1.The expression and significance of the cell cycle related genes in uveal melanoma
Linjie GUO ; Zhongyao WU ; Huling ZHENG
Chinese Journal of Ocular Fundus Diseases 1996;0(01):-
Objective To evaluate the role of the cell cycle related genes cyclinD1 and Bcl-2 protein expression in the pathogenesis and infiltration of the uveal melanoma. Methods Using immunohistochemistry to detect the cyclinD1 and bcl-2 protein expression in 96 cases of uveal melanoma. Results The expression content of bcl-2 was high in uveal melanoma, and there wasnt any relationship between bcl-2 cell positivity and tumor cell type and extrascleral extension. In contrast, cyclinD1 expression was higher in epithelial cell uveal melanoma than mix cell and spindle cell varieties. There was a positive correlation between cyclinD1 cell positivity and extrascleral extension. Conclusion The expression of bcl-2 protein is important for the survival of the uveal melanoma. CyclinD1 may serve as a sensitive index of its malignancy.
2.To induce uveal melanoma cells apoptosis by mixed structure bcl-2 antisense oligodeoxynucleotides multidrug resistance
Linjie GUO ; Zhongyao WU ; Sheng ZHANG
Chinese Journal of Ocular Fundus Diseases 1996;0(01):-
Objective To investigate the role of anti apoptosis gene bcl 2 in the survival of cultured uveal melanoma UM cells. Methods Antisense oligodeoxynucleotides (AS ODN) bcl 2 were delivered with cationic lipid to primary cultured UM cells. The inhibitory effect of AS ODN bcl 2 on proliferation of UM cells was examined by 3, 4,5 Dimethyliazol 2,5 diphenyl tetrazolium bromide (MTT) method. Using DNA ladder to determine if the UM cells had been apoptotic. Bcl 2 expression was detected by RT PCR and Westernblot technics. Results The effect of AS ODN bcl 2 in inhibiting the proliferation of cultured UM cells had opposite relation to dosage. It down regulated the mRNA and protein level of bcl 2 gene, and the sense ODN didn′t have this effect. Conclusion AS ODN bcl 2 can down regulate bcl 2 expression, inhibits UM cells proliferation and induces apoptosis.
3.Mechanism of apoptosis induced by Mcl-1 inhibitor UMI-77 on gastric cancer MGC-803 cells
Xueping ZHU ; Ping WU ; Linjie ZHANG
Acta Universitatis Medicinalis Anhui 2016;51(4):506-510,511
Objective To investigate the mechanism of apoptosis induced by UMI-77 , a novel selective inhibitor of Mcl-1, in gastric cancer MGC-803 cells. Methods MGC-803 cells were treated with UMI-77 in different concen-trations for 24 h, apoptotic rates were determined by Annexin V/PI method using flow cytometry. Mitochondrial membrane potential was determined by JC-1 staining on a flow cytometer. The activation of Caspase-9, Caspase-3 and cleavage of PARP were measured by Western blot analysis. The protein level of Bcl-2, Bcl-XL and Mcl-1 was monitored by Western blot as well. Chemically synthesized Mcl-1 siRNA was transfected into MGC-803 cells using Lipofectamine 2000 Reagent. The efficacy of gene silencing was confirmed by Western blot analysis, and opoptotic rates before and after transfection was measured by flow cytometry using Annexin V/PI staining. Results UMI-77 was effective in induction of apoptosis in gastric cancer MGC-803 cells, apoptotic rates were increased in a dose-de-pendent manner. Mitochondrial membrane potential was collapsed after UMI-77 treatment. Activation of Caspase-9, Caspase-3 and cleavage of PARP occurred at 24 h (P<0. 05). The expression level of Bcl-2 and Bcl-XL were not altered after exposure to UMI-77 , while Mcl-1 was down-regulated after 12 h ( P<0. 05 ) . Transfection with Mcl-1 siRNA successfully decreased the expression level of Mcl-1 in MGC-803 cells ( P<0. 05 ) and blocked apoptosis induced by UMI-77 ( P<0. 05 ) . Conclusion UMI-77 induces apoptosis through activation of the intrinsic path-way in gastric cancer MGC-803 cells, and knocking down Mcl-1 expression abrogates apoptosis by UMI-77.
4.Bioinformatics analysis of DNA demethylase genes in Lonicera japonica Thunb.
Linjie QI ; Yuan YUAN ; Chong WU ; Luqi HUANG ; Ping CHEN
Acta Pharmaceutica Sinica 2015;50(3):367-71
The DNA demethylase genes are widespread in plants. Four DNA demethylase genes (LJDME1, LJDME2, LJDME3 and LJDME4) were obtained from transcriptome dataset of Lonicera japonica Thunb by using bioinformatics methods and the proteins' physicochemical properties they encoded were predicted. The phylogenetic tree showed that the four DNA demethylase genes and Arabidopsis thaliana DME had a close relationship. The result of gene expression model showed that four DNA demethylase genes were different between species. The expression levels of LJDME1 and LJDME2 were even more higher in Lonicera japonica var. chinensis than those in L. japonica. LJDME] and LJDME2 maybe regulate the active compounds of L. japonica. This study aims to lay a foundation for further understanding of the function of DNA demethylase genes in L. japonica.
5.To strengthen the detection of biomarkers in the synchronous metastatic axillary lymph nodes of primary breast cancer
Lingquan KONG ; Linjie LU ; Hongyuan LI ; Guosheng REN ; Kainan WU
Chinese Journal of Endocrine Surgery 2016;10(2):99-103
Postoperative adjuvant therapy for primary invasive breast cancer patients with synchronous ax-illary metastases is mainly based on the characteristics of biomarker of the primary tumor. Recently, some studies have showed the discordance and clinical significance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer and synchronous axillary lymph node metastases. As local metastasis, the synchronous axillary metastases may represent the potentially metastatic breast cancer cells much better than the primary tumor. Hence, determination of biomarkers status should be performed in synchronous axillary metastasis, together with primary tumor, to guide therapy management and evaluate the prognosis of primary invasive breast cancer patients with synchronous axillary metastases.
6.Activation of caspase-4 was involved in TRAIL-induced apoptosis of gastric cancer cells
Ping WU ; Xueping ZHU ; Xudong ZHANG ; Linjie ZHANG
Chinese Pharmacological Bulletin 2014;(10):1437-1440,1441
Aim To investigate the potential involve-ment of caspase-4 in TRAIL ( tumor necrosis factor-re-lated apoptosis-inducing ligand )-induced apoptosis in gastric cancer cells. Methods The effect of treatment with TRAIL /z-LEVD-fmk alone or in combination for 24 h on the apoptotic rate of gastric cancer cells was detected by FCM ( flow cytometry) using propidium io-dide DNA staining. Chemically synthesized three siR-NAs targeting caspase-4 gene were transfected into gas-tric cancer cells by Lipofectamine 2000 Reagent. The efficacy of gene silencing was confirmed by Western blot analysis . The apoptotic rates of gastric cancer cells to TRAIL before and after transfection with caspase-4 siRNA were observed by FCM. The expression level of GRP78 (78-ku glucose-regulated protein) protein was examined by Western blot, the classic endoplasmic re-ticulum stress inducer tunicamycin ( TM) was used as a control. The expression levels of caspase-4 and caspase-3 after TRAIL treatment were also measured by Western blot. Results z-LEVD-fmk decreased TRAIL-induced apoptosis of gastric cancer cells signifi-cantly(P<0. 05). As compared with negative control, the expression level of caspase-4 protein was reduced after transfection, and the apoptotic rate was also de-creased ( P <0. 05 ) . While TM induced marked up-regulation of GRP78 , treatment with TRAIL resulted in, albeit to a lesser extent, increases in GRP78, in-dicative of induction of ER stress by TRAIL. Activa-tion of caspase-4 and caspase-3 occurred early after TRAIL treatment. Conclusion Activation of caspase-4 contributes to TRAIL-induced apoptosis and is asso-ciated with induction of ER stress by TRAIL in gastric cancer cells.
7.Protection of ovarian function for female breast cancer patients undergoing chemotherapy
Qingqing LUO ; Linjie LU ; Lingquan KONG ; Kainan WU
Chinese Journal of Endocrine Surgery 2017;11(3):249-253
Breast cancer is one of the most common malignant tumors in females.Recent years,surgery,chemotherapy as well as other systemic therapy had greatly improved the prognosis of the patients.However,damage of ovarian function by chemotherapy lowered life quality,especially for young females.At present,there are several methods to protect the ovarian function of female patients undergoing chemotherapy,such as administration of a gonadotropin-releasing hormone (GnRH) analogs,ovarian cryopreservation,unfertilized ova cryopreservation,embryo cryopreservation,inhibitors of apoptosis,etc.Each method has its advantage,disadvantage and indications.Issues related to ovarian protection are reviewed here.
8.The status of glucose intolerance in breast cancer patients without DM history after systemic treatment with surgery and/or chemo-therapy
Linjie LU ; Ruiyu WANG ; Lingquan KONG ; Guangyan JI ; Shengchun LIU ; Hongyuan LI ; Kainan WU
Chinese Journal of Clinical Oncology 2014;46(4):250-253
Objective:To determine the status of glucose intolerance in breast cancer patients without DM history after combined treatment with surgery and/or chemotherapy through an oral glucose tolerance test (OGTT). Methods:All 121 breast cancer patients more than 3 months after combined treatments with surgery and/or chemotherapy and without the diagnosis of diabetes underwent OGTT and fasting. Then, 2 h glucose levels were measured to identify glucose tolerance and diabetes. Meanwhile, six patients with a history of diagnosed diabetes did not undergo OGTT. Results:The median ages of all breast cancer patients and the mean duration after combined treatments with surgery and/or chemotherapy were 50.4 years and 19 months, respectively. Among the 121 breast cancer pa-tients without the history of diabetes, the incidences of diabetes, prediabetes, and normal glucose intolerance were 19.8%(24 cases), 45.5%(55 cases) and 34.7%(42 cases), respectively. Among all breast cancer patients, the incidences of previously diagnosed diabetes, undiagnosed diabetes, and prediabetes were 4.72%, 18.9%, and 43.3%, respectively. The ratio of previously undiagnosed diabetes was about 80%. About 80.0% of undiagnosed diabetes and 74.5% of prediabetes met the criteria for elevated 2 h plasma glucose levels through OGTT instead of elevated fasting glucose levels. Conclusion: Breast cancer patients during follow-up after combined treat-ments with surgery and/or chemotherapy highly suffer from glucose intolerance, with high incidences of undiagnosed diabetes and pre-diabetes. OGTT should be made for breast cancer patients after combined treatments for early diagnosis, prevention, and treatment of di-abetes.
9.Relationship of the gene of multidrug and drug resistance and the patients′ prognosis in uveal melanoma
Siming AI ; Linjie GUO ; Zhongyao WU ; Sheng ZHANG ; Jiaqi CHEN ; Huling ZHENG
Chinese Journal of Ocular Fundus Diseases 1996;0(01):-
Objective To probe the relationship between the patients′ prognosis and the gene of multidrugs and drug resistance in uveal melanoma. Methods The gene expression of cyclin D1, epithelial growth factor receptor (EGFR), non metastasis gene 23 (nm 23), P glucose protein (P gp), multidrug resistance relation protein (MRP) and lung resistance protein (LRP) expression in 96 cases of uveal melanoma were detected by depigment immunohistochemistry. The patients with complete anamnesis data were observed continuously, and the follow up results were classified. Results Among the 96 cases of uveal melanoma, the epithelioid cell type was in 21, the mixed cell type in 56, and the spindle cell type in 19; including 76 at intraocular stage and 20 at extraocular stage. As the level of metastasis suppress gene nm 23 expression decreased and the level of cyclin D1 and EGFR expression increased, the expression level of drug resistance genes increased. The levels of LRP and MRP had negative correlation to the expressions of nm 23 and postive correlation to the expressions of nm 23, Cyclin D1 and EGFR. In 58 patients′ who were observed continuously, 19 died in 5 years and 26 survived over 5 years. Conclusion There are significant association between patients′ prognosis and multidrug and drug resistance gene in uveal melanoma.
10.Research on the relationship between pathological features of the uveal melanoma and prognosis.
Linjie GUO ; Zhongyao WU ; Sheng ZHANG ; Jiaqi CHEN ; Siming AI ; Huling ZHENG
Chinese Journal of Pathology 2002;31(6):518-521
OBJECTIVETo study the pathological features of uveal melanoma and to evaluate their influence on patients' prognosis.
METHODSParaffin embedded uveal melanoma tissues of 115 cases were examined using routine pathologic methods. Three histological types were classified according to the modified Callender system and patients were followed clinically. The data were done regression and survival analysis by SPSS statistic soft.
RESULTSThe patient with epithelial cell type, mixed type, and spindle cell type uveal melanoma have different life times, the average life time is 35.6 +/- 21.5 months, 63.7 +/- 37.0 months, 69.5 +/- 36.5 months in turn, patients with epithelial uveal melanoma had shorter survival time than other two types. The survival time was negatively related to the largest diameter of contact area with the sclera, the largest height and the depth of tumor invasion to the sclera.
CONCLUSIONSEpithelial uveal melanoma is more malignant than the other two types. Histological classification of this tumor combined with other pathologic features can indicate the patient's prognosis.
Eye Neoplasms ; mortality ; pathology ; Humans ; Melanoma ; mortality ; pathology ; Prognosis ; Survival Rate ; Uveal Neoplasms ; mortality ; pathology