1.Research progress of RRx-001 as a sensitizer for radiotherapy
Yang GAO ; Cuihong YANG ; Liping CHU
Tianjin Medical Journal 2017;45(5):545-548
Radiotherapy is one of the most important methods to treat malignant tumors. Due to the presence of radiation resistance, the effect of radiotherapy is not entirely satisfactory. To alleviate radiation resistance and improve the radiotherapy effect, radiosensitizers have emerged. As a newly discovered radiosensitizer, RRx-001 has a good clinical application prospect. This paper reviewed the research progress of RRx-001 in source, safety, radiotherapy sensitizing activity and related mechanisms.
2.Isolation and Sequencing the Differential Gene Fragments Expressed in Human Stomach Cancer Tissue
Cuihong YANG ; Qianzheng ZHU ; Wu OU ; Peiying YANG ; Zhenchao QIAN
Chinese Journal of Cancer Biotherapy 1996;0(04):-
Objective: Identification of the genes specially expressed in tumor cell but not in normal cell is important for understanding the molecular mechanisms of carcinogencsis. This study will focus on identification of differentially expressed gene fragments in human stomach cancer. Methods: By using the new developing mRNA differential display (DD) technique, genes fragments differentially expressed in stomach cancer tissues from a patient and the adjacent normal tissues beyond the tumor mass were studied. Results: Two differentially displayed complementary DNA fragments from stomach cancer tissues, scgl and scg2 (stomach cancer-associated gene, scg), cofirmed by Northern Blot, were cloned and sequenced. The nucleotide length of scgl is 194 base pairs and that of scg2 is 343 base pairs. After searching against GenBank databases by BLASTN, neither scgl nor scg2 had significant homological gene sequences with the known genes. Conclusion: These results suggested scgl and scg2 might be complementary DNA fragments of novel genes expressed in stomach cancer tissues, but not in normal tissues and may play a role in the occurrence and development of stomach cancer. Further characterization of full-length of these two complementary DNA fragments will be continued.
3.Application of multimodal imaging in stem cell research
Honglin GAO ; Naling SONG ; Zhongli SUN ; Cuihong YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(5):407-409
In recent years,stem cell research has been developing quickly in biological science.As the key of regenerative medicine,stem cell therapy becomes another innovative treatment following drug therapy and surgery.In vivo stem cell tracking,including optical imaging,radionuclide imaging and MRI,can trace the viability,distribution and function of engrafted cells.Multimodal imaging integrates two or more types of imaging techniques to obtain the combined advantages of each technology,and therefore is able to accurately and effectively trace stem cell in vivo,hopefully promoting its clinical transformation.This paper reviews the application of multimodal imaging in stem cell research.
4.Expression and clinical significance of aldehyde dehydrogenase 1 in nasopharyngeal squamous carcinoma
Fengjiao YANG ; Xiangwei WU ; Shuai XIAO ; Cuihong JIANG ; Lili HE ; Jingshi LIU
Cancer Research and Clinic 2013;25(10):675-677,680
Objective To investigate the significance of aldehyde dehydrogenase 1 (ALDH1)expression in appraising the prognosis of nasopharyngeal squamous carcinoma (NPC).Methods The expression of ALDH1 protein was detected by immunohistochemistry in human specimens obtained from 120 NPC patients without the history of radiotherapy or chemothetapy.Results A relatively high expression of ALDH1 were observed in 40.0 % (48/120) patients of NPC,the expression of ALDH1 in the edge of the cancer nests and stroma,particularly spindle cancer cells were strongly positive.The positive expression of ALDH1 was closely associated with patients' nasopharyngeal tumor size (P =0.011),lymphatic metastasis (P =0.005) and clinic stage (P =0.001),but not associated with their gender and age (both P > 0.05).The Kaplan-Merier and Cox regression analysis indicated that ALDH 1 closely correlated with clinical progrosis of the patients.It showed that ALDH1 was an independent risk factor which may affect the prognosis of NPC patients.Conclusion The expression of ALDH1 protein closely correlate with clinic outcome of NPC,suggesting that ALDH1 is a risk factor for clinic progrosis of NPC patients.
5.Synthesis and biocompatibility of ethynylated open ring derivatives of polyasparamide
Honglin GAO ; Jinghua HAN ; Cuihong YANG ; Yajie LIU ; Naling SONG ; Yanming WANG
Chinese Journal of Biochemical Pharmaceutics 2015;(9):1-3,7
Objective To synthesize a new ethynylated open ring derivatives of polyasparamide as functional drug carrier.Methods L-phenylalanine methyl ester hydrochloride was prepared using L-phenylalanine and then was used for ring opening reaction of polysuccinimide.To synthesize the target product of PSI-Phe-OMe-PA, the obtained polyasparamide-g-phenylalanine derivatives ( PSI-Phe-OMe) was further ring opened by propargylamine.The structure of PSI-Phe-OMe-PA was confirmed by 1 H NMR.The biocompatibility of PSI-Phe-OMe-PA was evaluated by MTT method, inverted microscope observation and cell cycles analysis ( propidium iodide staining ) .Results The ring-opening rate of polyasparamide by L-phenylalanine methyl ester and propargylamine was 40%and 100%, respectively.All results of biocompatibility studies indicated that PSI-Phe-OMe-PA may be a good candidate for functional drug carrier.Conclusion Based on the ring-opening capability of amino-group and the specificity of click reaction, L-phenylalanine methyl ester hydrochloride and propargylamine were used successively to react with polyasparamide.PSI-Phe-OMe-PA is a biocompatible functional drug carrier.
6.Synthesis of acid-sensitive doxorubicin prodrug nanoparticle and its application in brain glioma treatment
Jinjian LIU ; Yumin ZHANG ; Cuihong YANG ; Liping CHU ; Fan HUANG ; Honglin GAO ; Jianfeng LIU
Tianjin Medical Journal 2016;44(1):33-37
Objective To synthesize a new kind of acid-sensitive doxorubicin prodrug nanoparticles and to evaluate its anti-brain glioma effect and efficiency through blood-brain barrier (BBB). Methods The prodrug acid-sensitive poly-ethylene glycol (PEG)-doxorubicin (PEG-DOX) copolymer was synthesized by Schiff base reaction, and PEG-DOX pro-drug nanoparticles (PEG-DOX NPs) were prepared by self-assembling. The character of PEG-DOX copolymer was detected by dynamic light scattering (DLS) instrument and 1H NMR. The morphology of PEG-DOX NPs was observed by transmission electron microscopy (TEM). The character of drug release was detected by UV mothed. The cellular uptake efficiency of glio-ma cells to PEG-DOX NPs was observed by inverted fluorescence microscope. The anti-brain glioma effects of PEG-DOX NPs and Free DOX were studied by MTT mothed. PS80-PEG-DOX NPs were gained by the modification of PEG-DOX NPs with Tween 80. Nine BALB/c mice were separated into Free DOX, PEG-DOX NPs and PS80-PEG-DOX NPs groups by ran-dom drawing lots. The mean fluorescence intensity of brain and main organs were observed by in vivo imaging system. Re-sults The copolymer of PEG-DOX can self-assemble into nanoparticles with the diameter of 100 nm. PEG-DOX NPs can quickly release DOX in acid environment. Although PEG-DOX NPs had slow cancer cell uptake than Free DOX, it had lon-ger accumulation. MTT results showed that PEG-DOX NPs had concentration dependent anti-brain glioma effect. Indepen-dent samples t-test indicated that the efficiency through BBB was significantly higher in PS80-PEG-DOX NPs group than that of Free DOX group and PEG-DOX NPs group. Conclusion PEG-DOX NPs show well anti-brain glioma effect in vi-tro, and can across BBB with high efficiency after modification, which make it possible for a potential therapeutic prodrug for brain glioma.
7.Predictive Value of Electrocardiogram Abnormality on Prognosis of Chronic Heart Failure in Patients With Dilated Cardiomyopathy
Jie YANG ; Cuihong HOU ; Zhouying LIU ; Lan REN ; Xinggou SUN ; Jielin PU
Chinese Circulation Journal 2016;31(3):218-222
Objective: To study the predictive value of 12-lead electrocardiogram (ECG) abnormality on prognosis of chronic heart failure in patients with dilated cardiomyopathy (DCM-CHF).
Methods: A prospective, multicenter follow-up study in 787 DCM-CHF patients was conducted, and the endpoints were obtained by clinical visit, mail contact and telephone conversation. The independent predictors for all cause death were determined by Cox regression analysis, QRS duration > 120 ms was studied and the survival rates were investigated by Kaplan-Meier analysis.
Results: There were 203 patients died during the follow-up period. Cox regression analysis found that the following indexes were related to all cause death: atrial fibrillation (AF) (HR=2.064, 95% CI 1.102-3.864,P<0.05), non-sustained ventricular tachycardia (NSVT) (HR=3.887, 95% CI 1.554-9.724,P<0.05) and QRS duration (HR=1.010, 95% CI 1.002-1.018, P<0.05). Kaplan-Meier analysis revealed that the survival rates were different by each stratiifcation of QRS duration,P<0.05.
Conclusion: ECG indexes of AF, NSVT and QRS duration had the important impact on the survival rate in DCM-CHF patients; there were signiifcant differences between QRS durations and survival rates.
8.Synthesis of poly asparagine derivatives and its cytotoxicity study
Cuihong YANG ; Jinghua HAN ; Jinjian LIU ; Yumin ZHANG ; Honglin GAO ; Wenhui DONG ; Yanming WANG
Tianjin Medical Journal 2015;(6):582-586
Objective To synthesize poly asparagine derivatives and to evaluate its safety at the cellular level, which provide research platform for its potential application as drug carrier. Methods Polysuccinimide was synthesized by ther?mal polymerization of L-polyaspartic acid, and the target product of PSI-Phe-EA was obtained by the ring-opening reaction of polysuccinimide using L-phenylalanine methyl ester hydrochloride and ethanol amine. The structure of PSI-Phe-EA were characterized by 1H NMR. The rate of ring-opening of PSI was calculated by internal standard method of 1H NMR. The change of hydrophilicity was studied by the comparison of solubility. The cytotoxicity and morphology modification by PSI-Phe-EA at designate concentrations was investigated by MTT method and inverted microscopy respectively. The effects on cell cycles were analyzed by flow cytometry after propidium iodide (PI) staining. Results 1H NMR results confirmed the structure of PSI-Phe-EA and the ring-openning rate of PSI was 40%. The hydrophilicity of PSI-Phe-EA was greatly in?creased upon ring opening using ethanol amine. MTT test showed that the cell survival rates of NIH 3T3 and HepG2 cells were higher than 80%under the examined concentration (<100 mg/L). Inverted microscopy showed that 50 mg/L of PSI-Phe-EA treatment had no adverse effects on cell morphology. Cell cycle analysis indicated that PSI-Phe-EA treatment had no in?fluence on cell cycles of NIH 3T3 and HepG2 cell lines. Conclusion PSI-Phe-EA showed high hydrophilicity without sig?nificant effects on the cells survival, cells morphology and cell cycles. It is a kind of safe polymer material.
9.The Effect of Amino Acid Configuration on the Biodistribution of Peptide Nanofiber
Hongyan XU ; Yumin ZHANG ; Cuihong YANG ; Jinjian LIU ; Liping CHU ; Yujun YAN ; Jianfeng LIU ; Naling SONG
Tianjin Medical Journal 2014;(2):143-147
Objective To compare the biodistribution difference of peptide nanofibers, which were self-assembled by peptide composed of L-or D-amino acids, respectively, and provide the guidance for the in vivo applications of peptide nanofibers. Methods The Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide, F and Y were D-configura-tion) were synthesized with solid phase peptide synthesis (SPPS). The structure of the two peptides was identified by nuclear magnetic resonance spectroscopy (1H NMR) and high-resolution mass spectrometry (HR-MS). The two peptides could self-assemble into nanofibers during the cooling process after being boiled. The morphology of the nanofibers was observed with transmission electron microscope (TEM). The peptides were radiolabeled with iodine-125 and self-assembled into nanofi-bers, which were then administered into BALB/c mice via tail vein. The blood samples were collected and then mice were sacrificed at 1, 3, 6 and 12 hours. The main organs (heart, liver, spleen, lung, kidney, stomach, large intestine, small intes-tine, muscle and brain) were isolated and weighed. The radioactivity of organs was detected with a gamma counter. Results The two peptides could self-assemble into nanofibers with diameter of 10-20 nanometers. There were no significant differ-ences in the diameter and morphology between two naofibers. There was significant difference in the biodistribution between two nanofibers. The blood concentration of D-fiber was (8.17±0.32)%ID/g at one hour after injection and then cleared rapid-ly from the blood. The blood concentration of L-fiber was (5.96±0.30)%ID/g at one hour after injection and maintained at a stable level for six hours. The L-fiber was mainly distributed in stomach while the D-fiber was mainly accumulated in liver. Conclusion The configuration of amino acids (D/L) could affect the biodistribution of peptide nanofibers dramatically, which may provide the guidance for the medical applications of peptide nanofibers.
10.Characterization of Sporothrix schenckii by random amplification of polymorphic DNA assay.
Xiaoming LIU ; Cuihong LIAN ; Liji JIN ; Lijia AN ; Guoling YANG ; Xiran LIN
Chinese Medical Journal 2003;116(2):239-242
OBJECTIVESTo investigate the DNA polymorphism of Sporothrix schenckii (S. schenckii) and to find the relationship between DNA patterns and geographic areas and clinical manifestations.
METHODThe total DNA was extracted with hexadecyltrimethyl-ammonium bromide. Random Amplification of Polymorphic DNA (RAPD) assay was used to study DNA typing of 24 strains of S. schenckii collected from different areas and isolated from different clinical types.
RESULTSOf seven random primers used, three primers (OPAA11, OPD18 and OPB07) gave good reactions, the sequences of which were 5'-ACCCGACCTG-3', 5'-GAGAGCCAAC-3', 5'-GGTGAC~GCAG-3' respectively. The RAPD patterns of the 24 isolates were not completely identical, showing certain degrees of hereditary variability. Different isolates showed a common conserved DNA band with the same primer. Different clinical types showed different genotypes.
CONCLUSIONRAPD analysis is useful in DNA typing of S. schenckii, the DNA band type of which is related to geographic origin and Clinical manifestation.
DNA, Fungal ; analysis ; Humans ; Random Amplified Polymorphic DNA Technique ; Sporothrix ; genetics