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Featured researches published by Yongsheng Jia.


Journal of Medicinal Chemistry | 2012

Guaianolide Sesquiterpene Lactones, a Source To Discover Agents That Selectively Inhibit Acute Myelogenous Leukemia Stem and Progenitor Cells

Quan Zhang; Yaxin Lu; Yahui Ding; Jiadai Zhai; Qing Ji; Weiwei Ma; Ming Yang; Hongxia Fan; Jing Long; Zhongsheng Tong; Yehui Shi; Yongsheng Jia; Bin Han; Wenpeng Zhang; Chuanjiang Qiu; Xiaoyan Ma; Qiuying Li; Qianqian Shi; Haoliang Zhang; Dongmei Li; Jing Zhang; Jianping Lin; Lu Yuan Li; Yingdai Gao; Yue Chen

Small molecules that can selectively target cancer stem cells (CSCs) remain rare currently and exhibit no common structural features. Here we report a series of guaianolide sesquiterpene lactones (GSLs) and their derivatives that can selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells. Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide (MCL), are able to reduce the proportion of AML stem cells (CD34⁺CD38⁻) in primary AML cells. Targeting of AML stem cells is further confirmed by a sharp reduction of colony-forming units of primary AML cells upon MCL treatment. Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in plasma and in vivo and demonstrates remarkable therapeutic efficacy in the nonobese diabetic/severe combined immunodeficiency AML models. These findings indicate that GSL is an ample source for chemical agents against AML stem or progenitor cells and that GSL is potentially highly useful to explore anti-CSC approaches.


OncoTargets and Therapy | 2015

Micheliolide overcomes KLF4-mediated cisplatin resistance in breast cancer cells by downregulating glutathione.

Yongsheng Jia; Chunze Zhang; Liyan Zhou; Huijun Xu; Yehui Shi; Zhongsheng Tong

Micheliolide (MCL) is a promising novel compound with broad-spectrum anticancer activity. However, little is known regarding its action and mechanism in breast cancer. To explore the potential therapeutic application of MCL as a chemosensitivity modulator, this study investigated the effects of MCL on cisplatin sensitivity in breast cancer and the underlying mechanisms. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and a xenograft tumor model, MCL enhanced the cisplatin sensitivity of the breast cancer cell line MCF-7 both in vitro and in vivo. Treatment of MCF-7 cells with low-dose cisplatin (10 µM) was sufficient to enrich the proportion of ALDH+ cells and upregulate Krüppel-like factor 4 (KLF4) expression. The results obtained from knockdown and overexpression experiments demonstrate that KLF4 is both necessary and sufficient to induce a cisplatin resistance phenotype in breast cancer cells. Furthermore, the glutathione (GSH) content was elevated in MCF-7 cells after overexpression of KLF4. KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. MCL induced GSH depletion and severe cell death in KLF4-overexpressing MCF-7 cells following exposure to cisplatin. Therefore, these results suggest that MCL-mediated direct depletion of GSH represents a major mechanism in reversing KLF4-induced cisplatin resistance in MCF-7 cells.


OncoTargets and Therapy | 2015

Dynamin-related protein 1 is involved in micheliolide-induced breast cancer cell death

Yongsheng Jia; Liyan Zhou; Chen Tian; Yehui Shi; Chen Wang; Zhongsheng Tong

Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic target for tumor initiation, migration, proliferation, and chemosensitivity. Thus, therapeutic strategies that focus on targeting Drp1 and its related signaling pathway pave a new way to address the ineffectiveness of traditional cancer therapies. Micheliolide (MCL), a guaianolide sesquiterpene lactone, can selectively eradicate acute myeloid leukemia stem or progenitor cells. But the effect of MCL on the mitochondrial dynamics of cancer cells is still not well demonstrated. In this study, we show that MCL inhibited the growth of MCF-7 human breast cancer cells, accompanied by increased mitochondrial fission and upregulation of Drp1. The results obtained from overexpression experiments of wild or dominant-negative mutant type of Drp1 demonstrate that Drp1 is both necessary and sufficient to induce MDA-MB-231 and MCF-7 cell death. Furthermore, mitochondrial membrane potential decreased, whereas reactive oxygen species (ROS) generation, cytochrome c release, and PARP cleavage were enhanced after overexpression of Drp1 wild type. On the other hand, overexpression of Drp1-K38A (a dominant-negative mutant of Drp1) rescued cells from increased apoptosis, confirming the role of MCL-induced Drp1 in the observed apoptosis. Finally, MCL-induced Drp1-mediated cell death could be reversed by N-acetyl-L-cysteine (the ROS scavenger) in breast cancer cells. Taken together, the present study shows a novel role for Drp1 in MCL-induced breast cancer cell death, potentially through regulation of ROS–mitochondrial apoptotic pathway.


International Journal of Molecular Medicine | 2018

Histone deacetylase inhibitors alter the expression of molecular markers in breast cancer cells via microRNAs

Yehui Shi; Yongsheng Jia; Weipeng Zhao; Liyan Zhou; Xiaojuan Xie; Zhongsheng Tong


Clinical Oncology and Cancer Research | 2017

Histone deacetylase inhibitor down-regulated the expression of HER-2 in breast cancer through the changes in miRNA

Yehui Shi; Weipeng Zhao; Xingyu Chen; Juping Zhang; Shuai Li; Yongsheng Jia; Zhongsheng Tong


Clinical Oncology and Cancer Research | 2017

Clinicopathological features and prognostic factors of patients with advanced luminal B-like breast cancer

Yafang Zheng; Yongsheng Jia; Ronggang Lang; Zhongsheng Tong


Clinical Oncology and Cancer Research | 2017

Clinical characteristics and prognosis of multiple primary cancers involving breast cancer

Xixi Zheng; Yongsheng Jia; Yehui Shi; Shufen Li; Zhongsheng Tong


Clinical Oncology and Cancer Research | 2016

The rare RET mutation Y606C in a Chinese family with familial medullary thyroid carcinoma

Junyi Wang; Yang Yu; Dapeng Li; Songfeng Wei; Xinwei Yun; Yongsheng Jia; Ming Gao


Clinical Oncology and Cancer Research | 2014

Clinicopathologic features and prognostic factors of 205 patients with pretreated metastatic breast cancer

Fang Wang; Chunfang Hao; Yongsheng Jia; Xiaodong Liu; Zhongsheng Tong


Clinical Oncology and Cancer Research | 2014

Anti-tumor effect of tumor vaccine combined with metronomic chemotherapy on breast cancer in mice

Yehui Shi; Liyan Zhou; Feng Wei; Jinpu Yu; Yongsheng Jia; Zhongsheng Tong

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Yehui Shi

Tianjin Medical University

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Zhongsheng Tong

Tianjin Medical University Cancer Institute and Hospital

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Liyan Zhou

Tianjin Medical University

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Ming Gao

Tianjin Medical University Cancer Institute and Hospital

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Weipeng Zhao

Tianjin Medical University

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Yang Yu

Tianjin Medical University

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Chen Tian

Tianjin Medical University

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Chen Wang

Tianjin Medical University

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Chunfang Hao

Tianjin Medical University

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Dapeng Li

Tianjin Medical University

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