Ramadori, Giuliano

[["dc.bibliographiccitation.firstpage","632"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","643"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Hafke, Angelika"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Braulke, Friederike"],["dc.contributor.author","Haase, Detlef"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Walson, Philip D."],["dc.date.accessioned","2018-11-07T08:51:25Z"],["dc.date.available","2018-11-07T08:51:25Z"],["dc.date.issued","2011"],["dc.description.abstract","Objectives: Trough total imatinib (t-IM) concentrations have been reported to be associated with therapeutic and toxic responses in patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST). Little is known about the relationships between effects and concentrations of either unbound imatinib (f-IM) or imatinib's major metabolite, N-desmethyl imatinib (NDI). In part, this is because of the lack of a single, validated, well-described clinically useful assay for these measurements. The authors report the development and application of such an assay. Materials and Methods: A single liquid-chromatography tandem-mass-spectrometry assay was used to monitor t-IM, f-IM, and t-NDI concentrations in CML and GIST patients treated at a tertiary German teaching hospital. The assay was also validated for measuring other kinase inhibitors, including t-nilotinib, sunitinib, and erlotinib. Ultrafiltration assays were validated and used to measure f-IM and to compare free fractions to plasma alpha(1)-acid glycoprotein concentrations (AGP). Results: The assays were linear over a working range (in micrograms per liter) of 8.4-8370, 8.3-4165, and 1.0-250 and had within-and between-run coefficient of variance of <7%, <12%, and <9% for t-IM, t-NDI, and f-IM, respectively. The f-IM assay was reproducible despite high (25.2%-31.6%) but concentration-independent binding to ultrafiltration devices. Clinically relevant results, such as nondetectable (ND) t-IM (<8.4 mu g/L) in non-responders and >1500 mu g/L in patients with major toxicity, were found. Of 156 total samples from 68 adult CML patients and 127 total samples from 42 adult GIST, only 48 samples from 22 CML patients and 40 samples from 20 GIST patients were trough samples with adequate dosing and collection information. More than half (27 of 48 CML and 24 of 40 GIST) had t-IM concentrations >= 10% below recommended target concentrations (1002 mu g/L for CML and 1100 mu g/L for GIST). Concentrations.50% over targets were also found in 6 of 48 CML and 4 of 40 GIST samples. Wide variations in concentrations of t-IM (range, ND to 2973 mu g/L), t-NDI (range, ND to 659 mu g/L), f-IM (range, 8.3-262 mu g/L), and t-IM:f-IM ratios (range, 2.6%-14%) were found both between and within patients. A statistically significant association (Spearman correlation coefficient and P value for all samples, r = 0.290 and P = 0.023; for trough only, r = -0.585 and P = 0.028) was found between AGP and f-IM concentrations but wide interpatient and intrapatient variations made individual predictions unreliable. Conclusions: The liquid-chromatography tandem-mass-spectrometry methods developed provided information useful to understand individual responses to therapy even though necessary sampling and dosing information was often not available. Wide unpredictable variations in t-IM, t-NDI, and f-IM were found. Clinical outcome trials are needed to examine whether f-IM or NDI monitoring can improve the ability to predict individual responses."],["dc.description.sponsorship","Novartis Pharma GmbH, Nuernberg, Germany"],["dc.identifier.doi","10.1097/FTD.0b013e3182263ac4"],["dc.identifier.isi","000295083000009"],["dc.identifier.pmid","21912334"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21930"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Use of Total and Unbound Imatinib and Metabolite LC-MS/MS Assay to Understand Individual Responses in CML and GIST Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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.firstpage","988"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","European Journal of Gastroenterology & Hepatology"],["dc.bibliographiccitation.lastpage","994"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Sobotta, Michael"],["dc.contributor.author","Fuzesi, Laszlo"],["dc.contributor.author","Grabbe, Eckhardt"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T10:56:09Z"],["dc.date.available","2018-11-07T10:56:09Z"],["dc.date.issued","2007"],["dc.description.abstract","Background Although modern chemotherapy of stage IV advanced colorectal cancer (CRC) has impressively improved overall survival, the response of the primary tumor has not been studied because surgical resection of the primary continues to be the standard procedure in stage IV CRC. Aim Long-term follow-up of the primary in patients with stage IV CRC under chemotherapy. Methods and results Here we report on the histological changes in the primary tumor in four patients suffering from stage IV CRC. Systemic chemotherapy was started immediately after endoscopic tumor debulking in three cases. In one case no endoscopic intervention was performed before chemotherapy. Neither macroscopic nor histological evidence for malignant tumor growth was found at the former site of the primary after 6, 23, 26 or 48 months, respectively. Two patients had a complete suppression of the primary, two patients had an adenoma at the former site of the primary. To date, three patients have died because of progression of liver metastases and one patient is still alive with no signs of tumor growth. Conclusion The four cases illustrate that today's chemotherapy may effectively induces suppression of the primary in CRC. The development of CRC may follow different pathways."],["dc.identifier.isi","000254356700013"],["dc.identifier.pmid","18049169"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49947"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0954-691X"],["dc.title","Chemotherapy-induced suppression to adenoma or complete suppression of the primary in patients with stage IV colorectal cancer: report of four cases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","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.artnumber","14"],["dc.bibliographiccitation.journal","BMC Gastroenterology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Lindhorst, Alexander"],["dc.contributor.author","Armbrust, Thomas"],["dc.date.accessioned","2018-11-07T11:04:02Z"],["dc.date.available","2018-11-07T11:04:02Z"],["dc.date.issued","2007"],["dc.description.abstract","Background: Incomplete or complete obstructive ileus due to colorectal cancer is generally treated by emergency surgery that has higher morbidity and mortality than elective surgery. Case Presentation: Here we describe an endoscopic technique by which a safe bowel decompression was performed instead of emergency surgery in two patients with complete tumorous obstruction of the colon. By means of a polypectomy snare, a soft wire, an ERCP catheter, a set of endoscopes with different diameters ( baby endoscope, gastroscope) and of argon plasma coagulation the tumor mass was reduced and the tumor stenosis was passed. The patients recovered from symptoms of colon obstruction, no procedure-associated complications were observed. One patient had surgery of the sigmoid tumor one week later (UICC-stage III), the other patient (UICC-stage IV) received systemic chemotherapy starting one week after endoscopic decompression. Conclusion: Complete tumorous obstruction of the colon may be managed by endoscopic tumor debulking avoiding high risk emergency surgery and allowing immediate medical treatment of the primary tumor and of metastases."],["dc.identifier.doi","10.1186/1471-230X-7-14"],["dc.identifier.isi","000245456100001"],["dc.identifier.pmid","17391506"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/1366"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51745"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-230X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Colorectal tumors with complete obstruction - Endoscopic recovery of passage replacing emergency surgery? A report of two cases"],["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"]]