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.

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.

Structural Deformation Sensing Based on Distributed Optical Fiber Monitoring Technology and Neural Network

Gong-Yu Hou,Zi-Xiang Li,Kai-Di Wang,Jin-Xin Hu 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.11

Structural deformation monitoring is vital to the safety of concrete structures. However, the distributed deformation of structures cannot be easily obtained using existing monitoring methods in civil engineering. To this end, this paper proposes a method to estimate the continuous deformation of concrete beams by utilizing the distributed optical fiber monitoring technology. In this method, optical fibers and a total station are used to obtain the strain and deformation distribution curves of a concrete beam, respectively. Subsequently, these curves are inputted to a back propagation network as training samples to learn their relationships. The results show that the deformation value of trained neural network is very close to that of the total station, with a maximum error of only 2.7% (0.3 mm). The linear regression analysis shows a goodness of fit R2 greater than 0.98, which confirms the reliability of the simulations results.

Preparation, Characterization, and In Vivo Evaluation of Mitoxantrone- loaded, Folate-conjugated Albumin Nanoparticles

Liang-ke Zhang,Shi-xiang Hou,Jing-qin Zhang,Wen-jing Hu,Cheng-yuan Wang 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8

Folic acid was covalently conjugated to bovine serum albumin nanoparticles (BSANP) to target the nanoparticles to SKOV3 cells expressing folate receptors. Mitoxantrone was incorporated into the folate-conjugated albumin nanoparticles, and the final nanoparticle size was 68 nm, as measured by a laser light scattering particle analyzer. The cytotoxic activity of mitoxantrone-loaded, folate-conjugated albumin nanoparticles (MTO-BSANP-folate), which was quantitated by 3H-thymidine incorporation, was higher than mitoxantrone-loaded BSANP (MTO-BSANP) and MTO solution, and could be inhibited by free folic acid. MTO-BSANPfolate may be endocytosed via the folate receptor on the surface of SKOV3 cells. MTO-BSANPfolate also inhibited tumor growth better than the MTO-BSANP and MTO solution in vivo. These results indicate that folate-conjugated BSANP may have therapeutic potential as a vector for anticancer drugs in cancer chemotherapy.

Lymph Node Ratio is an Independent Prognostic Factor in Node Positive Rectal Cancer Patients Treated with Preoperative Chemoradiotherapy Followed by Curative Resection

Zeng, Wei-Gen,Zhou, Zhi-Xiang,Wang, Zheng,Liang, Jian-Wei,Hou, Hui-Rong,Zhou, Hai-Tao,Zhang, Xing-Mao,Hu, Jun-Jie Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Background: The lymph node ratio (LNR) has been shown to be an important prognostic factor for colorectal cancer. However, studies focusing on the prognostic impact of LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection have been limited. The aim of this study was to investigate LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection. Materials and Methods: A total of 131 consecutive rectal cancer patients who underwent neoadjuvant CRT and total mesorectal excision were included in this study. Patients were divided into two groups according to the LNR (${\leq}0.2$ [n=86], >0.2 [n=45]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). Results: The median number of retrieved and metastatic lymph node (LN) was 14 (range 1-48) and 2 (range 1-10), respectively. The median LNR was 0.154 (range 0.04-1.0). In multivariate analysis, LNR was shown to be an independent prognostic factor for both overall survival (hazard ratio[HR]=3.778; 95% confidence interval [CI] 1.741-8.198; p=0.001) and disease-free survival (HR=3.637; 95%CI 1.838-7.195; p<0.001). Increased LNR was significantly associated with worse OS and DFS in patients with <12 harvested LNs, and as well as in those ${\geq}12$ harvested LNs (p<0.05). In addition, LNR had a prognostic impact on both OS and DFS in patients with N1 staging (p<0.001). Conclusions: LNR is an independent prognostic factor in ypN-positive rectal cancer patients, both in patients with <12 harvested LNs, and as well as in those ${\geq}12$ harvested LNs. LNR provides better prognostic value than pN staging. Therefore, it should be used as an additional prognostic indicator in ypN-positive rectal cancer patients.

Adaptive guided salp swarm algorithm with velocity clamping mechanism for solving optimization problems

Wang Zongshan,Ding Hongwei,Wang Jie,Hou Peng,Li Aishan,Yang Zhijun,Hu Xiang 한국CDE학회 2022 Journal of computational design and engineering Vol.9 No.6

Salp swarm algorithm (SSA) is a well-established population-based optimizer that exhibits strong exploration ability, but slow convergence and poor exploitation capability. In this paper, an endeavour is made to enhance the performance of the basic SSA. The new upgraded version of SSA named as ‘adaptive strategy-based SSA (ABSSA) algorithm’ is proposed in this paper. First, the exploratory scope and food source navigating commands of SSA are enriched using the inertia weight and boosted global best-guided mechanism. Next, a novel velocity clamping strategy is designed to efficiently stabilize the balance between the exploration and exploitation operations. In addition, an adaptive conversion parameter tactic is designed to modify the position update equation to effectively intensify the local exploitation competency and solution accuracy. The effectiveness of the proposed ABSSA algorithm is verified by a series of problems, including 23 classical benchmark functions, 29 complex optimization problems from CEC 2017, and five engineering design tasks. The experimental results show that the developed ABSSA approach performs significantly better than the standard SSA and other competitors. Moreover, ABSSA is implemented to handle path planning and obstacle avoidance (PPOA) tasks in autonomous mobile robots and compared with some swarm intelligent approach-based path planners. The experimental results indicate that the ABSSA-based PPOA method is a reliable path planning algorithm.

ANXA2 Regulates the Behavior of SGC-7901 Cells

Sun, Meng-Yao,Xing, Rui-Huan,Gao, Xiao-Jie,Yu, Xiang,He, Hui-Min,Gao, Ning,Shi, Hong-Yan,Hu, Yan-Yan,Wang, Qi-Xuan,Xu, Jin-Hui,Hou, Ying-Chun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC-7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ${\beta}$-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ${\beta}$-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.

Expression profiles of circular RNAs in sheep skeletal muscle

Cao, Yang,You, Shuang,Yao, Yang,Liu, Zhi-Jin,Hazi, Wureli,Li, Cun-Yuan,Zhang, Xiang-Yu,Hou, Xiao-Xu,Wei, Jun-Chang,Li, Xiao-Yue,Wang, Da-Wei,Chen, Chuang-Fu,Zhang, Yun-Feng,Ni, Wei,Hu, Sheng-Wei Asian Australasian Association of Animal Productio 2018 Animal Bioscience Vol.31 No.10

Objective: Circular RNAs (circRNAs) are a newfound class of non-coding RNA in animals and plants. Recent studies have revealed that circRNAs play important roles in cell proliferation, differentiation, autophagy and apoptosis during development. However, there are few reports about muscle development-related circRNAs in livestock. Methods: RNA sequencing analysis was employed to identify and annotate circRNAs from longissimus dorsi of sheep. Reverse transcription followed by real-time quantitative (q) polymerase chain reaction (PCR) analysis verified the presence of these circRNAs. Targetscan7.0 and miRanda were used to analyse the interaction of circRNA-microRNA (miRNA). To investigate the function of circRNAs, an experiment was conducted to perform enrichment analysis hosting genes of circRNAs using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Results: About 75.5 million sequences were obtained from RNA libraries of sheep skeletal muscle. These sequences were mapped to 729 genes in the sheep reference genome. We identified 886 circRNAs, including numerous circular intronic RNAs and exonic circRNAs. Reverse transcription PCR (RT-PCR) and DNA sequencing analysis confirmed the presence of several circRNAs. Real-Time RT-PCR analysis exhibited resistance of sheep circRNAs to RNase R digestion. We found that many circRNAs interacted with muscle-specific miRNAs involved in growth and development of muscle, especially circ776. The GO and KEGG enrichment analysis showed that hosting genes of circRNAs was involved in muscle cell development and signaling pathway. Conclusion: The study provides comprehensive expression profiles of circRNAs in sheep skeletal muscle. Our study offers a large number of circRNAs to facilitate a better understanding of their roles in muscle growth. Meanwhile, we suggested that circ776 could be analyzed in future study.

Risk of venous thromboembolism in Chinese pregnant women: Hong Kong venous thromboembolism study

Duo Huang,Emmanuel Wong,Ming-Liang Zuo,Pak-Hei Chan,Wen-Sheng Yue,Hou-Xiang Hu,Ling Chen,Li-Xue Yin,Xin-Wu Cui,Ming-Xiang Wu,Xi Su,Chung-Wah Siu,Jo-Jo Hai 대한혈액학회 2019 Blood Research Vol.54 No.3

BackgroundPrevious Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum peri-od in the Chinese population. We investigated the risk of venous thromboembolism in a “real-world” cohort of pregnant Chinese women with no prior history of venous thromboembolism.MethodsIn this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed.ResultsThe mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29‒36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pul-monary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester.ConclusionChinese women had a substantially lower risk of venous thromboembolism during preg-nancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early preg-nancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.