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1.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 293-297, 2015.
Article in Chinese | WPRIM | ID: wpr-479764

ABSTRACT

Objective To explore antitumor effect of 131I-Trastuzumab on human epidermal growth factor receptor(HER) 2 overexpressing breast cancer cells and investigate its possible mechanism.Methods The expression levels of HER2 of three different breast cancer cell lines (BT474,MCF-7,HCC1937) were detected with immunofluorescence.Trastuzumab was labeled with 131I using the Iodogen method and 131I-Trastuzumab was isolated with ultrafiltration membrane,then the labeling efficiency,radiochemical purity and immunoreactivity were measured.The effects of 131I,Trastuzumab and 131I-Trastuzumab on viability of BT474 cells were evaluated with cell counting kit-8 (CCK-8) assay.The levels of total Akt and phosphorylated Akt (p-Akt) were detected with Western blot analysis.One-way analysis of variance (ANOVA),ANOVA for factorial design,Bonferroni correction and Pearson correlation analysis were used for data analysis.Results The expression level of HER2 in BT474 cells was much higher than those in HCC1937 and MCF-7 cells.The labeling efficiency,radiochemical purity and immunoreactivity of 131I-Trastuzumab were (89.71± 2.93)%,(91.80±1.43)% and (58.84±3.35)% respectively.131I (4.625 GBq/L),Trastuzumab(125.0 rmg/L) and 131I-Trastuzumab(4.625 GBq/L) exhibited a dose-dependent cytotoxicity against BT474 cells (r =-0.964,-0.912,-0.618;all P<0.05).The cell viability of 131I-Trastuzumab treated gourp (34.73% ±5.03%) was significantly lower than those of 131I and Trastuzumab treated groups (64.36%± 1.51% and 58.09%±4.14%;t=10.373 and 8.180,both P<0.05),and the cell viability of control group was (100.00±4.54)%.131I-Trastuzumab shown a positive multiplicative interaction between 131I and Trastuzumab (F=9.226,P<0.05;CDI =0.929).Western blot results showed that there was no significant difference of total Akt expression among the control group,131I group,Trastuzumab group and 131I-Trastuzmab group (F=0.208,P>0.05).P-Akt expression in both Trastuzumab group and 131I-Trastuzumab group were much lower than those of control group and 131I group (t=12.524,15.984,7.347,10.807;all P<0.05),while there was no significant difference of p-Akt expression between Trastuzumab group and 131I-Trastuzumab group(t =3.460,P>0.05).Conclusions 131I-Trastuzumab may kill HER2 overexpressing breast cancer cells more effectively than Trastuzumab alone.The underlying mechanism may be attributed to that 131I-Trastuzumab may enhance the radiosensitivity by the inhibitory effect on PI3K/Akt pathway and thus exert synergistic effects with 131I.

2.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 222-226, 2015.
Article in Chinese | WPRIM | ID: wpr-466356

ABSTRACT

Objective To prepare 99Tcm-human epidermal growth factor receptor 2 (HER2) affibody (ABH2) and explore its feasibility as an imaging agent in HER2-positive breast cancer.Methods Sodium glucoheptonate and SnCl2 · 2H2O were used to label ABH2 with 99Tcm.The labeling yield and radiochemical purity of 99Tcm-ABH2 were determined.The stability of 99Tcm-ABH2 was tested in PBS and serum.The equilibrium disassociation constant (Kd) of 99Tcm-ABH2 was measured with MBA-MD-361 breast cancer cells.SPECT/CT imaging was carried out at 1.0 h and 4.5 h after injection of 37 MBq 99Tcm-ABH2 in nude mice (n=4) xenografted with MBA-MD-361 breast cancer.The T/NT (liver,brain,lung,heart,bone and muscle) ratios were deduced from SPECT/CT acquired data.For the blocking experiment,200 μg ABH2 was injected intravenously before 99Tcm-ABH2 injection.SPECT/CT imaging was performed in the same way.The T/NT ratios were compared between non-blocked and blocked groups by one-way analysis of variance.Results Fhe labeling yield of 99Tcm-ABH2 was above 99%.99Tcm-ABH2 was substantially stable in PBS and serum;the radiochemical purity was (95.0± 1.0)% after incubation with serum at 37 ℃ for 6.0 h.The Kd of 99Tcm-ABH2 was 1.7 nmol/L.The radioactive uptake in cancer was visualized at 1.0 h and 4.5 h after injection of 99Tcm-ABH2 in HER2 positive MDA-MB-361 breast cancer.99Tcm-ABH2 was cleared out mainly through urinary system.The ratios of tumor to liver,lung,brain,heart,muscle and bone were 1.81± 0.60,8.95±1.13,20.08±6.12,7.61±0.56,10.62±1.78,11.42±2.07,respectively at 4.5 h after 99Tcm-ABH2 injection.After ABH2 blocking,the corresponding T/NT ratios were 0.60±0.23,3.05± 1.38,5.24±2.17,2.42±1.02,8.16±2.66,2.76±0.48 (F=29.38,P<0.05) respectively.Conclusion 99Tcm-ABH2 could be synthesized with high purity,and this new agent could be used to image HER2-positive breast cancer specifically.

3.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 208-212, 2014.
Article in Chinese | WPRIM | ID: wpr-453559

ABSTRACT

Objective To prepare the 99Tcm-labeled human epidermal growth factor receptor type 2 (HER2) affibody molecule ZHER2:342 and evaluate its receptor binding specificity in vitro.Methods The molecular ZHERa:342 was labeled with 99Tcm using the ligand exchange method.The labeling efficiency and radiochemical purity were measured by HPLC.The major factors,such as the mass of SnC12 and NaOH and reaction time were analyzed,and the optimal method was summarized.Cell binding kinetics and cellular retention of the probe were investigated in HER2-expressing SKOV-3 cells and MDA-MB-231 cells with low HER2 expression respectively.HER2 binding specificity of 99Tcm-ZHER2:342 was analyzed by a pre-injection of excess unlabeled ZHER2:342 to saturate HER2 receptors.One-way analysis of variance and two-sample t test were used.Results The optimal labeling procedure was as follows:5 μg (1 g/L) of ZHER2:342 was mixed with 5 μg of NaOH (1 g/L),then 8.8 μg SnC12(1 g/L,solution) was added,followed by 150 μl (37 MBq) 99TcmO4-solution,and finally the mixture was slightly vortexed and incubated for 1 h at room temperature.99TcmZHER2:342 was stable in vitro with a high labeling efficiency of (98.10± 1.73)%.The radiochemical purity was > 98%,and was more than 85% after the incubation for 24 h in saline and fresh human serum.The cell binding of 99Tcm-ZHER2:342 with HER2-expressing SKOV-3 cells gradually increased over time with a peak of (9.95± 1.02)% at 6 h.The binding of 99Tcm-ZHER2:342 in SKOV-3 cells was significantly higher than that in MDA-MB-231 cells at every time point (5.68-9.88 vs 0.56-2.11 ; t:from-34.50 to-13.14,all P<0.01).The labeled molecular probe retained the capacity to bind specifically to HER2-expressing SKOV-3 cells since the cell binding decreased from (9.95 ± 1.02) % to (2.11 ±0.27) % after receptor saturation (t =-13.14,P<0.01).Conclusions 99Tcm-ZHER2:342 has a high labeling efficiency,good stability and optimal binding specificity.These characteristics enable it to be a promising molecular probe for HER2-targeting imaging.

4.
Chinese Journal of Nuclear Medicine ; (6): 170-175, 2010.
Article in Chinese | WPRIM | ID: wpr-642607

ABSTRACT

Objective To study the biodistribution of anti-HER-2/neu monoclonal antibody Herceptin labeled by 131I(131I-Herceptin) in healthy KM mice and nude mice bearing human ovarian cancer xenografts and radioimmunoimaging (RII) of the nude xenografts-bearing mice.Methods 131I-Herceptin was prepared using Iodogen method.The labeling efficiency, radiochemical purity, stability and immunocompetence were measured.The percentage activity of injection dose per gram of tissue (%ID/g) and the radioactivity ratio of tumor to non-tumor tissue (T/NT) were calculated for each time point.The optimal time for imaging was investigated by comparing the 131I-Herceptin SPECT for the nude mouse models bearing ovarian cancer xenografts at different time points.Results The labeling efficiency and radiochemical purity of 131I-Herceptin were 89.8% and 98.4%, respectively.The labeling was stable and had good immunocompetence.131 I-Herceptin was cleared rapidly mainly through liver, spleen and kidneys, consistent with first order two-compartment model.The uptake of 131I-Herceptin in the tumors bearing human SKOV-3 xenografts was much higher than that in nontumor tissue.The% ID/g was 18.08 in the tumor at 24 h post injection.The T/NT ratio increased with time and was 27.27 at 72 h post injection.The tumors in nude mice bearing SKOV-3 xenografts could be visualized on 131I-Herceptin SPECT imaging 2 h post injection; definitely identiffed 48 h post injection and the radioactivity ratio of tumor to contralateral tissue was 11.44 at 120 h post injection.However, the tumor in nude mice bearing HO-8910 xenografts did not show abnormal uptake of 131 I-Herceptin at each time point.Conclusions 131 I-Herceptin is a good radiopharmaceutical targeting SK-OV-3 xeuografts and it may be useful in imaging carcinoma of ovary and target therapy of its metastases with high HER-2/neu expression.

5.
Chinese Journal of Current Advances in General Surgery ; (4)1999.
Article in Chinese | WPRIM | ID: wpr-675117

ABSTRACT

Objective:To evaluate the expression of EGFR and gene nm23H1 and their relation to the tumor oncogenesis and progress of cholangiocarcinoma.Methods:SABC immunohistochemistry was used to detect the expression of EGFR and nm23H1 in cholangiocarcinoma and cholangitis tissue.Results:The positive rate of nm23H1 in cholangiocarcinoma was lower than cholangitis(P

6.
Chinese Journal of Dermatology ; (12)1994.
Article in Chinese | WPRIM | ID: wpr-518964

ABSTRACT

Objective To investigate expression of p63?PCNA and epidermal growth factor receptor(EGFr)in skin squamous cell carcinoma(SCC) . Method Tissue specimens from 68 cases of SCC were studied using immunohistochemistry staining method with monoclonal antibodies to p63?PCNA and EGFr. Results The expression of p63 protein and PCNA was principally restricted to basal cells with high proliferative potentiality and was absent in cells of stratum corneum that were undergoing terminal differentiation in normal or carcinoma epidermis. In highly differentiated tumors, the staining of p63 formed a ring surrounding carcinoma nests. In low differentiated tumors, p63 positive cells were increased and disorderly arranged. Diffuse expression of PCNA and EGFr was found through out all carcinoma nests. Expression of p63?PCNA and EGFr was significantly stronger in SCC and intraepithelial neoplasm(SIN)level Ⅲthan those in normal or proliferative epidermis near the carcinoma. A significant correlation was found between expression of p63,PCNA,EGFr and degree of differentiation of SCC,and between p63 and EGFr,p63 and PCNA,PCNA and EGFr, respectively. Conclusion Overexpression of p63?PCNA?EGFr may be contributed to acquisition of enhanced capability of proliferation, aggression and anaplasia in SCC.

7.
Chinese Journal of Pathophysiology ; (12)1986.
Article in Chinese | WPRIM | ID: wpr-516964

ABSTRACT

AIM:To observe the expression of epidermal growth factor receptors(EGFR) of gingival tissue in periodontitis. METHODS: The expression of EGFR was determined by using immunohistochemical techniques in gingival tissue of 15 healthy individual, 32 cases with adult periodontitis (AP) and 12 cases with juvenile periodontitis (JP). RESULTS: Expression of EGFR was mainly located on basal cell membranes in healthy gingiva, and the staining intensity was faint. In AP cases, expression of high level EGFR was mostly observed on the membranes of epithelial cell in the periodontal endopocket or junctional epithelium, intensity of staining appeared to decrease gradually with the differentiation of keratinocytes, and the horny cell layer was not stained by the antibody. In JP cases, strong positive staining was present on membrane of epithelial cells in the germinative layer of gingival tissue. There was an apparent difference between healthy gingiva and AP or JP (P< 0.01 ), or AP and JP (P< 0.01). CONCLUSION: The distribution and expression of EGFR in gingival epithelium of periodontitis showed obvious differ- euce. The data indicated that EGFR may affect apical migration of junctional epithelium, and may play a role in development of AP and JP.

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