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.
Article
Biochemistry & Molecular Biology
Samuel B. Bader, Tiffany S. Ma, Charlotte J. Simpson, Jiachen Liang, Sakura Eri B. Maezono, Monica M. Olcina, Francesca M. Buffa, Ester M. Hammond
Summary: This study demonstrates that fluctuating hypoxic conditions inducing replication catastrophe lead to increased expression and activity of APOBEC3B, contributing to the accumulation of APOBEC-mediated mutations. In contrast, stable hypoxic conditions do not significantly impact APOBEC3B. The number of APOBEC-mediated mutations in patient tumors is closely correlated with a hypoxia signature, indicating that hypoxia-induced replication catastrophe drives genomic instability in tumors through increasing the activity of APOBEC3B.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Oncology
Eduardo de Souza M. Fernandes, Camila V. Garcia Kyt, Felipe Pedreira Tavares de Mello, Leandro Savattone Pimentel, Ronaldo de Oliveira Andrade, Camila Girao, Camilla Cesar, Munique Siqueira, Maria Eduarda Monachesi, Anderson Brito, Claudia Cristina Tavares de Sousa, Wellington Andraus, Orlando Jorge M. Torres
Summary: Neuroendocrine tumors are a diverse group of tumors found in various organs such as the gastrointestinal tract, lungs, thymus, thyroid, and adrenal glands. These tumors, particularly in the small intestine, appendix, and pancreas, often have metastases upon diagnosis. Classification of neuroendocrine tumors is based on cell differentiation and proliferation index. Treatment options for metastatic neuroendocrine tumors include surgery, peptide receptor radionuclide therapy, percutaneous therapy, chemotherapy, and radiotherapy. Liver surgery, specifically orthotopic liver transplantation, has shown promising results in selected cases. The aim of this study is to review the literature on orthotopic liver transplantation as a curative treatment for gastroenteropancreatic neuroendocrine tumors with liver metastasis.
FRONTIERS IN ONCOLOGY
(2023)
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
Biochemistry & Molecular Biology
Valentina Melocchi, Elisa Dama, Francesco Mazzarelli, Roberto Cuttano, Tommaso Colangelo, Leonarda Di Candia, Enrico Lugli, Giulia Veronesi, Giuseppe Pelosi, Gian Maria Ferretti, Marco Taurchini, Paolo Graziano, Fabrizio Bianchi
Summary: This research identified a specific subset of lung adenocarcinoma called C1-LUAD, characterized by aggressive behavior, stem cell-like characteristics, mutator and immune evasion phenotypes. Using a 10-gene prognostic signature, poor prognosis patients with this molecular subtype can be identified, suggesting potential alternative therapeutic strategies for early-stage aggressive LUAD.
Article
Oncology
Charlie D. Zhou, Andreas Pettersson, Anna Plym, Svitlana Tyekucheva, Kathryn L. Penney, Howard D. Sesso, Philip W. Kantoff, Lorelei A. Mucci, Konrad H. Stopsack
Summary: Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. However, age-related genes are not consistently associated with risk of metastases and prostate cancer-specific death, suggesting that tumor genomic differences may not be the main explanation for age-related differences in prostate cancer prognosis.
CANCER PREVENTION RESEARCH
(2022)
Article
Oncology
Kyung Hwan Kim, Han Sang Kim, Seung-Seob Kim, Hyo Sup Shim, Andrew Jihoon Yang, Jason Joon Bock Lee, Hong In Yoon, Joong Bae Ahn, Jee Suk Chang
Summary: This study investigated the role of mutations in DNA damage repair genes on treatment outcomes after radiotherapy (RT). The results suggest that tumors with mutations in ATM and BRCA1/2 genes exhibit superior tumor response and local control after RT.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Cell Biology
Fan Zhang, Qilin Zhang, Jiajun Zhu, Boyuan Yao, Chi Ma, Nidan Qiao, Shiman He, Zhao Ye, Yunzhi Wang, Rui Han, Jinwen Feng, Yongfei Wang, Zhaoyu Qin, Zengyi Ma, Kai Li, Yichao Zhang, Sha Tian, Zhengyuan Chen, Subei Tan, Yue Wu, Peng Ran, Ye Wang, Chen Ding, Yao Zhao
Summary: Pituitary neuroendocrine tumor (PitNET) is a common intracranial tumor, and further studies are needed to explore the causative molecular mechanisms and potential therapeutic targets. Through integrative genomics analysis on 200 PitNET patients, potential therapeutic targets were identified, providing possibilities for improving current treatment strategies.
Article
Multidisciplinary Sciences
Kiyoun Yi, Gwang Ha Kim, Su Jin Kim, Cheol Woong Choi, Moon Won Lee, Bong Eun Lee, Geun Am Song
Summary: Endoscopic resection provides favorable long-term outcomes for d-NETs <= 10 mm in size, limited to the submucosal layer, and without lymph node or distant metastasis, when endoscopically complete resection is achieved.
SCIENTIFIC REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
Heng Zhang, Shao-Qiang Wang, Jie-Bo Zhu, Li-Na Wang, Hang Lin, Lin-Feng Li, Yuan-Da Cheng, Chao-Jun Duan, Chun-Fang Zhang
Summary: CALML3-AS1 is upregulated while BTNL9 is downregulated in NSCLC. Depletion of CALML3-AS1 inhibits malignant phenotypes, tumor growth, and liver metastasis in NSCLC. Mechanistically, ALKBH5 enhances the stability of CALML3-AS1 through m6A demethylation, while YTHDC2 destabilizes CALML3-AS1. Additionally, CALML3-AS1 represses BTNL9 transcription and expression through the recruitment of EZH2. Downregulation of BTNL9 counteracts the antitumor effects mediated by CALML3-AS1 in NSCLC.
CANCER GENE THERAPY
(2023)
Article
Surgery
Praveen D. Chatani, John G. Aversa, James D. McDonald, Tahsin M. Khan, Xavier M. Keutgen, Naris Nilubol
Summary: This study analyzed the association between preoperative serum chromogranin-A (CgA) levels and prognosis in patients with locoregional SB-NET using the National Cancer Database. The results showed that preoperative CgA levels above 139 ng/mL were significantly associated with shorter overall survival, with these patients being older with poorly differentiated tumors and larger primary tumors.
Review
Oncology
Shu Pang, Ye Zong, Kun Zhang, Haiying Zhao, Yongjun Wang, Junxiong Wang, Chuntao Liu, Yongdong Wu, Peng Li
Summary: This study reports 15 cases of rectal multiple neuroendocrine tumors (M-NETs) and reviews the previous literature. The clinical characteristics, endoscopic features, and pathological features of rectal M-NETs are discussed, aiming to analyze the treatments and follow-up strategies. The results show that patients with rectal M-NETs often have no obvious symptoms, and tumor size is associated with lymphovascular invasion. Most patients have no recurrence or metastasis after endoscopic resection.
FRONTIERS IN ONCOLOGY
(2022)
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.
Article
Cell Biology
Liang Liu, Peng Zhang, Xuchen Dong, Haoran Li, Suwen Li, Shan Cheng, Jiaqi Yuan, Xuejun Yang, Zhiyuan Qian, Jun Dong
Summary: The study reveals that circ_0001367 functions as a suppressor in glioma by targeting the miR-431/NRXN3 axis, potentially serving as a promising therapeutic target against gliomas.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Julia Rymuza, Paulina Kober, Natalia Rusetska, Beata J. J. Mossakowska, Maria Maksymowicz, Aleksandra Nyc, Szymon Baluszek, Grzegorz Zielinski, Jacek Kunicki, Mateusz Bujko
Summary: This study identified three transcriptomic groups of somatotroph PitNETs with different gene expression profiles and clinical implications. These subgroups show variations in growth hormone secretion, prognostic gene expression, and potential therapeutic targets.
Article
Oncology
Yumi Oh, Hae Rim Jung, Seoyeon Min, Jinjoo Kang, Dongjun Jang, Seungjae Shin, Jiwon Kim, Sang Eun Lee, Chang Ohk Sung, Won-Suk Lee, Charles Lee, Eui Man Jeong, Sung-Yup Cho
Summary: Cancer chemotherapeutic drugs that target BCL-X-L can increase intracellular ROS levels in KRAS-mutant colorectal cancer cells, and exhibit a synergistic effect with the superoxide dismutase inhibitor 2-ME by regulating the translation of the anti-apoptotic protein MCL1.
Article
Gastroenterology & Hepatology
Eun Hee Koh, Ji Eun Yoon, Myoung Seok Ko, Jaechan Leem, Ji-Young Yun, Chung Hwan Hong, Yun Kyung Cho, Seung Eun Lee, Jung Eun Jang, Ji Yeon Baek, Hyun Ju Yoo, Su Jung Kim, Chang Ohk Sung, Joon Seo Lim, Won-Il Jeong, Sung Hoon Back, In-Jeoung Baek, Sandra Torres, Estel Solsona-Vilarrasa, Laura Conde de la Rosa, Carmen Garcia-Ruiz, Ariel E. Feldstein, Jose C. Fernandez-Checa, Ki-Up Lee
Summary: The study revealed the significant role of free cholesterol and sphingomyelin synthases (SMS) in the pathogenesis of NASH, inducing hepatocyte pyroptosis and inflammasome activation. This novel pathway involving DAG-PKCd-NLRC4 axis mediated by SMS1 could potentially serve as a therapeutic target for NASH.
Article
Genetics & Heredity
Hyeonjin Lee, Eun Na Kim, Ji-Young Lee, Ji Hun Kim, Ji-Hye Oh, Won-Kyung Kim, Eun Jeong Cho, Jinyeong Lim, Sung-Min Chun, Chang Ohk Sung
Summary: Somatic mutations occurring even in early embryogenesis can affect specific organ development or disease. Multi-organ analysis is helpful for understanding genomic mosaicism, providing insights into the biological role of mosaicism in embryonic development and disease.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Oncology
Hee Sang Hwang, Jihyun An, Hyo Jeong Kang, Bora Oh, Yoo Jin Oh, Ji-Hye Oh, Wonkyung Kim, Chang Ohk Sung, Ju Hyun Shim, Eunsil Yu
Summary: This study identified S100P as a promising prognostic biomarker associated with early recurrence after HCC resection, and established five discrete molecular subtypes of HCC, with one subtype ('AMC-C4') showing the worst prognosis. The findings shed light on the molecular mediators of HCC and may contribute to more effective care for affected patients.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Letter
Gastroenterology & Hepatology
Jihyun An, Ha Il Kim, Bora Oh, Yoo-Jin Oh, Ji-Hye Oh, Wonkyung Kim, Chang Ohk Sung, Ju Hyun Shim
Article
Gastroenterology & Hepatology
Jihyun An, Deokhoon Kim, Bora Oh, Yoo-Jin Oh, Jihyun Song, Naomi Park, Ha Il Kim, Hyo Jeong Kang, Ji-Hye Oh, Wonkyung Kim, Eunjung Lee, Chang Ohk Sung, Gi-Won Song, Dae-Ghon Kim, Eunsil Yu, Eric Letouze, Jessica Zucman-Rossi, Han Chu Lee, Ju Hyun Shim
Summary: This study identified the landscape and mechanisms of HBV integration in iCCA tumors, revealing recurrent viral integration breakpoints at multiple sites including TERT and FAT2, and oncogenic effects through intergenic insertions activating the mTOR pathway. The mutational profiles of HBV-iCCA were found to be more similar to nonviral conventional iCCA, rather than HBV-related liver cancers like HBV-HCC and HBV-cHCC/CCA.
Article
Oncology
Jihyun An, Minyoung Oh, Seog-Young Kim, Yoo-Jin Oh, Bora Oh, Ji-Hye Oh, Wonkyung Kim, Jin Hwa Jung, Ha Il Kim, Jae-Seung Kim, Chang Ohk Sung, Ju Hyun Shim
Summary: This study aimed to explore the genomic and molecular characteristics of hepatocellular carcinoma (HCC) with increased FDG uptake in PET and identify therapeutic targets based on these findings. The results showed that high FDG avidity was associated with worse recurrence-free survival after HCC resection. The upregulation of mTOR pathway genes in FDG-avid tumors was identified, and treatment with an mTOR inhibitor resulted in decreased FDG uptake and effective tumor control. This PET-based radiogenomic analysis may have implications for precision care of HCC patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, Research & Experimental
Shin Ung Kang, Soo Youn Cho, Hyojin Jeong, Jinil Han, Ha Yeong Chae, Hobin Yang, Chang Ohk Sung, Yoon-La Choi, Young Kee Shin, Mi Jeong Kwon
Summary: The study demonstrated that MMP11 expression in mononuclear inflammatory cells, predominantly macrophages, is an independent negative prognostic factor in breast cancer. Furthermore, MMP11-overexpressing macrophages promote migration of HER2-positive breast cancer cells and monocyte recruitment through CCL2-CCR2 signaling, suggesting a pro-tumoral role of MMP11 in macrophages in HER2-positive breast cancer through interaction with cancer cells and other cells in the tumor microenvironment.
LABORATORY INVESTIGATION
(2022)
Article
Oncology
Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim
Summary: This study identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, with lymphocytic/neutrophilic infiltration and expansile tumor border being predictive of better response, while mucinous/signet-ring cell carcinoma was associated with poor response. Gene expression profiles revealed enrichment of the interferon response pathway in responders, with PRAME showing the highest fold change. The classification model using these genes demonstrated good performance in predicting treatment response.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Multidisciplinary Sciences
Keun-Woo Lee, So-Young Yeo, Jeong-Ryeol Gong, Ok-Jae Koo, Insuk Sohn, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yong Beom Cho, Mi-Ae Choi, Sugyun An, Juhee Kim, Chang Ohk Sung, Kwang-Hyun Cho, Seok-Hyung Kim
Summary: PRRX1 is identified as a master transcription factor determining a fibroblast lineage with myofibroblastic phenotype, which is associated with poor prognosis in cancer. This study reveals cancer-associated fibroblast subpopulations based on super-enhancer profiles, providing a new opportunity for cancer treatment by targeting fibroblasts.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Jihyun An, Ji-Hye Oh, Bora Oh, Yoo-Jin Oh, Jin-Sung Ju, Wonkyung Kim, Hyo Jung Kang, Chang Ohk Sung, Ju Hyun Shim
Summary: This study provides an in-depth examination of pathogenic germline variants and somatic variants in DNA damage response genes in hepatocellular carcinoma (HCC), exploring their clinical and genomic impacts. The findings suggest that germline HR defects in HCC tend to confer a poor prognosis and result in distinctive genomic scarring.
Article
Multidisciplinary Sciences
Minsuh Kim, Ji Min Kim, Eun Jeong Cho, Chang Ohk Sung, Joon Kim, Se Jin Jang
Summary: This article explores the role of fi-arrestin 2 in YAP phosphorylation in colon cancer. The analysis of 45 colon cancer organoids reveals a positive correlation between the expression of fi-arrestin 2 and phosphorylated YAP. These findings support the notion that fi-arrestin 2 suppresses the activation of YAP in colon cancer.
Article
Multidisciplinary Sciences
Hyun Ju Park, Eun Jeong Cho, Ji-Hun Kim, Sehun Lim, Chang Ohk Sung
Summary: This study identifies the expression of Epstein-Barr virus (EBV) in the tumor immune microenvironment (TIM) of colorectal cancer (CRC) tissue. EBV was detected in tumor-infiltrating lymphocytes, and its positivity was associated with older age, male sex, and SMAD4 mutations. EBV-positive tumors showed enrichment in chemokine/cytokine signaling pathways and altered immune cell composition, leading to poor prognosis.
Letter
Oncology
Jae-Il Choi, Eun Jeong Cho, Min Jae Yang, Hyun-Jin Noh, So Hyun Park, Seokhwi Kim, You-Sun Kim, Chang Ohk Sung, Dakeun Lee
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ji-Hye Oh, Sungyang Jo, Kye Won Park, Eun-Jae Lee, Seung Hyun Lee, Yun Su Hwang, Ha Ra Jeon, Yeonjin Ryu, Hee Jeong Yoon, Sung-Min Chun, Chong Jai Kim, Tae Won Kim, Chang Ohk Sung, Sehyun Chae, Sun Ju Chung
Summary: A whole-genome sequencing study of Korean individuals with Parkinson's disease (PD) has identified several new genetic risk factors, ranging from single nucleotide variations (SNVs) to larger DNA deletions. These findings provide a global, whole-genome view of PD and suggest that small genomic deletions in regulatory domains contribute to the risk of PD development.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
