Review
Biochemistry & Molecular Biology
Gyorgy Trencsenyi, Kata Nora Enyedi, Gabor Mezo, Gabor Halmos, Zita Kepes
Summary: Angiogenesis plays a key role in tumor progression and metastasis. Targeting angiogenesis using specific vectors has gained attention from researchers. The high expression of angiogenesis-associated aminopeptidase N (APN/CD13) on the surface of activated endothelial cells and various tumor cells makes it a promising target for cancer imaging and therapy. Radiolabeled NGR peptides, which selectively bind to APN/CD13, have been investigated for non-invasive, real-time imaging of APN/CD13 overexpressing malignancies.Various radioisotopes, such as Ga-68, Cu-64, (99)mTc, Lu-177, Re-188, and Bi-213, have been used for labeling tumor vasculature homing NGR sequences in preclinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Adrienn Kis, Noemi Denes, Judit P. Szabo, Viktoria Arato, Livia Beke, Orsolya Matolay, Kata Nora Enyedi, Gabor Mehes, Gabor Mezo, Peter Bai, Istvan Kertesz, Gyorgy Trencsenyi
Summary: The study showed that bestatin treatment effectively inhibited tumor growth and reduced Ga-68-NODAGA-c(NGR) uptake in both HT1080 and B16-F10 tumor models, while actinonin led to higher radio-tracer accumulation in HT1080 tumors but lower accumulation in B16-F10 melanoma tumors. The Ga-68-NODAGA-c(NGR) radiotracer is a useful tool for monitoring the efficacy of APN/CD13 inhibition-based anticancer therapies.
BIOMED RESEARCH INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Uwe Lendeckel, Farzaneh Karimi, Ruba Al Abdulla, Carmen Wolke
Summary: APN/CD13 is expressed in various cells/tissues and is associated with diverse physiological functions. Increased expression or activity of APN/CD13 has been described in various tumors, and is usually associated with reduced survival. The mechanisms of APN/CD13-mediated cellular effects have been largely determined.
Article
Biochemistry & Molecular Biology
Kairui Yue, Xiaohan Hou, Geng Jia, Liang Zhang, Jian Zhang, Leqiao Tan, Xuejian Wang, Zhaolin Zhang, Peixia Li, Wenfang Xu, Xiaoyang Li, Yuqi Jiang
Summary: In this study, four novel ubenimex-5FU conjugates were designed and synthesized, with compound 20 showing superior stability, CD13 inhibitory activity, and antiproliferative activity compared to BC-02. Compound 20 exhibited significant anti-invasion and anti-angiogenesis activities in vitro, as well as inhibiting tumor growth and metastasis in vivo. These findings suggest that compound 20 could serve as a lead compound for further drug design and development.
BIOORGANIC CHEMISTRY
(2021)
Review
Oncology
Gyoergy Trencsenyi, Gabor Halmos, Zita Kepes
Summary: Due to the increasing prevalence of malignant diseases and related metastases, there is a need for specific diagnostic vectors that can identify tumors in a timely and selective manner. Multi-target imaging using multivalent ligands has emerged as an effective way to increase the binding ability of peptide-based molecular vectors in cancer research. The colocalization of the asparagine-glycine-arginine (NGR) motif with angiogenesis-related Aminopeptidase N (APN/CD13) makes radiolabelled NGR-containing bispecific compounds valuable tools for molecular diagnostics of APN/CD13 overexpressing tumors. The establishment of vascular-homing heterobivalent probes not only expands the horizon of cancer diagnostics but also contributes to the goal of personalized tumor imaging.
Article
Pharmacology & Pharmacy
Zita Kepes, Viktoria Arato, Judit P. Szabo, Barbara Gyuricza, Daniel Szuecs, Istvan Hajdu, Aniko Fekete, Frank Bruchertseifer, Dezso Szikra, Gyoergy Trencsenyi
Summary: This study aimed to evaluate the in vivo tumor targeting capability of radiolabeled NGR-tripeptides (asparagine-glycine-arginine) that selectively target Aminopeptidase N (APN/CD13) on cancer cells. The study was conducted on CD13pos. HT1080 fibrosarcoma-bearing mice using [Bi-213]Bi-DOTAGA-cKNGRE. Positron emission tomography (PET) was performed for tumor verification and biodistribution studies were conducted post-injection. The results suggest that the therapeutic application of APN/CD13-affine [Bi-213]Bi-DOTAGA- cKNGRE shows promise in receptor-positive fibrosarcoma treatment.
Article
Immunology
Justin N. Nguyen, Eric C. Mohan, Gargee Pandya, Uzma Ali, Chunfeng Tan, Julia K. Kofler, Linda Shapiro, Sean P. Marrelli, Anjali Chauhan
Summary: CD13 is involved in the migration of monocytes and neutrophils after stroke, and acutely, it leads to decreased infarct size and improved behavioral outcomes. However, loss of CD13 reduces post-stroke angiogenesis by reducing CXCL12/CXCR4 signaling.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Chemistry, Multidisciplinary
Jiangying Cao, Chunlong Zhao, Hang Dong, Qifu Xu, Yingjie Zhang
Summary: A new series of pyrazoline-based derivatives were synthesized, among which compound 2k showed promising APN inhibitory activity and effectively prevented pulmonary metastasis of H22 hepatoma cells in vivo, indicating its potential as an anti-tumor agent.
Article
Oncology
Yu Long, Fuqiang Shao, Hao Ji, Xiangming Song, Xiaoying Lv, Xiaotian Xia, Qingyao Liu, Yongxue Zhang, Dexing Zeng, Xiaoli Lan, Yongkang Gai
Summary: Ovarian cancer has the highest mortality rate among gynecologic malignancies. Ga-68-NGR-RGD, a tracer targeting CD13 and integrin alpha(v)beta(3), shows better contrast and improved ability to differentiate inflammation compared to F-18-FDG in ovarian cancer imaging. It presents a promising imaging agent for the diagnosis, staging, and follow-up of ovarian tumors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Yi Yang, Jun Zhang, Huifeng Zou, Yang Shen, Shengming Deng, Yiwei Wu
Summary: The Ga-68-DOTA-c(NGR)(2) peptide was shown to have high radiochemical purity and stability, with favorable CD13-specific targeting ability in vitro and in microPET imaging with ovarian cancer xenografts. This suggests that it may be a potential PET imaging probe for evaluating CD13 receptor expression in tumors non-invasively.
Article
Medicine, Research & Experimental
Pei-Suen Tsou, Chenyang Lu, Mikel Gurrea-Rubio, Sei Muraoka, Phillip L. Campbell, Qi Wu, Ellen N. Model, Matthew E. Lind, Sirapa Vichaikul, Megan N. Mattichak, William D. Brodie, Jonatan L. Hervoso, Sarah Ory, Camila Amarista, Rida Pervez, Lucas Junginger, Mustafa Ali, Gal Hodish, Morgan M. O'Mara, Jeffrey H. Ruth, Aaron M. Robida, Andrew J. Alt, Chengxin Zhang, Andrew G. Urquhart, Jeffrey N. Lawton, Kevin C. Chung, Tristan Maerz, Thomas L. Saunders, Vincent E. Groppi, David A. Fox, M. Asif Amin
Summary: CD13, an ectoenzyme, circulates as a soluble protein (sCD13) and interacts with the bradykinin receptor B1 (B1R) to mediate arthritogenic actions. The high expression of B1R in rheumatoid arthritis (RA) synovial tissue and fibroblast-like synoviocytes (FLSs) suggests its potential as a therapeutic target for RA and other inflammatory diseases.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Chemistry, Inorganic & Nuclear
Noemi Denes, Adrienn Kis, Judit P. Szabo, Istvan Joszai, Istvan Hajdu, Viktoria Arato, Kata Nora Enyedi, Gabor Mezo, Janos Hunyadi, Gyorgy Trencsenyi, Istvan Kertesz
Summary: The study aims to involve new, easily accessible peptide sequences into neoangiogenesis in malignant processes, enabling PET imaging of neo-vascularization.
APPLIED RADIATION AND ISOTOPES
(2021)
Article
Biochemical Research Methods
Jong-Heon Kim, Ruqayya Afridi, Eunji Cho, Jong Hyuk Yoon, Yong-Hyun Lim, Ho-Won Lee, Hoon Ryu, Kyoungho Suk
Summary: Astrocytes, major supportive glia and immune modulators in the brain, communicate with other cell types through their secreted proteomes. The renin-angiotensin system (RAS) plays an important role in this communication, exacerbating neuroinflammation. This study found that soluble form of aminopeptidase N (sANPEP) and angiotensin IV (Ang IV) released by astrocytes increase neuroinflammation by interacting with angiotensin type 1 receptor on microglial cells.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Multidisciplinary Sciences
Li-Ting Wang, Abira Rajah, Claire M. Brown, Luke McCaffrey
Summary: The short intracellular domain of CD13 protein is essential for capturing endosomes at the apical site and is crucial for cell polarization.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Jianing Wang, Xiaoying Qin, Hao Sun, Meijun He, Qunyu Lv, Congcong Gao, Xinran He, Hong Liao
Summary: The study shows that NgR plays a crucial role in microglial clearance of Aβ, with increased NgR expression in aged microglia leading to decreased Aβ phagocytosis. Knockdown of NgR reduces amyloid burden and improves cognitive function in an AD mouse model. Moreover, NgR activation inhibits CD36 gene expression through Smad2/3 signaling, thereby reducing microglial Aβ uptake.
Article
Multidisciplinary Sciences
Yan-Bo Zheng, Jian-Hua Gong, Xiu-Jun Liu, Shu-Ying Wu, Yi Li, Xian-Dong Xu, Bo-Yang Shang, Jin-Ming Zhou, Zhi-Ling Zhu, Shu-Yi Si, Yong-Su Zhen
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Yan-Bo Zheng, Jian-Hua Gong, Xiu-Jun Liu, Yi Li, Yong-Su Zhen
MOLECULAR CARCINOGENESIS
(2017)
Article
Multidisciplinary Sciences
Xiu-Jun Liu, Yan-Bo Zheng, Yi Li, Shu-Ying Wu, Yong-Su Zhen
Article
Oncology
Jian-Hua Gong, Yan-Bo Zheng, Meng-Ran Zhang, Yue-Xuan Wang, Si-Qi Yang, Rui-Hai Wang, Qing-Fang Miao, Xiu-Jun Liu, Yong-Su Zhen
CANCER BIOLOGY & THERAPY
(2020)
Article
Cell Biology
Yan-Bo Zheng, Jian-Hua Gong, Yong-Su Zhen
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2020)
Article
Pharmacology & Pharmacy
Qi Zhao, Yanbo Zheng, Xing Lv, Jianhua Gong, Lijun Yang
Summary: IMB5036, a novel pyridazinone compound, exhibits potent cytotoxicity against pancreatic cancer cells by inducing necroptosis, leading to inhibiting tumor growth.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Article
Oncology
Xing Lv, Qi Zhao, Yanqun Dong, Lijun Yang, Jianhua Gong, Yanbo Zheng, Tao Yang
Summary: In this study, a small-molecule compound called IMB5036 exhibited potent antitumor activity against hepatocellular carcinoma (HCC). It induced apoptosis and inhibited cell motility in HCC cells. IMB5036 also regulated the expression of E-cadherin, N-cadherin, and Tau protein. Furthermore, in vivo experiments demonstrated that IMB5036 significantly inhibited the growth of HCC xenografts. These findings suggest that IMB5036 may be a promising therapeutic candidate for HCC patients.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Pharmacology & Pharmacy
Yan-Bo Zheng, Yan-Qun Dong, Shu-Yi Si, Yong-Su Zhen, Jian-Hua Gong
Summary: IMB5476, a novel nitrobenzoate microtubule inhibitor, exhibits increased aqueous solubility. It disrupts microtubule networks in cells, causing cell cycle arrest and inducing cell death through mitotic catastrophe and apoptosis. IMB5476 also inhibits angiogenesis and overcomes multidrug resistance.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Weizhuo Lu, Zhiwu Chen, Jiyue Wen
Summary: Ischemic stroke is a common and serious disease, and neuroinflammation plays a crucial role in its progression. Microglia, astrocytes, and infiltrating immune cells are involved in the complicated neuroinflammation cascade, releasing different molecules that affect inflammation. Flavonoids, plant-specific compounds, have shown protective effects against cerebral ischemia injury by modulating the inflammatory responses.
BIOMEDICINE & PHARMACOTHERAPY
(2024)