Ramadori, Giuliano

[["dc.bibliographiccitation.firstpage","327"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","European journal of gastroenterology & hepatology"],["dc.bibliographiccitation.lastpage","334"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Haller, Florian"],["dc.contributor.author","Dudas, Joszef"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Gunawan, Bastian"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Langer, Claus"],["dc.contributor.author","Füzesi, Laszlo"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2011-05-13T14:17:12Z"],["dc.date.accessioned","2021-10-27T13:10:51Z"],["dc.date.available","2011-05-13T14:17:12Z"],["dc.date.available","2021-10-27T13:10:51Z"],["dc.date.issued","2008"],["dc.description.abstract","INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are regarded as having relatively uniform histology, although their potential for malignant behavior varies. Despite a strong promoting role of tumor-infiltrating innate immune cells in neoplastic progression, the presence of immune cells in GISTs has not yet been studied. METHODS: A total of 47 untreated, c-kit-positive primary GISTs were immunohistochemically analyzed to distinguish histiocytic and dendritic cells (DCs) (KIM-1P, fascin, and CD68) from cells of lymphoplasmacellular origin (CD3, CD20, and CD56). Furthermore, the gene expression of proinflammatory cytokines was characterized by real-time, reverse transcription-PCR analysis of total RNA extracted from frozen tissue samples. RESULTS: KIM-1P+ cells were the dominant immune cells (851+/-295 cells/mm2) and were scattered among the tumor cells. Most of the KIM-1P+ cells showed cellular projections characteristic of DCs. Fascin positivity identified a subgroup of DCs. In comparison to KIM-1P+ cells, there were significantly fewer CD68+ macrophages (196+/-217 cells/mm2). CD3+ T cells were the dominant lymphocytes (201+/-331 cells/mm2), whereas B cells (60+/-126 cells/mm2) were few. On transcriptional level, a concomitant gene expression of cytokines for the classical acute phase cytokines TNF-alpha and IL-6 was missing, thus supporting the rather innate status of immune cells. CONCLUSION: GISTs contain, beside T lymphocytes, a high number of monocyte-derived cells, which we suggest are, at least in part, immature DCs. Together with the lack of gene expression of inflammatory cytokines in tumor tissue our results point to a possible 'symbiotic relationship' between the tumor and the local immune cells."],["dc.identifier.doi","10.1097/MEG.0b013e3282f3a403"],["dc.identifier.isi","000257628200013"],["dc.identifier.pmid","18334877"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6331"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91538"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0954-691X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Adult"],["dc.subject.mesh","Aged"],["dc.subject.mesh","Aged, 80 and over"],["dc.subject.mesh","Antigens, CD"],["dc.subject.mesh","Antigens, CD3"],["dc.subject.mesh","Antigens, Differentiation, Myelomonocytic"],["dc.subject.mesh","Cell Communication"],["dc.subject.mesh","Cell Transformation, Neoplastic"],["dc.subject.mesh","Cytokines"],["dc.subject.mesh","Dendritic Cells"],["dc.subject.mesh","Female"],["dc.subject.mesh","Gastrointestinal Stromal Tumors"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Male"],["dc.subject.mesh","Middle Aged"],["dc.subject.mesh","Phenotype"],["dc.subject.mesh","Proto-Oncogene Proteins c-kit"],["dc.subject.mesh","Stromal Cells"],["dc.title","Immune cells in primary gastrointestinal stromal tumors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","218"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Huenerbein, Diana"],["dc.contributor.author","Mansuroglu, Tuemen"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Schwoerer, Harald"],["dc.contributor.author","Fuezesi, Laszlo"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:28:01Z"],["dc.date.available","2018-11-07T08:28:01Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease. Methods: 20 patients [14 men, 6 women, median age 67 (39-82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy. Results: Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3-71) months. No complications due to the primary were observed. Conclusion: This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC."],["dc.identifier.doi","10.1186/1471-2407-9-218"],["dc.identifier.isi","000268497600002"],["dc.identifier.pmid","19570230"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5800"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16327"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2407"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1023"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Medical Oncology"],["dc.bibliographiccitation.lastpage","1026"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Schaefer, Inga-Marie"],["dc.contributor.author","Schueler, Philipp"],["dc.contributor.author","Enders, Christina"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Fuezesi, Laszlo"],["dc.date.accessioned","2018-11-07T08:49:35Z"],["dc.date.available","2018-11-07T08:49:35Z"],["dc.date.issued","2011"],["dc.description.abstract","Adenocarcinoma of the small intestine arising from heterotopic gastric mucosa is extremely rare. In this report, we present the case of a 68-year-old woman who complained of abdominal pain, weight loss and subileus. Gross examination of resected small bowel revealed multiple flat polypous lesions with cysts in the ileal submucosa, one of which containing an ulcerated, stenosing tumour. On microscopic examination, an adenocarcinoma of the ileum arising from multifocal gastric heterotopia with secondary gastritis cystica profunda was diagnosed. Comparative genomic hybridization of the adenocarcinoma revealed chromosomal gains at 1q, 3q, 5p, 8q, 11p, 12p, 13q and losses at Xp, 4q, 8p, 10p, 14q, 17p, 20p, compatible with a high degree of genomic instability."],["dc.identifier.doi","10.1007/s12032-010-9604-2"],["dc.identifier.isi","000297256400017"],["dc.identifier.pmid","20577832"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7381"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21497"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1357-0560"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","High chromosomal instability in adenocarcinoma of the ileum arising from multifocal gastric heterotopia with gastritis cystica profunda"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","505"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Case reports in oncology"],["dc.bibliographiccitation.lastpage","511"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Schaefer, Inga-Marie"],["dc.contributor.author","Schwoerer, Harald"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2019-07-09T11:40:50Z"],["dc.date.available","2019-07-09T11:40:50Z"],["dc.date.issued","2011-09-01"],["dc.description.abstract","Imatinib mesylate, as treatment for gastrointestinal stromal tumors (GIST), has dramatically changed the prognosis for survival - not only because it is efficacious, but also because it attracted attention to this malignant disease. GIST is now a well-known disease entity and a paradigm for targeted therapies in malignant diseases. A now 74-year-old patient presented with recurrence of a primary duodenal GIST (initial diagnosis and primary resection in 1998; diameter 10 cm, KIT exon 11 mutation, PM V559D) and liver metastasis after a second surgical resection was performed in 2000. Conventional chemotherapy with adriamycin and ifosfamide failed to control growth of the relapsed tumor and liver metastasis. In July 2001, compassionate use of imatinib was started. Tumor regression was observed at continuous follow-ups (every 2 months for the first 6 months, and 6 months thereafter) and persisted until now. The patient's physical performance has remained in good condition. Side effects consisted of periorbital edema and sudden muscle cramps of toes and fingers, pain of bones and joints, an intentional tremor, a paler color of the skin, as well as a slight anemia. Imatinib is the first orally administered anticancer drug. Our case shows that a sustained response is possible with continuous therapy over a long time, if the drug is well tolerated. This implies a high compliance of the patient and suggests that resistance to imatinib does not have to develop. Exon 11 (point) mutation might not only represent a positive predictor for imatinib response in general, but especially for imatinib response on long-term."],["dc.identifier.doi","10.1159/000333471"],["dc.identifier.pmid","22114577"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11386"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58264"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1662-6575"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Ten Years of Treatment with 400 mg Imatinib per Day in a Case of Advanced Gastrointestinal Stromal Tumor."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","819"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Gastroenterology & Hepatology"],["dc.bibliographiccitation.lastpage","823"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Sobotta, Michael"],["dc.contributor.author","Gunawan, Bastian"],["dc.contributor.author","Fuezesi, Laszlo"],["dc.contributor.author","Langer, Claus"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:28:08Z"],["dc.date.available","2018-11-07T08:28:08Z"],["dc.date.issued","2009"],["dc.description.abstract","Background Gastrointestinal stromal tumors (GIST) are mesenchymal tumors of the gastrointestinal tract supposed to arise from the cells of Cajal because of gain-of-function mutations of the tyrosine receptor kinases c-kit or platelet-derived growth factor receptor A. Imatinib selectively inhibits the kinase activity of both receptors. Despite this breakthrough in the treatment of GIST, resistance against imatinib has been reported to be as high as 50% after the first 2 years of treatment. Aim Outcome of 13 consecutive patients with relapsed or metastasized GIST who were treated with imatinib was analyzed. Results Mean duration of treatment was 53.5 months. Four patients developed progressive disease and died after a mean treatment time of 31 months in spite of increase of imatinib dosages to 800 mg daily. Two patients (23%) developed a progressive disease after 46 months or 52 months of treatment. Two patients had a stable disease and five had a partial response. The overall progression rate was 46%, the mean survival time since primary diagnosis was 85.8 months. Conclusion From our experience, frequency of resistance development to imatinib may be below that given in the literature (50% after 2 years). Individual treatment in specialized centers may improve compliance. Eur J Gastroenterol Hepatol 21:819-823 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins."],["dc.identifier.doi","10.1097/MEG.0b013e32830b0f76"],["dc.identifier.isi","000267120200016"],["dc.identifier.pmid","19369884"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6329"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16352"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1473-5687"],["dc.relation.issn","0954-691X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Does imatinib turn recurrent and/or metastasized gastrointestinal stromal tumors into a chronic disease? single center experience"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","581"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Colorectal Disease"],["dc.bibliographiccitation.lastpage","590"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Beham, Alexander W."],["dc.contributor.author","Schaefer, Inga-Marie"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","von Hammerstein, Katharina"],["dc.contributor.author","Fuezesi, Laszlo"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Ghadimi, Michael B."],["dc.date.accessioned","2018-11-07T09:26:20Z"],["dc.date.available","2018-11-07T09:26:20Z"],["dc.date.issued","2013"],["dc.description.abstract","The duodenum as primary site for gastrointestinal stromal tumors (GISTs) is rare and mitotic rate, tumor size, type of mutation and number of chromosomal aberrations have prognostic implications. We analyzed the outcome of 13 patients with duodenal GISTs who underwent surgical tumor resection. Either segmental duodenectomy or pylorus-preserving duodenopancreatectomy was performed. The tumors were histopathologically examined and the risk of progression was assessed based on tumor size and mitotic count. Additionally, mutation analysis of the KIT and PDGFRA receptor tyrosine kinase genes and comparative genomic hybridization (CGH) were performed in all cases. Eight patients underwent segmental duodenectomy and five patients were treated with pylorus-preserving duodenopancreatectomy. None of the five GISTs with low or no risk for malignancy according to the Miettinen classification developed tumor progress. In contrast, five of eight cases (62.5%) with high-risk tumors revealed tumor progress, and four of these patients died (50%). The median overall survival for all patients was 66 months, and the median disease-free survival 41 months. The operative procedure and type of mutation did not correlate with long-term survival. CGH analysis displayed -15q in 12/13 tumors, and -1p in 11/13 cases as characteristic chromosomal aberrations for intestinal origin. Notably, -22q was present in three of four cases with tumor progress. Both segmental duodenectomy and pylorus-preserving duodenopancreatectomy are appropriate options to treat duodenal GIST and should be implemented depending on resectability and the patient's performing state. The Miettinen classification and CGH findings correlate with the clinical course."],["dc.identifier.doi","10.1007/s00384-012-1432-8"],["dc.identifier.isi","000318368300017"],["dc.identifier.pmid","22350270"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10296"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30275"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0179-1958"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Duodenal GIST: a single center experience"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","353106"],["dc.bibliographiccitation.journal","BioMed Research International"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:29:26Z"],["dc.date.available","2018-11-07T09:29:26Z"],["dc.date.issued","2013"],["dc.description.abstract","The current study aimed to investigate radiation-induced regulation of iron proteins including ferritin subunits in rats. Rat livers were selectively irradiated in vivo at 25 Gy. This dose can be used to model radiation effects to the liver without inducing overt radiation-induced liver disease. Sham-irradiated rats served as controls. Isolated hepatocytes were irradiated at 8 Gy. Ferritin light polypeptide (FTL) was detectable in the serum of sham-irradiated rats with an increase after irradiation. Liver irradiation increased hepatic protein expression of both ferritin subunits. A rather early increase (3 h) was observed for hepatic TfR1 and Fpn-1 followed by a decrease at 12 h. The increase in TfR2 persisted over the observed time. Parallel to the elevation of AST levels, a significant increase (24 h) in hepatic iron content was measured. Complete blood count analysis showed a significant decrease in leukocyte number with an early increase in neutrophil granulocytes and a decrease in lymphocytes. In vitro, a significant increase in ferritin subunits at mRNA level was detected after irradiation which was further induced with a combination treatment of irradiation and acute phase cytokine. Irradiation can directly alter the expression of ferritin subunits and this response can be strongly influenced by radiation-induced proinflammatory cytokines. FTL can be used as a serum marker for early phase radiation-induced liver damage."],["dc.description.sponsorship","DFG [MA-5488/2-1]"],["dc.identifier.doi","10.1155/2013/353106"],["dc.identifier.isi","000328832300001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10734"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31028"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Hindawi Publishing Corporation"],["dc.relation.issn","2314-6141"],["dc.relation.issn","2314-6133"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Differential Regulation of Ferritin Subunits and Iron Transport Proteins: An Effect of Targeted Hepatic X-Irradiation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","213"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Medical Oncology"],["dc.bibliographiccitation.lastpage","218"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Savvoukidis, Theodoros"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Haller, Florian"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Fuezesi, Laszlo"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:42:55Z"],["dc.date.available","2018-11-07T08:42:55Z"],["dc.date.issued","2010"],["dc.description.abstract","The response of gastrointestinal stromal tumors (GISTs) to tyrosine kinase receptor inhibitors (TKR-I) has been a breakthrough for small molecular therapy. We report here on the very different long-term outcome of a synchronous metastatic GIST with complete remission of the primary tumor and progressive liver metastases under TKR-I therapy. In 2003, a 52-year-old patient was diagnosed with gastric GIST and synchronous multiple liver metastases. Therapy with imatinib, 400 mg daily, was started immediately. Fifteen months later, the primary was no longer detectable by endoscopy. In 2006, progression of the liver metastases was observed. Mutation analysis of the initial biopsy specimen from the primary, as well as the biopsy from the three main liver metastases after 3 years of imatinib treatment, revealed the common KIT exon 11 deletion (W557_K558del) in all tumor samples. Two of the metastases had a separate secondary mutation in KIT exon 14 and 17, respectively, while the largest cystic metastatic lesion had no other mutation. Imatinib was then increased to a daily dose of 800 mg, and in April 2007 the treatment was changed to sunitinib. Fifty-two months after initial diagnosis, the patient died of liver failure. At no time point, relapse of the gastric primary tumor was observed. Whilst TKR-Is are commonly very effective in treating GISTs, the present case illustrates their varying effects regarding the clinical behavior and genetic variations within different tumors of the same patient after long-term treatment."],["dc.identifier.doi","10.1007/s12032-009-9193-0"],["dc.identifier.isi","000277203200007"],["dc.identifier.pmid","19294538"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7707"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19819"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1357-0560"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Analysis of a case with disappearance of the primary gastrointestinal stromal tumor and progressive liver metastases under long-term treatment with tyrosine kinase inhibitors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2979"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","2994"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:42:27Z"],["dc.date.available","2018-11-07T09:42:27Z"],["dc.date.issued","2014"],["dc.description.abstract","AIM: To study KRAS/BRAF mutations in colorectalcancer (CRC) that influences the efficacy of treatment. To develop strategies for overcoming combination of treatment. METHODS: Five colonic cell-lines were investigated: DLD-1 with KRAS (G13D) mutation, HT 29 and Colo 205 with BRAF (V600E) mutation as well as the wild type (Wt) cell-lines Caco2 and Colo-320. DLD-1 (KRAS), HT-29 (BRAF) and Caco2 (Wt) cell lines were treated with cytokines (TNF alpha 50 ng, IL-1 beta 1 ng and IFN. 50 ng) and harvested at different time points (1-24 h). KRAS inhibition was performed by the siRNA-approach. Two colorectal cancer cells DLD-1 and Caco2 were used for KRAS inhibition. About 70% confluency were confirmed before transfection with small interferring RNA (siRNA) oligonucleotides. All the synthetic siRNA sequences were designed in our laboratory. Total RNA and protein was isolated from the cells for RT-PCR and Western blotting. Densitometry of the Western blotting was analyzed with the Image J software (NIH). Results are shown as mean +/- SD. RESULTS: RT-PCR analysis in non-stimulated cells showed a low basal expression of TNFa and IL-1 beta in the DLD-1 KRAS -mutated cell-line, compared to Caco2 wild type. No detection was found for IL-6 and IFN. in any of the studied cell lines. In contrast, pro-angiogenic chemokines (CXCL1, CXCL8) showed a high constitutive expression in the mutated cell-lines DLD-1 (KRAS), HT-29 and Colo205 (BRAF), compared to wild type (Caco2). The anti-angiogenic chemokine (CXCL10) showed a high basal expression in wild-type, compared to mutated cell-lines. KRAS down-regulation by siRNA showed a significant decrease in CXCL1 and CXCL10 gene expression in the DLD-1 (KRAS) cell-line in comparison to wild type (Caco2) at 72 h after KRAS silencing. In contrast, the specific KRAS inhibition resulted in an up-regulation of CXCL1 and CXCL10. The results of our study show a higher expression of pro-angiogenic chemokines at basal level in mutated cell-lines, which was further increased by cytokine treatment. CONCLUSION: To summarize, basal chemokine gene expression for pro-angiogenic chemokines was high in mutated as compared to wild type cell-lines. This reflects the likely existence of a different microenvironment in tumours consistent of wild type or mutated cells. This may help to rationalize the choice of molecular targets for suitable therapeutic investigation in clinical studies. c 2014 Baishideng Publishing Group Co., Limited. All rights reserved."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.3748/wjg.v20.i11.2979"],["dc.identifier.isi","000333667200026"],["dc.identifier.pmid","24659889"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10180"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33957"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Baishideng Publ Grp Co Ltd"],["dc.relation.issn","2219-2840"],["dc.relation.issn","1007-9327"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Differential gene expression of chemokines in KRAS and BRAF mutated colorectal cell lines: Role of cytokines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]