Review
Oncology
Megan L. Sulciner, Thomas E. Clancy
Summary: Pancreatic neuroendocrine tumors (PNETs) are rare malignancies characterized by secretion of hormones. Tumor grade, determined by Ki67 proliferation index and mitotic index, is the primary prognostic indicator. Surgery is the main treatment for PNETs, with functional PNETs requiring resection for symptom control and potential cure, while nonfunctional PNETs are increasingly managed nonoperatively. Evidence supports surgical management of metastatic disease and primary tumor in the presence of widespread metastases. In this review, we discuss the evolving surgical management of local and metastatic PNETs.
Review
Endocrinology & Metabolism
Arnaud Jannin, Anne-Frederique Dessein, Christine Do Cao, Marie-Christine Vantyghem, Benjamin Chevalier, Isabelle Van Seuningen, Nicolas Jonckheere, Lucie Coppin
Summary: Reprogramming of cellular metabolism is a hallmark of tumorigenesis. In this review, the metabolic pathways in pancreatic neuroendocrine tumors (pNETs) were investigated by analyzing transcriptomic and metabolomic data. Dysregulations in one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism were identified in pNETs, which are implicated in cell proliferation and metastasis and could potentially serve as prognostic biomarkers or therapeutic targets.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Jacques Greenberg, Jessica Limberg, Akanksha Verma, David Kim, Xiang Chen, Yeon J. Lee, Maureen D. Moore, Timothy M. Ullmann, Jessica W. Thiesmeyer, Zachary Loewenstein, Kevin J. Chen, Caitlin E. Egan, Dessislava Stefanova, Rohan Bareja, Rasa Zarnegar, Brendan M. Finnerty, Theresa Scognamiglio, Yi-Chieh Nancy Du, Olivier Elemento, Thomas J. Fahey III, Irene M. Min
Summary: This study investigates the therapeutic options for metastatic pancreatic neuroendocrine tumors (PNETs). The results suggest that remodeling the tumor microenvironment (TME) may enhance susceptibility to immunotherapy. The TMEs of localized and metastatic PNETs were analyzed, revealing activation of inflammatory and immune-related pathways in metastatic tumors. Additionally, a histone deacetylase inhibitor, vorinostat, was shown to increase chemokine expression and enhance recruitment of T cells in PNET tissues.
Article
Oncology
Alexander R. Siebenhuener, Melanie Langheinrich, Juliane Friemel, Niklaus Schafer, Dilmurodjon Eshmuminov, Kuno Lehmann
Summary: This review provides an updated view on treatment options for metastatic pancreatic neuroendocrine tumors (pNETs) and emphasizes the importance of selecting the right timing for surgery in the context of multimodal treatment.
Review
Gastroenterology & Hepatology
Jelani K. Williams, Jason L. Schwarz, Xavier M. Keutgen
Summary: Pancreatic neuroendocrine tumors (PanNETs) derived from the islet cells of the pancreas are increasing in incidence. Surgery is the main treatment for localized tumors, but there is controversy surrounding surgery for metastatic PanNETs. Many studies have shown a survival and symptomatic benefit to surgery and liver debulking in select groups of patients.
HEPATOBILIARY SURGERY AND NUTRITION
(2023)
Review
Gastroenterology & Hepatology
Jelani K. Williams, Jason L. Schwarz, Xavier M. Keutgen
Summary: Pancreatic neuroendocrine tumors (PanNETs) are increasing in incidence and have different treatment approaches depending on whether they are localized or metastatic. Surgery is the main treatment for localized tumors, but its role is controversial in metastatic PanNETs. This narrative review summarizes the current literature on surgery in metastatic PanNETs and highlights the need for further research.
HEPATOBILIARY SURGERY AND NUTRITION
(2023)
Article
Oncology
Sergey Klimov, Yue Xue, Arkadiusz Gertych, Rondell P. Graham, Yi Jiang, Shristi Bhattarai, Stephen J. Pandol, Emad A. Rakha, Michelle D. Reid, Ritu Aneja
Summary: This study presents a machine learning approach to predict the risk of metastasis in PanNET patients using morphological information. By analyzing tissue slides from PanNET patients, a model was developed to identify different tissues and predict the risk of metastasis. The results show that the model can effectively distinguish between high-risk and low-risk patients, with significant predictive performance for grade I/II patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Jordan M. Cloyd, George A. Poultsides
Summary: PNETs are a rare type of tumor originating from pancreatic islet cells, with surgical resection being the standard treatment for most patients and pancreas-preserving approaches being acceptable for smaller tumors. Observation is recommended for small, low-grade PNETs.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Yuanxiang Lu, Wensen Li, Senmao Mu, Lianyuan Tao, Guoyi Yan, Erwei Xiao, Liancai Wang, Deyu Li
Summary: This study investigated the prognostic significance of tumor budding in Grade 1-2 PNETs and found that high-grade budding is associated with aggressive histopathological parameters and is an independent predictive factor for postoperative liver metastasis. PNETs with high-grade budding also have worse overall survival and disease-free survival. Incorporating tumor budding into histopathological reports may aid in appropriate clinical management.
JOURNAL OF SURGICAL ONCOLOGY
(2021)
Article
Gastroenterology & Hepatology
Marc Altimari, John Abad, Akhil Chawla
Summary: The study found that there was no difference in survival rates between patients with PNETs <2 cm who underwent enucleation versus oncologic resection. Ten percent of clinically node-negative patients were node-positive after surgery. Therefore, patients who receive enucleation may benefit from enhanced surveillance for locoregional recurrence, especially those with higher grade and larger size tumors.
Article
Genetics & Heredity
Midie Xu, Jiuliang Yan, Beiyuan Hu, Chuntao Wu, Haitao Gu, Zihao Qi, Tao Chen, Wenting Yang, Yan Zheng, Hanguang Dong, Weiqi Sheng, Jiang Long
Summary: This study analyzed the genomic variations between primary and metastatic tumors in PanNETs patients, finding low genomic heterogeneity and evidence of polyclonal seeding during metastatic progression. Copy number variations of BRCA1/BRCA2 were associated with better prognosis. Pathways in cancer, DNA repair, and cell cycle regulation were significantly enriched. The study provides novel insight into genetic changes in metastatic tumors of PanNETs.
Article
Surgery
Zheng Zhang, Fei Wang, Zheng Li, Zeng Ye, Qifeng Zhuo, Wenyan Xu, Wensheng Liu, Mengqi Liu, Guixiong Fan, Yi Qin, Yue Zhang, Xuemin Chen, Xianjun Yu, Xiaowu Xu, Shunrong Ji
Summary: This study found that lymph node metastasis (LNM) is associated with poorer prognosis in pancreatic neuroendocrine tumors (pNET), but only in grade 2/3 tumors is there a significant correlation. Additionally, tumor grade and size appear to be independent predictors of LNM. Therefore, regional lymphadenectomy should be performed in grade 2/3 tumors, while functional sparing surgery or clinical monitoring may be considered for grade 1 tumors.
Article
Endocrinology & Metabolism
Yiying Guo, Chao Tian, Zixuan Cheng, Ruao Chen, Yuanliang Li, Fei Su, Yanfen Shi, Huangying Tan
Summary: The low treatment response to standard therapy in metastatic pancreatic neuroendocrine tumors (PanNETs) is mainly due to tumor heterogeneity. Investigating the heterogeneity between primary PanNETs and metastases can improve treatment precision. The study revealed that certain gene mutations in metastases have unfavorable prognostic effects, and there are a high number of potential targetable alterations in metastases.
NEUROENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Tincy Simon, Pamela Riemer, Armin Jarosch, Katharina Detjen, Annunziata Di Domenico, Felix Bormann, Andrea Menne, Slim Khouja, Nanna Monje, Liam H. Childs, Dido Lenze, Ulf Leser, Florian Rossner, Markus Morkel, Nils Bluethgen, Marianne Pavel, David Horst, David Capper, Ilaria Marinoni, Aurel Perren, Soulafa Mamlouk, Christine Sers
Summary: Pancreatic neuroendocrine neoplasms (PanNENs) can be classified into two subclasses: well-differentiated PanNETs and poorly-differentiated high-grade PanNECs. Recent studies have shown that high-grade PanNECs originate from exocrine cells, distinguishing them in cell lineage from other endocrine-origin PanNETs. This study provides a method to clearly distinguish PanNECs from G3 PanNETs, improving patient stratification.
Article
Oncology
Min Shi, Biao Zhou
Summary: This study analyzed the clinical characteristics and prognosis of patients under 50 years old with PNETs, and found that younger patients have unique clinicopathological characteristics compared with older patients, and they have better overall survival.
Article
Hematology
Yajie Shen, Jingqi Zhou, Kui Nie, Shuhua Cheng, Zhengming Chen, Wenhan Wang, Weiqing Wei, Daiji Jiang, Zijing Peng, Yizhuo Ren, Yirong Zhang, Qiuju Fan, Kristy L. Richards, Yitao Qi, Jinke Cheng, Wayne Tam, Jiao Ma
Summary: This study reveals that SOX9 overexpression, particularly in DLBCLs with IGH-BCL2 translocations, is associated with an advanced stage of disease. Silencing of SOX9 decreases cell proliferation and induces G1/S arrest and apoptosis in DLBCL cells, both in vitro and in vivo. The study identifies DHCR24 as a direct target of SOX9 and demonstrates that the SOX9-DHCR24-cholesterol biosynthesis axis plays a role in lymphomagenesis. The findings suggest that this axis could serve as a novel treatment target for DLBCLs.
Article
Oncology
Ok-Kyong Chaekal, Rosemary Soave, Zhengming Chen, Tsiporah Shore, Sebastian Mayer, Adrienne Phillips, Jing Mei Hsu, Alexandra Gomez-Arteaga, Hanna Rennert, Alex Drelick, Nina Orfali, Thomas J. Walsh, Catherine B. Small, Rosy Priya L. Kodiyanplakkal, Markus Plate, Michael J. Satlin, Koen van Besien
Summary: The study found that the incidence of adenovirus viremia was relatively high after allogeneic transplants, especially in patients receiving cord blood transplants. The control of adenovirus disease was mainly affected by the lymphocyte count.
LEUKEMIA & LYMPHOMA
(2022)
Article
Oncology
Meng Wu, Yun Li, Huiqiang Huang, Wei Xu, Yanyan Wang, Haiwen Huang, Weili Zhao, Shuo Liu, Pengpeng Xu, Zhengming Chen, Jun Zhu, Yuqin Song, Jia Ruan, Depei Wu
Summary: This study retrospectively analyzed data from 518 Chinese patients with mantle cell lymphoma (MCL) to determine the disease characteristics, initial treatment patterns, and survival in a real-world setting. The results showed that cytarabine-containing regimen and autologous stem cell transplantation (ASCT) in the first-line setting had a survival advantage.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Yuling Han, Jiajun Zhu, Liuliu Yang, Benjamin E. Nilsson-Payant, Romulo Hurtado, Lauretta A. Lacko, Xiaolu Sun, Aravind R. Gade, Christina A. Higgins, Whitney J. Sisso, Xue Dong, Maple Wang, Zhengming Chen, David D. Ho, Geoffrey S. Pitt, Robert E. Schwartz, Benjamin R. TenOever, Todd Evans, Shuibing Chen
Summary: This study investigates the impact of SARS-CoV-2 infection on the pacemaker cells of the heart, using a hamster model and human embryonic stem cells. The researchers found that the virus can infect the primary pacemaker cells in the heart and cause dysfunction. They also identified two drugs that can block the infection and virus-induced ferroptosis.
CIRCULATION RESEARCH
(2022)
Article
Oncology
Xiaonan Xu, Kaizhen Wang, Olga Vera, Akanksha Verma, Neel Jasani, Ilah Bok, Olivier Elemento, Dongliang Du, Xiaoqing Yu, Florian A. Karreth
Summary: The study reveals that ceRNAs play a crucial role in the oncogenic effects of somatic copy-number alterations (CNA), sequestering tumor suppressor microRNAs and promoting cancer progression and metastasis.
Article
Gastroenterology & Hepatology
Jacques A. Greenberg, Nikolay A. Ivanov, Caitlin E. Egan, Yeon Joo Lee, Rasa Zarnegar, Thomas J. Fahey, Brendan M. Finnerty, Irene M. Min
Summary: This study investigated sex-based differences in clinicopathologic features and survival among patients with PNETs, as well as correlations with mutational signatures. Men tended to have larger tumors compared to women, but differences in mutational signatures between the sexes did not significantly impact overall survival.
JOURNAL OF GASTROINTESTINAL SURGERY
(2022)
Article
Surgery
Timothy M. Ullmann, Heng Liang, Hector Mora, Jacques Greenberg, Katherine D. Gray, Jessica Limberg, Dessislava Stefanova, Xin Zhu, Brendan Finnerty, Toni Beninato, Rasa Zarnegar, Irene Min, Thomas J. Fahey
Summary: The study investigated the effects of polybrominated diphenyl ethers (PBDEs) and tris(2-chloroethyl) phosphate (TCEP) on thyrocytes. PBDEs demonstrated genotoxicity but not cytotoxicity in follicular thyrocytes in vitro. These findings suggest that PBDEs may have carcinogenic potential in human thyroid cells.
JOURNAL OF SURGICAL RESEARCH
(2022)
Article
Oncology
Rachel Martini, Princesca Delpe, Timothy R. Chu, Kanika Arora, Brittany Lord, Akanksha Verma, Deepa Bedi, Balasubramanyam Karanam, Isra Elhussin, Yalei Chen, Endale Gebregzabher, Joseph K. Oppong, Ernest K. Adjei, Aisha Jibril Suleiman, Baffour Awuah, Mahteme Bekele Muleta, Engida Abebe, Ishmael Kyei, Frances S. Aitpillah, Michael O. Adinku, Kwasi Ankomah, Ernest Baawuah Osei-Bonsu, Dhananjay A. Chitale, Jessica M. Bensenhaver, David S. Nathanson, LaToya Jackson, Lindsay F. Petersen, Erica Proctor, Brian Stonaker, Kofi K. Gyan, Lee D. Gibbs, Zarko Monojlovic, Rick A. Kittles, Jason White, Clayton C. Yates, Upender Manne, Kevin Gardner, Nigel Mongan, Esther Cheng, Paula Ginter, Syed Hoda, Olivier Elemento, Nicolas Robine, Andrea Sboner, John D. Carpten, Lisa Newman, Melissa B. Davis
Summary: Women of sub-Saharan African descent have a higher incidence and mortality rate of triple-negative breast cancer (TNBC). This study conducted RNA sequencing on African Americans and Africans with TNBC, revealing associations between African ancestry and gene expression profiles and immunologic landscapes. These findings may explain the racial differences in clinical outcomes.
Article
Medicine, Research & Experimental
Jacques Greenberg, Jessica Limberg, Akanksha Verma, David Kim, Xiang Chen, Yeon J. Lee, Maureen D. Moore, Timothy M. Ullmann, Jessica W. Thiesmeyer, Zachary Loewenstein, Kevin J. Chen, Caitlin E. Egan, Dessislava Stefanova, Rohan Bareja, Rasa Zarnegar, Brendan M. Finnerty, Theresa Scognamiglio, Yi-Chieh Nancy Du, Olivier Elemento, Thomas J. Fahey III, Irene M. Min
Summary: This study investigates the therapeutic options for metastatic pancreatic neuroendocrine tumors (PNETs). The results suggest that remodeling the tumor microenvironment (TME) may enhance susceptibility to immunotherapy. The TMEs of localized and metastatic PNETs were analyzed, revealing activation of inflammatory and immune-related pathways in metastatic tumors. Additionally, a histone deacetylase inhibitor, vorinostat, was shown to increase chemokine expression and enhance recruitment of T cells in PNET tissues.
Article
Endocrinology & Metabolism
Jessica W. Thiesmeyer, Caitlin E. Egan, Jacques A. Greenberg, Toni Beninato, Rasa Zarnegar, Thomas J. Fahey III, Brendan M. Finnerty
Summary: Pediatric papillary thyroid carcinomas (PTCs) are more invasive than adult PTCs. Younger children with PTC present with more extensive disease burden and a higher likelihood of nodal and distant metastases at the time of diagnosis, although survival is high.
Article
Oncology
Prashasti Agrawal, Kevin A. A. David, Zhengming Chen, Suchitra Sundaram, Seo-Hyun Kim, Ryan Vaca, Yong Lin, Samuel Singer, Mary-Kate Malecek, Jordan Carter, Adam Zayac, Myung Sun Kim, Nishitha Reddy, Douglas Ney, Alma Habib, Christopher Strouse, Jerome Graber, Veronika Bachanova, Sidra Salman, Jean A. A. Vendiola, Nasheed Hossain, Mazie Tsang, Ajay Major, Maher K. K. Gandhi, Colm Keane, David A. A. Bond, Matthew Folstad, Julie Chang, Angel Mier-Hicks, Pallawi Torka, Priya Rajakumar, Parameswaran Venugopal, Stephanie Berg, Michael Glantz, Samuel A. A. Goldlust, Rahul Matnani, Pallavi Kumar, Thomas A. A. Ollila, Johnny Cai, Stephen E. E. Spurgeon, Alex G. G. Sieg, Joseph Cleveland, Narendranath Epperla, Reem Karmali, Seema Naik, Sonali M. M. Smith, James L. L. Rubenstein, Brad S. S. Kahl, Amy Chadburn, Andrew M. M. Evens, Peter Martin
Summary: The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. The study found that 11.7% of CNSL patients aged ≥ 60 had EBV + tumors, mainly solid organ transplant-related post-transplant lymphoproliferative disorders (PTLD). EBV positive tumors were associated with younger age, solid organ transplant or autoimmune disease, and immunosuppressive treatment. Furthermore, EBV + PTLD had a shorter median overall survival compared to EBV + non-PTLD and EBV-negative patients.
LEUKEMIA & LYMPHOMA
(2023)
Article
Multidisciplinary Sciences
Yanping Yang, Huan Yang, Yago Alcaina, Janusz Puc, Alyssa Birt, Yogindra Vedvyas, Michael Gallagher, Srinija Alla, Maria Cristina Riascos, Jaclyn E. McCloskey, Karrie Du, Juan Gonzalez-Valdivieso, Irene M. M. Min, Elisa de Stanchina, Matt Britz, Eric von Hofe, Moonsoo M. M. Jin
Summary: This study describes a strategy to promote the recognition of tumor cells while sparing normal cells by combining affinity tuning and inducible interleukin-12 expression.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Jessica Limberg, Caitlin E. Egan, Katherine D. Gray, Mandeep Singh, Zachary Loewenstein, Yanping Yang, Maria Cristina Riascos, Hala Al Asadi, Parima Safe, Steve El Eshaky, Heng Liang, Timothy M. Ullmann, Weibin Wang, Wei Li, Tuo Zhang, Jenny Xiang, Dessislava Stefanova, Moonsoo M. Jin, Rasa Zarnegar, Thomas J. Fahey III, Irene M. Min
Summary: A subset of thyroid cancers, including recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat with current methods. A study found that the BRAFV600E mutation, while effective in melanoma, only showed temporary activation of the molecular pathway in thyroid cancer cells. However, further analysis revealed that the JAK/STAT pathway is significantly activated in response to BRAFi and is associated with recurrence and prognosis in thyroid cancer patients.
MOLECULAR CANCER RESEARCH
(2023)
Article
Oncology
Yanping Yang, Raymond Louie, Janusz Puc, Yogindra Vedvyas, Yago Alcaina, Irene M. Min, Matt Britz, Fabio Luciani, Moonsoo M. Jin
Summary: This study investigates the interactions between CAR T cells targeting EpCAM and tumor cells in a xenograft model of gastric cancer. The research reveals that within resistant tumors, CAR T cells proliferate but become largely dysfunctional, and CD4 T cells transform into regulatory T cells. The resistant tumor cells also exhibit specific gene changes that promote cancer growth. The study provides valuable insights into the mechanisms of resistance to CAR T cell therapy and may guide future developments in cancer treatment.