A Novel Molecular Grading Model: Combination of Ki67 and VEGF in Predicting Tumor Recurrence and Progression in Non-invasive Urothelial Bladder Cancer

Chen, Jun-Xing,Deng, Nan,Chen, Xu,Chen, Ling-Wu,Qiu, Shao-Peng,Li, Xiao-Fei,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

Evolution of the effect of sulfur confinement in graphene-based porous carbons for use in Li-S batteries

Jia, Xiangling,Zhang, Chen,Liu, Juanjuan,Lv, Wei,Wang, Da-Wei,Tao, Ying,Li, Zhengjie,Zheng, Xiaoyu,Yu, Jong-Sung,Yang, Quan-Hong The Royal Society of Chemistry 2016 Nanoscale Vol.8 No.8

<P>A controllable drying strategy is proposed for the precise and non-destructive control over the structure of a 3D graphene assembly. Such an assembly is used as a model carbon material to investigate the pore structure-dependent shuttle effect and cycling performance of the cathode of a Li-S battery.</P>

Phthalocyanines as medicinal photosensitizers: Developments in the last five years

Li, Xingshu,Zheng, Bing-De,Peng, Xiao-Hui,Li, Song-Zi,Ying, Jia-Wen,Zhao, Yuanyuan,Huang, Jian-Dong,Yoon, Juyoung Elsevier 2019 Coordination Chemistry Reviews Vol.379 No.-

<P><B>Abstract</B></P> <P>Owing to their high extinction coefficients, long absorption wavelengths, and modification tunable photophysical and photochemical properties, phthalocyanines (Pcs) have been widely used as photosensitizers for photodynamic therapy (PDT). Advances made in the past five years on the development of Pcs as medicinal photosensitizers are reviewed and the main design considerations for medicinal applications of these substances are discussed.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Recent progresses made in the development of phthalocyanines for photodynamic therapy are outlined. </LI> <LI> Representative water-soluble phthalocyanines are presented. </LI> <LI> Main targeting strategies are discussed. </LI> <LI> Future challenges are also presented. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis through up-regulation of ATF-4

Liu, Xiaojun,Jiang, Yanan,Wu, Jianfu,Zhang, Wenjuan,Liang, Yupei,Jia, Lijun,Yu, Jinha,Jeong, L.S.,Li, Lihui Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>It has been reported that MLN4924 can inhibit cell growth and metastasis in various kinds of cancer. We have reported that MLN4924 is able to inhibit angiogenesis through the induction of cell apoptosis both in vitro and in vivo models. Moreover, Neddylation inhibition using MLN4924 triggered the accumulation of pro-apoptotic protein NOXA in Human umbilical vein endothelial cells (HUVECs). However, the mechanism of MLN4924-induced NOXA up-regulation has not been addressed in HUVECs yet. In this study, we investigated how MLN4924 induced NOXA expression and cellular apoptosis in HUVECs treated with MLN4924 at indicated concentrations. MLN4924-induced apoptosis was evaluated by Annexin V-FITC/PI analysis and expression of genes associated with apoptosis was assessed by Quantitative RT-PCR and western blotting. As a result, MLN4924 triggered NOXA-dependent apoptosis in a dose-dependent manner in HUVECs. Mechanistically, inactivation of Neddylation pathway caused up-regulation of activating transcription factor 4 (ATF-4), a substrate of Cullin-Ring E3 ubiquitin ligases (CRL). NOXA was subsequently transactivated by ATF-4 and further induced apoptosis. More importantly, knockdown of ATF-4 by siRNA significantly decreased NOXA expression and apoptotic induction in HUVECs. In summary, our study reveals a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs, which may help extend further study of MLN4924 for angiogenesis inhibition treatment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MLN4924 triggered NOXA-dependent apoptosis in a dose-dependent manner in HUVECs. </LI> <LI> Inactivation of neddylation caused up-regulation of ATF4, a substrate of CRL. </LI> <LI> NOXA was transactivated by ATF4 and further induced apoptosis. </LI> <LI> Knockdown of ATF-4 significantly decreased NOXA expression and apoptotic induction. </LI> <LI> We revealed a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs. </LI> </UL> </P>

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Liposomal honokiol, a potent anti-angiogenesis agent, in combination with radiotherapy produces a synergistic antitumor efficacy without increasing toxicity

Jia Hu,Li Liu,Xiang Chen,Ping Chen,Guang-li Yang,Wen-li Hou,Ming-hai Tang,Fan Zhang,Xian-huo Wang,Xia Zhao,Yu-quan Wei,Li-juan Chen 생화학분자생물학회 2008 Experimental and molecular medicine Vol.40 No.6

Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy. Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy.

Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and can be a prognostic factor in epithelial ovarian cancer

Jia Li,Kuo Jiang,Xiu Chun Qiu,Meng Li,Qiang Hao,Li Wei,Wei Zhang,Bi Liang Chen,Xiao Yan Xin 생화학분자생물학회 2014 BMB Reports Vol.47 No.1

Bioremediation of Coastal Saline-Alkali Marshy Soil by the Irrigation with Pulp & Paper Wastewater

LI Jia-liang,LU Zhao-hua,TIAN Jia-yi,WANG Lin,LI Peng-hui,XIAO Zhong-feng 대전대학교 환경문제연구소 2009 환경문제연구소 논문집 Vol.13 No.-

Based on the importance of coastal saline-alkali soil remediation in Yellow River Delta, China, the Cl-、Na+ transferring tendency in soil and the saline-alkali soil eco-remediation effects were researched by measuring soil Cl-、Na+ 、soluble salt、soil respire rate and dry biomass weight of reed, etc. periodically. The results shows: the concentration of irrigated soil Cl-、Na+ and soluble salt were decreased 57.7-70%、45.7-47.1% and 53.2-59.7%, respectively, and soil salt decreasing level were little influenced by the hydraulic load, inundation depth varies in some degree, but it was influenced by dry-wet alternative irrigating mode The concentration of soil total nitrogen、organic mass、microbial respire rate, and the reed biomass above ground were increased averagely to 2.17、1.20、1.46 and 1.34 multiple respectively afterirrigation with wastewater, which have complex remediation effects on the coastal saline-alkali wetland, but there are some differences among the different irrigating crafts.

Expression of Endogenous Hypoxia Markers in Vulvar Squamous Cell Carcinoma

Li, Yu-Zhu,Li, Shu-Ling,Li, Xia,Wang, Li-Jie,Wang, Jiu-Ling,Xu, Jia-Wen,Wu, Zhi-Hong,Gong, Li,Zhang, Xiao-Dan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-$1{\alpha}$ expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-$1{\alpha}$, GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC.

New neo-lignan from Acanthopanax senticosus with protein tyrosine phosphatase 1B inhibitory activity

Jia Lin Li,Na Li,Shan-Shan Xing,Nan Zhang,BanBan Li,JianGuang Chen,안종석,Long Cui 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.11

New neo-lignan, (7S, 8R)-3-hydroxyl-4-methoxyl-balanophonin (1), together with seven known compounds(2–8)were isolated fromthe EtOAc-soluble extract ofAcanthopanax senticosus. The structure of the newneo-lignanwas elucidated with spectroscopic and physico-chemicalanalyses. All the isolates were evaluated for in vitro inhibitoryactivity against PTP1B, VHR and PP1. Among them, the newcompound (1) was found to exhibit selective inhibitoryactivity on PTP1B with IC50 value 15.2 ± 1.4 lM.