OBJECTIVETo study the relationship between nucleotide excision repair gene ERCC1 and resistance to cisplatin in ovarian cancer.

METHODSThe expression of gene ERCC1 in 58 ovarian cancer tissues and 4 cell lines were examined and its relationship with resistance to cisplatin were analyzed, the changes of sensitivity to cisplatin were observed after interference of ERCC1 gene with small interfering RNA (siRNA) in ovarian cancer cell lines.

RESULTSIn 58 ovarian cancer tissues, the positive rate of ERCC1 protein in chemoresistant cases (57.89%) was higher than that in chemo-sensitive cases (28.21%, P = 0.029). The mRNA levels of ERCC1 gene in ovarian cancer cell lines ES-2, SKOV3, COC1, COC1/DDP were related to cisplatin IC50 values (r = 0.932, P <0.05). The sensitivity of cell lines ES-2, SKOV3, COC1/DDP cells to cisplatin was increased by 53.88, 5.07, and 3.75 times, respectively, after RNA interfering ERCC1 gene.

CONCLUSIONERCC1 gene is associated with the resistance to cisplatin and the sensitivity to cisplatin can be enhanced by RNA interfering ERCC1 in ovarian cancer.

Adult ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; DNA Repair ; DNA-Binding Proteins ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Female ; Humans ; Inhibitory Concentration 50 ; Middle Aged ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Young Adult

OBJECTIVE: To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). MATERIALS AND METHODS: Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15–61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20–65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS. RESULTS: Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7–4.9%, p < 0.05 and 1.8–3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2–2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2–3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS. CONCLUSION: The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.
Brain ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Methods ; Niemann-Pick Diseases ; Proton Magnetic Resonance Spectroscopy ; Water