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Dive into the research topics where Kun Meng is active.

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Featured researches published by Kun Meng.


Oncotarget | 2015

A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway

Hong Zhao; Yuming Guo; Shu Li; Ruiqin Han; Jianming Ying; Hai Zhu; Yuanyuan Wang; Li Yin; Yuqing Han; Lingzhi Sun; Zhaoyi Wang; Qingcong Lin; Xinyu Bi; Yuchen Jiao; Hongying Jia; Jianjun Zhao; Zhen Huang; Zhiyu Li; Jianguo Zhou; Wei Song; Kun Meng; Jianqiang Cai

Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM-positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3. Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC.


Cell Research | 2018

Tamoxifen enhances stemness and promotes metastasis of ERα36 + breast cancer by upregulating ALDH1A1 in cancer cells

Qiang Wang; Jun Jiang; Guoguang Ying; Xiao-Qing Xie; Xia Zhang; Wei Xu; Xuemin Zhang; Erwei Song; Hong Bu; Yi-Fang Ping; Xiao-hong Yao; Bin Wang; Shilei Xu; Ze‐Xuan Yan; Yanhong Tai; Baoquan Hu; Xiaowei Qi; Yan-Xia Wang; Zhi-Cheng He; Yan Wang; Ji Ming Wang; You-Hong Cui; Feng Chen; Kun Meng; Zhaoyi Wang; Xiuwu Bian

The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.


Oncotarget | 2017

Targeting BCR-ABL + stem/progenitor cells and BCR-ABL-T315I mutant cells by effective inhibition of the BCR-ABL-Tyr177-GRB2 complex

Min Chen; Ali G. Turhan; Hongxia Ding; Qingcong Lin; Kun Meng; Xiaoyan Jiang

Treatment of BCR-ABL+ human leukemia has been significantly improved by ABL tyrosine kinase inhibitors (TKIs), but they are not curative for most patients and relapses are frequently associated with BCR-ABL mutations, warranting new targets for improved treatments. We have now demonstrated that protein expression of human estrogen receptor alpha 36 (ERα36), an alternative splicing variant of human estrogen receptor alpha 66 (ERα66), is highly increased in TKI-insensitive CD34+ chronic myeloid leukemia (CML) cells and BCR-ABL-T315I mutant cells, and is abnormally localized in plasma membrane and cytoplasm. Interestingly, new pre-clinically-validated analogs of Icaritin (SNG162 and SNG1153), which target abnormal ERα36 activity, inhibit cell growth and induce apoptosis of BCR-ABL+ leukemic cells, particularly BCR-ABL-T315I mutant cells. A combination of SNG inhibitors and TKI selectively eliminates treatment-naïve TKI-insensitive stem/progenitor cells while sparing healthy counterparts. Oral TKI dasatinib combined with potent SNG1153 inhibitor effectively eliminates infiltrated BCR-ABL+ blast cells and enhances survival of mice. Importantly, a unique mechanism of SNG inhibition was uncovered by demonstrating a marked interruption of the BCR-ABLTyr177-GRB2 interaction, leading to inhibition of the downstream RAS/MAPK pathway. This new combination therapy may lead to more effective disease eradication, especially in patients at high risk of TKI resistance and disease progression.


Oncotarget | 2016

A novel anticancer agent SNG1153 inhibits growth of lung cancer stem/progenitor cells

Shiyang Liu; Yuming Guo; Jing Wang; Hai Zhu; Yuqing Han; Mingji Jin; Jun Wang; Congya Zhou; Junfeng Ma; Qingcong Lin; Zhaoyi Wang; Kun Meng; Xueqi Fu

Lung cancer is the leading cause of cancer-related death in both men and women. Lung cancer contains a small population of cancer cells with stem-like features known as cancer stem cells (CSCs). CSCs are often more resistant to current therapeutic treatments. Thus, it is urgent to develop a novel agent that is able to inhibit CSCs growth. In this study, we examined the ability of SNG1153, a novel chemical agent to inhibit the growth of lung CSCs. We found that SNG1153 inhibited growth and induced apoptosis in established lung cancer cells. We also found that SNG1153 inhibited the tumorsphere formation and decreased CD133-positive (lung CSC marker) cancer cells. SNG1153 was able to attenuate tumor formation in NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice injected with lung tumorsphere cells. We further demonstrated that SNG1153 induced β-catenin phosphorylation and down-regulated β-catenin. Our results thus demonstrate that SNG1153 effectively inhibits the growth of lung CSCs and suggest that SNG1153 may be a novel therapeutic agent to treat human lung cancer.


Cancer Research | 2015

Abstract 949: An ER-α36 monoclonal antibody exhibits anticancer activity in triple-negative breast cancer cells

Qingcong Lin; Junma Zhou; Jing Wang; Zonghui Wang; Jun Wang; Feng Chen; Xueming Qian; Xiao Shang; Jun Bao; Zhaoyi Wang; Kun Meng

ER-α36 is a novel variant of ER-α, plays an important role in mitogenic estrogen signaling and tamoxifen resistance in both ER-positive and -negative breast cancer. ER-α36 is highly expressed on the plasma membrane of both ER-positive and -negative breast cancer stem/progenitor cells and critical for maintenance of the breast cancer stem/progenitor cells, which make it a promising target for antibody-based breast cancer treatment. In this study, we have screened and identified a candidate of therapeutic antibody named 3C11 that specifically recognizes ER-α36 at its unique C-terminal residues. The antibody 3C11 showed pM affinity to ER-α36 in the BiaCore assay and potent growth inhibitory activity in multiple breast cancer cell lines in vitro. In addition, 3C11 also showed dose-dependent inhibition of tumor growth in a xenograft model formed by a triple-negative breast cancer cell line SUM159 that was generated from a refractory breast cancer. Furthermore, we found that 3C11 was quickly and efficiently internalized into cells, which makes it a potential candidate for development of the antibody-drug conjugate approaches. These results demonstrated that ER-α36 is promising cancer target for development of antibody-based therapeutic approaches. Citation Format: Qingcong Lin, Junma Zhou, Jing Wang, Zonghui Wang, Jun Wang, Feng Chen, Xueming Qian, Xiao Shang, Jun Bao, Zhaoyi Wang, Kun Meng. An ER-α36 monoclonal antibody exhibits anticancer activity in triple-negative breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 949. doi:10.1158/1538-7445.AM2015-949


Cancer Research | 2014

Abstract 2707: In vitro and in vivo evaluation of SNG1153, a synthetic modulator of ER-α36

Bo Zhang; Kun Meng; Xiao Shang; Zhaoyi Wang; Yanzhong Zhang; Fang Fang; Jing Wang; Zonghui Wang; Jun Wang; Yuming Guo; Shiyang Liu; Feng Chen; Hongxia Ding; Jiancun Zhang; Jun Bao

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: ER-α36, a novel truncated variant of estrogen receptor α, was recently discovered and extensively studied as a potential therapeutic target. ER-α36 was found to be overexpressed in many cancers including estrogen-positive and negative breast cancer, lung cancer, prostate cancer, endometrial cancer, liver cancer and other cancers. This suggests that ER-α36 is potentially a promising target for the development of novel anticancer agents with broader clinical applications. This study aims to evaluate the in vitro and in vivo performance of SNG1153, an orally available, synthetic modulator of ER-α36. Methods: the viabilities of ER-α36 overexpressed cancer cells were evaluated using a CCK-8 assay after exposure to SNG1153. Pharmacokinetic study was conducted in rat and SNG1153 was administered orally in escalated doses. In-vivo efficacies of SNG1153 were evaluated in Bcap-37 xenograft model, Ishikawa xenograft model and SPC-A-1 xenograft model. Results: SNG1153 showed significant inhibition at low micromolar concentrations in ER-α36 overexpressed cell lines including the one resistant to tamoxifen. SNG1153 exhibited a linear PK profile with a bioavailability of more than 55% in the rat PK study. In the in-vivo efficacy studies, 3 doses were investigated and SNG1153 showed dose-dependent inhibition. The tumor growth inhibition at high dose was 57% in the breast cancer Bcap-37 xenograft model, 65% in the endometrial cancer Ishikawa xenograft model and 52% in lung adenocarcinoma SPC-A-1 xenograft model. No signs of toxicity were observed in these models. Conclusion: SNG1153, as a synthetic ER-α36 modulator, showed promising activities in many in vitro and in vivo models. It is currently in preclinical development stage. Citation Format: Bo Zhang, Kun Meng, Xiao Shang, Zhaoyi Wang, Yanzhong Zhang, Fang Fang, Jing Wang, Zonghui Wang, Jun Wang, Yuming Guo, Shiyang Liu, Feng Chen, Hongxia Ding, Jiancun Zhang, Jun Bao. In vitro and in vivo evaluation of SNG1153, a synthetic modulator of ER-α36. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2707. doi:10.1158/1538-7445.AM2014-2707


Archive | 2014

Use of icaritin for the preparation of composition for treating cancer

Kun Meng; Hongxia Ding; Shu Li; Ya Tuo; Yueqiu Shen


Journal of Clinical Oncology | 2018

A multicenter, single arm phase II trial of a small molecule immune-modulator icaritin: Safety, overall survival, immune dynamics, and PD-L1 expression in advanced hepatocellular carcinoma.

Sun Y; Qing Li; Jianming Xu; Jun Liang; Ying Cheng; Shu Li; Limin Zheng; Bin Ye; Kun Meng; Shukui Qin


Journal of Clinical Oncology | 2017

Icaritin efficacy and tolerability in advanced hepatocellular carcinoma: Final phase Ib result.

Ying Fan; Binghe Xu; Xiaoyan Ding; Fei Ma; Jiayu Wang; Peng Yuan; Qing Li; Pin Zhang; Kun Meng; Zhaoyi Wang; Shu Li; Jun Bao


Archive | 2014

Use of icaritin for preparation of composition for treating cancer

孟坤; Kun Meng; 丁紅霞; Hongxia Ding; 李抒; Shu Li; Ya Tuo; 沈月秋; Yueqiu Shen

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Jun Wang

Chinese Academy of Sciences

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Min Chen

University of Poitiers

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Xiaoyan Jiang

University of British Columbia

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Qing Li

Peking Union Medical College

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Li Yin

Creighton University

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Wei Xu

University of Wisconsin-Madison

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Bin Wang

Third Military Medical University

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