CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

Jingbo Ma,Xiaolong Xu,Chunjin Fu,Peng Xia,Ming Tian,Liuhai Zheng,Kun Chen,Xiaolian Liu,Yilei Li,Le Yu,Qinchang Zhu,Yangyang Yu,Rongrong Fan,Haibo Jiang,Zhifen Li,Chuanbin Yang,Chengchao Xu,Ying Long,J 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. Methods: Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. Results: Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. Conclusions: The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobodybased immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.

Brain Metabolic Network Redistribution in Patients with White Matter Hyperintensities on MRI Analyzed with an Individualized Index Derived from 18F-FDG-PET/MRI

Ma Jie,Hua Xu-Yun,Zheng Mou-Xiong,Wu Jia-Jia,Huo Bei-Bei,Xing Xiang-Xin,Gao Xin,Zhang Han,Xu Jian-Guang 대한영상의학회 2022 Korean Journal of Radiology Vol.23 No.10

Objective: Whether metabolic redistribution occurs in patients with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is unknown. This study aimed 1) to propose a measure of the brain metabolic network for an individual patient and preliminarily apply it to identify impaired metabolic networks in patients with WMHs, and 2) to explore the clinical and imaging features of metabolic redistribution in patients with WMHs. Materials and Methods: This study included 50 patients with WMHs and 70 healthy controls (HCs) who underwent 18F-fluorodeoxyglucose-positron emission tomography/MRI. Various global property parameters according to graph theory and an individual parameter of brain metabolic network called “individual contribution index” were obtained. Parameter values were compared between the WMH and HC groups. The performance of the parameters in discriminating between the two groups was assessed using the area under the receiver operating characteristic curve (AUC). The correlation between the individual contribution index and Fazekas score was assessed, and the interaction between age and individual contribution index was determined. A generalized linear model was fitted with the individual contribution index as the dependent variable and the mean standardized uptake value (SUVmean) of nodes in the whole-brain network or seven classic functional networks as independent variables to determine their association. Results: The means ± standard deviations of the individual contribution index were (0.697 ± 10.9) x 10-3 and (0.0967 ± 0.0545) x 10-3 in the WMH and HC groups, respectively (p < 0.001). The AUC of the individual contribution index was 0.864 (95% confidence interval, 0.785–0.943). A positive correlation was identified between the individual contribution index and the Fazekas scores in patients with WMHs (r = 0.57, p < 0.001). Age and individual contribution index demonstrated a significant interaction effect on the Fazekas score. A significant direct association was observed between the individual contribution index and the SUVmean of the limbic network (p < 0.001). Conclusion: The individual contribution index may demonstrate the redistribution of the brain metabolic network in patients with WMHs.

Three Treatment Methods via the Hepatic Artery for Hepatocellular Carcinoma - A Retrospective Study

Ma, Teng-Chuang,Shao, Hai-Bo,Xu, Yang,Xu, Ke Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Background: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery. Materials and Methods: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison. Results: The overall average change of areas was $240.8{\pm}72.1mm^2$. In the three groups it was $265.0{\pm}58.0mm^2$ vs. $250.5{\pm}51.9mm^2$ vs. $123.7{\pm}26.2mm^2$. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases ($24.0{\pm}13.5$ vs. $20.9{\pm}12.1$ vs. $5.47{\pm}8.20$ and $25.6{\pm}13.5$ vs.$23.2{\pm}12.28$ vs.$5.48{\pm}14.3$) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs. Conclusion: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.

One-Pot Hydrothermal Synthesis of Sulfur-Doped SnO2 Nanoparticles and their Enhanced Photocatalytic Properties

Lin Ma,Limei Xu,Xuyao Xu,Xiaoping Zhou,Lingling Zhang 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2016 NANO Vol.11 No.3

Sulfur-doped SnO2 nanoparticles with ultrafine sizes have been successfully prepared by a one-pot hydrothermal method. The obtained samples are characterized by X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), high resolution transmission electron microscopy (HRTEM), thermogravimetric (TG), analyzer UV-Vis spectroscopy, photoluminescence (PL) and electrochemical impedance spectroscopy (EIS). The experimental results indicate that the doping level of sulfur element as well as the bandgaps of SnO2 can be controlled to a certain extent by varying the amount of L-cysteine (L-cys). When evaluated as photocatalysts in the degradation of rhodamine B (RhB) and reduction of Cr(VI) under visible light region, the resultant sulfur-doped SnO2 nanoparticles demonstrate obviously enhanced photocatalytic activities due to the markedly improved visible light response and effective separation of the photo-generated electron–hole pairs.

Microwave-Assisted Hydrothermal Preparation of SnO2/MoS2 Composites and Their Electrochemical Performance

Lin Ma,Xiaoping Zhou,Limei Xu,Xuyao Xu,Lingling Zhang 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2016 NANO Vol.11 No.2

We introduce a two-step hydrothermal and microwave method to prepare novel SnO2/MoS2 composites. The as-prepared samples are well characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM). The experimental results indicate that the SnO2/MoS2 composites are composed of MoS2 nanosheets and ultrafine SnO2 nanoparticles with mean size of 3–4 nm which are well-distributed and anchored on the surface of MoS2 nanosheets. The resultant composites demonstrate prominently improved electrochemical performances, which could be attributed to the unique and robust microstructures and synergetic effect between MoS2 and SnO2.

Developmental Effects of Dietary Nucleotides in Second-Generation Weaned Rats

Meihong Xu,Yi Ma,Linlin Xu,Yajun Xu,Yong Li 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.12

The aim of the present study was to evaluate dietary effects of dietary nucleotides (NTs) on developmental parameters in second-generation Sprague-Dawley rats. Experimental design was set up as six groups, including one control and five nucleotide administered groups, doses ranged from 0.01% to 1.28% nucleotides. First-generation (F0) rats were divided into two terms: (1) fed for 90-day study; (2) mated for offspring (F1). After weaning, each group of second-generation F1 rats was fed the control diet. Evaluating parameters were weight gain and food utilization ratios of rats, hematological and biochemical parameters, and organ pathology. The results showed that there was a greater weight gain and food utilization ratio in weaned rats (F0 and F1). Furthermore, weight gain and food utilization ratios were increased in the first 2 weeks of F1 male and the first week of F1 female rats. There were no significant changes in blood indicators of NT groups with the exception of decrease in aspartate aminotransferase and serum uric acid levels. Overall, it was demonstrated that NT supplements could promote the early growth and development at a 0.01% dose. Although NTs may have cumulative reproductive effects, they were safe even at a high-dose supplementation. Additionally, NT supplementation could promote restoration and optimize liver function.

Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area

Cheng Xu,Shi-Ping Yang,Yuan Zhang,Ling-Long Tang,Guan-Qun Zhou,Xu Liu,Yan-Ping Mao,Rui Guo,Wen-Fei Li,Lei Chen,Ai-Hua Lin,Ying Sun,Jun Ma 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil after IC-1, all patients were categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. Results Grade 1-2/grade 3-4 neutropenia were associated with poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel– cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin ( 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin  1.33 were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. Conclusion Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Comparative transcriptome analyses provide insights into the adaptation mechanisms to acute salt stresses in juvenile Sinonovacula constricta

Bin Ma,Zhaoshou Ran,Xiaorong Xu,Jilin Xu,Kai Liao,Jiayi Cao,Xiaojun Yan 한국유전학회 2019 Genes & Genomics Vol.41 No.5

Background Sinonovacula constricta is an economically important bivalve species in China, Korea and Japan that widely resides in estuarine and coastal areas where salinity fluctuates rapidly. However, little is known about its adaptation mechanisms to acute salt stresses. Objective To reveal the underlying molecular mechanisms involved in acute salt stresses in juvenile S. constricta. Methods Nine cDNA libraries (triplicate each trial) were established from juvenile S. constricta, which were subjected to low salinity (5 psu), optimal salinity (15 psu) and high salinity (25 psu) for 6 h, respectively. Results Illumina sequencing generated 478,587,310 clean reads totally, which were assembled into 427,057 transcripts of 246,672 unigenes. Compared with the control, 1259 and 2163 differentially expressed genes (DEGs) were identified under acute low and high salt stresses, respectively. GO and KEGG enrichment analyses of DEGs revealed that several key metabolic modulations were mainly responsible for the acute salt stresses. According to the significantly highlighted KEGG pathways, some key DEGs were identified and discussed in details. Notably, based on which, some potential osmolytes were further speculated. Conclusion Here, we carried out a unique report of comparative transcriptome analyses in juvenile S. constricta in response to acute salt stresses. The identified DEGs and their significantly enriched GO terms and KEGG pathways were critical for understanding and further investigating the underlying the physical and biochemical performances, and ultimately facilitated S. constricta breeding. Besides, the transcriptome data greatly enriched the genetic information of S. constricta, which were valuable for promoting its molecular biology researches.

Screening and Selection of Medium Components by Plackett-Burman Design for Improved Production of Rifamycin B by Amycolatopsis mediterranei S699

Feng Xu Ma,Jung Hun Kim,Sung Bae Kim,Yang-Gon Seo,Chang-Joon Kim 한국생물공학회 2007 한국생물공학회 학술대회 Vol.2007 No.4

The Production Characteristics of Amycolatopsis mediterranei S699 in Bioreactor Culture Using Optimal Medium

Feng Xu Ma,Jung Hun Kim,Sung Bae Kim,He Li,Chang-Joon Kim 한국생물공학회 2007 한국생물공학회 학술대회 Vol.2007 No.10