Humans ; Ovarian Neoplasms/drug therapy* ; Folate Receptor 1/metabolism* ; Female ; Immunohistochemistry/standards* ; Consensus ; Biomarkers, Tumor/metabolism* ; Fallopian Tube Neoplasms/pathology*

OBJECTIVETo study the expression level of folate receptor α (FR-α) in glioma tissue and its clinical significance.

METHODSForty-eight human glioma specimens were collected from patients who underwent surgery from March 2012 to March 2013. These specimens were as follows:12 cases of glioblastoma (WHO IV), 6 cases of astrocytoma of each malignancy grade(WHO II, III), 6 cases of oligodendroastrocytoma of each malignancy grade (WHO II, III), 6 cases of oligodendroglioma of each malignancy grade (WHO II, III ). In addition, 6 cases of normal brain tissue resected from brain traumatic patients were taken as negative control, and one case of placental tissue (had got the consent of the parents and their families) was taken as positive control. The expression level of FR-α in tumor tissues was evaluated by Western blot analysis. The results of Western blot analysis were analyzed by t-test. The expression level of FR-α and Ki-67 in tumor tissues was evaluated immunohistochemistry, the results were analyzed by Kruskal-Wallis test and Nemenyi test. The correlation between the expression level of FR-α and cell proliferation index Ki-67 was analyzed by Pearson correlation analysis.

RESULTSWestern blot analysis showed that the FR-α was not expressed in normal brain tissue and oligodendroglioma tissue, but highly expressed in astrocytoma, oligodendroastrocytoma and gliomablastoma. The expression level in WHO III astrocytoma was significantly higher than in WHO II (t = 4.497, P < 0.05). FR-α was also highly expressed in oligodendroastrocytoma and its expression level in WHO III was also significantly higher than in the WHO II (t = 2.876, P < 0.05). Foremore, immunohistochemistry analysis also showed that FR-α was not expressed in oligodendroglioma, but expressed in astrocytoma, oligodendroastrocytoma and gliomablastoma. The positive rate of FR-α of WHO III was significantly higher than the WHO II astrocytoma(57.8% ± 2.2% vs. 45.7% ± 2.3%,χ(2) = 3.871, P = 0.034). In oligodendroastrocytoma, the positive rate of FR-α of WHO III was significantly higher than the WHO II(56.5% ± 5.4% vs. 37.1% ± 5.2%,χ(2) = 4.454, P = 0.021). Moreover, the expression level of FR-α in gliomablastoma was highest in all histological types of gliomas, the positive rate of FR-α was up to 65.0% ± 4.5%. Pearson correlation analysis showed that the positive rate of FR-α was positively correlated with Ki-67 index (r = 0.903, P < 0.05).

CONCLUSIONSFR-α is expressed in astrocytoma, oligodendroastrocytoma and glioblastoma, and the expression level of FR-α is positively correlated with malignancy grade and Ki-67 index. Therefore, FR-α may be applied as a special target for diagnosis and treatment of glioma.

Adolescent ; Adult ; Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Folate Receptor 1 ; metabolism ; Glioma ; metabolism ; Humans ; Infant ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Young Adult

The gamma-cyclodextrin-folate (gamma-CD/FA) inclusion-coated CdSe/ZnS quantum dots (QDs) with folate-receptor (FR) targeted were synthesized by simple and convenient sonochemical method. The products were studied using Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), utraviolet-visible spectrometry (UV-vis), fluorescence spectrum and transmission electron micrographs (TEM). The results showed that the gamma-CD/FA-coated CdSe/ZnS QDs not only have good monodispersity and smaller size, but also have good optical performance, such as higher quantum yield (QY) and a long fluorescence lifetime. The cytotoxicity experiments showed that the gamma-CD/FA-coated CdSe/ZnS QDs have lower cytotoxicity and could more effectively enter cancer cells with FR over-expression. The QDs with 4-5 nm in diameter were relatively easy to enter the cell and to be removed through kidneys, so it is more suitable for biomedical applications for bioprobes and bioimaging.
Cadmium Compounds ; chemical synthesis ; chemistry ; metabolism ; toxicity ; Cell Survival ; drug effects ; Folate Receptor 1 ; chemistry ; Folic Acid ; chemistry ; HeLa Cells ; Hep G2 Cells ; Humans ; Magnetic Resonance Spectroscopy ; Microscopy, Electron, Transmission ; Molecular Imaging ; methods ; Quantum Dots ; chemistry ; metabolism ; toxicity ; Selenium Compounds ; chemical synthesis ; chemistry ; metabolism ; toxicity ; Spectrophotometry, Ultraviolet ; Spectroscopy, Fourier Transform Infrared ; Sulfides ; chemical synthesis ; chemistry ; metabolism ; toxicity ; Zinc Compounds ; chemical synthesis ; chemistry ; metabolism ; toxicity ; gamma-Cyclodextrins ; chemistry

Through this research a lentiviral vector expressing the gene of folate-binding protein-1 (FOLR1) was constructed and the corrsponding expression products were identified. Firstly, full-length of the FORL1 gene was amplified by PCR and cloned into the plasmid pWPI. Then it was further confirmed by PCR and sequencing. Secondly, after the recombinant pWPI and its helper plasmid co-transfected the virus packaging 293T cells, SKOV3 cells were infected with the virus particles and sorted by flow cytometry. Thirdly, the FOLR1 gene was detected by RT-PCR and its protein expression was detected by Western blot. Finally, the recombinant expression vector was successfully constructed, and lentiviruses were successfully packaged by the 293T cells. A great quantity of green fluorescent cells could be seen after the SKOV3 cells were effectively infected with the lentiviruses carrying the FOLR1 gene. The sorting could be done and detected by cytometrying the FORL1 gene and its stable expression by the two methods above, which laid experimental foundation for exploring its biological function in ovarian cancers.
Cell Line ; Cell Line, Tumor ; Cloning, Molecular ; Female ; Folate Receptor 1 ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Humans ; Kidney ; cytology ; Lentivirus ; genetics ; metabolism ; Ovarian Neoplasms ; pathology ; Polymerase Chain Reaction ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection

Brain ; metabolism ; pathology ; Child, Preschool ; Chromatography, High Pressure Liquid ; Diagnosis, Differential ; Folate Receptor 1 ; genetics ; metabolism ; Folic Acid ; blood ; cerebrospinal fluid ; metabolism ; Folic Acid Deficiency ; diagnosis ; drug therapy ; etiology ; Humans ; Infant ; Leucovorin ; therapeutic use ; Malnutrition ; complications ; diagnosis ; Tetrahydrofolates ; cerebrospinal fluid ; metabolism

OBJECTIVEto investigate the expression of folate receptor(FR)α in ovarian epithelial tumors and its clinopathological significance.

METHODStissue microarrays (TMAs) were constructed from 86 epithelial ovarian cancers and 29 borderline ovarian tumors, followed by the FRα expression evaluation by immunohistochemistry. FRα mRNA expression was investigated by quantitative real-time PCR using fresh-frozen tissues from 40 cases of ovarian carcinoma and 14 cases of borderline tumor. FRα expression levels in ovarian tumors were also analyzed in correlation with tumor morphology, pathogenesis and FIGO stage.

RESULTSFRα expression was detected in 40 of 86 (46.5%) of ovarian cancers, with the highest rate of expression observed in serous carcinomas (62.7%, 32/51) compared with that of the other cancer types (P = 0.000). Depending on pathogenesis type, FRα expressions in type II ovarian carcinomas were significantly higher than those in type I ovarian carcinomas (P = 0.001). Ovarian carcinomas had a tendency to express higher FRα than the borderline tumors (46.5% vs 27.6%), although statistically not significant (P = 0.074). FRα expressions in ovarian carcinomas showed no correlation with the FIGO stage (P = 0.498). However, real-time PCR showed that FRα mRNA levels were significantly higher in ovarian carcinomas compared with that of the borderline tumors (P = 0.000) and also higher in serous ovarian borderline tumors compared with mucinous type (P = 0.007).

CONCLUSIONhigher level of FRα expression occurs frequently in ovarian epithelial tumors, especially in carcinomas and ovarian serous tumors.

Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adult ; Aged ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; Female ; Folate Receptor 1 ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Young Adult