1.Application of organoids in drug screening of gynecological malignant tumors
Yuanyuan JIANG ; Wenfei WEI ; Jingya WU ; Huawen LI
China Oncology 2024;34(11):1053-1060
Gynecologic malignant tumors are among the leading diseases threatening women's lives and health,with the highest morbidity and mortality rates among all female diseases.These tumors originate from female reproductive organs and are typically classified based on the affected site.Ovarian cancer(OC),endometrial cancer(EC)and cervical cancer(CCA)are the most common types.Currently,gynecologic malignant tumors are primarily treated with a combination of surgery,chemotherapy and radiotherapy,where drugs play a critical role in the treatment process.However,the actual clinical effectiveness is often influenced by various factors,such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients,which limit improvements in patient survival rates.Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals,which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor.To achieve individualized and precise treatment for gynecologic malignant tumors,there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research.Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects,providing doctors with scientific guidance on drug use,thereby avoiding blind drug testing and reducing patients'therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions.Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies.Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture,capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs.This approach has largely overcome the limitations of traditional tumor models,such as patient-derived cancer cell models and patient-derived tumor xenograft models,becoming an essential research tool in oncology.It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies.This paper compared the advantages and disadvantages of several preclinical cancer models,reviewed the development process of organoids,and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian,endometrial,and cervical cancers.Additionally,we discussed the current limitations of organoid technology in its application and envisioned its future development,aiming to provide insights for future medical research,particularly in new drug discovery and personalized medicine.
2.Intraoperative obeservation of laparoscopic splenectomy assisted with splenic artery embolization in patients with hypersplenism secondary to portal hypertension and splenomegaly
Pengfei JIN ; Huawen WU ; Dexi JIN ; Guofu CHEN
Chinese Journal of Postgraduates of Medicine 2018;41(12):1090-1093
Objective To discuss introperative value of laparoscopic splenectomy (LS) treatment assisted with preoperative splenic artery embolization (SAE) in the patients with the hypersplenism secondary to portal hypertension and splenomegaly. Methods The clinical data of 38 patients with the hypersplenism secondary to portal hypertension and splenomegaly admitted to the First People′s Hospital of Wenling from April 2015 to April 2018 were analyzed. Among them, 21 patients underwent LS alone (alone group) and 17 patients underwent LS assisted with preoperative SAE (combined group). Including length of the spleen and liver function Child-Pugh grade, operative time, blood transfusion rate, intraoperative blood loss, intraoperative blood transfusion volume and conversion rate were compared between two groups. Then the clinical value of LS treatment assisted with preoperative splenic artery embolization was discussed. Results The splenic volume of combined group was significantly reduced after SAE: (627 ± 195) cm3vs. (998 ± 251) cm3, P<0.05. The conversion rate was 23.8%(5/21) in alone group, while no patient required open surgery in the combined group. Compared with that in alone group, operative time of the combined group was shorter [(143 ± 27) min vs. (189 ± 33) min], the blood loss volume was less [(155 ± 49) ml vs. (302 ± 76) ml)], and the differences were statistically significant (P< 0.05). The blood transfusion rates of combined group was lower [2/17 vs. 33.3% (7/21)], and intraoperative blood transfusion volume was less [(192 ± 42) ml vs. (399 ± 87) ml] . The differences were statistically significant (P<0.05). Conclusions LS treatment assisted with preoperative SAE has some advantages, such as shorter operative time, lower surgical laparotomy rate, less intraoperative blood transfusion, less bleeding and shorter length of stay.
3.Association of HLA-B*1502 Genetic Polymorphism with Cyclosporine-induced Liver Injury in Chinese Re-nal Transplant Recipients
Huawen XIN ; Huiming LIU ; Yuanqi LI ; Hui HUANG ; Li ZHAO ; Airong YU ; Qing LI ; Xiaochun WU ; Weiliang LI ; Lei XIONG
China Pharmacist 2015;(5):704-706,707
Objective:To investigate the effects of HLA-B?1502 genetic polymorphism on cyclosporine( CsA)-induced liver injury in Chinese renal transplant recipients. Methods:HLA-B?1502 genotypes were determined by polymerase amplification chaln reaction of sequence-specific primers( PCR-SSP) in a total of 339 renal transplant recipients receiving CsA. All the subjects were divided into the CsA-induced liver injury group, non-CsA-induced liver injury group and the control group according to the liver injury occurrence. Results:In the 339 renal transplant recipients, the frequency of HLA-B?1502 mutation allele was 22. 64%. The distribution frequen-cy of HLA-B?1502 mutation allele had no significant difference among the three groups. There were no significant differences in the clinical characteristics of HLA-B?1502 genotypes among three groups(P>0. 05). Conclusion: No association is observed between HLA-B?1502 genetic polymorphism and cyclosporine-induced liver injury in Chinese renal transplant recipients.
4.Association between SLC30A8 gene polymorphisms and diabetes mellitus after renal transplantation
Airong YU ; Xing FAN ; Huiming LIU ; Huawen XIN ; Xiaochun WU
Chinese Journal of Tissue Engineering Research 2013;(31):5613-5619
BACKGROUND:Previous studies have found that the susceptibility genes of adiponectin gene and calpain 10 gene of type 2 diabetes are closely related with the incidence of diabetes in Chinese renal transplantation patients. So, are other susceptibility genes of type 2 diabetes also associated with posttransplantation diabetes mel itus? OBJECTIVE:To investigate the association between the zinc transporter solute carrier family 30 member 8 (SLC30A8) gene polymorphism and the posttransplantation diabetes mel itus. METHODS:A total of 97 patients with posttransplantation diabetes mel itus and 301 patents without posttransplantation diabetes mel itus (control group) were selected, and then the SLC30A8 gene rs13266634 genotype was detected with real-time PCR method. The association between gene polymorphism and posttransplantation diabetes mel itus was analyzed with Logistic regression test. RESULTS AND CONCLUSION:There were significant differences in al ele frequencies and genotype distributions of rs13266634 between the patients with and without posttransplantation diabetes mel itus (P<0.05). After adjustments of age, sex, body weight and body mass index, the incidence of posttransplantation diabetes mel itus of the CC genotype patients was 2.108 times to that of the TT genotype patients (odds ratio=2.108, 95%confidence interval:1.075-4.131, P=0.044);and the incidence of posttransplantation diabetes mel itus of the CC+CT genotype patients was 1.862 times to that of the TT genotype patients (odds ratio=1.862, 95%confidence interval:1.049-3.306, P=0.034). The results suggest that the C-al ele in rs13266634 of SLC30A8 gene is the independent risk factor of posttransplantation diabetes mel itus.
5.Effect and mechanism of preptin on connective tissue growth factor expression in human osteoblasts
Huawen WANG ; Youshuo LIU ; Junkun ZHAN ; Hui XIE ; Xianping WU ; Lingqing YUAN ; Eryuan LIAO
Chinese Journal of Endocrinology and Metabolism 2010;26(11):978-980
Objective To investigate the effect and mechnism of preptin on connect tissue growth factor (CTGF) in human osteoblasts. Methods Recombinant human preptin was used to treat primary human osteoblasts, and Western blot was used to detect CTGF protein level. Mitogen-activated protein kinase p38(p38MAPK), extracellular signal-regulated kinase (ERK1/2), c-jun N-terminal Kinase (JNK), and their phosphorylation levels were also detected by Western blot. MAPK inhibitors (PD98059, SP600125, or SB203580)were used to elucidate the mechnism of preptin induced expression of CTGF in human osteoblasts. Results Treatment of human osteoblasts with preptin caused a time and dose-dependent increase in CTGF secretion. Preptin induced activation of ERK, but not p38MAPK or JNK in human osteoblasts. Furhermore, pretreatment of human osteoblasts with the ERK inhibitor PD98059 abolished the preptin-induced CTGF secretion. Conclusion Preptin induces CTGF expression in human osteoblasts by means of ERK/MAPK pathway.
6.Comparison of the influence of intravenously infused xylitol and glucose on blood glucose variability in type 2 diabetic patients
Jiahua ZHU ; Youshuo LIU ; Yanjiao WANG ; Huawen WANG ; Hongfeng ZHAO ; Wu HUANG ; Yi WANG ; Junkun ZHAN
Chinese Journal of Clinical Nutrition 2009;17(4):201-204
,and 17.47%.Conclusions Xylitol can lower the blood glucose a littte but without significant difference.It has little effect on blood glucose variability of patients with type 2 diabetes mellitus and can be safely used for rehydration.
7.Efficacy and Safety of Fluvastatin vs. Xuezhikang for Hyperlipidemia after Renal Transplantation
Airong YU ; Huawen XIN ; Xiaochun WU ; Qing LI
China Pharmacy 2007;0(29):-
OBJECTIVE:To evaluate the efficacy and safety of Fluvastatin vs. Xuezhikang for hyperlipidemia in patients after renal transplantation. METHODS: 56 hyperlipidemia patients after renal transplantation were enrolled: 32 were assigned to receive Fluvastatin (40~80 mg) po qd for 8 weeks and 24 to receive Xuezhikang (0.6 g) po bid for 8 weeks. Total cholesterol (TC),triglyceride (TG),low-density lipoprotein-cholesterol (LDL),high-density lipoprotein-cholesterol (HDL),liver function and renal function in two groups were measured before and after treatment. RESULTS: In Fluvastatin-treated group,the TC decreased from(7.39?1.98)mmol?L-1 to(5.62?0.93)mmol?L-1,LDL reduced from(3.68?1.13)mmol?L-1 to (2.86?0.83)mmol?L-1;in Xuezhikang-treated group,TC decreased from(6.82?1.29)mmol?L-1 to (5.56?1.19) mmol?L-1 and LDL decreased from (3.26?0.73) mmol?L-1 to (2.78?0.80) mmol?L-1,all showing significant differences as compared with before treatment(P 0.05). No obvious adverse effect was noted in either group during treatment. CONCLUSION: Both Fluvastatin and Xuezhikang are safe and effective for hyperlipidemia in patients after renal transplantation.
8.Effect of Cyclosporin Based Triple Immunosuppressive Therapy on Glucose Tolerance in Renal Transplant Recipients
Airong YU ; Huawen XIN ; Xiaochun WU ; Qing LI ;
Chinese Journal of Pharmacoepidemiology 2007;0(05):-
Objective:To study the effect of cyclosporin A based triple immunosuppressive therapy on the plasma glucose in renal transplant recipients.Method:680 renal transplant recipients treated with cyclosporine A combined with prednisone and mycophenolate mofefil from Jan.1996 to May 2007 were analysed.Result:The morbidities of impaired fast- ing glucose,impaired glucose tolerance and post-transplantation diabetes mellitus (PTDM) were 3.97%,5.15% and 8.09%,respectively.The daily doses and concentrations of CsA and the daily doses of prednisone in the impaired glucose tolerance group and PTDM group were significantly higher than those in the normal plasma glucose group.Conclusion:The daily doses and concentrations of CsA and the daily doses of prednisone were closely related to the impaired glucose toler- ance and PTDM of renal transplant recipients.
9.Analysis of Blood Tacrolimus Concentrations in Renal Transplant Recipients
Huawen XIN ; Qing LI ; Xiaochun WU ; Dan SU ; Lei XIONG ; Airong YU ; Yang SHEN ; Guowei ZHANG ;
Chinese Journal of Pharmacoepidemiology 2006;0(01):-
Objective:To investigate the therapeutic range of tacrolimus and effects of tacrolimus on liver and re- nal functions and blood routine in renal transplant recipients.Method:The whole blood tacrolimus concentration was meas- ured by micro-particle enzyme immunoassay(MEIA).Blood tacrolimus concentrations in 390 cases of renal transplant re- cipients were analyzed.The effects of tacrolimus on liver and renal function and blood routine were also studied.Result: The blood tacrolimus concentrations in 377 of 390 cases were within the range from 3 to 15?g?L~(-1).Their blood tacrolimus concentration differed greatly in renal transplant recipients within 6 months after transplantation.Their blood tacrolimus concentration was gradually decreased as time went on.Tacrolimus with therapeutic dosage had no effects on liver and renal function and blood routine.Conclusion:The therapeutic ranges of tacrolimus with MEIA were as follows:5 to 15?g?L~(-1) within 3 months after transplantation,5 to 10?g?L~(-1)between 4 to 6 months after transplantation,3 to 10?g?L~(-1)6 months after transplantation.The administration of tacrolimus had no effects on the liver and renal function and blood routine in re- nal transplant recipients.
10.Effects of Different Anti-rejection Regimens on Liver Function in Renal Transplant Recipients
Qing LI ; Guoqiong LUO ; Kai TANG ; Airong YU ; Xiaochun WU ; Huawen XIN ;
Chinese Journal of Pharmacoepidemiology 2006;0(04):-
Objective:To study the effects of cyclosporine A coadministrated with azathioprine,mycophenolate, mizorihine,rapamycin and/or prednisone on liver function in renal transplant recipients.Method:The drug history records of 600 renal transplant recipients in 1995 to 2005 were retrospectively investigated.Biochemical indexes before and after the treatment with cyclosporine A coadministrated with other immunosuppressants were analyzed.Result:The liver damage was found in 109 cases(18.2%)among 600 cases.The blood concentrations of cyclosporine A in the group with abnormal liver functions were significantly higher than those in the group with normal liver functions(P

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