1.Preparation of curcumin prodrugs and their in vitro anti-tumor activities.
Peng, LU ; Qiangsong, TONG ; Fengchao, JIANG ; Liduan, ZHENG ; Fangmin, CHEN ; Fuqing, ZENG ; Jihua, DONG ; Yuefeng, DU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2005;25(6):668-70, 678
The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6 - 24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 micromol/L - 40 micromol/L NVC and NGC for 6 - 24 h, the growth inhibitory effects on EJ cells were 6.71% - 65.13% (P < 0.05), 10.96% - 73.01% (P < 0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P < 0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumor-targeted chemotherapeutic drugs.
Antineoplastic Agents, Phytogenic/*pharmacology
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Curcumin/*pharmacology
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Dose-Response Relationship, Drug
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Prodrugs/*chemical synthesis
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Prodrugs/*pharmacology
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Tumor Cells, Cultured
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Urinary Bladder Neoplasms/*pathology
2.Forecast study on the expression grade of antigen Ki-67 in breast ductal carcinoma by contrast enhanced ;ultrasound
Rui DU ; Weiwei SHU ; Baoding CHEN ; Xin ZHANG ; Ying CHEN ; Xincai WU ; Yuefeng LI
Chinese Journal of Ultrasonography 2016;25(3):218-222
Objective To investigate the correlation between the hemodynamic characteristics of time intensity curve(TIC) by contrast enhanced ultrasound(CEUS) and the expression of antigen Ki-67 of the 4 different clinic stages (T0 andTis,T1 ,T2,T3) in ductal carcinoma in order to predict the grade of the expression of antigen Ki-67 and clinic stages.Methods Masses founded in 80 cases proved by pathological test after resection or needle biopsy were divided into 4 groups base on clinic stages:group 1(T0 andTis) , group 2(T1),group 3(T2),and group 4(T3).Some parameters gained after analyzing TIC of CEUS would be used to make a rank correlation analysis with the expression grade of antigen Ki-67 through immunohistochemical diagnosis.A regression equation would be gained from those parameters which had a correlation with the expression grade of antigen Ki-67 (P < 0.05). Results Most TIC of ductal carcinomas were possessed of the characteristics of fast in and slow-out.Compared to the other three groups,group 4(T3) had significant differences in arrive time,time to peak,arrive intensity,peak intensity and area under curve.Compared to group 1(T0 andTis),group 4(T3) had significant differences in continuous time and rising curve's slope and group 3(T2) has significant differences in arrive intensity and area under curve. Parameters entered the regression equation through mult-variable linear regression analysis were arrive time,continuous time,peak intensity and rising curve's slope.R square was 0.83 1 and adjust R square was 0.822.Through the regression equation verification,5 cases accorded with the clinic stages standard of ductal carcinoma.Conclusions The hemodynamic characteristics of time intensity curve (TIC) by contrast enhanced ultrasound had a good correlation with the expression grade of antigen Ki-67 of the 4 different clinic stages in ductal carcinoma.The regression equation had a good explanatory and degree of fitting,it can be used to predict the expression grade of antigen Ki-67 and indirectly forecasts clinic stages of ductal carcinoma.
3.Comparison of therapeutic efficacy among 3 different regimens of neoadjuvant chemotherapy for FIGO stage Ⅰb2-Ⅱb cervical squamous carcinoma before operation
Yuefeng FAN ; Long JIN ; Nan HONG ; Jian GAO ; Lei CHEN ; Jianliu WANG ; Xiangke DU
Chinese Journal of Interventional Imaging and Therapy 2010;7(2):133-136
Objective To compare the short-time effect of 3 different regimens of neoadjuvant chemotherapy (NACT) in patients with FIGO stage Ⅰb2-Ⅱb cervical squamous carcinoma.Methods A total of 50 patients with FIGO stage Ⅰb2-Ⅱb cervical squamous carcinoma were divided into 3 groups:systemic chemotherapy group (n=13) ,trans-arterial chemotherapy group (TAC,n=19) ,trans-arterial chemoembolization group (TACE,n=18) .After 1-3 periods of NACT,all patients received surgical operation.Tumor response and reduction ratio after NACT,side effects,hemorrhage volume in surgery and bad prognostic factors (including intraluminal tumor thrombi,pelvic lymph node metastasis,parametrial involvernent,positive surgical margin,ovary metastasis) of operation sample were statistically analyzed.Results Tumor response,reduction ratio and hemorrhage volume in surgery were significantly better in TAC group and TACE group than those in systemic chemotherapy group (P<0.05) ,but no significant difference was found between TAC group and TACE group (P>0.05) .The incidence rate of intraluminal tumor thrombi and lymph node metastasis was lower in TACE group than in systemic chemotherapy group and TAC group,but there was no statistical difference.No difference of parametrial involvement,positive surgical margin,ovary metastasis and side effects was found among 3 groups.Conclusion For stage Ⅰb2-Ⅱb cervical squamous carcinoma,preoperative TAC and TACE have more advantages than systemic chemotherapy.In comparison with TAC,TACE is expected to reduce the incidence rate of bad prognostic factors such as intraluminal tumor thrombi and pelvic lymph node metastasis.
4.Comparative Study on Quality of Angelica Formula Particles and Angelica Pieces
Yuefeng LI ; Zeguo ZHANG ; Fuju XU ; Hui JIN ; Lidong DU ; Ruiqiong WANG ; Jilong WANG ; Xingke YAN
Chinese Journal of Information on Traditional Chinese Medicine 2014;(4):70-72
Objective To determine the content of ferulic acid, water and extract of Angelica formula particles, provide a reliable method for evaluation and quality control, and compare the quality of Angelica formula particles and Angelica pieces. Methods HPLC method was used with Kromasil C18 column (4.6 mm×250 mm, 5μm), flow rate of 1.0 mL/min, detection wavelength of 316 nm, column temperature at 28 ℃. The mobile phase was acetonitrile-0.05%phosphoric acid in water gradient elution system. Results Ferulic acid showed good linear relationship in the range of 0.033-0.165 μg (r=0.999 8). The average recovery was 98.78% and RSD=0.99%. Angelica formula particles met the quality requirement in the content indicators, the content of ferulic acid was higher than Angelica pieces. Conclusion The HPLC method for determination of ferulic acid in Angelica formula particles is simple and reliable, with good reproducibility, and can be used as the quality control method of Angelica formula particles.
5.Preparation of Curcumin Prodrugs and Their in Vitro Anti-tumor Activities
Peng LU ; Qiangsong TONG ; Fengchao JIANG ; Liduan ZHENG ; Fangmin CHEN ; Fuqing ZENG ; Jihua DONG ; Yuefeng DU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2005;25(6):668-670,678
The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6-24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 μmol/L- 40 μmol/L NVC and NGC for 6 - 24 h, the growth inhibitory effects on EJ cells were 6.71% -65.13 % (P<0.05), 10.96 % -73.01% (P <0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P<0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumortargeted chemotherapeutic drugs.
6.Predictive value of quantitative analysis of contrast-enhanced ultrasound gradient features of perfusion-deficient areas in early-stage breast cancer in sentinel lymph node metastasis
Rui DU ; Weiwei SHU ; Xincai WU ; Xin ZHANG ; Yuefeng LI
Chinese Journal of Ultrasonography 2023;32(10):880-885
Objective:To investigate the predictive value of perfusion defect gradient features of early breast cancer using contrast-enhanced ultrasound (CEUS) in sentinel lymph node (SLN) metastasis.Methods:A retrospective analysis was performed on 147 patients with single early breast cancer confirmed by surgery and pathology in the Affiliated Hospital of Jiangsu University from January 2017 to December 2022, which were divided into SLN positive group (78 cases) and SLN negative group (69 cases) according to whether there are positive lesions in the biopsy SLN. The quantitative characteristics of CEUS in the perfusion defect and marginal high perfusion area of breast cancer in the two groups were analyzed. The differential gradient features between them were analyzed by multivariate Logistic regression and ROC curves.Results:The univariate analysis revealed statistically significant differences between the two groups for peak-arrival time gradient (ΔTTP), peak intensity gradient (ΔPI), ascending branch slope gradient (ΔRS) and area gradient under the curve (ΔAUC) (all P<0.05). Multivariate Logistic regression analysis showed that ΔTTP, ΔPI and ΔAUC were independent predictors of SLN status in early breast cancer (all P<0.05). The sensitivity (74.57%), specificity (84.42%) and area under the curve (0.789) of that combination of the three indexes for predicting SLN status were higher than the prediction efficiency of a single index.In addition, ΔTTP ( r=-0.578, P<0.05) was negatively correlated with average positive rate of SLN, and ΔPI ( r=0.629, P<0.05) and ΔAUC ( r=0.703, P<0.05) were positively correlated with average positive rate of SLN. Conclusions:The perfusion defect gradient features of early breast cancer are closely related to the SLN status and can effectively predict whether SLN metastasis occurrs.
7.Predictive value of infiltrating zone contrast-enhanced ultrasound gradient features in Nottingham grading and pathologically true infiltration of invasive ductal carcinoma
Rui DU ; Weiwei SHU ; Xincai WU ; Xin ZHANG ; Yuefeng LI
Chinese Journal of Ultrasonography 2024;33(2):119-125
Objective:To investigate the predictive value of infiltrating zone contrast-enhanced ultrasound(CEUS) gradient features in Nottingham grading and pathologically true infiltration of invasive ductal carcinoma(IDC).Methods:A retrospective analysis was performed on 78 female breast cancer patients (95 masses) confirmed by surgical and pathology in the Affiliated Hospital of Jiangsu University from July 2019 to June 2022, which were divided into Grade-Ⅰ (22 masses), Grade-Ⅱ (28 masses), and Grade-Ⅲ (45 masses) according to the Nottingham histological grading system. The differences in the maximum diameter of the infiltration zone and the characteristic parameters of the gradient of the inner and outer edges of the infiltration zone among the three groups of masses were compared, and the differential gradient features among them were analyzed by multivariate ordered Logistic regression and ROC curves. The relationship between the differential gradient characteristics of the infiltration zone and the pathologically true infiltration of the mass was further explored.Results:The univariate analysis showed statistically significant differences among the three groups for peak-arrival time gradient (ΔTTP), ascending branch slope gradient (ΔRS), peak intensity gradient (ΔPI) and area gradient under the curve (ΔAUC) (all P<0.05). Multiple ordered logistic regression analysis showed that ΔTTP, ΔPI and ΔAUC had independent influences on the histologic grading of IDC (all P<0.05), and the area under the curve for the combination of the three in predicting IDC histology grades Ⅰ, Ⅱ and Ⅲ was 0.692, 0.705 and 0.765, respectively. In addition, the maximum diameter of pathologically true infiltration of the mass was positively correlated with ΔTTP ( r=0.621, P<0.05) and negatively correlated with ΔPI ( r=-0.605, P<0.05) and ΔAUC ( r=-0.719, P<0.05). Conclusions:Infiltration zone CEUS gradient features are effective in predicting the histologic grade of IDC and strongly correlate with the degree of pathologically true infiltration of the mass.
8.Regulation of tumor suppressor microRNA-218 on malignant progression and cancer stem cell properties of prostate cancer
Lijun MU ; Bing GUAN ; Juanhua TIAN ; Yuefeng DU ; Xudong LI
Journal of Modern Urology 2023;28(2):161-165
【Objective】 To investigate the role of microRNA-218 (miR-218) in regulating prostate cancer (PCa) cell stemness and epithelial-mesenchymal transition (EMT). 【Methods】 PCa cell line stably overexpressing miR-218 was constructed with lentivirus transfection. The expression of miR-218 was detected with real-time fluorescence quantitative polymerase chain reaction (q-PCR). The migration ability was detected with Transwell assay. The expression of EMT related proteins were detected with Western blot. The properties of cells were determined with colony formation and tumor sphere formation assays. 【Results】 The results of q-PCR showed that the mRNA level of miR-218 was significantly lower in PCa cell lines LNCaP and C4-2 than in BPH-1. Transwell assay showed that miR-218 inhibited the migration of PCa cells. Western blot showed that the expression of EMT related proteins were inhibited by miR-218. Colony formation and tumor sphere formation assays showed that overexpression of miR-218 significantly inhibited the properties of cells. 【Conclusion】 The expression of miR-218 is downregulated in PCa cell lines. miR-28 can inhibit cell migration, EMT and cancer stem cell properties.
9.Safety and efficacy of neoadjuvant chemotherapy combined with immunotherapy in 101 patients with muscle-invasive bladder cancer
Chaosheng GAN ; Tao LI ; Junjie FAN ; Zhangdong JIANG ; Guojing WANG ; Ke XU ; Qiyuan KANG ; Yangqingqing ZHOU ; Yuefeng DU ; Jinhai FAN ; Lei LI ; Dalin HE ; Kaijie WU
Journal of Modern Urology 2024;29(9):790-796
【Objective】 To explore the safety and efficacy of neoadjuvant chemotherapy (NAC) combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection (RC-PLND) for muscle-invasive bladder cancer (MIBC). 【Methods】 The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed, including 71 patients (70.3%) who received NAC (NAC group) and 30 (29.7%) who received NAC combined with immunotherapy (NAC combine immunotherapy group). The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response (pCR) and pathological partial response (pPR). 【Results】 There were no significant differences in the baseline data between the two groups (P>0.05).However, the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group (69.0% vs. 46.7%, P=0.034).Compared with NAC group, NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR (60.6% vs. 83.3%, P=0.026; 45.1% vs. 70.0%, P=0.022).Furthermore, the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC, but the difference was not significant (53.3% vs. 33.8%, P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR (P<0.05).In addition, the most common adverse events during neoadjuvant therapy were anemia, decreased white blood cells, nausea, and vomiting, but most of them were grade 1—2 and could be relieved through symptomatic treatment. 【Conclusion】 NAC combined with immunotherapy is safe and effective, which can improve the rate of pathological downstaging, pPR and pCR, without increasing the incidence of adverse reactions.