Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells

Noh, Hyangsoon,Zhao, Qingnan,Yan, Jun,Kong, Ling-Yuan,Gabrusiewicz, Konrad,Hong, Sungguan,Xia, Xueqing,Heimberger, Amy B.,Li, Shulin Elsevier 2018 Cancer letters Vol.433 No.-

<P><B>Abstract</B></P> <P>Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor. The current standard therapy, which includes radiation and chemotherapy, is frequently ineffective partially because of drug resistance and poor penetration of the blood-brain barrier. Reducing resistance and increasing sensitivity to chemotherapy may improve outcomes. Glioma stem cells (GSCs) are a source of relapse and chemoresistance in GBM; sensitization of GSCs to temozoliomide (TMZ), the primary chemotherapeutic agent used to treat GBM, is therefore integral for therapeutic efficacy. We previously discovered a unique tumor-specific target, cell surface vimentin (CSV), on patient-derived GSCs. In this study, we found that the anti-CSV monoclonal antibody 86C efficiently increased GSC sensitivity to TMZ. The combination TMZ+86C induced significantly greater antitumor effects than TMZ alone in eight of 12 GSC lines. TMZ+86C–sensitive GSCs had higher CSV expression overall and faster CSV resurfacing among CSV<SUP>−</SUP> GSCs compared with TMZ+86C–resistant GSCs. Finally, TMZ+86C increased apoptosis of tumor cells and prolonged survival compared with either drug alone in GBM mouse models. The combination of TMZ+86C represents a promising strategy to reverse GSC chemoresistance.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anti-CSV monoclonal antibody 86C sensitize GSCs to TMZ treatment. </LI> <LI> GSCs with higher CSV expression are more sensitive to TMZ+86C. </LI> <LI> GSCs with higher CSV resurfacing rate among CSV<SUP>−</SUP> cells are more sensitive to TMZ+86C. </LI> <LI> TMZ+86C increased apoptosis and prolonged survival in GBM models. </LI> <LI> Tumor-specific CSV antibody 86C can efficiently target human GSCs to increase their sensitivity to TMZ. </LI> </UL> </P>

Damage assessment of shear connectors with vibration measurements and power spectral density transmissibility

Li, Jun,Hao, Hong,Xia, Yong,Zhu, Hong-Ping Techno-Press 2015 Structural Engineering and Mechanics, An Int'l Jou Vol.54 No.2

Shear connectors are generally used to link the slab and girders together in slab-on-girder bridge structures. Damage of shear connectors in such structures will result in shear slippage between the slab and girders, which significantly reduces the load-carrying capacity of the bridge. Because shear connectors are buried inside the structure, routine visual inspection is not able to detect conditions of shear connectors. A few methods have been proposed in the literature to detect the condition of shear connectors based on vibration measurements. This paper proposes a different dynamic condition assessment approach to identify the damage of shear connectors in slab-on-girder bridge structures based on power spectral density transmissibility (PSDT). PSDT formulates the relationship between the auto-spectral densities of two responses in the frequency domain. It can be used to identify shear connector conditions with or without reference data of the undamaged structure (or the baseline). Measured impact force and acceleration responses from hammer tests are analyzed to obtain the frequency response functions at sensor locations by experimental modal analysis. PSDT from the slab response to the girder response is derived with the obtained frequency response functions. PSDT vectors in the undamaged and damaged states can be compared to identify the damage of shear connectors. When the baseline is not available, as in most practical cases, PSDT vectors from the measured response at a reference sensor to those of the slab and girder in the damaged state can be used to detect the damage of shear connectors. Numerical and experimental studies on a concrete slab supported by two steel girders are conducted to investigate the accuracy and efficiency of the proposed approach. Identification results demonstrate that damages of shear connectors are identified accurately and efficiently with and without the baseline. The proposed method is also used to evaluate the conditions of shear connectors in a real composite bridge with in-field testing data.

City Development and Green Space Protection

Li, Jun-hong The Korean Institute of Landscape Architecture 2001 Journal of the Korean institute of landscape archi Vol.1 No.-

The author has analyzed the ecological problems caused by city development and the comprehensive benefits of green space(e.g. ecological, social and economic benefits). The important role of green space in city sustainable development was discussed. Through benefits analysis of green space in city development in Kunming City, the author offered specific measures for green space protection in Kunming: strengthen plant management according to law; enhance nation awareness of plant protection; rationally plan city green land system;and use scientific forms of green land.

In vivo evaluation of novel particle-free polycaprolactone fillers for safety, degradation, and neocollagenesis in a rat model

( Jun Ki Hong ),( Young Gue Koh ),( Ji Yeon Hong ),( Kwang Ho Yoo ),( Kapsok Li ),( Beom Joon Kim ) 대한피부과학회 2021 대한피부과학회 학술발표대회집 Vol.73 No.1

Roles of mTOR and p-mTOR in Gastrointestinal Stromal Tumors

Li, Jun-Chuan,Zhu, Hong-Yu,Chen, Ting-Xuan,Zou, Lan-Ying,Wang, Xiao-Yan,Zhao, Hui-Chuan,Xu, Jun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Objective: This study aimed to examine the relationship between expression of mammal target of rapamycin (mTOR) and phosphorylation of mTOR (p-mTOR) protein in the PI3K/Akt/mTOR signaling pathways in gastrointestinal stromal tumors and relatiuonships with clinical factors. Methods: Immunohistochemistry was used to detect the expression of the associated proteins mTOR, p-mTOR, and phosphorylation of the tumor suppressor genes PTEN, P27, VEGF, and EGFR in 40 cases of gastrointestinal stromal tumors, with division into a very low and low risk group as well as a moderate and high risk group. Results: The positive rate of mTOR and p-mTOR was significantly increased in the moderate and high risk group compared with the very low and low risk group. The difference was statistically significant (P<0.05). When grouped according to size, the positive mTOR expression rate exhibited a statistical difference (P<0.05), which was significantly increased in the group of tumors larger than 5 cm. The difference in the positive mTOR and p-mTOR expression rate exhibit no statistical significance among the PTEN, P27, VEGF, and EGFR expression subgroups (P>0.05). Conclusion: The different expressions of mTOR and p-mTOR in the signal transduction pathway of gastrointestinal stromal tumor in the different degree-of-risk groups suggested that the mTOR and p-mTOR of the signal transduction pathway serve an important function in the occurrence and development of gastrointestinal stromal tumors.

Clinical Profles and Short-Term Outcomes of Acute Disseminated Encephalomyelitis in Adult Chinese Patients

Hong-Qi Yang,Wen-Cong Zhao,Wei-Min Yang,Yong-Li Li,Zhi-Kun Sun,Shuai Chen,Wei Li,Jian-Jun Ma 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.3

Background and PurposezzAcute disseminated encephalomyelitis (ADEM) is an infammatory demyelinating disorder that predominantly afects children. Previous studies have mostly involved children in Western developed countries. MethodszzTis study retrospectively reviewed the clinical profles of ADEM in adult Chinese patients. ResultszzADEM occurred during summer and autumn in about two-thirds of the 42 included patients. Prior infection was found in fve patients and no preimmunization was recorded. Te most frequent clinical presentations were alterations in consciousness (79%) and behavior changes (69%), followed by motor defcits (64%) and fever (50%). About one-quarter (26%) of the patients showed positive results for oligoclonal bands, and about half of them exhibited increases in the IgG index and 24-hour IgG synthesis rate. Magnetic resonance imaging showed white- and gray-matter lesions in 83% and 23% of the patients, respectively. Steroids were the main treatment, and full recovery occurred in 62% of the patients, with residual focal neurological defcits recorded in a few patients. Afer a mean follow-up period of 3.4 years, two patients exhibited recurrence and one patient exhibited a multiphasic course. One patient was diagnosed with multiple sclerosis (MS). ConclusionszzWith the exception of the seasonal distribution pattern and prior vaccine rate, the clinical profles of ADEM in adult Chinese patients are similar to those in pediatric populations. No specifc markers are available for distinguishing ADEM from MS at the initial presentation. Careful clinical evaluations, cerebrospinal fuid measurements, and neuroradiological examinations with long-term follow-up will aid the correct diagnosis of ADEM.

Evaluating the safety and efficacy of 532-nm and 1064-nm picosecond-domain neodymium:yttriumaluminum- garnet lasers using a diffractive optical element for non-ablative skin rejuvenation

( Jun Ki Hong ),( Hye Sung Han ),( Byung Cheol Park ),( Kui Young Park ),( Kapsok Li ),( Seong Jun Seo ) 대한피부과학회 2021 대한피부과학회 학술발표대회집 Vol.73 No.1

Radiological gastrostomy: A comparative analysis of different image-guided methods

Hong-Tao Hu,Hang Yuan,Chen-Yang Guo,Quan-Jun Yao,Xiang Geng,Hong-Tao Cheng,Jun-Li Ma,Yan Zhao,Li Jiang,Yu-Qing Zhao,Hai-Liang Li 소화기인터벤션의학회 2021 Gastrointestinal Intervention Vol.10 No.2

Background: Radiographic guided percutaneous gastrostomy has become a safe and effective enteral nutrition method for patients who can not eat by mouth. Fluoroscopy, computed tomography (CT) and cone-beam CT have been routinely used clinically. The aim of this study was to compare the advantages and disadvantages of percutaneous gastrostomy using different radiographic guided methods. Methods: We retrospectively analyzed the clinical data of 538 patients undergoing percutaneous gastrostomy in our department. According to the image guidance method used in gastrostomy, the patients were divided into groups A by fluoroscopy guidance, group B by fluoroscopy combined with C-arm CT guidance, and group C with the whole process CT guidance. The gastrostomy success rate, complication rate, procedure time, and patient radiation dose were analyzed in the three groups. Results: Among 538 patients, 534 were successful and the success rates are 94.3%, 99.3%, and 100% in group A, B, and C, respectively (P > 0.05). There were 3 cases occurred postoperative bleeding as serious adverse events and transferred to surgical gastrostomy. The minor complications include local infection, hyperplasia of granulation tissue, tube obstruction or prolapse, and local pain of the ostomy. The minor complication rates were 10.5%, 10.4%, and 7.7% in group A, B, and C, respectively (P > 0.05). The average procedure time was 25.57 ± 5.99 minutes, 29.01 ± 6.63 minutes, and 45.47 ± 8.98 minutes, respectively (χ2 = 87.98, P < 0.001). The average radiation dosage was 27.30 ± 19.27 mGy, 145.07 ± 106.08 mGy, and 2,590.26 ± 1,088.22 mGy, respectively (χ2 = 204.44, P < 0.001). Conclusion: There were no significant differences in the success rates and complication rates of gastrostomy under the three guiding methods. For difficult cases, CT-guided gastrostomy may be a very useful supplemental method.

Identification of a Methyltransferase Encoded by Gene ste16 and Its Function in Ebosin Biosynthesis of Streptomyces sp. 139

Hong-Guan Xie,Yong-Gang Bao,Li-ping Bai,Jun-Jie Shan,Rong Jiang,Yang Zhang,Lian-Hong Guo,Ren Zhang,Yuan Li 한국미생물학회 2009 The journal of microbiology Vol.47 No.2

Streptomyces sp. 139 generates a novel exopolysaccharide (EPS) designated as Ebosin, which exerts an antagonistic effect on IL-1R in vitro and anti-rheumatic arthritis activity in vivo. A ste gene cluster for Ebosin biosynthesis consisting of 27 ORFs was previously identified in our laboratory. In this paper, ste16 was expressed in Escherichia coli BL21 and the recombinant protein was purified, which has the ability to catalyze the transfer of the methyl group from S-adenosylmethionine (AdoMet) to dTDP-4-keto-6-deoxy-D-glucos, which was thus identified as a methyltransferase. In order to determine the function of ste16 in Ebosin biosynthesis, the gene was disrupted with a double crossover via homologous recombination. The monosaccharide composition of EPS-m generated by the mutant strain Streptomyces sp. 139 (ste16-) was found to differ from that of Ebosin. The IL-1R antagonist activity of EPS-m was markedly lower than that of Ebosin. These experimental results have shown that the ste16 gene codes for a methyltransferase which is involved in Ebosin biosynthesis.

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.