1.Current research of the role of Sox2 in Glioblastoma Multiforme
Jinman GUO ; Chao TAN ; Huojun HU ; Yuan TAN
Tianjin Medical Journal 2015;(12):1467-1469
Glioblastoma (GBM) is one of the WHO gradeⅣmalignancies, which is an acentral nervous system cancer with poor prognosis unless the lesion is in the brain stem. The incidence of GBM accounts for 80%of human primary malignant tumors in brain. Only 5%GBM can survive up to 5-years. Many researches showed that Sox2 is a pluripotent regulator, and muta?tion or abnormal function of Sox2 are closely related to the development of GBM. There are studies demonstrated the possibil?ity of using Sox2 gene as apotential target for GBM therapy. This paper reviewed recent progress in GBM.
2.Research progress of MicroRNAs involved in the tumor microenvironment regulation in non-cell-autonomous mechanisms
Jinman GUO ; Chao TAN ; Huojun HU ; Yuan TAN
Tianjin Medical Journal 2016;44(2):247-250
As an internal environment of tumor occurrence, tumor microenvironment is composed of a variety of cells and extracellular matrix, and plays a crucial role in tumor formation, transfer and resistance to drugs. The regulation of tumor microenvironment will be a potential target to control the cancer. MicroRNAs (miRNAs) are a kind of 21 to 25 nucleotides single-stranded RNA, and are mainly involved in regulating gene expression. Recently, with the suggestion of cellular auton-omous tumor inhibition mechanism, the regulation of tumor microenvironment by miRNAs has received great attention. This review summarizes recent findings on the non-cell-autonomous mechanisms of miRNAs-mediated regulation of tumor micro-environments, which provides foundations and perspective on the design of therapeutic interventions.
3.Effects of preoperative acute hypervolemic hemodilution on coagulation and fibrinolysis of elderly patients undergoing hepatic carcinectomy
Jinman DU ; Jianrong GUO ; Jun YU ; Xiaohong YUAN ; Baowei JIN ; Wei GUO
Journal of Chinese Physician 2010;12(7):887-890
Objective To observe the effects of preoperative acute hypervolemic hemodilution (AHH) on coagulation and fibrinolysis on the elderly patients undergoing hepatic carcinectomy.Methods Thirty ASA Ⅰ~Ⅱ liver cancer patients over sixty years old undergoing scheduled elective hepatic carcinectomy were random divided into AHH group ( n = 15) and control group ( n = 15).AHH was performed by infusing 15 ~20ml/kg 6% Voluven ( 130/0.4) in a rate of 30ml/min on patients in AHH group,and the patients in control group were infused routinely lactated Ringer's solution.Blood samples were collected for measuring coagulation function and platelet activation before anesthesia (T1) ,30 minutes after AHH (T2),1 hour ( T3 ), immediately (T4) and 24 hours (T5) after operation in group AHH, and the similar procure was used in control group.Results There was significant difference in the volume of allergenic blood transfusions between the two groups(20% vs 53.3%, P <0.05).PT and APTT in both groups prolonged significantly after T2, but they all remained in normal range.TT and DD had no significant changes between the two groups.SFMC and F1 + 2 increased in both groups, but it had no significant changes.PAC-1 and CD62P expressions of group AHH were significantly lower T2, T3 ,respectively ( 1.37 ±0.4) %, (1.28 ±0.4) %, than those at T1 [( 1.96 ± 0.6) %] ( P < 0.05 ).Compared with control group, CD62P was significantly lower in AHH group at T2 and T5.Conclusion It is safe to take AHH of Hct 25% to 30% during hepatic carcinectomy for elderly liver cancer patients without cardiac and pulmonary disease.And it could decrease allergenic blood transfusions, with no apparently influence on coagulation function.
4.Study on neuron apoptosis in the patients with temporal lobe epilepsy characterized by hippocampus sclerosis
Huojun HU ; Yiling HUANG ; Lei WANG ; Xiongwei WANG ; Jinman GUO ; Jinyang MA
Chinese Journal of Postgraduates of Medicine 2014;37(32):10-12
Objective To explore the role and expression of cell apoptosis regulatory genes in patients with temporal lobe epilepsy characterized by hippocampus sclerosis.Methods The experimental specimens were obtained from 15 patients with temporal lobe epilepsy (epilepsy group) and 6 control samples (control group) were obtained from temporal lobe excision of brain trauma decompression,investigated neuron apoptosis by HE stain,TdT-mediated dUTP-biotin nick end labeling (TUNEL) method,and determined the expression of bcl-2,bax and caspase-3 by immunohistochemistry.Results The evidence of neuron apoptosis was not found by HE stain in both control group and epilepsy group.Positive cells was not found in control group,but was obviously observed in epilepsy group by TUNEL staining [(4.39 ± 2.04) numbers/100].Unlike that in normal adult brain,bcl-2 immunoreactivity was obviously observed in some neurons in epilepsy group[(6.72 ± 3.36) numbers/100] (P < 0.01).Compared with control group,bax protein in epilepsy group was mild expression (P > 0.05).Two cases in control group were detected the expression of caspase-3 protein,and caspase-3 significantly increased in epilepsy group [(1.07 ± 0.43),(9.54 ± 3.68) numbers/100] (P < 0.01).Conclusions Neuron apoptosis is an important cause of hippocampal sclerosis of human epilepsy.bcl-2 and caspase-3 may play an important role in this process.
5.Clinical observation of herombopag combined with recombinant human thrombopoietin in the treatment of primary immune thrombocytopenia
Xing GUO ; Dan ZHAO ; Jinman ZUO
China Pharmacy 2023;34(23):2910-2914
OBJECTIVE To investigate the clinical efficacy and safety of herombopag combined with recombinant human thrombopoietin (rhTPO) in the treatment of primary immune thrombocytopenia (ITP) in the real world. METHODS A retrospective study was conducted on the patients diagnosed with ITP in the Second Affiliated Hospital of Bengbu Medical College from January 2021 to December 2022. Among them, 98 patients who were treated with a combination of herombopag and rhTPO were included in the observation group, and 157 patients who were treated with rhTPO alone were included in the control group. The changes in platelet count, clinical efficacy, bleeding, platelet transfusion rate and adverse drug reactions before and after treatment were observed and compared between the two groups. RESULTS Since the 8th day of treatment, there was a statistically significant difference in platelet count between the two groups ([ 61.04±13.46)×109 L-1 in observation group, (52.11±12.06)× 109 L-1 in control group] (P<0.05), and there also was a statistically significant difference in the peak and stable values of platelet count between the two groups (P<0.05). The total effective rates of the observation group and the control group were 79.59% and 66.88%, with cumulative response rates of 81.32% and 68.68%, and median response durations of 8 days and 10 days, respectively; these differences were statistically significant (P<0.05). During the treatment period, the bleeding rates of the observation group and control group were 3.06% and 8.28% (P<0.05), bleeding events were categorized as grade 1 or 2, and platelet transfusion rates were 31.63% and 40.76%; the differences in bleeding rates and platelet transfusion rates between the two groups was statistically significant (P<0.05). The incidences of adverse drug reactions in the two groups were 11.22% and 9.55%, respectively, with no statistically significant difference (P>0.05), and no moderate to severe adverse drug reaction was found. CONCLUSIONS The combination of herombopag and rhTPO can significantly increase platelet levels and response rate, and reduce bleeding rate and platelet transfusion rate in ITP patients, with good safety.
6.Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response
Qiao XU ; Ying SHAO ; Jinman ZHANG ; Huikun ZHANG ; Yawen ZHAO ; Xiaoli LIU ; Zhifang GUO ; Wei CHONG ; Feng GU ; Yongjie MA
Cancer Research and Treatment 2020;52(1):218-245
Purpose:
Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.
Materials and Methods:
AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.
Results:
AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.
Conclusion
AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.
7.Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region.
Yinhong ZHANG ; Lei WANG ; Jing HE ; Jingjing GUO ; Chanchan JIN ; Xinhua TANG ; Jinman ZHANG ; Hong CHEN ; Jie ZHANG ; Jie SU ; Baosheng ZHU
Chinese Journal of Medical Genetics 2020;37(4):384-388
OBJECTIVE:
To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies.
METHODS:
Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers.
RESULTS:
In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis.
CONCLUSION
No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.
China
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Female
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Genetic Carrier Screening
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Genetic Counseling
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Genetic Variation
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Heterozygote
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Humans
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Male
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Muscular Atrophy, Spinal
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genetics
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Pregnancy
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Prenatal Diagnosis
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Survival of Motor Neuron 1 Protein
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genetics
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Survival of Motor Neuron 2 Protein
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genetics
8.miR-205-5p/E2F1 signal axis is involved in the regulation of radiosensitivity of glioma cells through suppressing the classical Wnt/β-catenin signaling pathway
Youdong ZHOU ; Ran LUO ; Yanting LIU ; Yuanxun DONG ; Jinyang MA ; Huojun HU ; Xuguang WANG ; Jinman GUO ; Song HUANG ; Gao YUAN ; Changtao FU ; Lei WANG ; Yan GAO
Chinese Journal of Radiation Oncology 2021;30(11):1188-1194
Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.
9.Analysis of in vivo components and metabolism pathway in rats after intragastric administration of aqueous extract from Abrus cantoniensis
Kuikui CHEN ; Yuxin NONG ; Zhonghui GUO ; Yong TAN ; Hongting HUANG ; Jinman LI ; Jinrui WEI ; Zhiying WEI ; Jie LIANG
China Pharmacy 2024;35(13):1576-1581
OBJECTIVE To analyze the chemical components that were the absorbed in blood and liver tissue of rats after intragastric administration of aqueous extract from Abrus cantoniensis, and to speculate its possible metabolic pathways, providing reference for basic analysis of pharmacological substance in A. cantoniensis. METHODS Male SD rats were randomly divided into A. cantoniensis group (0.63 g/kg, calculated by crude drug) and blank group; they were given relevant drug solution/ultrapure water intragastrically. After a single dose, plasma and liver samples of rats in each group were collected. UPLC-Q-TOF/MS technology was used to identify chemical components that were absorbed in the blood and liver tissue of rats. RESULTS Totally, 30 chemical constituents were identified from the water extracts of A. cantoniensis, including alkaloids, flavonoids, organic acids, iridoids (such as L-abrine, schaftoside, isoshaftoside). Ten prototype components and nine metabolites (such as decarboxylation and sulfation metabolites of protocatechuic acid, reduced sulfated metabolites of p-hydroxybenzoic acid) were identified from plasma samples; six prototype components and five metabolites (such as sulfated metabolites of p-hydroxybenzoic acid, decarboxylation and sulfation metabolites of p-hydroxybenzoic acid) were identified from liver samples. The main metabolic pathways included hydroxylation, demethylation, methylation, sulfation, glucuronidation, etc. CONCLUSIONS Alkaloids, flavonoids and organic acids are the main components of the aqueous extract from A. cantoniensis that are absorbed into the blood and liver, their metabolism mainly involves hydroxylation,demethylation, and sulfation.