majority of mutations found in colorectal cancer (CRC), including alterations in the WNT pathway as well as activation of RAS/MAPK and PI3K/AKT and, subsequently, mTOR signaling, lead to deregulation of the translational machinery. Besides mutations in upstream signaling pathways, deregulation of global protein synthesis occurs through additional mechanisms including altered expression or activity of initiation and elongation factors (e.g., eIF4F, eIF2α/eIF2B, eEF2) as well as upregulation of components involved in ribosome biogenesis and factors that control the adaptation of translation in response to stress (e.g., GCN2). Therefore, influencing mechanisms that control mRNA translation may open a therapeutic window for CRC. Over the last decade, several potential therapeutic strategies targeting these alterations have been investigated and have shown promising results in cell lines, intestinal organoids, and mouse models. Despite these encouraging in vitro results, patients have not clinically benefited from those advances so far. In this review, we outline the mechanisms that lead to deregulated mRNA translation in CRC and highlight recent progress that has been made in developing therapeutic strategies that target these mechanisms for tumor therapy.},
  language  = {en}
}
@article{LehmannKlingerDiersetal.2021,
  author    = {Lehmann, Kai S. and Klinger, Carsten and Diers, Johannes and Buhr, Heinz-Johannes and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Safety of anastomoses in colorectal cancer surgery in octogenarians: a prospective cohort study with propensity score matching},
  series = {BJS Open},
  volume    = {5},
  journal   = {BJS Open},
  number    = {6},
  doi       = {10.1093/bjsopen/zrab102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265044},
  year      = {2021},
  abstract  = {Background Up to 20 per cent of all operations for patients with colorectal cancer (CRC) are performed in octogenarians. Anastomotic leakage is a leading cause of morbidity and death after resection for CRC. The aim of this study was to assess the rate of anastomosis creation, the risk of anastomotic leakage and death in surgery for left-sided CRC in elderly patients. Methods This prospective cohort study compared patients less than 80 and 80 or more years with left-sided CRC resection performed between 2013 and 2019. Data were provided from a risk-adjusted surgical quality-assessment system with 219 participating centres in Germany. Outcome measures were the rate of anastomoses, anastomotic leakages, death at 30 days and 2-year overall survival (OS). Propensity score matching was used to control for selection bias and compare subgroups of patients of less than 80 and 80 or more years. Results Out of 18 959 patients, some 3169 (16.7 per cent) were octogenarians. Octogenarians were less likely to receive anastomoses (82.0 versus 92.9 per cent, P < 0.001; odds ratio 0.50 (95 per cent c.i. 0.44 to 0.58), P < 0.001). The rate of anastomotic leakages did not differ between age groups (8.6 versus 9.7 per cent, P = 0.084), but 30-day mortality rate after leakage was significantly higher in octogenarians (15.8 versus 3.5 per cent, P < 0.001). Overall, anastomotic leakage was the strongest predictor for death (odds ratio 4.95 (95 per cent c.i. 3.66 to 6.66), P < 0.001). In the subgroup with no leakage, octogenarians had a lower 2-year OS rate than younger patients (71 versus 87 per cent, P < 0.001), and in the population with anastomotic leakage, the 2-year OS was 80 per cent in younger and 43 per cent in elderly patients (P < 0.001). After propensity score matching, older age remained predictive for not receiving an anastomosis (odds ratio 0.54 (95 per cent c.i. 0.46 to 0.63), P < 0.001) and for death (odds ratio 2.60 (95 per cent c.i. 1.78 to 3.84), P < 0.001), but not for the occurrence of leakages (odds ratio 0.94 (95 per cent c.i. 0.76 to 1.15), P = 0.524). Conclusion Anastomotic leakage is not more common in octogenarians, but an age of 80 years or older is an independent factor for not receiving an anastomosis in surgery for left-sided CRC. The mortality rate in the case of leakage in octogenarians was reported to exceed 15 per cent.},
  language  = {en}
}
@article{SchmidtHaywardCoelhoetal.2019,
  author    = {Schmidt, Thomas S. B. and Hayward, Matthew R. and Coelho, Luiis P. and Li, Simone S. and Costea, Paul I. and Voigt, Anita Y. and Wirbel, Jakob and Maistrenko, Oleksandr M. and Alves, Renato J. C. and Bergsten, Emma and de Beaufort, Carine and Sobhani, Iradj and Heintz-Buschart, Anna and Sunagawa, Shinichi and Zeller, Georg and Wilmes, Paul and Bork, Peer},
  title     = {Extensive transmission of microbes along the gastrointestinal tract},
  series = {eLife},
  volume    = {8},
  journal   = {eLife},
  doi       = {10.7554/eLife.42693},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228954},
  pages     = {e42693, 1-18},
  year      = {2019},
  abstract  = {The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.},
  subject      = {Barrier},
  language  = {en}
}
@article{MoenchGrimmigKannenetal.2016,
  author    = {Moench, Romana and Grimmig, Tanja and Kannen, Vinicius and Tripathi, Sudipta and Faber, Marc and Moll, Eva-Maria and Chandraker, Anil and Lissner, Reinhard and Germer, Christoph-Thomas and Waaga-Gasser, Ana Maria and Gasser, Martin},
  title     = {Exclusive inhibition of PI3K/Akt/mTOR signaling is not sufficient to prevent PDGF-mediated effects on glycolysis and proliferation in colorectal cancer},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {42},
  doi       = {10.18632/oncotarget.11899},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176910},
  pages     = {68749-68767},
  year      = {2016},
  abstract  = {Platelet-derived growth factor (PDGF) and signaling via its receptors plays a crucial role in tumor cell proliferation and thus may represent an attractive target besides VEGF/EGFR-based antibody therapies. In this study we analyzed the influence of PDGF in colorectal cancer. PDGF was expressed intensively in early and even more intensively in late stage primary CRCs. Like VEGF, PDGF enhanced human colon cancer proliferation, and increased oxidative glycolytic activity, and activated HIF1α and c-Myc in vitro. PDGF activated the PI3K/Akt/mTOR pathway while leaving MAPK signaling untouched. Further dissection showed that inhibition of Akt strongly impeded cancer cell growth while inhibition of PI3K did not. MAPK analysis suggested an inhibitory crosstalk between both pathways, thus explaining the different effects of the Akt and PI3K inhibitors on cancer cell proliferation. PDGF stimulates colon cancer cell proliferation, and prevents inhibitor induced apoptosis, resulting in tumor growth. Therefore inhibition of PDGF signaling seems to be a promising target in colorectal cancer therapy. However, due to the multifaceted nature of the intracellular PDGF signaling, careful intervention strategies are needed when looking into specific signaling pathways like PI3K/Akt/mTOR and MAPK.},
  language  = {en}
}
@phdthesis{Pfann2020,
  author    = {Pfann, Christina},
  title     = {Untersuchungen zu neuen therapeutischen Ans{\"a}tzen zur Beeinflussung der MYC-Expression im kolorektalen Karzinom},
  doi       = {10.25972/OPUS-21668},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216687},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Eine ver{\"a}nderte Expression des Transkriptionsfaktors MYC wird als entscheidender Faktor f{\"u}r Tumorentstehung und -progress im kolorektalen Karzinom gesehen. Somit ist die Hemmung dessen Expression und Funktion ein zentraler Ansatz bei der zielgerichteten Tumortherapie. Als geeignete Strategie, sowohl die Halbwertszeit als auch die Translation von MYC zu verringern, erschien eine duale PI3K-/mTOR-Hemmung durch den small molecule-Inhibitor BEZ235. Gegenteilig ist jedoch unter Behandlung mit BEZ235 eine verst{\"a}rkte MYC-Expression in verschiedenen Kolonkarzinom-Zelllinien zu beobachten. Neben verst{\"a}rkter Transkription, konnte eine verst{\"a}rkte IRES-abh{\"a}ngige Translation von MYC nach Hemmung der mTOR-/5´Cap-abh{\"a}ngigen Translation durch BEZ235, als Ursache der MYC-Induktion nachgewiesen werden. Es konnte gezeigt werden, dass die Induktion von MYC nach PI3K-/mTOR-Hemmung durch eine kompensatorische Aktivierung des MAPK-Signalwegs in Folge einer FOXO-abh{\"a}ngigen Induktion von Rezeptortyrosinkinasen, stattfindet. Eine m{\"o}gliche Strategie, diese Feedback-Mechanismen zu umgehen, ist die direkte Hemmung der Translationsinitiation. Hierf{\"u}r wurden Rocaglamid und dessen Derivat Silvestrol als small molecule-Inhibitoren der eIF4A-Helikase verwendet. Im Gegensatz zur PI3K/mTOR-Hemmung, ist durch eIF4A-Inhibition eine Reduktion der MYC-Proteinexpression in verschiedenen Kolonkarzinom-Zelllinien zu erreichen - ohne einhergehende MAPK-Aktivierung. Anhand der Ergebnisse kann postuliert werden, dass Silvestrol das Potential besitzt, sowohl die Cap-/eIF4F-abh{\"a}ngie als auch die somit eIF4A-abh{\"a}ngige IRES-vermittelte Translation von MYC zu hemmen. Weiterhin kann eine proliferationshemmende Wirkung durch Silvestrol auf Kolonkarzinom-Zellen in vitro, via Zellzyklusarrest und Induktion von Apoptose, gezeigt werden. Dies stellt die Voraussetzung f{\"u}r eine potentielle Eignung als tumorhemmender Wirkstoff in der Therapie des kolorektalen Karzinoms dar.},
  language  = {de}
}
@article{BaurNietzerKunzetal.2020,
  author    = {Baur, Florentin and Nietzer, Sarah L. and Kunz, Meik and Saal, Fabian and Jeromin, Julian and Matschos, Stephanie and Linnebacher, Michael and Walles, Heike and Dandekar, Thomas and Dandekar, Gudrun},
  title     = {Connecting cancer pathways to tumor engines: a stratification tool for colorectal cancer combining human in vitro tissue models with boolean in silico models},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {1},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12010028},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193798},
  pages     = {28},
  year      = {2020},
  abstract  = {To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.},
  language  = {en}
}
@phdthesis{Baur2019,
  author    = {Baur, Florentin Philipp},
  title     = {Establishment of a 3D tumour model and targeted therapy of BRAF-mutant colorectal cancer},
  doi       = {10.25972/OPUS-17412},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174129},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Cancer remains after cardiovascular diseases the leading cause of death worldwide and an estimated 8.2 million people died of it in 2012. By 2030, 13 million cancer deaths are expected due to the growth and ageing of the population. Hereof, colorectal cancer (CRC) is the third most common cancer in men and the second in women with a wide geographical variation across the world. Usually, CRC begins as a non-cancerous growth leading to an adenomatous polyp, or adenoma, arising from glandular cells. Since research has brought about better understanding of the mechanisms of cancer development, novel treatments such as targeted therapy have emerged in the past decades. Despite that, up to 95\% of anticancer drugs tested in clinical phase I trials do not attain a market authorisation and hence these high attrition rates remain a key challenge for the pharmaceutical industry, making drug development processes enormously costly and inefficient. Therefore, new preclinical in vitro models which can predict drug responses in vivo more precisely are urgently needed. Tissue engineering not only provides the possibility of creating artificial three-dimensional (3D) in vitro tissues, such as functional organs, but also enables the investigation of drug responses in pathological tissue models, that is, in 3D cancer models which are superior to conventional two-dimensional (2D) cell cultures on petri dishes and can overcome the limitations of animal models, thereby reducing the need for preclinical in vivo models. In this thesis, novel 3D CRC models on the basis of a decellularised intestinal matrix were established. In the first part, it could be shown that the cell line SW480 exhibited different characteristics when grown in a 3D environment from those in conventional 2D culture. While the cells showed a mesenchymal phenotype in 2D culture, they displayed a more pronounced epithelial character in the 3D model. By adding stromal cells (fibroblasts), the cancer cells changed their growth pattern and built tumour-like structures together with the fibroblasts, thereby remodelling the natural mucosal structures of the scaffold. Additionally, the established 3D tumour model was used as a test system for treatment with standard chemotherapeutic 5-fluorouracil (5-FU). The second part of the thesis focused on the establishment of a 3D in vitro test system for targeted therapy. The US Food and Drug Administration has already approved of a number of drugs for targeted therapy of specific types of cancer. For instance, the small molecule vemurafenib (PLX4032, Zelboraf™) which demonstrated impressive response rates of 50-80\% in melanoma patients with a mutation of the rapidly accelerated fibrosarcoma oncogene type B (BRAF) kinase which belongs to the mitogen active protein kinase (MAPK) signalling pathway. However, only 5\% of CRC patients harbouring the same BRAF mutation respond to treatment with vemurafenib. An explanation for this unresponsiveness could be a feedback activation of the upstream EGFR, reactivating the MAPK pathway which sustains a proliferative signalling. To test this hypothesis, the two early passage cell lines HROC24 and HROC87, both presenting the mutation BRAF V600E but differing in other mutations, were used and their drug response to vemurafenib and/or gefitinib was assessed in conventional 2D cell culture and compared to the more advanced 3D model. Under 3D culture conditions, both cell lines showed a reduction of the proliferation rate only in the combination therapy approach. Furthermore, no significant differences between the various treatment approaches and the untreated control regarding apoptosis rate and viability for both cell lines could be found in the 3D tumour model which conferred an enhanced chemoresistance to the cancer cells. Because of the observed unresponsiveness to BRAF inhibition by vemurafenib as can be seen in the clinic for patients with BRAF mutations in CRC, the cell line HROC87 was used for further xenografting experiments and analysis of activation changes in the MAPK signalling pathway. It could be shown that the cells presented a reactivation of Akt in the 3D model when treated with both inhibitors, suggesting an escape mechanism for apoptosis which was not present in cells cultured under conventional 2D conditions. Moreover, the cells exhibited an activation of the hepatocyte growth factor receptor (HGFR, c-Met) in 2D and 3D culture, but this was not detectable in the xenograft model. This shows the limitations of in vivo models. The results suggest another feedback activation loop than that to the EGFR which might not primarily be involved in the resistance mechanism. This reflects the before mentioned high attrition rates in the preclinical drug testing.},
  subject      = {Dickdarmtumor},
  language  = {en}
}
@article{WeidnerRousseauPlauthetal.2016,
  author    = {Weidner, Christopher and Rousseau, Morten and Plauth, Annabell and Wowro, Sylvia J. and Fischer, Cornelius and Abdel-Aziz, Heba and Sauer, Sascha},
  title     = {Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species and Inhibits Colon Cancer},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0152398},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167044},
  pages     = {e0152398},
  year      = {2016},
  abstract  = {Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC\(_{50}\)) of 6 and 9 μg/ml, respectively, and further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M phase cell cycle arrest including reduced expression of various regulatory marker proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular formation of reactive oxygen species (ROS). Consistent with predictions derived from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4 weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor xenograft model. Taken together, Iberis amara extracts could become useful alternatives for preventing and treating the progression of colon cancer.},
  language  = {en}
}
@article{VogtmannHuaZelleretal.2016,
  author    = {Vogtmann, Emily and Hua, Xing and Zeller, Georg and Sunagawa, Shinichi and Voigt, Anita Y. and Hercog, Rajna and Goedert, James J. and Shi, Jianxin and Bork, Peer and Sinha, Rashmi},
  title     = {Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0155362},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166904},
  pages     = {e0155362},
  year      = {2016},
  abstract  = {Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39\% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect associations that are reproducible and significant after correction for multiple testing.},
  language  = {en}
}
@article{HefnerBerberichLanversetal.2017,
  author    = {Hefner, Jochen and Berberich, Sara and Lanvers, Elena and Sanning, Maria and Steimer, Ann-Kathrin and Kunzmann, Volker},
  title     = {New insights into frequency and contents of fear of cancer progression/recurrence (FOP/FCR) in outpatients with colorectal carcinoma (CRC) receiving oral capecitabine: a pilot study at a comprehensive cancer center},
  series = {Patient Preference and Adherence},
  volume    = {11},
  journal   = {Patient Preference and Adherence},
  doi       = {10.2147/PPA.S142784},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158476},
  pages     = {1907-1914},
  year      = {2017},
  abstract  = {Background: Fear of cancer progression/recurrence (FOP/FCR) is considered one of the most prevalent sources of distress in cancer survivors and associated with lower quality of life and functional impairment. Detailed measures of FOP/FCR are needed because little is known about the knowledge of FOP/FCR, its associations with the patient-doctor relationship, and the rate of adequate therapy. Colorectal cancer (CRC) is one of the most prevalent cancer entities, and oral capecitabine is widely prescribed as treatment. Therefore, we initiated a pilot study to expand the literature on FOP/FCR in CRC outpatients receiving capecitabine and to generate hypotheses for future investigations. Methods: This study included 58 patients treated at a comprehensive cancer center. FOP/FCR was assessed with the Fear of Progression Questionnaire (FOP-Q-SF). Satisfaction with the relationships with doctors was assessed with the Patient-Doctor Relationship Questionnaire-9 (PRDQ-9). Levels of side effects were rated by the patients on a visual analog scale. Clinical data were extracted from the charts. Results: A total of 19 out of 58 patients (36\%) suffered from FOP/FCR according to our assessment. Levels of FOP/FCR seemed to be mostly moderate to high. Only four out of the 19 distressed patients (21\%) were treated accordingly. Typical side effects of oncological treatment were associated with higher FOP/FCR. Satisfaction with doctor-patient relationships was not associated with FOP/FCR. Regarding single items of FOP/FCR, three out of the five most prevalent fears were associated with close relatives. Discussion: FOP/FCR occurred frequently in more than one in three patients, but was mostly untreated in this sample of consecutive outpatients with CRC receiving oral capecitabine. In detail, most fears were related to family and friends. In addition to an unmet need of patients, our data indicate sources of distress not considered thus far. If replicated in larger studies, results may help to inform intervention development and improve patient care.},
  language  = {en}
}
@article{WiegeringRiegelWagneretal.2017,
  author    = {Wiegering, Armin and Riegel, Johannes and Wagner, Johanna and Kunzmann, Volker and Baur, Johannes and Walles, Thorsten and Dietz, Ulrich and Loeb, Stefan and Germer, Christoph-Thomas and Steger, Ulrich and Klein, Ingo},
  title     = {The impact of pulmonary metastasectomy in patients with previously resected colorectal cancer liver metastases},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0173933},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158036},
  pages     = {e0173933},
  year      = {2017},
  abstract  = {Background 40-50\% of patients with colorectal cancer (CRC) will develop liver metastases (CRLM) during the course of the disease. One third of these patients will additionally develop pulmonary metastases. Methods 137 consecutive patients with CRLM, were analyzed regarding survival data, clinical, histological data and treatment. Results were stratified according to the occurrence of pulmonary metastases and metastases resection. Results 39\% of all patients with liver resection due to CRLM developed additional lung metastases. 44\% of these patients underwent subsequent pulmonary resection. Patients undergoing pulmonary metastasectomy showed a significantly better five-year survival compared to patients not qualified for curative resection (5-year survival 71.2\% vs. 28.0\%; p = 0.001). Interestingly, the 5-year survival of these patients was even superior to all patients with CRLM, who did not develop pulmonary metastases (77.5\% vs. 63.5\%; p = 0.015). Patients, whose pulmonary metastases were not resected, were more likely to redevelop liver metastases (50.0\% vs 78.6\%; p = 0.034). However, the rate of distant metastases did not differ between both groups (54.5 vs.53.6; p = 0.945). Conclusion The occurrence of colorectal lung metastases after curative liver resection does not impact patient survival if pulmonary metastasectomy is feasible. Those patients clearly benefit from repeated resections of the liver and the lung metastases.},
  language  = {en}
}
@article{BeckerOelschlaegerWullaertetal.2013,
  author    = {Becker, Svetlana and Oelschlaeger, Tobias A. and Wullaert, Andy and Pasparakis, Manolis and Wehkamp, Jan and Stange, Eduard F. and Gersemann, Michael},
  title     = {Bacteria Regulate Intestinal Epithelial Cell Differentiation Factors Both In Vitro and In Vivo},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0055620},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131168},
  pages     = {e55620},
  year      = {2013},
  abstract  = {Background: The human colon harbours a plethora of bacteria known to broadly impact on mucosal metabolism and function and thought to be involved in inflammatory bowel disease pathogenesis and colon cancer development. In this report, we investigated the effect of colonic bacteria on epithelial cell differentiation factors in vitro and in vivo. As key transcription factors we focused on Hes1, known to direct towards an absorptive cell fate, Hath1 and KLF4, which govern goblet cell. Methods: Expression of the transcription factors Hes1, Hath1 and KLF4, the mucins Muc1 and Muc2 and the defensin HBD2 were measured by real-time PCR in LS174T cells following incubation with several heat-inactivated E. coli strains, including the probiotic E. coli Nissle 1917+/- flagellin, Lactobacilli and Bifidobacteria. For protein detection Western blot experiments and chamber-slide immunostaining were performed. Finally, mRNA and protein expression of these factors was evaluated in the colon of germfree vs. specific pathogen free vs. conventionalized mice and colonic goblet cells were counted. Results: Expression of Hes1 and Hath1, and to a minor degree also of KLF4, was reduced by E. coli K-12 and E. coli Nissle 1917. In contrast, Muc1 and HBD2 expression were significantly enhanced, independent of the Notch signalling pathway. Probiotic E. coli Nissle 1917 regulated Hes1, Hath1, Muc1 and HBD2 through flagellin. In vivo experiments confirmed the observed in vitro effects of bacteria by a diminished colonic expression of Hath1 and KLF4 in specific pathogen free and conventionalized mice as compared to germ free mice whereas the number of goblet cells was unchanged in these mice. Conclusions: Intestinal bacteria influence the intestinal epithelial differentiation factors Hes1, Hath1 and KLF4, as well as Muc1 and HBD2, in vitro and in vivo. The induction of Muc1 and HBD2 seems to be triggered directly by bacteria and not by Notch.},
  language  = {en}
}
@article{PeterBultinckMyantetal.2014,
  author    = {Peter, Stefanie and Bultinck, Jennyfer and Myant, Kevin and Jaenicke, Laura A. and Walz, Susanne and M{\"u}ller, Judith and Gmachl, Michael and Treu, Matthias and Boehmelt, Guido and Ade, Casten P. and Schmitz, Werner and Wiegering, Armin and Otto, Christoph and Popov, Nikita and Sansom, Owen and Kraut, Norbert and Eilers, Martin},
  title     = {H Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase},
  series = {EMBO Molecular Medicine},
  volume    = {6},
  journal   = {EMBO Molecular Medicine},
  number    = {12},
  issn      = {1757-4684},
  doi       = {10.15252/emmm.201403927},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118132},
  pages     = {1525-41},
  year      = {2014},
  abstract  = {Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF-BP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high-throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells.},
  language  = {en}
}
@article{WiegeringPfannUtheetal.2013,
  author    = {Wiegering, Armin and Pfann, Christina and Uthe, Friedrich Wilhelm and Otto, Christoph and Rycak, Lukas and M{\"a}der, Uwe and Gasser, Martin and Waaga-Gasser, Anna-Maria and Eilers, Martin and Germer, Christoph-Thomas},
  title     = {CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075292},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97252},
  year      = {2013},
  abstract  = {The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.},
  language  = {en}
}
@phdthesis{Riehle2011,
  author    = {Riehle, Verena},
  title     = {Regulation von Hepatoma-derived Growth Factor durch Zytokine},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72607},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Das Ziel dieser Arbeit war die Darstellung der Einfl{\"u}sse verschiedener Interleukine auf die HDGF-Expression in verschiedenen Kolonzelllinien. HDGF stellt einen Wachstumsfaktor dar, der nicht nur physiologisch bei der Entwicklung einiger Gewebe wie der Niere, der Leber und des Darms von Be-deutung ist, sondern auch eine wichtige Rolle in der Karzinogenese verschie-dener Tumoren spielt. Hierzu z{\"a}hlen unter anderem das hepatozellul{\"a}re Karzi-nom, das NSCLC und das Melanom. Von besonderer Relevanz ist seine Rolle in der Pathogenese des kolorektalen Karzinoms. Die verwendeten Interleukine (1beta, 4, 5, 8 und 13) zeigen sowohl inhibierende als auch f{\"o}rdernde Eigenschaften in Bezug auf die Karzinogenese von kolorektalen Tumoren. Dies steht im Einklang mit fr{\"u}heren Resultaten der Literatur. Die vier verschiedenen Zelllinien, eine Adenomzelllinie, zwei Adenokarzinomzelllinien sowie eine Zelllinie aus Lymphknotenmetastasenzellen wurden mit den verschiedenen Interleukinen inkubiert und mittels REAL TIME-RT-PCR analysiert. Die Ergebnisdarstellung in Blockdiagrammen zeigt semiquantitativ die relative HDGF-Expression. So lassen sich Aussagen {\"u}ber Anstieg oder Abfall der Expression durch den Einfluss der verschiedenen Interleukine machen. Die hier gezeigten Ergebnisse lassen, wie auch schon teilweise in der Literatur beschrieben, f{\"u}r alle Interleukine außer f{\"u}r IL 1beta, sowohl hemmende als auch tumorunterst{\"u}tzende Effekte beobachten. Interleukin 1beta zeigt in Kongruenz der vorbeschriebenen Studien, im Gegensatz zu den anderen Zytokinen, in allen Zelllinien tumorf{\"o}rdernde Eigenschaften. F{\"u}r IL 4 ist zun{\"a}chst in den Adenomzellen ein antitumor{\"o}ser Effekt zu erkennen, dieser kehrt sich in der Metastasenzelllinie in eine f{\"o}rderndene Wirkung um. In den Adenokarzinomzelllinien sind weder eindeutige suppressive noch unterst{\"u}tzende Wirkungen zu verzeichnen. {\"U}ber einen Zusammenhang zwischen dem Grad der malignen Transformation und unterschiedlichem Ansprechen auf IL 4 l{\"a}sst sich jedoch bisher nur spekulieren. F{\"u}r IL 5 ist ein {\"a}hnliches Verhalten zu beobachten. Eine anf{\"a}ngliche inhibitorische Wirkung auf die HDGF-Expression in den Adenomzellen sowie Adenokarzinomzellen kehrt sich in der Metastasenzelllinie in den gegenteiligen Effekt um. Auch hier l{\"a}sst sich eine Umkehr der ausgel{\"o}sten Effekte mit fortschreitender maligner Transformation vermuten. IL 8 zeigt kongruente Effekte zu IL 4 und IL 5, jedoch lassen sich f{\"u}r IL 8 in der Literatur bisher nur tumorunterst{\"u}tzende Wirkungen finden. Hier l{\"a}sst sich in den Adenomzellen eine suppressive Wirkung verzeichnen, wohingegen in den beiden Adenokarzinomzelllinien f{\"o}rdernde Effekte beobachtet werden. In der Metastasenzelllinie lassen sich jedoch weder positive noch negative Auswirkungen feststellen. Des Weiteren spiegeln auch die Ergebnisse des Einflusses von IL 13 die Vielgestaltigkeit der Wirkweisen dieses Interleukins dar, mit tumorhemmenden Effekten in den Adenom- sowie Metastasenzellen und f{\"o}rdernder Wirkung in den HT29-Zellen. {\"U}ber die genauen Mechanismen, inwiefern ein Interleukin die Expression von HDGF hochreguliert oder supprimiert, kann zum momentanen Zeitpunkt nur spekuliert werden. Es kann jedoch vermutet werden, dass ein gewisser Zu-sammenhang zwischen dem Grad der malignen Transformation und der Wirk-weise der Interleukine existiert. Entscheidend sind hier sicherlich klonal erwor-bene Alterationen einzelner Signalkaskaden. Festzuhalten ist zum einen, dass bis auf IL 1beta f{\"u}r alle Zytokine der Einfluss auf HDGF vom jeweiligen Zellsystem abh{\"a}ngt. Diese Ergebnisse machen eine Schl{\"u}sselrolle von HDGF eher unwahrscheinlich, vielmehr scheint seine Regulation hier in teilweise komplexe Regulationsmechanismen mit eingebunden zu sein. Dass diese Alterationen m{\"o}glicherweise auch im Rahmen der Karzinogenese bzw. der Akquise der Metastasierungsf{\"a}higkeit entstehen k{\"o}nnten, zeigen die teilweise bestehenden Unterschiede zwischen der verwendeten Adenomzelllinie und den Karzinomzelllinien respektive zwischen Karzinom- und Metastasenzelllinie. Die beschriebenen Ergebnisse geben einen Anhaltspunkt, in welche Richtung die einzelnen Interleukine wirken, zumindest in wie weit hier ein Einfluß auf die Transkription von HDGF als Surrogatmarker der Mitogenese erfolgt. Um die Komplexit{\"a}t und Vielfalt der Effekte von Interleukinen in Bezug zu Tumorstadium, Invasivit{\"a}t sowie Metastasierungsf{\"a}higkeit in Einklang zu bringen, bedarf es jedoch weiterf{\"u}hrender Studien. Es lies sich zeigen, dass die angewendeten Interleukine generell Einfluss auf die Expressionsh{\"o}he von HDGF in verschiedenen Kolonzelllinien haben und als exogene Faktoren in die Regulation eingreifen k{\"o}nnen. Dies k{\"o}nnte ein weiterer Ansatz zur Etablierung immunmodulatorischer Therapieoptionen in soliden Neoplasien in der Zukunft sein.},
  subject      = {Hepatoma-derived Growth Factor},
  language  = {de}
}
@phdthesis{Eller2011,
  author    = {Eller, David Michael},
  title     = {Einfluss und Wirkung des HDAC-Inhibitors LBH589 auf Proliferation und Differenzierung der kolorektalen Karzinomzelllinien SW480 und SW620},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70659},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Zahlreiche Studien schreiben Histondeacetylase-Inhibitoren einen Anti-Tumor-Effekt auf verschiedene h{\"a}matologische und solide Tumoren durch Apoptoseinduktion, vermehrte Zelldifferenzierung und verminderte Zellproliferation zu. Als Mechanismus wird eine Einflussnahme auf die Genexpression durch Modulation von Histondeacetylasen und deren Auswirkung auf den Acetylierungsstatus von Histonen und Nicht-Histon-Proteinen angenommen. Ziel dieser Arbeit war es, die Auswirkungen des Histondeacetylase-Inhibitors LBH589 auf Proliferation und Differenzierung von Kolonkarzinomzellen und dessen Metastasenzellen in Zellkulturexperimenten zu untersuchen. Die Untersuchungen wurden an Zellen der Zellkulturlinien SW480 (kolorektales Karzinom) und SW620 (Metastase des kolorektalen Karzinoms) durchgef{\"u}hrt. F{\"u}r die Zellproliferation wurden die Zellen nach entsprechender Vorbehandlung in einer Neubauer-Zellz{\"a}hlkammer ausgez{\"a}hlt. Zur Feststellung des Verlaufs der Zelldifferenzierung diente die Bestimmung der Intestinalen Alkalischen Phosphatase als Marker. Unter LBH589-Inkubation kam es zu einer Hemmung der Zellproliferation sowohl bei SW480-Zellen als auch bei SW620-Zellen. Allerdings ergab sich kein signifikanter Unterschied bei der Auswertung der Kontrolll{\"o}sungen mit jeweils {\"a}quimolaren Mengen DMSO. Daher konnte dem HDAC-Inhibitor LBH589 im Rahmen dieser Arbeit kein sicherer Effekt auf die Inhibition der Zellproliferation zugeschrieben werden. LBH589 hatte keinen nachweisbaren relevanten Einfluss auf die Differenzierung von Zellen der beiden Zelllinien. Allenfalls konnte ein leicht hemmender Einfluss auf die Zelldifferenzierung gezeigt werden, der jedoch nicht signifikant ausfiel. Weitere Untersuchungen sind anzustreben, um den Verlauf der Zellproliferation und weiterer Differenzierungsmarker unter dem Einfluss von LBH589 sowie {\"a}quimolaren Mengen DMSO detaillierter zu charakterisieren. Zuk{\"u}nftige Arbeiten zu Histondeacetylase-Inhibitoren und deren Effekt auf Zellen des kolorektalen Karzinoms, sowie Histondeacetylase-Inhibitoren in der Kombinationstherapie von kolorektalen Tumoren sind sicher sinnvoll.},
  subject      = {Dickdarmkrebs},
  language  = {de}
}