The Experts below are selected from a list of 42333 Experts worldwide ranked by ideXlab platform
Christoph J Auernhammer - One of the best experts on this subject based on the ideXlab platform.
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Neuroendocrine Tumor recurrence diagnosis with 68ga dotatate pet ct
Radiology, 2013Co-Authors: Alexander Haug, Christoph J Auernhammer, Ramona Cindeadrimus, Martin Reincke, Felix Beuschlein, Bjorn Wangler, Christopher Uebleis, Gerwin P Schmidt, Christine Spitzweg, Peter BartensteinAbstract:In the follow-up of patients after curative resection of a Neuroendocrine Tumor, 68Ga-DOTATATE PET/CT is accurate, thus substantiating its use in clinical routine diagnostic imaging.
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compensatory activation of akt in response to mtor and raf inhibitors a rationale for dual targeted therapy approaches in Neuroendocrine Tumor disease
Cancer Letters, 2010Co-Authors: Kathrin Zitzmann, Janina Von Rüden, Jennifer Lichtl, Gerald Spöttl, Burkhard Goke, Stephan Brand, Christoph J AuernhammerAbstract:Abstract Several studies have established a link between aberrant PI(3)K–Akt–mTOR- and Ras–Raf–MEK–Erk1/2 signaling and Neuroendocrine Tumor disease. In this study, we comparatively investigate the antiTumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antiTumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K-Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K–Akt–mTOR- and Ras–Raf–MEK–Erk1/2 signaling in NET disease.
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Compensatory activation of Akt in response to mTOR and Raf inhibitors - A rationale for dual-targeted therapy approaches in Neuroendocrine Tumor disease
Cancer Letters, 2010Co-Authors: Kathrin Zitzmann, Janina Von Rüden, Jennifer Lichtl, Gerald Spöttl, Burkhard Goke, Stephan Brand, Christoph J AuernhammerAbstract:Several studies have established a link between aberrant PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling and Neuroendocrine Tumor disease. In this study, we comparatively investigate the antiTumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antiTumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K-Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling in NET disease. © 2010 Elsevier Ireland Ltd.
James R. Howe - One of the best experts on this subject based on the ideXlab platform.
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The Landmark Series: Neuroendocrine Tumor Liver Metastases
Annals of Surgical Oncology, 2020Co-Authors: Alexandra Gangi, James R. HoweAbstract:Background Neuroendocrine Tumors are becoming increasingly prevalent, with many patients presenting with or developing metastatic disease to the liver. Methods In this landmark series paper, we highlight the critical studies that have defined the surgical management of Neuroendocrine Tumor liver metastases, as well as several randomized control trials which have investigated strategies for systemic control of metastatic disease. Results Liver-directed surgical approaches and locally ablative procedures are recommended for patients with limited, resectable, and in some cases, nonresectable Tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, chemoembolization, and radioembolization, offer another approach for management in patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising therapy for patients with hepatic and/or extrahepatic metastases. Various systemic medical therapies are also available as adjunct or definitive therapy for patients with metastatic disease. Conclusions This article reviews current data regarding management of Neuroendocrine liver metastases and highlights areas for future study.
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the north american Neuroendocrine Tumor society consensus paper on the surgical management of pancreatic Neuroendocrine Tumors
Pancreas, 2020Co-Authors: James R. Howe, Nipun B Merchant, Claudius Conrad, Xavier M Keutgen, Julie Hallet, Jeffrey A Drebin, Rebecca M Minter, Terry C Lairmore, Jennifer F Tseng, Steven K LibuttiAbstract:AbstractThis manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic Neuroendocrine Tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients wit
Kathrin Zitzmann - One of the best experts on this subject based on the ideXlab platform.
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compensatory activation of akt in response to mtor and raf inhibitors a rationale for dual targeted therapy approaches in Neuroendocrine Tumor disease
Cancer Letters, 2010Co-Authors: Kathrin Zitzmann, Janina Von Rüden, Jennifer Lichtl, Gerald Spöttl, Burkhard Goke, Stephan Brand, Christoph J AuernhammerAbstract:Abstract Several studies have established a link between aberrant PI(3)K–Akt–mTOR- and Ras–Raf–MEK–Erk1/2 signaling and Neuroendocrine Tumor disease. In this study, we comparatively investigate the antiTumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antiTumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K-Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K–Akt–mTOR- and Ras–Raf–MEK–Erk1/2 signaling in NET disease.
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Compensatory activation of Akt in response to mTOR and Raf inhibitors - A rationale for dual-targeted therapy approaches in Neuroendocrine Tumor disease
Cancer Letters, 2010Co-Authors: Kathrin Zitzmann, Janina Von Rüden, Jennifer Lichtl, Gerald Spöttl, Burkhard Goke, Stephan Brand, Christoph J AuernhammerAbstract:Several studies have established a link between aberrant PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling and Neuroendocrine Tumor disease. In this study, we comparatively investigate the antiTumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antiTumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K-Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling in NET disease. © 2010 Elsevier Ireland Ltd.
Patrick Michl - One of the best experts on this subject based on the ideXlab platform.
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interaction between somatostatin analogues and targeted therapies in Neuroendocrine Tumor cells
PLOS ONE, 2019Co-Authors: Sebastian Krug, Janphilipp Mordhorst, Fabian Moser, Katharina Theuerkorn, Claudia Ruffert, Maren Egidi, Anja Rinke, Thomas M Gress, Patrick MichlAbstract:Somatostatin analogues (SSA) represent the standard of care for symptom control in patients with functional gastro-entero-pancreatic Neuroendocrine Tumors (GEP-NET). In addition, SSA exert significant anti-proliferative effects in mid-gut and pancreatic NET (PanNET). In parallel, molecularly targeted therapies (MTT) have been shown to improve progression free survival (PFS) in patients with PanNET. However, due to either primary or acquired resistance to MTT, their impact on overall survival (OS) remains unclear. To date, various hypotheses exist to explain differences in patient responsiveness to SSA and MTT. However, data addressing one of the most pivotal questions, whether combining SSA with novel MTT will result in synergistic or additive efficacy compared to monotherapy, are lacking. The aim of this study is to characterize the interaction, optimal sequence and dosing of SSA-based and molecularly targeted therapies in PanNET. Somatostatin receptor subtypes 1–5 (SSTR) were evaluated in the Neuroendocrine cell lines Bon1, QGP1 and Ins-1 via immunoblot and qRT-PCR. The impact of the SSA-analogue lanreotide alone or in combination with the MTT sunitinib, everolimus and regorafenib on intracellular signalling, hormone secretion and cell proliferation was determined in cell lysates and supernatants. In addition, synergistic effects of SSA and MTT in various sequential therapeutic approaches were investigated. SSTR were differently expressed in the examined Neuroendocrine Tumor cell lines. SSTR modulation via lanreotide moderately influenced proliferation, mainly via modulating AKT and ERK signalling, which was paralleled by decreased chromogranin A (CgA) expression and secretion. Interestingly, MTT treatment with regorafenib upregulated the expression of SSTR-2 and -5, while sunitinib and everolimus did not significantly alter SSTR expression. Cell viability was significantly reduced by all MTT, with regorafenib exerting the most significant effects. However, compared to the marked effects of MTT alone, synergistic effects of combined MTT and lanreotide treatment were only modest and time- and dose-dependent. SSTR are differentially expressed in various NEN cell lines. Their expression is influenced by MTT treatment. Various sequential or simultaneous combinations of lanreotide and MTT did not lead to significant synergistic effects.
Chigusa Morizane - One of the best experts on this subject based on the ideXlab platform.
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surgery for pancreatic Neuroendocrine Tumor g3 and carcinoma g3 should be considered separately
Annals of Surgical Oncology, 2019Co-Authors: Tsukasa Yoshida, Susumu Hijioka, Waki Hosoda, Makoto Ueno, Masayuki Furukawa, Noritoshi Kobayashi, Masafumi Ikeda, Tetsuhide Ito, Yuzo Kodama, Chigusa MorizaneAbstract:Background The role of surgery in pancreatic Neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic Neuroendocrine Tumor-G3 (pNET-G3) and pancreatic Neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively.
