1.Lethal effects of nanoliposome encapsulated cisplatin on Saos-2 cells and its distribution in nude mice bearing human osteosarcoma xenografts
Guowen WANG ; Wei GUO ; Xiaodong TANG ; Changliang PENG ; Hui ZHAO
Journal of Peking University(Health Sciences) 2003;0(05):-
Objective:To investigate the killing effect of nanoliposome encapsulated cisplatin(NLE-CDDP) on human osteosarcoma cell line Saos-2 and explore the distribution of platinum(Pt) in tumor-bearing mice.Methods: Saos-2 cells were cultured at different concentrations of NLE-CDDP.MTT assay,inverted microscopic observation and flow cytometry assay(FCM)were used to observe the antiproli-ferative effect of NLE-CDDP on the human osteosarcoma cells.Antitumor effect of NLE-CDDP was determined using the xenografts models of human osteosarcoma cell Saos-2 in nude mice.The Pt concentration in the tissues of tumor-transplanted mice was determined by atomic spectrophotometer.Results: When treated at different concentrations of NLE-CDDP for 24-96 hours,the survival rate of Saos-2 cells decreased significantly(P
2.Differential Expression of Sox9 in Conventional Chondrosarcoma and Dedifferentiated Chondrosarcoma
Guowen WANG ; Xiaodong TANG ; Wei GUO ; Changliang PENG ; Hui ZHAO
Chinese Journal of Clinical Oncology 2010;37(5):250-253
Objective: To investigate the differential expression of Sox9 in conventional chondrosarcoma,dedifferentiated chondrosarcoma and normal cartilage. Methods: We reported 12 cases of chondrosarcomas,which were initially diagnosed as chondrosarcomas(6 cases of conventional chondrosarcoma and 6 cases of dedifferentiated chondrosarcoma)at Peking University People's Hospital between January 2003 and January 2007.We used genechip method to identify difierentially expressed genes involved in conventional chondrosarcoma,dedifferentiated chondrosarcoma and in normal cartilage(6 cases)and found thousands of differentially expressed genes after extensive statistical analysis.With Sox9 which played crucial roles in the process of both differentiation and maturation of chondrocyte as a candidate,we used Real-time PCR,Westem blot and immunohistochemistry to confirm the results found by gene chip. Results: DNA microarray results showed that Sox9 was up-regulated about 1.6 times in conventional chondrosarcoma compared with that in normal cartilage.But in dedifferentiated chondrosarcoma,the expression level of Sox9 was significantly down-regulated,0.082 times of that in normal cartilage.Real-time PCR results showed that the expression levels of Sox9 mRNA in conventional chondrosarcomas and dedifferentiated chondrosarcomas were 1.68±0.119 and 0.088±0.017,respectively.Sox9 protein level was significantly higher in humen conventional chondrosarcomas than that in normal cartilage.Sox9 protein level in dedifferentiated chondrosarcomas was significantly lower than that in normal cartilage tissue.All of the 6 cases of conventional chondrosarcomas showed diffuse and strong staining of Sox9.However,Only scattered staining was observed in dedifferentiated chondrosarcomas. Conclusion: Compared with that in normal cartilage,Sox9 expression is up-regulated in conventional chondrosarcomas and down-regulated in dedifferentiated chondrosarcomas.Decrease of Sox9 expression in dedifferentiated chondrosarcoma is correlated with poor survival,indicating that Sox9 may serve as a molecular prognostic marker for chondrosarcomas and disease progression.
3.Imaging findings of solitary fibrous tumors of the lower extremity: Two cases report and review of the literatures
Changliang YU ; Yongqiang YU ; Cheng ZHANG ; Bensheng ZHAO ; Yinfeng QIAN
Chinese Journal of Interventional Imaging and Therapy 2009;6(6):541-544
Objective To analyze the imaging appearances of solitary fibrous tumors (SFT) of the lower limb.Methods The imaging manifestations of SFT of the lower limb proved with pathology in 2 patients were reported and the relevant literatures were reviewed.All patients underwent MR examination,and 1 received skeletal radiography.Results Both tumors were mainly located within the biceps muscle of thigh.MR demonstrated that the tumor appeared as a solitary round or oval well circumscribed mass,with inhomogeneous low to intermediate intensity signal on T1WI and heterogeneous low to high intensity signal on T2WI.Inhomogeneous enhancement was demonstrated on T1WI.Marked enhancement of solid components in the tumor was identified.No bone destruction was found on plain film.Conclusion There are some characteristics on the imaging of SFT of the lower extremity.MRI is the optimal imaging method for the diagnosis of this disease.
4.Secondary lymphoid-tissue chemokine and CCR7 in it's relation with lymphangiogenesis of pancreatic adenocarcionoma
Wenhua ZHAO ; Changliang WANG ; Kai CUI ; Bo ZHANG ; Wuyuan ZHOU ; Hongyu ZHANG ; Weixia ZHONG ; Sheng LI
Chinese Journal of General Surgery 2009;24(8):658-662
Objective To study the expression of secondary lymphoid-tissue chemokine (SLC)、 CCR7 and its correlation with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC). Methods The tissue specimens including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were obtained from 30 patients with PAC. The expressions of SLC and CCR7 in these tissues were assayed by immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR). MIND marked by VEGFR-3 was detected by morphometric analysis, and the relationship between MLND and clinical pathology of PAC was analyzed. Results In all the specimens, the positive rates of SLC protein in PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were respectively 16. 7%, 43. 3%, 76. 7% and 46. 6%. The positive rates of CCR7 protein in PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were respectively 76. 7%, 66. 7%, 30. 0% and 70. 0%. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CCR7 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lymph nodes were higher than that in the normal pancreatic tissues ( P <0. 01 ). There was no significant correlation between the expression of SLC protein with MLVD of PAC ( P > 0. 05 ). There was 23 specimens that the CCR7 protein was positive, and among these specimens the MIND was higher than that in negative group of CCR7 protein (P = 0.004). Conclusions The expression of SLC was not related to lymphatic metastasis and TNM stages of PAC. The expression of CCR7 was significantly associated with lymphatic metastasis and TNM stages of PAC, and the high expression of CCR7 in PAC tissues was significantly associated with lymphangiogenesis of PAC.
5.The analysis of bacteriological changes and susceptible factor of nosocomial infection in neonatal intensive care unit
Haiying HE ; Haiyan JIANG ; Lijun LIU ; Fenghua DU ; Yanhui LI ; Changliang ZHAO
Journal of Clinical Pediatrics 2016;34(12):922-925
Objetive To explore bacteriological changes and susceptible factor of nosocomial infection in neonatal intensive care unit (NICU). Methods The clinical data from 5543 hospitalized neonates during January 2010 to December 2015 were retrospectively analyzed. Results Nosocomial infection rate during the study period was 8 . 75 %. The most common pathogen of nosocomial infection was Staphylococcus epidermidis, followed by Escherichia coli and Klebsiella pneumoniae. Respiratory infection accounted for 37.73% and blood infection 37.53%. 36.74% blood samples were tested to be positive, and 32.67% sputum were positive. In the first three years, the main pathogens of nosocomial infection were Candida albicans, Klebsiella pneumonia, and Staphylococcus aureus; in the last three years, the main pathogens were Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. The susceptible factors of nosocomial infection in NICU were gestational age?37 week (OR?=?2.29, 95%CI:1.89-2.77), birth body mass?1500 g (OR?=?37.91, 95%CI:29 . 85 - 48 . 16 ), mechanical ventilation (OR?=?23 . 16 , 95 %CI: 5 . 72 - 71 . 31 ), male (OR?=?1 . 24 , 95 %CI: 1 . 03 - 1 . 49 ), and indwelling catheter (OR?=?3 . 73 , 95 %CI: 1 . 94 - 19 . 36 ). Conclusions Neonatal nosocomial infections mainly were respiratory tract infections and blood infections. Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae were the common pathogens. Premature, very low birth weight, male, indwelling catheter, and mechnical ventilation were the major risk factors.
6.Correlation analysis of CXCL12,CXCR4 and VEGF-C expression and clinical significance in pancreatic cancer
Hongyu ZHANG ; Liming FEI ; Changliang WANG ; Wenhua ZHAO ; Bo ZHANG ; Wuyuan ZHOU ; Wensheng YU ; Weixia ZHONG
Chinese Journal of Current Advances in General Surgery 1999;0(04):-
Objective:To investigate the expression of CXCL12-CXCR4 and VEGF-C in pancreatic cancer and relation to clinical pathology.Methods:The tissue samples including PAC,the cancerous peripheral tissues,the normal pancreatic tissues and peripheral lympho nodes were obtained from 30 patients with PAC.The expressions of CXCL12,CXCR4and VEGF-C proteins in these tissues were assayed by immunohistochemical staining.The expressions of CXCL12,CXCR4 and VEGF-C mRNA in PAC were also investigated by fluorescence quantitative real-time PCR.Results:In all the samples,the positive rates of CXCL12 protein in PAC,the cancerous peripheral tissues,the normal pancreatic tissues and peripheral lympho nodes were respectively 13.3%(4/30),46.7%(14/30),56.7%(17/30) and 50.0%(15/30).The positive rates of CXCR4 protein in PAC,the cancerous peripheral tissues,the normal pancreatic tissues and peripheral lympho nodes were respectively 80.0%(24/30),70.0%(21/30),26.7%(8/30) and 73.3%(22/30).The expression levels of CXCR4 mRNA in PAC tissues,the cancerous peripheral tissues and peripheral lympho nodes were higher than that in the normal pancreatic tissues(P
7.Application of amide proton transfer imaging in differentiating glioma from treatment effect
Changliang SU ; Jiaxuan ZHANG ; Shun ZHANG ; Jingjing JIANG ; Rifeng JIANG ; Nanqian SHEN ; Ju ZHANG ; Chengxia LIU ; Lingyun ZHAO ; Wenzhen ZHU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2017;37(6):337-341
Objective To explore the application of amide proton transfer (APT) imaging in differentiating glioma from treatment effect and to evaluate the diagnostic efficiency of the quantitative APT-related parameters.Methods A total of 23 patients (15 males, 8 females, age: 13-80 years) with 27 lesions who had underwent APT imaging in Tongji Hospital(Wuhan, China) from October 2014 to June 2015 were enrolled in this prospective study.The scan protocols were MRI normal plain scanning, diffusion WI, contrast-enhancement T1WI and APT imaging.Both the magnetization transfer ratio (MTR) and the relative MTR (rMTR) of lesions were manually measured by drawing ROI in the functional post-processing workstation.The results were compared with those of pathologic examinations and radiographic follow-up (≥3 months).Mann-Whitney u test was used to analyze the data.Results Compared with contralateral white matter, the primary gliomas (n=12) and recurrent gliomas (n=8) manifested hyper-intensity, while the treatment induced injuries (n=7) showed iso-or hypo-intensity.The difference of MTR between tumors and treatment effects was significant (102.78(101.93,103.84) vs 100.17(99.94, 100.63);z=-3.76, P<0.01), so was the difference of rMTR between tumors and treatment effects (3.92%(2.69%,4.67%) vs 0.47%(-0.79%,1.11%);z=-3.43, P<0.01).Both those two quantitative parameters exhibited excellent diagnostic performance with the AUC of 0.986 and 0.943.The sensitivity, specificity and accuracy of MTR were 100%(20/20), 6/7 and 96.3%(26/27) in the threshold of 100.68, while those of rMTR were 95.0%(19/20), 6/7 and 92.6%(25/27) in the threshold of 1.66%.Conclusions Combined with the routine MRI images, APT imaging can provide excellent qualitative and quantitative information in differentiating glioma from treatment effect.Both MTR and rMTR are helpful for the differentiation with high sensitivity and specificity and can be used as non-invasive imaging biomarkers in evaluating treatment effect of glioma.
8.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.