1.Expression of PTEN and MGMT protein in gynecomastia
Lingdong ZHU ; Jinglong CAI ; Hong DONG ; Chengjun ZHOU
Basic & Clinical Medicine 2006;0(08):-
Objective To detect the expression of a novo tumor suppressor gene PTEN and DNA direct repair enzyme MGMT in gynecomastia. Methods Immunohistochemical SP method was used to detect expression of PTEN and MGMT protein in 68 cases of gynecomastia(experiment group) and 24 cases of mammary gland of control group. The selected examples were divided into three different age groups and three different histological types. Results The PTEN and MGMT protein were all expressed in nucleusr of ductal cellula epithelialis. The expression level of PTEN and MGMT proteins in gynecomastia was significantly lower than that of mammary gland of control(P
2.New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.
Yuyu ZHU ; Zijun OUYANG ; Haojie DU ; Meijing WANG ; Jiaojiao WANG ; Haiyan SUN ; Lingdong KONG ; Qiang XU ; Hongyue MA ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(11):4011-4039
Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.
3.SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2019;9(2):304-315
Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.