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201. Tropomyosin receptor kinase: a novel target in screened neuroendocrine tumors.

Author

Prada, Elke Tatjana Aristizabal, Heinzle, Vera, Knösel, Thomas, Nölting, Svenja, Spöttl, Gerald, Maurer, Julian, Spitzweg, Christine, Angele, Martin, Schmidt, Nina, Beuschlein, Felix, Stalla, Günter K., Blaser, Rainer, Kuhn, Klaus A., and Auernhammer, Christoph J.

Subjects
CANCER treatment, TROPOMYOSINS, KINASE inhibitors, NEUROENDOCRINE tumors, CANCER cells, EVEROLIMUS
Abstract

Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines were treated with GNF-5837 alone and in combination with everolimus. Cell viability decreased in a time- and dosedependent manner in GOT1 cells in response to GNF-5837 treatment, while treatment in BON1 and NCI-H727 cells showed no effect on cellular viability. Trk receptor expression determined GNF-5837 sensitivity. GNF-5837 caused downregulation of PI3K-Akt-mTOR signaling, Ras-Raf-MEK-ERK signaling, the cell cycle and increased apoptotic cell death. The combinational treatment of GNF-5837 with everolimus showed a significant enhancement in inhibition of cell viability vs single substance treatments, due to a cooperative PI3K-Akt-mTOR and Ras-Raf-MEK-ERK pathway downregulation, as well as an enhanced cell cycle component downregulation. Immunohistochemical staining for Trk receptors were performed using a tissue microarray containing 107 tumor samples of gastroenteropancreatic NETs. Immunohistochemical staining with TrkA receptor and pan-Trk receptor antibodies revealed a positive staining in pancreatic NETs in 24.2% (8/33) and 33.3% (11/33), respectively. We demonstrated that the pan-Trk inhibitor GNF-5837 has promising anti-tumoral properties in human NET cell lines expressing the TrkA receptor. Immunohistochemical or molecular screening for Trk expression particularly in pancreatic NETs might serve as predictive marker for molecular targeted therapy with Trk inhibitors. [ABSTRACT FROM AUTHOR]

Published
2018
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202. Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial.

Author

Issels, Rolf D., Lindner, Lars H., Verweij, Jaap, Wessalowski, Rüdiger, Reichardt, Peter, Wust, Peter, Ghadjar, Pirus, Hohenberger, Peter, Angele, Martin, Salat, Christoph, Vujaskovic, Zeljko, Daugaard, Soeren, Mella, Olav, Mansmann, Ulrich, Dürr, Hans Roland, Knösel, Thomas, Abdel-Rahman, Sultan, Schmidt, Michael, Hiddemann, Wolfgang, and Jauch, Karl-Walter

Published
2018
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203. Ergebnisse nach Resektion von Lebermetastasen eines Aderhautmelanoms

Author

Altendorf-Hofmann, Annelore, Schüle, Silke, Dittmar, Yves, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Das Aderhautmelanom ist der häufigste maligne Tumor des Auges. Je nach primärem Tumorstadium entwickeln 15-25% der Patienten Fernmetastasen, diese sind in 80-90% isolierte Lebermetastasen. Literaturberichte zur chirurgischen Metastasentherapie sind widersprüchlich:[for full text, please go to the a.m. URL], 129. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2012

204. Prognostische molekular Marker bei intrahepatischen Cholangiokarzinomen

Author

Altendorf-Hofmann, Annelore, Schüle, Silke, Dittmar, Yves, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Die Mehrzahl der Daten über den Prognostischen Wert von molekularen Biomarkern bei intrahepatischen Cholangiokarzinomen kommt aus Südostasien. Möglicherweise unterscheidet sich das biologische Verhalten dieser Tumoren aufgrund der unterschiedlichen Ätiologie von denen[for full text, please go to the a.m. URL], 129. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2012

205. Lebertransplantation bei Cholangiokarzinomen

Author

Schüle, Silke, Altendorf-Hofmann, Annelore, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Cholangiokarzinome gehören zu den selteneren Tumoren des Gastrointestinaltrakts und werden häufig erst in einem fortgeschrittenen Stadium diagnostiziert. Bei irresektablen Karzinomen kann die Lebertransplantation eine Heilungschance bieten. Angesichts von zunächst enttäuschenden[for full text, please go to the a.m. URL], 129. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2012

206. Langzeitergebnisse nach Resektion von Lebermetastasen beim Nierenzellkarzinom

Author

Altendorf-Hofmann, Annelore, Schüle, Silke, Dittmar, Yves, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Fernmetastasen des Nierenzellkarzinoms finden sich zu 75% in der Lunge und zu 20% in der Leber. Berichte über mehr als 10 kurativ resezierte Patienten mit Lebermetastasen eines Nierenzellkarzinoms sind selten. Wir stellen im Folgenden unsere Ergebnisse nach Leberresektion[for full text, please go to the a.m. URL], 129. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2012

207. Inzidentelle Gallenblasenkarzinome - Ergebnisse der Nachresektion

Author

Altendorf-Hofmann, Annelore, Schüle, Silke, Dittmar, Yves, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Die Mehrzahl der Gallenblasenkarzinome präsentiert sich dem Chirurgen in einem inkurablen Tumorstadium. Unter den resektablen Tumoren wird ein Großteil als histologischer Zufallsbefund nach Cholezystektomie entdeckt. Wir berichten im Folgenden über unsere Ergebnisse in der[for full text, please go to the a.m. URL], 129. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2012

208. Ergebnisse nach Resektion nicht-kolorektaler, nicht-neuroendokriner Lebermetastasen

Author

Altendorf-Hofmann, Annelore, Schüle, Silke, Dittmar, Yves, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Während die Resektion von Lebermetastasen ein etabliertes Therapieverfahren für kolorektale oder neuroendokrine Primärtumoren darstellt, ist dies für alle anderen Tumorentitäten weniger gut belegt. Im Folgenden präsentieren wir die Ergebnisse unserer Klinik [for full text, please go to the a.m. URL], 129. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2012

209. Desmogleins as prognostic biomarkers in resected pancreatic ductal adenocarcinoma.

Author

Ormanns, Steffen, Altendorf-Hofmann, Annelore, Jackstadt, Rene, Horst, David, Assmann, Gerald, Zhao, Yue, Bruns, Christiane, Kirchner, Thomas, Knösel, Thomas, and Knösel, Thomas

Subjects
DESMOGLEINS, BIOMARKERS, PANCREATIC duct, ADENOCARCINOMA, CANCER treatment, IMMUNOHISTOCHEMISTRY, CANCER, PROGNOSIS, ANTIGENS, BIOCHEMISTRY, GLYCOPROTEINS, PHENOMENOLOGY, PANCREATIC tumors, PROBABILITY theory, RESEARCH funding, SURVIVAL analysis (Biometry), TUMOR markers, PROPORTIONAL hazards models, RECEIVER operating characteristic curves, DUCTAL carcinoma, DATA analysis software, KAPLAN-Meier estimator, SEQUENCE analysis
Abstract

Background: Frequent disease relapse and a lack of effective therapies result in a very poor outcome in pancreatic ductal adenocarcinoma (PDAC) patients. Thus, identification of prognostic biomarkers and possible therapeutic targets is essential. Besides their function in cell-cell adhesion, desmogleins may play a role in tumour progression and invasion that has not been investigated in PDAC to date. This study evaluated desmoglein expression as a biomarker in PDAC.Methods: Using immunohistochemistry, we examined desmoglein 1 (DSG1), desmoglein 2 (DSG2) and desmoglein 3 (DSG3) expression in the tumour tissue of 165 resected PDAC cases. Expression levels were correlated to the patients' clinicopathological parameters and postoperative survival times. We confirmed these results in two independent gene expression data sets.Results: A total of 36% of the tumours showed high DSG3 expression that correlated significantly with shorter patient survival (P=0.011) and poor tumour differentiation (P<0.001), whereas no such association was detected for DSG1 or DSG2. In RNA-Seq data and in microarray expression data, high DSG3 expression correlated significantly with poor survival (P=0.000356 and P=0.00499).Conclusions: We identify DSG3 as a negative prognostic biomarker in resected PDAC, as high DSG3 expression is associated with poor overall survival and poor tumour-specific survival. These findings suggest DSG3 and its downstream signalling pathways as possible therapeutic targets in DSG3-expressing PDAC. [ABSTRACT FROM AUTHOR]

Published
2015
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210. Einfluß der Expression von CK7 auf die Rezidivrate beim duktalen Pankreaskarzinom

Author

Altendorf-Hofmann, Annelore, Knösel, Thomas, and Settmacher, Utz

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Der Verlauf von Patienten mit duktalen Pankreaskarzinomen ist auch nach R0-Resektion gekennzeichnet durch eine hohe Rückfallrate und damit verbunden geringe mediane Überlebenszeiten und Überlebensraten. Dennoch werden in Einzelfällen lange rezidivfreie Verläufe beobachtet.[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2011
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214. FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

Author

Briest, Franziska, primary, Berg, Erika, additional, Grass, Irina, additional, Freitag, Helma, additional, Kaemmerer, Daniel, additional, Lewens, Florentine, additional, Christen, Friederike, additional, Arsenic, Ruza, additional, Altendorf-Hofmann, Annelore, additional, Kunze, Almut, additional, Sänger, Jörg, additional, Knösel, Thomas, additional, Siegmund, Britta, additional, Hummel, Michael, additional, and Grabowski, Patricia, additional

Published
2015
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215. Nuclear export is essential for the tumor-promoting activity of survivin

Author

Knauer, Shirley, Krämer, Oliver H., Knösel, Thomas, Engels, Knut, Rödel, Franz, Kovács, Adorján F., Dietmaier, Wolfgang, Klein-Hitpaß, Ludger, Habtemichael, Negusse, Schweitzer, Andrea, Brieger, Jürgen, Rödel, Claus, Mann, Wolf, Petersen, Iver, Heinzel, Thorsten, and Stauber, Roland H.

Subjects
neoplasms, Biologie
Abstract

Survivin appears to function as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Here we report the molecular characterization of the nucleocytoplasmic transport of survivin and its potential implications for tumorigenesis. We identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. In dividing cells, the NES is essential for tethering survivin and the survivin/Aurora-B kinase complex to the mitotic machinery, which in turn appears to be essential for proper cell division. In addition, export seems to be required for the cytoprotective activity of survivin, as export-deficient survivin fails to protect tumor cells against chemo- and radiotherapy-induced apoptosis. These findings appear to be clinically relevant since preferential nuclear localization of survivin correlated with enhanced survival in colorectal cancer patients. Targeting survivin’s nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We demonstrate that nuclear export is essential for the biological activity of survivin and promote the identification of molecular decoys to specifically interfere with survivin’s nuclear export as potential anticancer therapeutics.

Published
2007

216. Chromosomale Signaturen und Immunprofile in der Tumorprogression kolorektaler Karzinome

Author

Knösel, Thomas

Subjects
immunohistochemistry, metastasis, colorectal cancer, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, CGH, TMA´s
Abstract

Habilitationsschrift, Bösartige Neubildungen des Kolorektums sind die zweithäufigste Krebstodesursache bei Männern und die dritthäufigste Krebstodesursache bei Frauen. Die Tumorprogression und die Metastasierung sind verantwortlich für die meisten Todesfälle. Deshalb ist ein primäres Ziel unserer Forschung nicht nur die molekulare Kanzerogenese des Primärtumors, sondern auch der Prozeß der Metastasierung. Mit Hilfe der Comparativen Genomischen Hybridisierung (CGH) wurden 85 kolorektale Karzinome analysiert und verschiedene neue genomische Alterationen detektiert, die mit bestimmten Metastasierungwegen assoziiert sind. Einzelne Tumorzellen scheinen ein Metastasierungpotential („ready to go package“) zu haben, das es den Zellen ermöglicht, die verschiedenen Schritte der Metastasierung, wie Ablösung vom Primärverband, Fähigkeit zur Intravasation, zur Extravasation und zum klonalen Wachstum einer Metastase im ortsfremden Gewebe, zu vollziehen. Diese Alterationen scheinen zum Teil schon im Primärtumor zu existieren. Die Ergebnisse werden auch von anderen Arbeitsgruppen bestätigt, die chromosomale Alterationen von einzeln disseminierten Tumorzellen im Knochenmark untersuchten und feststellten, dass z. T. die gleichen Alterationen bereits im Primärtumor vorlagen. Um einen zytogenetischen Einblick in den komplexen Vorgang der Metastasierung und auch der organspezifischen Metastasierung zu geben, stellen wir anhand unserer Ergebnisse ein Tumorprogressionsmodell mit typischen chromosomalen Veränderungen auf. Zum anderen sind entsprechende Kandidatengene auf Proteinebene mittels Immunhistochemie validiert und mit den CGH Ergebnissen korreliert worden, wie COX-2 auf 1q25.2-q25.3 und c-erbB2 auf 17q12-q21, welche mit einem kürzeren Überleben korrelierten. Diese Untersuchungen erfolgten bereits mit den sogenannten Gewebearrays (TMAs), mit deren Hilfe ein großes und gut charakterisiertes Tumorkollektiv erstellt worden ist. Mit Hilfe einer multiplexen Analyse dieser TMAs in aufeinanderfolgenden Serienschnitten (3D-TMAs) konnten mehrere interessante Kandidatengene analysiert und evaluiert werden. Es konnte gezeigt werden, dass mit Hilfe des hierarchischen Clusterns verschiedene Immunprofile erstellt werden, die signifikant mit den klinisch- pathologischen Parametern korrelierten und somit als prognostisch und diagnostisch wichtige Signaturen dienen können. Diese Signaturen werden die morphologisch ähnlichen oder gleichen Neoplasien molekularpathologisch weiter subklassifizieren und eine individualisierte Therapieplanung möglich machen., Aims: Metastasis is responsible for most cancer deaths. It represents the essential step during cancer progression from a locally growing tumor to a metastatic killer. Methods: To provide cytogenetic and immunohistological (IHC) data in colorectal carcinomas (CRC) we investigated 85 tumor specimens with Comparative Genomic Hybridization (CGH), 36 primary tumors, metastasis from the lung (n=13), liver (n=13), lymph nodes (n=12), brain (n=6), abdominal wall (n=4) and ovary (n=1). Furthermore, 6721 specimens of CRC were analyzed with IHC by the synergy of TMAs and unsupervised hierarchical clustering. Results: In general, hematogenous metastases showed more alterations than lymph node metastases, particularly more deletions at 1p, 3, 4, 5q, 10q, 14 and 21q2 and gains at 1q, 7p, 12qter, 13, 16 and 22q. Additionally liver and lung metastases showed distinct signatures, particularly lung metastases gains on 2q, 5p and losses at 1p, 3p, 8p, 9q, 12q, 17q, 19p, 21q21 and 22q. Furthermore we show that unsupervised hierarchical clustering of the IHC data identified specific diagnostic and prognostic subgroups. Conclusions: Based our results we wish to suggest a metastatic progression model. Specific sub- populations of metastatic cells have a distinct metastatic potential which is reflected by a non-random accumulation of chromosomal alterations. Furthermore the synergy of hiercharchical clustering and TMA-IHC is a useful, promising and very powerful tool to decipher diagnostic and prognostic signatures of cancer subtypes and may refine the morphological histopathological classification.

Published
2007
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217. Novel strategies to target the survivin pathway in cancer – interference with nuclear export prevents the tumor promoting activites of survivin : meeting abstract

Author

Knauer, Shirley, Knauer, Shirley K., Krämer, Oliver Holger, Knösel, Thomas, Engels, Knut, Rödel, Franz, Brieger, Jürgen, Mann, Wolf, Habtemichael, Negusse, Petersen, Ivar, Heinzel, Thorsten, and Stauber, Roland

Subjects
ddc:610, neoplasms
Abstract

Survivin functions as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Since survivin is a highly relevant target for tumor therapy, we investigated whether interference with it’s dynamic cellular localization represents a novel strategy to inhibit survivin’s cancer promoting functions. We confirmed survivin overexpression in head and neck as well as in colorectal cancers and identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. Importantly, nuclear export was required for survivin mediated protection against chemo- and radiotherapy-induced apoptosis by securing efficient interference with cytoplasmic caspases. In dividing cells, the NES was required for tethering of survivin and of the survivin/Aurora-B kinase complex to the mitotic machinery, which was inevitable for proper cell division. The clinical relevance of our findings was supported by showing that preferential nuclear localization of survivin correlated with enhanced survival in a cohort of colorectal cancer patients. Targeting survivin’s nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We here show that nuclear export is essential for the tumor promoting activities of survivin and encourage the identification of chemical inhibitors to specifically interfere with survivin’s nuclear export as a novel class of anticancer therapeutics.

Published
2006

218. Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma.

Author

Zhao, Yue, Altendorf-Hofmann, Annelore, Pozios, Ioannis, Camaj, Peter, Däberitz, Therese, Wang, Xiaoyan, Niess, Hanno, Seeliger, Hendrik, Popp, Felix, Betzler, Christopher, Settmacher, Utz, Jauch, Karl-Walter, Bruns, Christiane, and Knösel, Thomas

Subjects
PANCREATIC cancer, INTERFERONS, PROGNOSIS, MULTIVARIATE analysis, PROTEIN microarrays
Abstract

Purpose: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. Methods: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3.6pl) and one established gemcitabine resistant cell variant-L3.6plGres. Second, we analyzed the protein expression in tissue microarrays (TMA) from specimens of 254 radically resected patients with pancreatic adenocarcinoma. The prognostic relevance of IFIT3 was evaluated by the Kaplan-Meier and Cox regression analysis. Results: L3.6pl cells with an aggressive capacity showed a significant higher expression of IFIT3 as compared to FG cells. IFIT3 was accumulated in gemcitabine resistant cells. Overexpression of IFIT3 increased the resistance of apoptosis against gemcitabine treatment. Patients who had high expression of IFIT3 (32%) and received chemotherapy had a statistically significant reduced survival in multivariate analysis. Conclusions: High expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of PDAC cells. High expression of IFIT3 was independently correlated to shorter patients' survival and may serve as a prognostic marker. [ABSTRACT FROM AUTHOR]

Published
2017
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219. Is There Evidence for the Presence and Relevance of the PD-1/PD-L1 Pathway in Oral Squamous Cell Carcinoma? Hints From an Immunohistochemical Study.

Author

Troeltzsch, Matthias, Woodlock, Timothy, Pianka, Alix, Otto, Sven, Troeltzsch, Markus, Ehrenfeld, Michael, and Knösel, Thomas

Abstract

Purpose: To examine oral squamous cell carcinoma (OSCC) specimens for programmed death ligand-1 (PD-L1) expression and presence of programmed death-1 (PD-1)-positive tumor-infiltrating lymphocytes (TILs) and to determine possible clinicopathologic implications. It was hypothesized that PD-L1 expression and PD-1-positive TIL presence in OSCC would have no clinical relevance.Materials and Methods: The authors implemented a retrospective cohort study design. The study cohort was chosen in compliance with predefined inclusion criteria. Demographic, clinical, and histopathologic data were gathered. Tissue microarrays were obtained from paraffin-embedded OSCC specimens and analyzed immunohistochemically for PD-L1 expression and PD-1-positive TIL infiltration. PD-L1 positivity of OSCC specimens served as the predictor variable and neck node metastasis served as the primary outcome variable. Descriptive and inferential statistics were computed and the significance level was set at a P value less than or equal to .05.Results: The study sample was composed of 88 patients (48 men, 40 women; mean age, 61.34 yr). Marked PD-L1 expression was detected in 29% of OSCC specimens (26 of 88) and 83% of specimens (73 of 88) exhibited a high rate of PD-1-positive TIL infiltration. PD-L1 positivity of OSCC samples was significantly associated with the anatomic origin of OSCC (P = .039), presence of cervical metastasis (P = .039), and high PD-L1-positive TIL infiltration (P = .033).Conclusion: A considerable proportion of OSCCs exhibited marked PD-L1 expression. This could be associated with clinical parameters. PD-L1 expression in OSCC might differ depending on its anatomic origin. PD-1-positive TILs could be detected in most OSCC specimens. These findings might indicate a potential role for the PD-1 and PD-L1 pathway in OSCC. [ABSTRACT FROM AUTHOR]

Published
2017
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220. A pilot trial of doxorubicin containing phosphatidyldiglycerol based thermosensitive liposomes in spontaneous feline soft tissue sarcoma.

Author

Zimmermann, Katja, Hossann, Martin, Hirschberger, Johannes, Troedson, Karin, Peller, Michael, Schneider, Moritz, Brühschwein, Andreas, Meyer-Lindenberg, Andrea, Wess, Gerhard, Wergin, Melanie, Dörfelt, René, Knösel, Thomas, Schwaiger, Markus, Baumgartner, Christine, Brandl, Johanna, Schwamberger, Sabine, and Lindner, Lars H.

Subjects
SOFT tissue tumors, TREATMENT of cat diseases, DOXORUBICIN, PHOSPHATIDYLGLYCEROL, LIPOSOMES, POSITRON emission tomography, THERAPEUTICS, TUMOR treatment
Abstract

Purpose:Doxorubicin (DOX)-loaded phosphatidyldiglycerol-based thermosensitive liposomes (DPPG2-TSL-DOX) combined with local hyperthermia (HT) was evaluated in cats with locally advanced spontaneous fibrosarcomas (soft tissue sarcoma [STS]). The study was designed to evaluate the safety and pharmacokinetic profile of the drug. Results from four dose-levels are reported. Methods:Eleven client-owned cats with advanced STS were enrolled. Five cats received escalating doses of 0.1–0.4 mg/kg DOX (group I), three received 0.4 mg/kg constantly (group II) and three 0.6 mg/kg (group III) IV over 15 min. HT with a target temperature of 41.5 °C was started 15 min before drug application and continued for a total of 60 min. Six HT treatments were applied every other week using a radiofrequency applicator. Tumour growth was monitored by magnetic resonance imaging (MRI) and for dose level III also with18F-FDG PET. Results:Treatment was generally well tolerated and reasons for premature study termination in four cats were not associated with drug-induced toxicity. No DPPG2-TSL-DOX based hypersensitivity reaction was observed. One cat showed simultaneous partial response (PR) in MRI and positron emission tomography (PET) whereas one cat showed stable disease in MRI and PR in PET (both cats in dose level III). Pharmacokinetic measurements demonstrated DOX release triggered by HT. Conclusion:DPPG2-TSL-DOX + HT is a promising treatment option for advanced feline STS by means of targeted drug delivery. As MTD was not reached further investigation is warranted to determine if higher doses would result in even better tumour responses. [ABSTRACT FROM PUBLISHER]

Published
2017
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221. 18F-FDG PET/CT for Monitoring of Disease Progression in Metastatic Perivascular Epithelioid Cell Tumor

Author

Holzgreve, Adrien, Fabritius, Matthias P., Knösel, Thomas, Renz, Bernhard W., Lindner, Lars H., Di Gioia, Dorit, Bartenstein, Peter, Rübenthaler, Johannes, and Tiling, Reinhold

Abstract

A 38-year-old woman presented for 18F-FDG PET/CT after multiple intra-abdominal surgical resections of a rare recurrent perivascular epithelioid cell tumor of the gastrointestinal tract. A solitary pelvic metastasis was detected, but surprisingly exhibited neither increased glucose consumption nor contrast enhancement on CT. Follow-up 18F-FDG PET/CT staging in the further disease course revealed multiple abdominal metastases, now, however, with markedly increased 18F-FDG uptake and intraoperatively correlating widespread peritoneal sarcomatosis. This case gives preliminary insight into monitoring of disease progression in metastatic perivascular epithelioid cell tumor, although the underlying pathophysiological bases for varying 18F-FDG uptake in PET/CT are not yet fully understood.

Published
2021
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222. PET Response Criteria in Solid Tumors Predicts Progression-Free Survival and Time to Local or Distant Progression After Chemotherapy with Regional Hyperthermia for Soft-Tissue Sarcoma

Author

Fendler, Wolfgang P., primary, Lehmann, Mona, additional, Todica, Andrei, additional, Herrmann, Ken, additional, Knösel, Thomas, additional, Angele, Martin K., additional, Dürr, Hans Roland, additional, Rauch, Josefine, additional, Bartenstein, Peter, additional, Cyran, Clemens C., additional, Hacker, Marcus, additional, and Lindner, Lars H., additional

Published
2015
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224. Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression

Author

Frampton, Adam E, primary, Castellano, Leandro, additional, Colombo, Teresa, additional, Giovannetti, Elisa, additional, Krell, Jonathan, additional, Jacob, Jimmy, additional, Pellegrino, Loredana, additional, Roca-Alonso, Laura, additional, Funel, Niccola, additional, Gall, Tamara M H, additional, Ahmad, Raida, additional, Habib, Nagy A, additional, Knösel, Thomas, additional, Stebbing, Justin, additional, and Jiao, Long R, additional

Published
2015
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225. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer

Author

Rad, Roland, primary, Rad, Lena, additional, Wang, Wei, additional, Strong, Alexander, additional, Ponstingl, Hannes, additional, Bronner, Iraad F, additional, Mayho, Matthew, additional, Steiger, Katja, additional, Weber, Julia, additional, Hieber, Maren, additional, Veltkamp, Christian, additional, Eser, Stefan, additional, Geumann, Ulf, additional, Öllinger, Rupert, additional, Zukowska, Magdalena, additional, Barenboim, Maxim, additional, Maresch, Roman, additional, Cadiñanos, Juan, additional, Friedrich, Mathias, additional, Varela, Ignacio, additional, Constantino-Casas, Fernando, additional, Sarver, Aaron, additional, ten Hoeve, Jelle, additional, Prosser, Haydn, additional, Seidler, Barbara, additional, Bauer, Judith, additional, Heikenwälder, Mathias, additional, Metzakopian, Emmanouil, additional, Krug, Anne, additional, Ehmer, Ursula, additional, Schneider, Günter, additional, Knösel, Thomas, additional, Rümmele, Petra, additional, Aust, Daniela, additional, Grützmann, Robert, additional, Pilarsky, Christian, additional, Ning, Zemin, additional, Wessels, Lodewyk, additional, Schmid, Roland M, additional, Quail, Michael A, additional, Vassiliou, George, additional, Esposito, Irene, additional, Liu, Pentao, additional, Saur, Dieter, additional, and Bradley, Allan, additional

Published
2014
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226. Nuclear relocation of STAT6 reliably predictsNAB2-STAT6fusion for the diagnosis of solitary fibrous tumour

Author

Koelsche, Christian, primary, Schweizer, Leonille, additional, Renner, Marcus, additional, Warth, Arne, additional, Jones, David T W, additional, Sahm, Felix, additional, Reuss, David E, additional, Capper, David, additional, Knösel, Thomas, additional, Schulz, Birte, additional, Petersen, Iver, additional, Ulrich, Alexis, additional, Renker, Eva Kristin, additional, Lehner, Burkhard, additional, Pfister, Stefan M, additional, Schirmacher, Peter, additional, von Deimling, Andreas, additional, and Mechtersheimer, Gunhild, additional

Published
2014
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230. Advanced neuroendocrine tumours of the small intestine and pancreas: clinical developments, controversies, and future strategies

Author

Auernhammer, Christoph J, Spitzweg, Christine, Angele, Martin K, Boeck, Stefan, Grossman, Ashley, Nölting, Svenja, Ilhan, Harun, Knösel, Thomas, Mayerle, Julia, Reincke, Martin, and Bartenstein, Peter

Abstract

In this Review, we discuss clinical developments and controversies in the treatment of neuroendocrine tumours (NETs) that are relevant for clinicians and clinical researchers. We describe advances in genetics, blood-based biomarkers, functional imaging, and systemic therapy of advanced NETs and discuss results of recent phase 3 studies, systemic treatment of advanced disease with peptide receptor radionuclide therapy, biotherapy, chemotherapy, and molecularly targeted therapy, and the potential role of immunotherapy in the treatment of NETs. Suggested treatment algorithms for NETs of ileal or jejunal origin and of pancreatic origin are presented.

Published
2018
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231. Case report: Extended Isolated Stopflow Limb Infusion (EISLI) for highly malignant osteosarcoma - complete pathological tumor remission and implantation of a knee joint prosthesis.

Author

Aigner, Kornelia, Selak, Emir, Gailhofer, Sabine, Knösel, Thomas, SrinivasRaju, Jayadeepa, and Aigner, Karl Reinhard

Abstract

An 18-year old osteosarcoma patient with a huge tumor mass at the distal femur and inguinal metastases was treated with the intention to preserve the leg and additionally treat the pelvic metastases locally. Therefore we modulated the technique of isolated limb perfusion. Isolated Limb Perfusion was performed as an Extended Isolated Limb Stop-Flow Infusion (EISLI) where the pelvis was included into the perfusion bed. Balloon catheters were placed in the arterial and venous bifurcation in the pelvis. For increasing the drug concentration at the tumor site, an angiographic catheter was placed arterially with the tip right in front of the tumor region. A Stop-Flow phase before the perfusion phase was applied. After 4 cycles of EISLI the lesions in the pelvis disappeared and surgical resection of the tumor and implantation of an endoprosthesis was possible and successful. Histopathological findings showed no vital cells in the resected tumor region. Currently the patient is tumor free and does not show recurrence or pulmonal metastases for 18 months after the last induction treatment cycle. With EISLI the inclusion of the pelvis is possible during isolated limb perfusion. In addition with low total dosages EISLI enabled drug concentrations many times higher at the tumor site than possible during systemic chemotherapy or standard isolated limb perfusion. It is a technique that allows limb preservation and treatment of positive lymphnodes in the groin. Quality of life is maintained during the Regional Chemotherapy (RCT). • Isolated Limb Perfusion can be extended to the pelvic region with balloon catheters at the arterial and venous bifurcation. • Drug concentrations at a tumor can be increased by stopflow infusion. • Increased drug concentrations during 5 min stopflow phase might cause sufficient tissue drug uptake. • Extended Isolated Limb Infusion (EISLI) can be an alternative to limb amputation. [ABSTRACT FROM AUTHOR]

Published
2023
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233. MicroRNAs Cooperatively Inhibit a Network of Tumor Suppressor Genes to Promote Pancreatic Tumor Growth and Progression

Author

Frampton, Adam E., primary, Castellano, Leandro, additional, Colombo, Teresa, additional, Giovannetti, Elisa, additional, Krell, Jonathan, additional, Jacob, Jimmy, additional, Pellegrino, Loredana, additional, Roca-Alonso, Laura, additional, Funel, Niccola, additional, Gall, Tamara M.H., additional, De Giorgio, Alexander, additional, Pinho, Filipa G., additional, Fulci, Valerio, additional, Britton, David J., additional, Ahmad, Raida, additional, Habib, Nagy A., additional, Coombes, R. Charles, additional, Harding, Victoria, additional, Knösel, Thomas, additional, Stebbing, Justin, additional, and Jiao, Long R., additional

Published
2014
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238. Erratum: Corrigendum: The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma

Author

Pérez-Mancera, Pedro A., primary, Rust, Alistair G., additional, van der Weyden, Louise, additional, Kristiansen, Glen, additional, Li, Allen, additional, Sarver, Aaron L., additional, Silverstein, Kevin A. T., additional, Grützmann, Robert, additional, Aust, Daniela, additional, Rümmele, Petra, additional, Knösel, Thomas, additional, Herd, Colin, additional, Stemple, Derek L., additional, Kettleborough, Ross, additional, Brosnan, Jacqueline A., additional, Li, Ang, additional, Morgan, Richard, additional, Knight, Spencer, additional, Yu, Jun, additional, Stegeman, Shane, additional, Collier, Lara S., additional, ten Hoeve, Jelle J., additional, de Ridder, Jeroen, additional, Klein, Alison P., additional, Goggins, Michael, additional, Hruban, Ralph H., additional, Chang, David K., additional, Biankin, Andrew V., additional, Grimmond, Sean M., additional, Initiative, Australian Pancreatic Cancer Genome, additional, Wessels, Lodewyk F. A., additional, Wood, Stephen A., additional, Iacobuzio-Donahue, Christine A., additional, Pilarsky, Christian, additional, Largaespada, David A., additional, Adams, David J., additional, and Tuveson, David A., additional

Published
2013
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240. Schimmel attackiert schlagendes Herz

Author

Weig, Thomas, primary, Irlbeck, Michael, additional, Neurohr, Claus, additional, Winter, Hauke, additional, Schramm, Rene, additional, Knösel, Thomas, additional, and Horst, David, additional

Published
2013
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245. FGFR1 expression and gene copy numbers in human lung cancer

Author

Kohler, Lukas H., primary, Mireskandari, Masoud, additional, Knösel, Thomas, additional, Altendorf-Hofmann, Annelore, additional, Kunze, Almut, additional, Schmidt, Andreas, additional, Presselt, Norbert, additional, Chen, Yuan, additional, and Petersen, Iver, additional

Published
2012
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246. Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes

Author

Winter, Christof, primary, Kristiansen, Glen, additional, Kersting, Stephan, additional, Roy, Janine, additional, Aust, Daniela, additional, Knösel, Thomas, additional, Rümmele, Petra, additional, Jahnke, Beatrix, additional, Hentrich, Vera, additional, Rückert, Felix, additional, Niedergethmann, Marco, additional, Weichert, Wilko, additional, Bahra, Marcus, additional, Schlitt, Hans J., additional, Settmacher, Utz, additional, Friess, Helmut, additional, Büchler, Markus, additional, Saeger, Hans-Detlev, additional, Schroeder, Michael, additional, Pilarsky, Christian, additional, and Grützmann, Robert, additional

Published
2012
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249. Diagnostic accuracy of biopsy after neoadjuvant treatment for well-differentiated and dedifferentiated retroperitoneal liposarcoma

Author

Gold, Lukas, Moser, Christian, Fabritius, Matthias P., Seidensticker, Max, Ricke, Jens, Albertsmeier, Markus, Angele, Martin K., Knösel, Thomas, Di Gioia, Dorit, Lindner, Lars H., Armbruster, Marco, and Kunz, Wolfgang G.

Abstract

Accurate histopathological grading of percutaneous biopsies is essential to guide adequate management of patients with suspected retroperitoneal liposarcoma. In this regard, however, limited reliability has been described. Therefore, we conducted a retrospective study to assess the diagnostic accuracy in retroperitoneal soft tissue sarcomas and simultaneously investigate its impact on patients' survival.

Published
2023
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250. High KIT and PDGFRA are associated with shorter patients survival in gastroenteropancreatic neuroendocrine tumors, but mutations are a rare event

Author

Knösel, Thomas, primary, Chen, Yuan, additional, Altendorf-Hofmann, Annelore, additional, Danielczok, Christine, additional, Freesmeyer, Martin, additional, Settmacher, Utz, additional, Wurst, Christine, additional, Schulz, Stefan, additional, Yang, Lin Lin, additional, and Petersen, Iver, additional

Published
2011
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