1.Expressions of HER-2,p53,Estrogen Receptor,and Progesterone Receptor in Tissues of Invasive Ductal Breast Carcinoma with Different Clinical Stages
Luying TANG ; Yi JIN ; Yong LIU ; Zhiying FENG ; Chunkui SHAO ; Zefang REN
Journal of Sun Yat-sen University(Medical Sciences) 2009;30(4):454-457
[Objective] Expressions of human epidermal growth factor receptor 2(HER-2),p53,estrogen receptor (ER),and progesterone receptor (PR) in tissues of breast invasive ductal carcinoma are not only applied to determine the therapeutic regimen,but they may also be related to the prognosis.We investigated the levels of these proteins among different clinical stages and the correlations.[Method] One hundred and thirty-eight tissues from cases with breast invasive ductal carcinoma were tested with immunohistochemistry.New scoring standards and rank test were applied.The indices were digitalized and semi-quantified.[Results] In the tissues from high clinical stage,the expression of HER2 was significantly increased,while expression of PR was markedly decreased.[Conclusion] Expression of HER2 and PR might be better markers for predicting clinical stages and prognosis.
2.Carbazole and tetrahydro-carboline derivatives as dopamine D3 receptor antagonists with the multiple antipsychotic-like properties.
Zhongtang LI ; Fan FANG ; Yiyan LI ; Xuehui LV ; Ruqiu ZHENG ; Peili JIAO ; Yuxi WANG ; Guiwang ZHU ; Zefang JIN ; Xiangqing XU ; Yinli QIU ; Guisen ZHANG ; Zhongjun LI ; Zhenming LIU ; Liangren ZHANG
Acta Pharmaceutica Sinica B 2023;13(11):4553-4577
Dopamine D3 receptor (D3R) is implicated in multiple psychotic symptoms. Increasing the D3R selectivity over dopamine D2 receptor (D2R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D3R selective ligands. Through a structure-based virtual screen, ZLG-25 (D3R Ki = 685 nmol/L; D2R Ki > 10,000 nmol/L) was identified as a novel D3R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D3R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD3R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.