Article
Biochemistry & Molecular Biology
Jing Wang, Jingjing Li, Lijuan Yin, Tianjie Pu, Jing Wei, Varsha Karthikeyan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: This study reveals that neuropilin 2 (NRP2) is upregulated in NEPC and plays a role in driving NEPC development and resistance. NRP2 interacts with AR to suppress AR signaling, and activates STAT3 phosphorylation by interacting with VEGFR2, promoting NEPC differentiation and growth.
Article
Biochemistry & Molecular Biology
Damian Jacenik, Eric J. Lebish, Ellen J. Beswick
Summary: The study demonstrates the important role of MK2 in PNETs, with its inhibition improving survival rates in mice and preventing disease progression. MK2 was also found to play a crucial role in regulating tumor metabolism and immune response, providing a new target for PNETs treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Anna M. W. ten Voorde, Annemijn P. A. Wierenga, Rogier J. Nell, Pieter A. van der Velden, Gregorius P. M. Luyten, Robert M. Verdijk, Martine J. Jager
Summary: In uveal melanoma, ANG-2 is identified as an important prognostic factor, with high expression associated with high-risk tumors and metastasis development, making it a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Chandra K. Maharjan, Shaikamjad Umesalma, Courtney A. Kaemmer, Viviane P. Muniz, Casey Bauchle, Sarah L. Mott, K. D. Zamba, Patrick Breheny, Mariah R. Leidinger, Benjamin W. Darbro, Samuel B. Stephens, David K. Meyerholz, Dawn E. Quelle
Summary: The study indicates the significant role of RABL6A in the progression of pNETs, showing that its loss can delay pancreatic tumor formation, reduce tumor angiogenesis and mitoses, and extend survival.
Article
Gastroenterology & Hepatology
Hussein A. Assi, Kathleen Hornbacker, Shagufta Shaheen, Theresa Wittenberg, Robyn Silberman, Pamela L. Kunz
Summary: PRRT is an effective treatment option for somatostatin receptor-positive, unresectable or metastatic neuroendocrine tumors, but some patients may experience rapid disease progression post-therapy. Further research is needed to identify predictive factors of PRRT response/nonresponse for better patient selection.
Article
Gastroenterology & Hepatology
Hussein A. A. Assi, Kathleen Hornbacker, Shagufta Shaheen, Theresa Wittenberg, Robyn Silberman, Pamela L. L. Kunz
Summary: PRRT is an effective treatment option for somatostatin receptor-positive NETs, however, some patients with mixed cell populations may have limited response. In this study, 7 patients treated with Lu-177-DOTATATE PRRT at Stanford Cancer Center showed progression of disease within or shortly after treatment, suggesting the need for further research on predictive factors for treatment response.
Article
Oncology
Shota Amano, Teijiro Hirashita, Yoko Kawano, Haruto Nishida, Hiroki Orimoto, Masahiro Kawamura, Takahide Kawasaki, Takashi Masuda, Yuichi Endo, Masayuki Ohta, Tsutomu Daa, Masafumi Inomata
Summary: Survivin and XIAP expression correlated with the malignancy of PanNET, with XIAP expression associated with a poor prognosis. The expression of these proteins may serve as useful indicators for selecting optimal therapeutic agents in PanNET.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Cell Biology
Yu Chen, Tatsuki Yamamoto, Yura Takahashi, Tomoka Moro, Tomoko Tajima, Yukiko Sakaguchi, Naoaki Sakata, Akihiko Yokoyama, Susumu Hijioka, Akane Sada, Yuko Tabata, Rieko Ohki
Summary: Insulin signaling plays a role in cancer regulation, and the PI3K-Akt-mTOR pathway is hyperactivated in PanNETs. A ketogenic diet resulted in lower PI3K-Akt-mTOR signaling, reducing the formation and progression of PanNETs. Lower blood glucose levels in non-functional PanNET patients are associated with better prognosis. This preclinical study highlights the suppressive effect of a dietary intervention on pancreatic and pituitary NETs through lower insulin signaling.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Ha -Ram Park, Anahita Shiva, Portia Cummings, Seoyeon Kim, Sungsoo Kim, Eunhyeong Lee, Alessandra Leong, Subrata Chowdhury, Carrie Shawber, Richard Carvajal, Gavin Thurston, Joon-Yong An, Amanda W. Lund, Hee Won Yang, Minah Kim
Summary: The position of T-cells in the tumor microenvironment affects their ability to encounter the tumor and kill it. The vascular destabilizing factor ANGPT2 causes vascular integrity issues in the tumor periphery, leading to a lack of T-cell infiltration in the tumor core, which is associated with a poor response to immunotherapy.
Review
Oncology
Ugo Marchese, Martin Gaillard, Anna Pellat, Stylianos Tzedakis, Einas Abou Ali, Anthony Dohan, Maxime Barat, Philippe Soyer, David Fuks, Romain Coriat
Summary: This review focuses on the classification and treatment options for pancreatic neuroendocrine tumors (pNETs), with a special emphasis on benign tumors. The article discusses different treatment approaches from the perspectives of oncologists and surgeons, and highlights the advantages of minimally invasive surgery.
Article
Immunology
Amelie Marguier, Caroline Laheurte, Benoit Lecoester, Marine Malfroy, Laura Boullerot, Adeline Renaudin, Evan Seffar, Abhishek Kumar, Charlee Nardin, Francois Aubin, Olivier Adotevi
Summary: This study investigates a novel subset of monocytic MDSCs called TIE-2(+) M-MDSCs in melanoma patients. These cells show a highly immunosuppressive phenotype and are associated with the pro-angiogenic factor ANGPT2. The study demonstrates that exposure to ANGPT2 increases the immune suppressive function of TIE-2(+) M-MDSCs and that active TIE-2 signaling is required for optimal suppressive activity. This suggests that the TIE-2(+) M-MDSC/ANGPT2 axis may play a role in immune escape in melanoma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Junfeng Xu, Zeng Ye, Qifeng Zhuo, Heli Gao, Yi Qin, Xin Lou, Wuhu Zhang, Fei Wang, Yan Wang, Desheng Jing, Guixiong Fan, Yue Zhang, Xuemin Chen, Jie Chen, Xiaowu Xu, Xianjun Yu, Shunrong Ji
Summary: Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors in the pancreas. The MEN1 protein expression in PanNETs is regulated by the neddylation pathway and DCAF7-mediated ubiquitination. Inhibition of neddylation increases MEN1 protein expression and represses cancer-related malignant phenotypes. Downregulation of DCAF7 overcomes resistance to everolimus and synergizes with it to suppress mTOR activation and inhibit cancer cell growth. The study identifies potential therapeutic targets for treating MEN1-associated PanNETs.
Review
Pathology
Sylvia L. Asa, Ozgur Mete, Michael D. Cusimano, Ian E. McCutcheon, Arie Perry, Shozo Yamada, Hiroshi Nishioka, Olivera Casar-Borota, Silvia Uccella, Stefano La Rosa, Ashley B. Grossman, Shereen Ezzat
Summary: The classification of adenohypophysial neoplasms as pituitary neuroendocrine tumors (PitNETs) reflects their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors. Tumor growth and hormone hypersecretion can cause significant morbidity and mortality in patients. The intense study of PitNETs has provided important information about the importance of cellular differentiation in tumor prognosis.
Article
Cell Biology
Lin Wang, Shengnan Wang, Aijuan Xue, Jieru Shi, Cuifang Zheng, Ying Huang
Summary: Thalidomide can effectively reduce the levels of VEGF and Ang-2 in pediatric CD patients, thereby inhibiting angiogenesis in the intestines and potentially alleviating the disease.
Article
Dentistry, Oral Surgery & Medicine
Chenxi Jiang, Siqi Yao, Yi Guo, Li Ma, Xiaoxuan Wang, Yuan Chen, Huihui Zhang, Zhengguo Cao
Summary: The study demonstrates an anti-inflammatory effect of ANGPTL2 in murine periodontitis, showing its critical and protective role in protecting alveolar bone and reducing inflammatory reactions.
JOURNAL OF PERIODONTOLOGY
(2022)
Review
Endocrinology & Metabolism
Katharina Detjen, Linda Hammerich, Burcin Oezdirik, Munevver Demir, Bertram Wiedenmann, Frank Tacke, Henning Jann, Christoph Roderburg
Summary: GEP-NENs are rare and heterogeneous tumors originating from the endocrine system of the gastrointestinal tract and pancreas. Limited data from large prospective clinical trials are available for treatment recommendations, which are mainly based on retrospective analyses or case series. More tractable disease models are needed to better understand and predict treatment response in patients.
NEUROENDOCRINOLOGY
(2021)
Article
Gastroenterology & Hepatology
Kate Young, Rita T. Lawlor, Chanthirika Ragulan, Yatish Patil, Andrea Mafficini, Samantha Bersani, Davide Antonello, David Mansfield, Sara Cingarlini, Luca Landoni, Antonio Pea, Claudio Luchini, Liliana Piredda, Nagarajan Kannan, Gift Nyamundanda, Daniel Morganstein, Ian Chau, Bertram Wiedenmann, Michele Milella, Alan Melcher, David Cunningham, Naureen Starling, Aldo Scarpa, Anguraj Sadanandam
Summary: This study performed a comprehensive analysis of the immune landscape of PanNETs, identifying the MLP-1 subtype as an immune-high phenotype characterized by broad and robust activation of immune-related genes. The MLP-1 subtype was strongly associated with elevated levels of immune-related genes, poor prognosis, and various tumor evolutionary events, providing potential for future precision immunotherapy studies to select patients who may respond more favorably.
Article
Endocrinology & Metabolism
Bruno Niederle, Andreas Selberherr, Detlef K. Bartsch, Maria L. Brandi, Gerard M. Doherty, Massimo Falconi, Pierre Goudet, Thorvardur R. Halfdanarson, Tetsuhide Ito, Robert T. Jensen, Alberto Larghi, Lingaku Lee, Kjell Oberg, Marianne Pavel, Aurel Perren, Samira M. Sadowski, Francesco Tonelli, Frederic Triponez, Gerlof D. Valk, Dermot O'Toole, David Scott-Coombes, Rajesh V. Thakker, Geoffrey B. Thompson, Giorgio Treglia, Bertram Wiedenmann
Summary: An international consortium of experts systematically reviewed the literature on the diagnosis and treatment of DP-NENs within the MEN1 syndrome based on the highest levels of evidence, aiming to standardize and improve treatment and follow-up. The consensus statement builds upon previously published guidelines and aims to supplement recommendations from national and international societies.
NEUROENDOCRINOLOGY
(2021)
Article
Medicine, General & Internal
Burcin ozdirik, Henning Jann, Philip Bischoff, Uli Fehrenbach, Frank Tacke, Christoph Roderburg, Bertram Wiedenmann
Summary: Although ICIs have been approved for the treatment of various cancers, their efficacy in neuroendocrine neoplasia is limited and poorly understood. Current treatment options based on surgery, tumor-targeted medical treatments, PRRT, and locoregional therapies often lose efficacy over time, highlighting the need for novel therapies.
Article
Endocrinology & Metabolism
Rodney J. Hicks, Clarisse Dromain, Wouter W. de Herder, Frederico P. Costa, Christophe M. Deroose, Andrea Frilling, Anna Koumarianou, Eric P. Krenning, Eric Raymond, Lisa Bodei, Halfdan Sorbye, Staffan Welin, Bertram Wiedenmann, Damian Wild, James R. Howe, James Yao, Dermot O'Toole, Anders Sundin, Vikas Prasad
Summary: ENETS aims to improve the standard of care for patients with neuroendocrine neoplasms (NEN) by providing standardized reporting guidance for diagnostic studies, including pathology, radiology, endoscopy, and molecular imaging. A reporting template for personalized therapies in molecular imaging procedures has been developed and is undergoing pilot implementation within the ENETS Center of Excellence network, with plans for harmonization with other specialist imaging societies.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Surgery
Federica Branchi, Rolf Klingenberg-Noftz, Kristina Friedrich, Nataly Burgel, Severin Daum, Juliane Buchkremer, Elena Sonnenberg, Michael Schumann, Christoph Treese, Hanno Troger, Donata Lissner, Hans-Jorg Epple, Britta Siegmund, Andrea Stroux, Andreas Adler, Winfried Veltzke-Schlieker, Daniel Autenrieth, Silke Leonhardt, Andreas Fischer, Christian Jurgensen, Ulrich-Frank Pape, Bertram Wiedenmann, Oliver Moschler, Maximilian Schreiner, Mathias Z. Strowski, Volkmar Hempel, Yvonne Huber, Helmut Neumann, Christian Bojarski
Summary: PuraStat gel is an effective tool for treating gastrointestinal bleeding, safely applicable as both primary and secondary therapy, and can serve as a bridge to surgery for temporary haemostasis. It shows high efficacy with low rebleeding rates.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2022)
Article
Oncology
E. Merola, A. Pascher, A. Rinke, D. K. Bartsch, A. Zerbi, G. Nappo, C. Carnaghi, M. Ciola, M. G. McNamara, W. Zandee, E. Bertani, S. Marcucci, R. Modica, R. Gruetzmann, N. Fazio, W. de Herder, J. W. Valle, T. M. Gress, G. Delle Fave, G. de Pretis, A. Perren, B. Wiedenmann, M. E. Pavel
Summary: This retrospective study analyzed completely resected EP-NETs and found that approximately 30% of patients experience recurrence within 5 years after radical surgery. Through multivariable analysis, a prognostic score was determined, which includes TNM stage, lymph node ratio, margin status, and grading. The results of this study aid in identifying high-risk patients for recurrence and selecting appropriate adjuvant treatments and intensive follow-up programs.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anja Klussmeier, Stefan Aurich, Lars Niederstadt, Bertram Wiedenmann, Carsten Groetzinger
Summary: This study demonstrates high overexpression of SCTR in esophageal and pancreatic cancer and identifies key amino acids that play a crucial role in the binding and activation of secretin with SCTR. Alterations in these structures affect their activity in cells. Future research needs to explore the application of further enhanced secretin analogues in tumor imaging and therapy.
Editorial Material
Oncology
E. Merola, A. Pascher, A. Rinke, D. K. Bartsch, A. Zerbi, G. Nappo, C. Carnaghi, M. Ciola, M. G. McNamara, W. Zandee, E. Bertani, S. Marcucci, R. Modica, R. Gruetzmann, N. Fazio, W. de Herder, J. W. Valle, T. M. Gress, G. Delle Fave, G. de Pretis, A. Perren, B. Wiedenmann, M. E. Pavel
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
Elettra Merola, Aurel Perren, Anja Rinke, Alessandro Zerbi, Mairead G. McNamara, Ruza Arsenic, Nicola Fazio, Wouter de Herder, Juan W. Valle, Thomas M. Gress, Bertram Wiedenmann, Andreas Pascher, Marianne E. Pavel
Summary: The study found that in more than half of the cases with relapse after radical surgery for entero-pancreatic neuroendocrine tumors, a higher proliferative index and potentially more aggressive behavior were observed. Therefore, histological reassessment should be considered at disease recurrence to guide tailored therapeutic strategies.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Gastroenterology & Hepatology
Leonie Schuhmacher, Christian Bojarski, Victoria Reich, Andreas Adler, Winfried Veltzke-Schlieker, Christian Jurgensen, Bertran Wiedenmann, Britta Siegmund, Federika Branchi, Julianne Buchkremer, Steffen Hornoff, Dirk Hartmann, Christoph Treese
Summary: This study retrospectively compared the complication rates of the classical pull-through and direct puncture techniques for percutaneous endoscopic gastrostomy (PEG). The results showed that the direct puncture technique had a lower complication rate compared to the pull-through technique.
ENDOSCOPY INTERNATIONAL OPEN
(2022)
Article
Oncology
Raik Otto, Katharina M. Detjen, Pamela Riemer, Melanie Fattohi, Carsten Groetzinger, Guido Rindi, Bertram Wiedenmann, Christine Sers, Ulf Leser
Summary: Machine learning approaches can improve the classification accuracy of neuroendocrine neoplasms (NEN), but usually require large amounts of training data. This study used machine learning-aided classification based on the similarity between NEN and non-transformed pancreatic cell types to predict patient survival time, neoplastic grading, and carcinoma versus tumor subclassification, providing additional criteria for confident classification of ambiguous cases.
Article
Oncology
Wiebke Werner, Katharina Detjen, Alix Bruneau, Isabella Lurje, Natalie Nestel, Henning Jann, Frank Tacke, Bertram Wiedenmann, Christoph Roderburg, Linda Hammerich
Summary: In a retrospective study on neuroendocrine tumors, the levels of FLT3LG mRNA were found to be correlated with the abundance of immune cells cDC and T cells, which also predicted disease-specific survival. The combination of FLT3LG and T cell counts improved this prediction, suggesting their potential as prognostic markers.
ENDOCRINE-RELATED CANCER
(2023)
Article
Oncology
Evelyn Kidess, Yvonne Giesecke, Ines Eichhorn, Raphael Mohr, Henning Jann, Christian Fischer, Bertram Wiedenmann, Christoph Roderburg, Frank Tacke, Michael Sigal
Summary: The study aimed to analyze plasma concentrations of OPN in patients with NEN and explore its diagnostic and prognostic value. The results showed that OPN levels were significantly higher in NEN patients compared to healthy controls, with the highest levels in high-grade tumors (grade 3). In addition, patients with initial OPN levels above 200 ng/ml had a poor prognosis in terms of shorter progression-free survival, both in the overall NEN patient group and within the subgroup of well-differentiated G1/G2 tumors. Therefore, OPN can serve as a surrogate prognostic biomarker in NEN patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Oncology
Frederico Costa, Bertram Wiedenmann, Christoph Roderburg, Raphael Mohr, Ghassan K. Abou-Alfa
Summary: Hepatocellular carcinoma (HCC) is a leading cause of death in liver cirrhosis patients. Immuno-oncology has revolutionized the treatment for advanced HCC, but most trials exclude patients with moderate liver dysfunction. Patients with HCC and moderate liver dysfunction have a low overall survival rate with sorafenib treatment, indicating the need for improved treatment strategies.
