Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Isolation and Molecular Characterization of a New CRT Binding Factor Gene from Capsella bursa-pastoris

( Xing Long Wang ),( Li Liu ),( Si Xiu Liu ),( Xiao Qing Sun ),( Zhong Xiang Deng ),( Yan Pi ),( Xiao Fen Sun ),( Ke Xuan Tang ) 생화학분자생물학회 2004 BMB Reports Vol.37 No.5

A new CRT binding factor (CBF) gene designated Cbcbf25 was cloned from Capsella bursa pastoris, a wild grass, by the rapid amplification of cDNA ends (RACE). The full-length cDNA of Cbcbf25 was 898 bp with a 669 bp open reading frame (ORF) encoding a putative DRE/CRT (LTRE)-binding protein of 223 amino acids. The predicted CbCBF25 protein contained a potential nuclear localization signal (NLS) in its N-terminal region followed by an AP2 DNA-binding motif and a possible acidic activation domain in the C-terminal region. Bioinformatic analysis revealed that Cbcbf25 has a high level of similarity with other CBF genes like cbfl, cbf2, and cbf3 from Arabidopsis thaliana, and Bncbf5, Bncbf7, Bncbfl6, and Bncbfl7 from Brassica napus. A cold acclimation assay showed that Cbcbf25 was expressed immediately after cold triggering, but this expression was transient, suggesting that it concerns cold acclimation. Our study implies that Cbcbf25 is an analogue of other CBF genes and may participate in cold-response, by for example, controlling the expression of cold-regulated genes or increasing the freezing tolerance of plants.

Overlapping Stents-Assisted Coiling for Vertebral Artery Dissecting Aneurysm : LVIS Stent within Neuroform EZ Stent

Liu, Xing-Long,Wang, Bin,Zhao, Lin-Bo,Jia, Zhen-Yu,Shi, Hai-Bin,Liu, Sheng The Korean Neurosurgical Society 2022 Journal of Korean neurosurgical society Vol.65 No.4

Objective : To evaluate the safety and efficacy of an overlapped stenting-assisted coiling technique in treating vertebral artery dissecting aneurysm (VADA) via Low-profile Visualized Intraluminal Support (LVIS) stent-within-Neuroform EZ stent. Methods : From January 2017 to June 2019, 18 consecutive patients with VADAs (ruptured : unruptured=5 : 13) were treated with the overlapping stents assisted-coiling technique in our center. The overlapping manner was a Neuroform EZ stent being deployed first, followed by LVIS stents placement using the 'shelf' technique. The patients' clinical characteristics, technical feasibility and safety, and immediate and follow-up angiographic results were retrospectively reviewed. Results : Seventeen (94.4%) procedures were technically successful with an exact deployment of the stents and patent parent or perforator arteries. The immediate angiographies after procedure confirmed Raymond class I, II, and III occlusion of VADAs were in 12 (66.7%), two (11.1%), and four cases (22.2%), respectively. Post-procedural complications developed in one patient (5.6%) with minor brainstem infarctions, which resulted from an in-stent thrombosis during the procedure. Angiographic follow-up at 5.7 months (range 3 to 9 months) demonstrated Raymond class I and II occlusion were in all cases (100%). The modified Rankin Scale scores at 21.3 months (range 15 to 42 months) 0-2 in 17 cases (94.4%) and three in one case (5.6%). Conclusion : Overlapping stents via LVIS stent-within-Neuroform EZ stent combined with coiling is safe and effective for patients with VADA in the midterm results.

Imaging Anatomy of Waldeyer's Ring and PET/CT and MRI Findings of Oropharyngeal Non-Hodgkin's Lymphoma

Zhang, Chun-Xing,Liang, Long,Zhang, Bin,Chen, Wen-Bo,Liu, Hong-Jun,Liu, Chun-Ling,Zhou, Zheng-Gen,Liang, Chang-Hong,Zhang, Shui-Xing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: This study was conducted to analyze positron emission tomography (PET) / computed tomography (CT) and magnetic resonance imaging (MRI) performance with oropharyngeal non-Hodgkin's lymphoma (ONHL).Materials and Methods: The complete image data of 30 ONHL cases were analyzed, all patients were performed PET / CT and MRI examination before the treatment, with the time interval of these two inspections not exceeding 14 days. The distribution, morphology, MRI signal characteristics, enhancement feature, standardized uptake value (SUV) max value and lymph node metastasis way of the lesions were analyzed. Results: Among the 30 cases, 23 cases were derived from the B-cell (76.7%), 5 cases were derived from the peripheral T cells (16.7%) and 2 cases were derived from the NK/T cells (6.7%). 19 cases exhibited the palatine tonsil involvement (63.3%). As for the lesion appearance, 10 cases appeared as mass, 8 cases were the diffused type and 12 cases were the mixed type. 25 cases exhibited the SUVmax value of PET / CT primary lesions as 11 or more (83.3%). MRI showed that all patients exhibited various degrees of parapharyngeal side-compressed narrowing, but MRI still exhibited the high-signal fat, and the oropharyngeal mucosa was intact. 25 cases were associated with the neck lymph node metastasis, among who 22 cases had no necrosis in the metastatic lymph nodes, while the rest 3 cases exhibited the central necrosis in the metastatic lymph nodes. Conclusions: PET / CT and MRI have important value in diagnosing and determining the lesion extent of ONHL.

β-elemene Induces Caspase-dependent Apoptosis in Human Glioma Cells in vitro through the Upregulation of Bax and Fas/FasL and Downregulation of Bcl-2

Li, Chen-Long,Chang, Liang,Guo, Lin,Zhao, Dan,Liu, Hui-Bin,Wang, Qiu-Shi,Zhang, Ping,Du, Wen-Zhong,Liu, Xing,Zhang, Hai-Tao,Liu, Yang,Zhang, Yao,Xie, Jing-Hong,Ming, Jian-Guang,Cui, Yu-Qiong,Sun, Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA

Chunping Yu,Yi Zhang,Ning Wang,Wensu Wei,Ke Cao,Qun Zhang,Peiying Ma,Dan Xie,Pei Wu,Biao Liu,Jiahao Liu,Wei Xiang,Xing Hu,Xuewen Liu,Jianfei Xie,Jin Tang,Zhi Long,Long Wang,Hongliang Zeng,Jianye Liu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.1

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/sicircPRMT5 regulated the miR-30c/SNAIL1/E-adherin axis, inhibiting bladder cancer growth and progression. Conclusion: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

Ce3+ triggers fenton-like processes in neutral solutions for effective catechol degradation

Xing Chen,Xu Liu,Hai-Bo Wang,Kang-Ping Cui,Rohan Weerasooriya,Shi-Long He,Guang-Hong Li,Jun Pan,Kai Zhou 대한환경공학회 2022 Environmental Engineering Research Vol.27 No.1

Classical Fenton and Fenton-like processes destruct organic pollutants in water non-selectively to complete mineralization. However, the usage of classical Fenton or Fenton-like processes is often limited due to the narrow operational pH window, sludge accumulation, inefficient H₂O₂ and efficiency decline. To overcome these constraints, in this study, we used a homogeneous Fe<SUP>3+</SUP>-Ce<SUP>3+</SUP>-H₂O₂ Fenton-like process to degrade catechol at different experimental conditions. At pH 7, almost 97% of 10 mM catechol can be destructed within 60 min while the degradation by Classical Fenton or Fe<SUP>3+</SUP>-H₂O₂ Fenton-like process only 36.2% and 23.7%. The resultant solution after the degradation contains only traces of cerium ions. The sludge created by the process was extensively characterized by FTIR and XPS spectroscopy to elucidate the fate of cerium ions. Electron spin resonance (ESR) data confirmed •OH as the major free radical in Fe<SUP>3+</SUP>-Ce<SUP>3+</SUP>-H₂O₂ process. Our Fenton-like process widens the optimal pH values to neutral condition.

Phase Structure and Fine Microstructure of In-Situ Vanadium Carbides in Cast High-Vanadium High-Speed Steel

Xu, Liu-Jie,Wei, Shi-Zhong,Xing, Jian-Dong,Li, Yan,Long, Rui 대한금속ᆞ재료학회 2006 METALS AND MATERIALS International Vol.12 No.5

Video-assisted Thoracoscopic Surgery for Treatment of Earlystage Non-small Cell Lung Cancer

Fan, Xing-Long,Liu, Yu-Xia,Tian, Hui Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Objectives: To evaluate the safety, efficacy, and invasiveness of lobectomy by video-assisted thoracoscopic surgery (VATS) in the treatment of stage I/II non-small cell lung cancer (NSCLC). Methods: A total of 148 patients presenting with Stage I or II NSCLC were enrolled into our study, comprising 71 who underwent VATS and 77 patients undergoing conventional thoracotomic lobectomy, in combination with systematic lymph node resection. Results: It was found that VATS was superior to conventional thoracotomy in terms of the duration of surgery, intraoperative blood loss, frequency of the need to administer postoperative analgesia, thoracic intubation indwelling time, post-operative hospital stay, and survival rate (P<0.05). We saw no obvious difference in the number of resected lymph nodes with either approach. Conclusions: VATS lobectomy is a safe and reliable surgical approach for the treatment of Stage I/II NSCLC, characterized by significantly minimal invasiveness, rapid post-operative recovery, and markedly lower loss of blood.

Identification of putative carboxylesterase and aldehyde oxidase genes from the antennae of the rice leaffolder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae)

Yu-Xing Zhang,Wen-Long Wang,Mao-Ye Li,Shi-Guang Li,Su Liu 한국응용곤충학회 2017 Journal of Asia-Pacific Entomology Vol.20 No.3

In insects, odorant-degrading enzymes (ODEs) play essential roles in the degradation of volatile odorants and maintenance of olfactory sensitivity. ODEs include several enzyme families with detoxification functions, such as carboxylesterases (CXEs) and aldehyde oxidases (AOXs). The rice leaffolder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), is a serious rice insect pest in Asia. In this study, 18 putative CXE genes and four AOX genes were identified from the antennae of C. medinalis by retrieving a previously released transcriptome dataset. BLASTX searching and phylogenetic analyses showed that these genes are closely related to their respective orthologs in other lepidopteran species. Expression patterns of these genes were determined by reverse transcription- quantitative PCR (RT-qPCR). Four candidate genes, including three CmedCXEs (CmedCXE17, CmedCXE20 and CmedCXE24) and one CmedAOX (CmedAOX2) were antenna-enriched and considered potentially involved in odorant degradation. Our findings provide a comprehensive sequence resource and expression profiles of CXE and AOX genes in C. medinalis antennae, which may facilitate further studies of the odorant degradation mechanisms in this insect species.