1.Effect of 5-FU on expression of Bmi-1, Sca-1 and Oct-4 in human breast cancer cell line MDA-MB-468
Wengang SONG ; Chunling LIU ; Xu YANG ; Huazhen DU
Chinese Journal of Clinical and Experimental Pathology 2015;(5):523-527
Purpose To explore the relation between the expression of Bmi-1 and cancer stem cells and its relation to chemotherapy re-sistance in breast cancer. Methods MTT method was applied to detect the inhibition effect on proliferation of different concentrations (0. 01, 0. 1, 1, 10 μg/ml) of 5-Fluorouracil (5-FU) to MDA-MB-468 cells with 48 and 72 hours culture, a curve of proliferation in-hibition rate was drawn, and a suitable experiment concentration of 5-FU was chosen. MDA-MB-468 cells was serially passaged under continuous interference with the suitable concentration of 5-FU, 6 generations of cells were collected, cells with 5-FU interference were designed as experiment group and a corresponding control group with no 5-FU was set. RT-PCR and Western blot were employed to ex-amine mRNA and protein expression of Bmi-1 and Sca-1, Oct-4 in the 6 generations of cells of both control group and experiment group. Results Results of the MTT test showed that 5-FU could inhibit the proliferation of human breast cancer cell line MDA-MB-468, the 5-FU concentration of 0. 1 μg/ml was chosen as the suitable experiment concentration. RT-PCR tests showed that the differ-ences between the relative mRNA expression values of Bmi-1 and Sca-1, Oct-4 in the 6 generations of MDA-MB-468 cells were not sta-tistically significant in control group (all P>0. 05) and that the differences between the relative mRNA expression values of Bmi-1 and Sca-1, Oct-4 in the 6 generations of MDA-MB-468 cells were of statistical significance in experiment group cells (all P<0. 05). The mRNA expression of Bmi-1, Sca-1 and Oct-4 showed the following tendency in the 6 generations of passaged cells:decrease (1st gen-eration)—increase (2nd generation)—continuous increase (3rd generation)—decrease (4th generation)—increase (5th genera-tion)—decrease (6th generation). Western blot tests indicated that the differences between the relative protein expression values of Bmi-1 and Sca-1, Oct-4 in the 6 generations of MDA-MB-468 cells were not statistically significant in control group and that the differ-ences between the relative protein expression values of Bmi-1 and Sca-1, Oct-4 in the 6 generations of MDA-MB-468 cells were of sta-tistical significance in experiment group cells (all P<0. 05). The expression of Bmi-1 was positively correlated with stem cell associat-ed factors Sca-1, Oct-4 (r=1, all P<0. 01). Conclusions The expression of Bmi-1 gene is positively correlated with expression of stem cell associated factors Sca-1 and Oct-4 in breast cancer cell line MDA-MB-468 cell, and Bmi-1 may be a novel marker for cancer stem cells in breast cancer. Administration of 5-FU can affect the expression level of Bmi-1 and the ration of cancer stem cells in breast cancer cell line MDA-MB-468. Bmi-1 gene may be associated with drug resistance to chemotherapy and recurrence in breast cancer.
2.Sex-specific association between coffee consumption and incident chronic kidney disease: a population-based analysis of 359,906 participants from the UK Biobank
Lei TANG ; Lina YANG ; Wenwen CHEN ; Chunyang LI ; Yu ZENG ; Huazhen YANG ; Yao HU ; Yuanyuan QU ; Huan SONG ; Xiaoxi ZENG ; Ping FU
Chinese Medical Journal 2022;135(12):1414-1424
Background::The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee–CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods::A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data ( n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. Results::Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed ( P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee–CKD association. Conclusions::In addition to the overall inverse coffee–CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.
3.Ultrasound Diagnosis and Misdiagnosis Analysis of Accessory Cavitated Uterine Malformation
Fei JI ; Na SU ; Huazhen LIU ; Zijing FU ; Zhenhong QI ; Meng YANG
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1100-1106
To explore the ultrasound characteristics of accessory cavitated uterine malformation (ACUM) and the causes of misdiagnosis, in order to better understand the disease and improve the diagnostic ability of radiologists. We retrospectively collected clinical, pathological and imaging data of ACUM patients who were diagnosed after surgery at Peking Union Medical College Hospital from December2013 to December 2023. Besides, we analyzed ultrasound features of ACUM and the cause of misdiagnosis. A total of 11 patients were included, with a mean age of diagnosis of (27.1±7.4)years. There was a mean interval of (6.1±5.5)years between menarche and onset of dysmenorrhea. Preoperative ultrasound showed that ACUM appeared as solitary lesions located under the insertion of the round ligament, with a mean maximum diameter of (3.0±1.0)cm. Lesions were round or oval (90.9%, 10/11) and not connected to the uterine cavity (100%, 11/11) with clear boundaries (72.7%, 8/11), presenting as regular thick-walled cystic-solid structures. Cystic areas were observed within the mass (100%, 11/11) with a ground-glass-like appearance (90.9%, 10/11) and hyperechoic endometrial lining (90.9%, 10/11). The surrounding of the mass showed hypoechoic or isoechoic areas resembling the muscular layer and circular or semi-circular vascularity was detected around the mass. No adenomyosis or other uterine lesions were found. Analysis of misdiagnosis: Among the 11 ACUM cases, 6 were correctly diagnosed by the initial ultrasound examination, and 5 cases by MRI. Two patients were misdiagnosed as residual horn uterus by MRI, despite ultrasound suggesting ACUM with visible bilateral uterine horns. ACUM exhibits distinct ultrasound characteristics. When young women present with progressive dysmenorrhea and ultrasound reveals a regular cystic-solid mass with thick wall located under the round ligament insertion, ACUM should be considered.