1.Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer.
Senlin LI ; Siyu CHEN ; Zhihui DONG ; Xingdong SONG ; Xiuling LI ; Ziqi HUANG ; Huiru LI ; Linzhuo HUANG ; Ganyuan ZHUANG ; Ran LAN ; Mingyan GUO ; Wende LI ; Phei Er SAW ; Lei ZHANG
Acta Pharmaceutica Sinica B 2023;13(3):967-981
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
2. FABP5 promotes cell growth, invasion and metastasis in cervical cancer
Yinzhu ZHAN ; Feng LIU ; Yan ZHANG ; Xiaoyu MO ; Wende CHENG ; Wei WANG
Chinese Journal of Oncology 2019;41(3):200-207
Objective:
To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer.
Methods:
The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stage Ⅰa2-Ⅱa2 and 40 cases of normal cervical tissues by real-time PCR and Western blotting. Then, the cells were infected with lentivirus-mediated siRNA-targeting FABP5. CCK-8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on
3.Minimally invasive surgical strategy for acoustic neuromas: an analysis of 415 cases
Lihua CHEN ; Ruxiang XU ; Wende LI ; Bin YU ; Kai SUN ; Hao ZHAO ; Hongtian ZHANG ; Yi YANG
Chinese Journal of Neuromedicine 2019;18(3):263-267
Objective To explore the surgical strategy of minimally invasive treatment for acoustic neuroma and to improve the tumor removal rate and facial nerve function preservation rate. Methods Four hundred and fifteen patients suffering from acoustic neuromas, admitted to and treated by minimally invasive surgery via trans-suboccipital retrosigmoid transmeatus approach in our hospital from January 2008 to December 2016, were chosen in our study. Their clinical data were analyzed retrospectively. Postoperative Karnofsky behavioral status scale (KPS) was used to evaluate the prognoses of the patients. Postoperative routine enhanced MR imaging was performed to determine the degrees of tumor resection. Three months after surgery, House-Brackmann facial function grading (H-B) was used to evaluate the facial function of all patients. Results KPS indicated that excellent prognosis was noted in 399 patients (96.10%), good prognosis in 14 (3.37%), and poor prognosis in 2 (0.48%); the larger the tumor diameter, the smaller the proportion of patients with good prognosis. Total resection of the tumors was achieved in 387 patients (93.25%), sub-total resection in 24 (5.78%), and partial resection in 4 (0.96%); the larger the tumor diameter, the smaller the proportion of patients with total resection. There were 398 patients with facial nerve preservation in anatomy, and the anatomic preservation rate of facial nerve was 95.9%; there were 17 without anatomic preservation, and 12 received end to end anastomosis of facial nerve. Three months after operation, H-B grading I-II was noted in 334 patients (80.5%), grading III-IV in 76 patients (18.3%), grading V-VI in 5 patients (1.2%); the larger the tumor diameter, the smaller the proportion of patients with H-B grading I-II. No surgically related deaths occurred. Conclusion Early diagnosis and early microsurgical treatment of acoustic neuroma is helpful in improving the safety and efficacy of tumor resection.
4.FABP5 promotes cell growth, invasion and metastasis in cervical cancer
Yinzhu ZHAN ; Feng LIU ; Yan ZHANG ; Xiaoyu MO ; Wende CHENG ; Wei WANG
Chinese Journal of Oncology 2019;41(3):200-207
Objective To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stageⅠa2?Ⅱa2 and 40 cases of normal cervical tissues by real?time PCR and Western blotting. Then, the cells were infected with lentivirus?mediated siRNA?targeting FABP5. CCK?8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase?2 and metalloproteinase?9 using Enzyme linked immunosorbent assay ( ELISA ), real?time PCR and Western blotting.Results FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues ( P<0.05). Compared with the Siha?NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha?FABP5?RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha?NC group and Siha?FABP5?RNAi group were (84.6± 4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)/HPF, (72.6± 3.3)/HPF and ( 21.4± 2.3)/HPF, respectively. All of the difference was statistically significant (P<0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo ( P<0.001). The subcutaneously xenografted volume in uninfected group, Siha?NC group and Siha?FABP5?RNAi group was (921.4±63.0) mm3, (1 021.4±56.0) mm3 and (139.6±36.0) mm3, respectively. The real?time quantitative PCR results showed that the relative expression levels of MMP?2 and MMP?9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha?NC group and Siha?FABP5?RNAi group, respectively. MMP?2 and MMP?9 was significantly downregulated after FABP5 inhibition(P<0.05). Additionally, the protein expression trend of MMP?2 and MMP?9 in three groups was consistent with the mRNA levels. Conclusion FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up?regulating MMP?2 and MMP?9.
5.FABP5 promotes cell growth, invasion and metastasis in cervical cancer
Yinzhu ZHAN ; Feng LIU ; Yan ZHANG ; Xiaoyu MO ; Wende CHENG ; Wei WANG
Chinese Journal of Oncology 2019;41(3):200-207
Objective To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stageⅠa2?Ⅱa2 and 40 cases of normal cervical tissues by real?time PCR and Western blotting. Then, the cells were infected with lentivirus?mediated siRNA?targeting FABP5. CCK?8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase?2 and metalloproteinase?9 using Enzyme linked immunosorbent assay ( ELISA ), real?time PCR and Western blotting.Results FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues ( P<0.05). Compared with the Siha?NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha?FABP5?RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha?NC group and Siha?FABP5?RNAi group were (84.6± 4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)/HPF, (72.6± 3.3)/HPF and ( 21.4± 2.3)/HPF, respectively. All of the difference was statistically significant (P<0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo ( P<0.001). The subcutaneously xenografted volume in uninfected group, Siha?NC group and Siha?FABP5?RNAi group was (921.4±63.0) mm3, (1 021.4±56.0) mm3 and (139.6±36.0) mm3, respectively. The real?time quantitative PCR results showed that the relative expression levels of MMP?2 and MMP?9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha?NC group and Siha?FABP5?RNAi group, respectively. MMP?2 and MMP?9 was significantly downregulated after FABP5 inhibition(P<0.05). Additionally, the protein expression trend of MMP?2 and MMP?9 in three groups was consistent with the mRNA levels. Conclusion FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up?regulating MMP?2 and MMP?9.
6.HRCT and contrast-enhanced MRI in diagnosis of facial nerve injuries
Yunyun ZHAO ; Wende NING ; Jiping DONG ; Yanjun GAO ; Junjian ZHANG ; Hongsheng LIU ; Xiangchun YANG
Chinese Journal of Interventional Imaging and Therapy 2018;15(4):230-233
Objective To explore the value of HRCT and contrast-enhanced MRI in diagosis of facial nerve injuries.Methods HRCT and contrast-enhanced MRI were performed in 18 cases of facial nerve injuries.CPR of the facial nerve and canal was performed on the Philips EBW workstation,and the temporal bone involved location,fracture type and involvement of facial nerve and canal and its course were observed.The involved location,size,signal variation of facial nerve were analyzed compared with contralateral side on the GE AW 4.5 workstation.Results Among 18 cases,8 cases of longitudinal fractures,5 cases of transverse fractures and 5 cases of mixed fractures were found.HRCT axial scan and CPR of facial canal revealed that 18 cases had temporal bone fractures,including 1 case of labyrinthine segment,2 cases of geniculate fossa,4 cases of tympanic segment,2 cases of geniculate fossa,tympanic segment and hematoma of middle ear cavity,3 cases of tympanic segment with adjacent hematoma of middle ear cavity and 6 cases without obvious fracture of facial canal.Contrast-enhanced MRI and CPR of facial nerve revealed facial nerve injuries in all 18 cases,including 12 cases of internal auditory meatus segment,14 cases of labyrinthine segment,18 cases of geniculate ganglion,16 cases of tympanic segment and 15 cases of mastoid segment.Signal intensity ratio of affected internal auditory meatus segment,labyrinthine segment,geniculate ganglion,tympanic segment and mastoid segment were higher than those of contralateral side (all P< 0.001).Conclusion HRCT and contrast-enhanced MRI can clearly reveal the involvement of different segment of traumatic facial nerve,HRCT CPR and MR CPR are helpful to visualiz the involvement of traumatic facial nerve and canal.
7.HRCT for diagnosis of internal ear injuries caused by temporal bone trauma
Yunyun ZHAO ; Jiping DONG ; Wende NING ; Hongsheng LIU ; Junjian ZHANG ; Xiaoping WU
Chinese Journal of Medical Imaging Technology 2017;33(10):1493-1496
Objective To explore the value of HRCT for the diagnosis of internal ear injuries caused by temporal bone trauma.Methods Totally 106 patients with temporal bone trauma were scanned by HRCT,and 12 patients with internal ear injuries were collected.MPR of temporal bone (cochlea,vestibule,horizontal semicircular canal,anterior semicircular canal and posterior semicircular canal) was performed on Philips workstation.The locations,types,and the involving structures were observed.Results Among the 106 cases of temporal bone trauma,12 cases were internal ear injuries,including 8 cases of fractures of inner ear,3 cases of pneumolabyrinth,and 1 case of foreign body in the cochlea,which 3 cases complicated with traumatic labyrinthine ossification.Conclusion HRCT and MPR can clearly reveal internal ear injuries,which are effective methods for diagnosis of internal ear injuries.
8.Host immune responses to avian influenza A H5N1 virus in a BALB/c model
Ren HUANG ; Shaochang DENG ; Yingyan WANG ; Yu ZHANG ; Yue WU ; Wende LI ; Weibo ZHAO ; Xiangmei LIU ; Zheng GUO
Chinese Journal of Microbiology and Immunology 2011;31(5):406-412
Objective To study the cell immunity and eytokines responses to avian influenza A H5N1 virus infections in a BALB/c model to better understand the pathogenesis of H5N1 avian influenza disease. Methods Two hundred and twenty BALB/c mice of the infected group were inoculated with 0.1 ml (10-4.875 TCID50) of A/Goose/Guangdong/NH/2003 ( H5N1 ) virus intra-nasally. Fifty control mice received noninfectious allantoic fluid and another fifty control mice received normal sodium. Blood and spleen samples were collected from the live mice every 24 h during the 14 d post-infection. The changes of CD3 + T cells , CD4 + T cells, CD8 + T cells for cell immunity in blood circulation and spleen were detected by flow cytometry. And the cytokines and antibody responses in blood circulation were detected by ELISA. Necropsy was performed on mice that died during the experiment and those euthanized at end of study. Results Avian influenza A( H5N1) virus infections can make damages to the cell immune system transiently. The CD3 + T cells, CD4 + T cells, CDS + T cells declined at 24 days post infection in blood circulation and declined at 5-8 days in spleen, then recovered to the normal level gradually. The eytokines responses to the infections can be detected: the level of IFN-γ,TNF-α declined, IL-4, IL-18, IL-10 increased, and IL-2 changed little. The antibody increased rapidly from day 7 post infection until the end of the study (day 14 post infection). Conclusion Collectively, avian influenza A(H5N1) virus can cause cell immunity deficiency and an imbalance in the level of eytokines, which may contribute to the unusual severity of disease caused by the H5N1 avian influenza virus.
9.Comparison of the Pathogenicity of Avian Influenza A(H5N1) Virus in Five Strains of Mice
Ren HUANG ; Yingyan WANG ; Shaochang DENG ; Peigen HUANG ; Yu ZHANG ; Zhonghua LIU ; Yue WU ; Wende LI ; Fangui MIN ; Xiangmei LIU
Acta Laboratorium Animalis Scientia Sinica 2010;18(4):271-277,后插1
Objective To test our hypothesis that sensitivity to avian influenza A(H5N1)virus varies among mouse strain backgrounds, we compared the pathogenicity of H5N1 viral infection in 5 mouse strains. Methods Onehundred-fifty mice from 2 inbred strains(BALB/c and C57BL/6), and 3 outbred stocks(ICR, NIH Swiss, and KM Swiss)were used. Thirty mice of each strain were subjected to an infected group(20 mice), in which mice were inoculated with 0. 1 mL(104.875 TCID50)of A/Goose/Guangdong/NH/2003(H5N1)virus intra-nasally; ten control mice received noninfectious allantoic fluid. Clinical signs were assessed daily for 14 days post-infection. Necropsy was performed on mice that died during the experiment and those euthanized at end of study. Tissue samples were collected for viral isolation and pathological analysis. Results H5N1 virus infection can cause respiratory illness in all 5 strains with severe or minor acute respiratory distress symptoms, but with different mortality rates: 70% in BALB/c; 50% in ICR; 40% in NIH Swiss; 25% in C57BL/6; and 10% in KM Swiss mice. Necrotizing interstitial pneumonia was found in all cases of death. The virus was isolated from the lungs of all infected dead mice. Conclusion A/Goose/Guangdong/NH/2003 (H5N1)virus can infect all mouse strains used in this study, and can cause clinical symptoms and pathological changes similar to those found in humans infected with HSN1 viruses. However, the pathogenicity of H5N1 viral infection varies significantly between the different mouse strains. Thus, in future study of H5N1 virus infections the mouse strain most relevant to their particular research purpose should be selected as animal model.
10.MRI diagnosis and differential diagnosis of transient bone marrow edema syndrome of the hip
Xiaoping WU ; Chunying LIU ; Dong ZHANG ; Wende NING ; Junle YANG ; Jiping DONG ; Xiaohui YIN
Journal of Third Military Medical University 2003;0(20):-
Objective To study MR imaging features of transient bone marrow edema syndrome of the hip so as to improve its diagnosis and differential diagnosis.Methods MR images of transient bone marrow edema syndrome of the hip in 13 patients were retrospectively analyzed in combination with literature review.Results The bilateral hips were affected in 4 patients.The single hip was affected in 9 patients,left hip in 6 and right hip in 3.The MR images demonstrated low signal intensity in all 13 patients on T1WI,and normal signal intensity in 2 patients,moderate or high signal intensity in 11 patients on T2WI,and high signal on T2 fat suppressed or STIR images in all 13 patients.The bone marrow edema pattern involved the femoral head and neck in 13 hips,the femoral head and neck and the intertrochanteric region in 4 hips.A small joint effusion was observed in 8 hips on T2WI.The configuration of femoral heads were normal.Conclusion Correct judgement of MRI manifestations of transient bone marrow edema syndrome of the hip can improve its diagnosis and differential diagnosis.

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