Article
Endocrinology & Metabolism
Gabriella Fioravanti, Phuong Q. Hua, Ryan E. Tomlinson
Summary: Gambogic amide (GA) as a TrkA agonist promotes load-induced bone formation without inducing hyperalgesia. Treatment with GA increases periosteal bone formation rate, osteoblast numbers, and upregulates expression of related genes.
Article
Biochemistry & Molecular Biology
Jiaorong Qu, Bojun Qiu, Yuxin Zhang, Yan Hu, Zhixing Wang, Zhiang Guan, Yiming Qin, Tongtong Sui, Fan Wu, Boyang Li, Wei Han, Xiaozhong Peng
Summary: In this study, a small molecule called GA-amide was found to effectively penetrate the blood-brain barrier and accumulate in the tumor region. GA-amide showed significant efficacy in inhibiting tumor growth in various in vivo glioma models. The direct binding target of GA-amide was identified as WDR1, and through interaction with WDR1, GA-amide promoted the formation of a complex involving WDR1, MYH9, and Cofilin, resulting in the inhibition of glioma cell invasion and induction of apoptosis.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Oncology
Maolin Ge, Qiongyu Xu, Ting Kang, Dan Li, Ruiheng Wang, Zhihong Chen, Shufeng Xie, Wenbin Wang, Han Liu
Summary: Drug resistance is a major challenge in cancer treatment, and regulating cyclin A1 to alter reversible cell cycle dynamics can promote the development of PI tolerance. Combination therapy with PI and DUB inhibitors can overcome this drug resistance.
Article
Biology
Yongying Jiang, Gongyun Lei, Ting Lin, Nan Zhou, Jintao Wu, Zhou Wang, Yihui Fan, Hongzhuan Sheng, Renfang Mao
Summary: In this study, the potential role of liquid-liquid phase separation (LLPS) inhibitor 1,6-HD in angiogenesis and endothelial function was investigated. Results showed that 1,6-HD significantly decreased neovascularization and angiogenesis response, inhibited microvessel outgrowth and endothelial network formation, and suppressed endothelial migration, proliferation, and cell growth. RNA-sequencing analysis revealed that 1,6-HD specifically blocked cell cycle and downregulated CCNA1. These findings suggest that LLPS could be a novel player in modulating angiogenesis and a potential therapeutic target for angiogenesis-related diseases.
Article
Biochemistry & Molecular Biology
Monika Tomanova, Karolina Kozlanska, Radek Jorda, Lukas Jedinak, Tereza Havlikova, Eva Reznickova, Miroslav Perina, Pavel Klener, Alexandra Dolnikova, Petr Cankar, Vladimir Krystof
Summary: The therapy of FLT3-positive acute myeloid leukemia remains complicated, despite the availability of newly approved kinase inhibitors. This study reports the development of a new FLT3 inhibitor and provides structure-activity relationship studies. Cellular analyses and in vivo experiments demonstrate the inhibitory activity of the compound.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Xiaoyang Yang, Mengjie Wan, Feng Yu, Xiuji Wu
Summary: This study elucidates that upregulation of CCNA1 in AML cells promotes chemoresistance, while downregulation of FOXA2 and the action of EZH2 increase sensitivity of AML cells to drugs.
CELLULAR SIGNALLING
(2021)
Article
Chemistry, Medicinal
Kai Yuan, Minghui Ji, Shengnan Xie, Zhixia Qiu, Weijiao Chen, Wenjian Min, Fei Xia, Mingming Zheng, Xiao Wang, Jiaxing Li, Yi Hou, Wenbin Kuang, Liping Wang, Wanjian Gu, Zhiyu Li, Peng Yang
Summary: Researchers discovered and synthesized a potent dual CDK6/PIM1 inhibitor, compound 51, through virtual screening, showing high kinase selectivity, excellent safety profile, and strong potency in reducing AML burden, offering a new direction for AML treatment and a promising lead compound for preclinical studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Bin Zhou, Yaqian Qin, Jingying Zhou, Jichen Ruan, Fang Xiong, Jinglai Dong, Xingzhou Huang, Zhijie Yu, Shenmeng Gao
Summary: Bortezomib selectively targets leukemia stem cells in AML with MLL rearrangements, inhibiting cell proliferation and colony formation while extending overall survival. The mechanism involves downregulation of CDK6 and NF B, demonstrating potential as a promising drug for AML patients with MLL rearrangements.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Oncology
Reham Abdel Haleem Abo Elwafa, Magdy El Bordiny, Mostafa Salama, Amira Fawzy, Omneya Magdy Omar
Summary: This study evaluated the association of CCND2 rs3217927 single nucleotide polymorphisms (SNP) with acute lymphoblastic leukemia (ALL) susceptibility in Egyptian children. It found that the G allele of CCND2 rs3217927 SNP might be associated with increased risk for ALL and acted as an independent negative prognostic marker.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Ahmed Al Otaibi, Subuhi Sherwani, Salma Ahmed Al-Zahrani, Eida Mohammed Alshammari, Wahid Ali Khan, Abdulmohsen Khalaf D. Alsukaibi, Shahper Nazeer Khan, Mohd Wajid Ali Khan
Summary: Advanced stage cancers pose challenges to mono-therapeutics, leading to low patient survival rates. This study explores a novel combinational therapy using biologically active alpha-amino amide analogs to increase cytotoxicity against leukemia cells, especially when combined with gamma delta T cells. This unique approach may offer promising potential for cancer therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Xueliang Gao, Shenghui Qin, Yongxia Wu, Chen Chu, Baishan Jiang, Roger H. Johnson, Dong Kuang, Jie Zhang, Xi Wang, Anand Mehta, Kenneth D. Tew, Gustavo W. Leone, Xue-Zhong Yu, Haizhen Wang
Summary: PFKP, the major isoform of PFK1 in T-ALL, functions as a nucleocytoplasmic shuttling protein with nuclear export and localization sequences. Nuclear PFKP promotes the expression of CXCR4 to facilitate T-ALL cell invasion, which can be blocked with CXCR4 antagonists. The presence of nuclear PFKP in T cell malignancy correlates with poor survival and suggests its potential as a diagnostic marker.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Tomas Kyca, Lucia Pavlikova, Viera Bohacova, Anton Misak, Alexandra Poturnayova, Albert Breier, Zdena Sulova, Mario Seres
Summary: Bortezomib showed varying effects on different cell variants, but these effects were not sufficient to decrease cell sensitivity to bortezomib.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Yixin Zou, Hanning Tang, Yi Miao, Huayuan Zhu, Li Wang, Lei Fan, Jianxin Fu, Wei Xu, Jianyong Li, Yi Xia
Summary: NOTCH1 mutation is a significant molecular abnormality in chronic lymphocytic leukemia (CLL), which leads to an unfavorable prognosis and poor response to chemoimmunotherapy. This study investigates the mechanism of adverse prognosis caused by NOTCH1 mutation from the perspective of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), a splicing factor. The results demonstrate that RNA splicing plays a vital role in NOTCH1-mutated CLL cells, and the overexpression of c-Myc-dependent hnRNPA1 promotes cell proliferation and inhibits apoptosis, contributing to the poor prognosis of patients with NOTCH1 mutation.
CHINESE MEDICAL JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Affidah Sabran, Endang Kumolosasi, Ibrahim Jantan, Jamia Azdina Jamal, Norazrina Azmi, Malina Jasamai
Summary: The study found that selected phytoestrogens can induce apoptosis, cell cycle arrest, and phagocytosis in leukemia cells, while reducing the levels of ANXA1.
SAUDI PHARMACEUTICAL JOURNAL
(2021)
Article
Chemistry, Medicinal
Tong Han, Chunyu Jiang, Xing Wei, Meilin Sheng, Qin Xie, Jiqiang Zhang, Yongyi Zhang, Chenghao Jin
Summary: A unique series of amide-scutellarin derivatives were synthesized and evaluated for their antiproliferative and neuroprotective activities. Some of the compounds showed significant antitumor and neuroprotective effects.
MEDICINAL CHEMISTRY RESEARCH
(2022)