Article
Oncology
Monique B. Nilsson, Yan Yang, Simon Heeke, Sonia A. Patel, Alissa Poteete, Hibiki Udagawa, Yasir Y. Elamin, Cesar A. Moran, Yukie Kashima, Thiruvengadam Arumugam, Xiaoxing Yu, Xiaoyang Ren, Lixia Diao, Li Shen, Qi Wang, Minying Zhang, Jacqulyne P. Robichaux, Chunhua Shi, Allyson N. Pfeil, Hai Tran, Don L. Gibbons, Jason Bock, Jing Wang, John D. Minna, Susumu S. Kobayashi, Xiuning Le, John V. Heymach
Summary: This study identified CD70 as a significantly upregulated cell surface protein in non-small cell lung cancer (NSCLC) patients with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) through epithelial-to-mesenchymal transition (EMT). CD70 promotes cell survival and invasiveness by reactivating signal transduction pathways associated with acquired TKI resistance. Anti-CD70 antibody drug conjugates (ADCs) as well as CD70-targeting chimeric antigen receptor (CAR) T cells and CAR NK cells showed strong activity against EGFR TKI-resistant cells. These findings suggest that CD70 could serve as a therapeutic target for EGFR mutant tumors with acquired TKI resistance.
Article
Biotechnology & Applied Microbiology
Gaofeng Yuan, Wenwen Ding, Bingjie Sun, Lin Zhu, Yuewen Gao, Lulu Chen
Summary: The study revealed that CircRNA_102231 is significantly upregulated in gastric cancer tissues and plasma, serving as a potential biomarker for diagnosis and prognosis. Functional experiments demonstrated that inhibition of CircRNA_102231 can suppress GC cell proliferation and invasion in vitro and in vivo. CircRNA_102231 binds to IRTKS, enhancing IRTKS protein stability to promote GC progression.
Article
Cell Biology
Ruiting Guo, Xixi Cui, Xue Li, Wen Zang, Mingjie Chang, Zenghui Sun, Zhifang Liu, Yundong Sun, Jihui Jia, Wenjuan Li
Summary: This study found that Helicobacter pylori can induce the upregulation of circMAN1A2 in gastric cancer cells, and the downregulation of circMAN1A2 can inhibit the growth and invasion of gastric cancer cells. Furthermore, circMAN1A2 promotes the progression of H. pylori-induced gastric cancer by regulating the expression of MTA2. This study suggests that circMAN1A2 may be a potential diagnostic marker and therapeutic target for gastric cancer.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Haixiang Qin, Yang Yang, Bo Jiang, Chun Pan, Wei Chen, Wenli Diao, Meng Ding, Wenmin Cao, Zhenxing Zhang, Mengxia Chen, Jie Gao, Xiaozhi Zhao, Xuefeng Qiu, Hongqian Guo
Summary: The study revealed a novel insight into the molecular mechanism where cancer-associated fibroblasts promote SOX9 expression in prostate cancer cells through the HGF/c-Met-ERK1/2-FRA1 axis. SOX9 may serve as an alternative marker for the activated HGF/c-Met signaling in selecting optimal patients for treatment.
Article
Cell Biology
Yi Lu, Dan Li, Yixin Cao, Leqian Ying, Qing Tao, Fen Xiong, Zhangmin Hu, Yufei Yang, Xuehan Qiao, Chen Peng, Dongqin Zhu, Deqiang Wang, Xiaoqin Li
Summary: The study showed that evaluating CAF infiltration in tumors using FAMscore can independently predict prognosis and immunotherapy outcomes. High FAMscore is associated with immune-related genomic biomarkers, immune cell infiltration, and abnormal immune signaling pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Ge-Xin Liu, Yu-Zhen Tan, Guo-Chao He, Qin-Lin Zhang, Pan Liu
Summary: This study identified 63 prognostic-associated eRNAs in gastric cancer, with EMX2OS as the top performer. EMX2OS was found to be correlated with age, grade, stage, and cancer status, and associated with poor survival outcomes in several malignancies. The findings suggest that EMX2OS may serve as a novel therapeutic target in clinical practice.
Article
Immunology
Sasipa Tanyaratsrisakul, Alane Blythe C. Dy, Francesca Polverino, Mari Numata, Julie G. Ledford
Summary: This study aimed to determine if MYADM expression patterns were altered in asthma and/or rhinovirus infection and if increased MYADM expression is associated with increased asthma-associated factors. The results showed that MYADM expression was increased in the lungs from ova-treated mice and in primary human airway epithelial cells after infection with RV-1B, and MYADM expression was strongly associated with increases in inflammatory genes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gaurab Roy, Ting Yang, Shangxin Liu, Yi-Ling Luo, Yuantao Liu, Qian Zhong
Summary: This study identifies MAP3K8 as a super-enhancer (SE)-associated gene in Epstein-Barr virus-associated gastric carcinoma (EBVaGC) cells. Repression of MAP3K8 SEs reduces MAP3K8 expression and inhibits EBVaGC cell proliferation. It is found that MAP3K8 inhibits the Notch signaling pathway and epithelial-mesenchymal transition (EMT) in EBVaGC. Moreover, increased MAP3K8 expression is observed in gastric cancer and is inversely correlated with disease-free progression, while positively correlated with the expressions of Notch pathway and EMT-related genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Christophe Gallard, Nadjet Lebsir, Hira Khursheed, Emma Reungoat, Marie-Laure Plissonnier, Jennifer Bre, Maud Michelet, Yasmina Chouik, Fabien Zoulim, Eve-Isabelle Pecheur, Birke Bartosch, Boyan Grigorov
Summary: This study investigates the impact of chronic hepatitis C virus (HCV) infection on the liver extracellular matrix (ECM) and reveals that heparanase-1 (HPSE) plays a promoting role in HCV infection, enhancing the release of the virus by increasing CD63 synthesis and exosome secretion. The study also suggests that virus-induced oxidative stress may regulate HPSE expression through NF-kappa B activation.
JOURNAL OF HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rokeya Akter, Kwangmin Kim, Hye Youn Kwon, Youngwan Kim, Young Woo Eom, Hye-mi Cho, Mee-Yon Cho
Summary: EMR1 expression in tumor cells is significantly associated with lymph node metastasis and tumor-associated macrophages (CD68 and CD163) in colorectal cancer. The expression of EMR1 in cancer cells may be related to M2 macrophage polarization.
Article
Biochemistry & Molecular Biology
Xuemin Chen, Yong An, Yue Zhang, Dong Xu, Tongbing Chen, Yue Yang, Weibo Chen, Di Wu, Xiaoying Zhang
Summary: The study demonstrated that nab-paclitaxel increased the expression of CCL26 in CAFs, which in turn enhanced the invasive potential of pancreatic cancer cells by activating the PI3K/AKT/mTOR axis. This suggests that CCL26 may serve as a potential prognostic biomarker for pancreatic cancer.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2021)
Article
Rheumatology
Oliver C. Orji, Maria B. Lopez-Dominguez, Gabriela Sandoval-Plata, Tamar Guetta-Baranes, Ana M. Valdes, Michael Doherty, Kevin Morgan, Abhishek Abhishek
Summary: This study found that the expression of FFAR2 and SOCS3 genes is significantly upregulated in gout flares and inter-critical gout. FFAR2 may be associated with gout flares, while SOCS3 may play a role in ameliorating gout flares.
Article
Biochemistry & Molecular Biology
Xi Kang, Weilin Li, Weixin Liu, Han Liang, Jingyu Deng, Chi Chun Wong, Sinan Zhao, Wei Kang, Ka Fai To, Philip Wai Yan Chiu, Guiying Wang, Jun Yu, Enders Kwok Wai Ng
Summary: This study identified LIMK1 as a key promoter of gastric cancer peritoneal metastasis and suggested dabrafenib as a potential therapeutic target. The findings showed that targeting LIMK1 with dabrafenib could inhibit migration and invasion of gastric cancer cells in vitro and prevent metastasis in vivo, by suppressing phosphorylation of cofilin.
Article
Oncology
Liang Xu, Xiuxiu Chen, Hongtao Jiang, Jian Xu, Lixia Wang, Yuemin Sun
Summary: Gastric cancer is a common primary tumor of the digestive system. The study found that overexpression of NDUFC1 in gastric cancer is associated with more severe tumor infiltrates and lymphatic metastasis. Knockdown of NDUFC1 inhibited proliferation and migration, promoted apoptosis, and may exacerbate NSCLC progression through the PI3K/Akt pathway. Targeting NDUFC1 could be a potential new approach for the treatment of gastric cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Lei Cheng, Yuanyuan Chang, Zuguang Xia, Yizhen Liu, Xiao Liu, Liwen Xiong, Chenchen Liu, Xiaodong Zhu, Mengyun Wang, Lixin Qiu
Summary: The protein WWOX is involved in cancer progression through interactions with mTOR and DNA repair pathway. Genetic variants in the WWOX gene were found to be associated with the survival of gastric cancer (GCa) patients. Specifically, the variant rs9922483 was found to be associated with increased death risk for GCa patients and hindered the transcriptional activity driven by WWOX promoter. This study highlights the importance of genetic variants in modulating the survival of GCa patients and the regulatory effects of these variants on gene expression.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Iori Motoo, Sohachi Nanjo, Takayuki Ando, Satoshi Yamashita, Toshikazu Ushijima, Ichiro Yasuda
Summary: The study reveals that in diffuse-type gastric cancers, ULK2 is methylated and knockdown of ULK2 can induce autophagy, cell migration, and EMT. mRNA microarray analysis showed that knockdown of ULK2 altered the expressions of oncogenic genes associated with cell migration and EMT.
Article
Oncology
Chun-Dong Zhang, Hideyuki Takeshima, Shigeki Sekine, Satoshi Yamashita, Yu-Yu Liu, Naoko Hattori, Hiroyuki Abe, Hiroharu Yamashita, Masahide Fukuda, Yu Imamura, Tetsuo Ushiku, Hitoshi Katai, Hiroshi Makino, Masayuki Watanabe, Yasuyuki Seto, Toshikazu Ushijima
Summary: The study aimed to develop a marker for predicting the tissue origin of esophagogastric junction adenocarcinomas based on DNA methylation profiles, identifying two highly specific GAC markers. These markers successfully predicted the tissue origin of EGJ adenocarcinoma in FFPE samples.
Review
Multidisciplinary Sciences
Toshikazu Ushijima, Susan J. Clark, Patrick Tan
Summary: Cancer, driven by genomic and epigenomic derangements, requires multimodal data integration to understand the molecular evolution of malignant cell states across its lifecycle. Driver mutations and epigenetic alterations in normal-appearing tissues prompt a reassessment of cancer initiation, while studying clonal selection, epigenomic adaptation, and persister cells in metastasis and therapy resistance is an emerging field. The importance of tumor ecosystems in cancer development is being unveiled by advancing single-cell and spatial technologies.
Article
Gastroenterology & Hepatology
Chihiro Takeuchi, Junichi Sato, Satoshi Yamashita, Akiko Sasaki, Takemi Akahane, Rika Aoki, Mitsue Yamamichi, Yu-Yu Liu, Masayoshi Ito, Takahisa Furuta, Shigemi Nakajima, Yoshiki Sakaguchi, Yu Takahashi, Yosuke Tsuji, Keiko Niimi, Shuta Tomida, Mitsuhiro Fujishiro, Nobutake Yamamichi, Toshikazu Ushijima
Summary: Autoimmune gastritis induces aberrant DNA methylation in gastric mucosa, but to a lesser extent than H. pylori-associated gastritis. The patterns of methylation are also distinct between the two conditions.
JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Oncology
Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
Summary: This study aimed to identify markers for evaluating ovarian cancer cell fraction. Using genome-wide DNA methylation data, SIM1 and ZNF154 were found to be highly correlated with pathological cancer cell fractions. Pyrosequencing primers were successfully designed for cost-effective analysis. In an independent validation cohort, ZNF154 methylation showed a significant correlation with the pathological cancer cell fraction.
Article
Oncology
Harumi Yamada, Hideyuki Takeshima, Ryoji Fujiki, Satoshi Yamashita, Shigeki Sekine, Takayuki Ando, Naoko Hattori, Atsushi Okabe, Takaki Yoshikawa, Kazutaka Obama, Hitoshi Katai, Atsushi Kaneda, Toshikazu Ushijima
Summary: The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. This study demonstrates that mutations in the SWI/SNF chromatin remodeling complex, particularly ARID1A, are associated with CIMP induction in gastric cancer, as well as in uterine endometrial and colorectal cancers. The loss of ARID1A function causes aberrant DNA methylation and is likely a potential mechanism for CIMP induction.
Article
Multidisciplinary Sciences
Sho Uedaa, Satoshi Yamashita, Miho Nakajima, Tadashi Kumamoto, Chitose Ogawa, Yu-Yu Liu, Harumi Yamada, Emi Kubo, Naoko Hattori, Hideyuki Takeshima, Mika Wakabayashi, Naoko Iida, Yuichi Shiraishi, Masayuki Noguchi, Yukio Sato, Toshikazu Ushijima
Summary: This study developed a cost-effective pipeline called EcoSeq, which utilizes duplex sequencing to accurately count somatic mutations in single DNA molecules. The researchers used this method to analyze normal blood cells from pediatric sarcoma patients and found that the mutation frequency significantly increased in patients who received chemotherapy, with the increased frequency persisting even months after chemotherapy. This suggests that mutation accumulation poses a risk of secondary leukemia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
Summary: A quantitative method was established to evaluate the DNA methylation level of the immediate upstream region of major BRCA1 transcriptional start sites (TSSs). The methylation of this region was found to be an independent favorable prognostic factor in high-grade serous ovarian cancer patients.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Cell Biology
Takatsune Shimizu, Eiji Sugihara, Hideyuki Takeshima, Hiroyuki Nobusue, Rui Yamaguchi, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Toshikazu Ushijima, Akihiro Muto, Hideyuki Saya
Summary: Mutant p53 in osteosarcoma cells does not suppress the activity of wild-type p53. Targeting mutant p53 R270C (equivalent to human R273C) has limited therapeutic potential, as it does not prevent invasion and metastasis in cells.
Article
Hematology
Yuki Kurahashi, Tatsuro Watanabe, Yuta Yamamoto, Hiroshi Ureshino, Kazuharu Kamachi, Nao Yoshida-Sakai, Yuki Fukuda-Kurahashi, Satoshi Yamashita, Naoko Hattori, Hideaki Nakamura, Atsushi Kawaguchi, Toshikazu Ushijima, Eisaburo Sueoka, Shinya Kimura
Summary: Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Epigenetic abnormalities, such as DNA methylation and trimethylation at histone H3Lys27 (H3K27me3), contribute to ATL development. Combination treatment with DNA demethylating agents and enhancer of zeste homolog 2 (EZH2) inhibitors showed synergistic anti-ATL effects by inducing gene expression reprogramming and restoring DUSP5, a key molecule that inactivates the ERK signaling pathway. This study suggests that dual targeting of aberrant DNA and histone methylation is a feasible therapeutic approach for ATL.
Article
Oncology
Nobuaki Arai, Naoko Hattori, Satoshi Yamashita, Yu-Yu Liu, Takahiro Ebata, Chihiro Takeuchi, Hideyuki Takeshima, Satoshi Fujii, Haruhiko Kondo, Hirofumi Mukai, Toshikazu Ushijima
Summary: The aim of this study was to explore the methylation-silencing mechanism of the HSD17B4 gene in HER2-positive breast cancer. Knocking out the HSD17B4 gene led to suppressed cell proliferation, enhanced sensitivity to lapatinib, accumulation of VLCFA, decrease in polyunsaturated fatty acids, increased Akt phosphorylation, and upregulation of genes involved in oxidative phosphorylation and electron transport chain.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Meeting Abstract
Oncology
Takahrio Ebata, Satoshi Yamashita, Hiroshi Yoshida, Tomoyasu Kato, Toshikazu Ushijima
