Background and purpose:TGF-?/EGFR autocrine loop is markedly activated in wide malignant tumor. It is closely correlated with the tumorigenesis and development of different cancers. Our study is to investigate the biological behavior and signaling molecule changes in TGF- induced ovarian cancer cell line Caov-3, and to study the effect and molecular mechanism of the activation of TGF- /EGFR autocrine loop in ovarian cancer.Methods:The tetrazolium-based colorimetry assay was used to evaluate the cell growth treated by TGF-?. The vitro invasion assay was used to examine the invasiveness of Caov-3 treated by TGF-?.Expression of EGFR、 ERK1/2、PI3K、AKT、P70S6K were determined by western blotting.Results:Exogenous TGF-? enhanced significantly the proliferation and invasiveness of Caov-3 cells. The proliferation rate of Caov-3 was in a dose-dependent manner to TGF-? within the concentration of 0.5~25ng/ml.Exogenous TGF-? up-regulated the expression of EGFR、PI3K、AKT、P70S6K but not ERK1/2.Conclusions:The activation of TGF-?/EGFR autocrine loop could promote the growth,invasion and metastasis of ovarian cancer through PI3K/AKT/P70S6K signaling survival pathway.

Collagen Type IV ; genetics ; Female ; Fetal Development ; Humans ; Nephritis, Hereditary ; diagnosis ; genetics ; Pregnancy ; Prenatal Diagnosis ; methods

Humans ; Molecular Biology ; Nephrotic Syndrome ; genetics

Objective To explore the correlation between phenotypes in female with X-linked Alport syndrome(XLAS) and X-inactivation of different tissues.Methods Thirty-six female diagnosed as XLAS were studied,and proteinuria was taken as a marker of the severity of clinical phenotypes.X-inactivation patterns were analyzed in peripheral blood cells of 36 XLAS female and in skin fibroblasts of 12 XLAS female.The X-inactivation analysis was performed by using Hpa Ⅱ predigestion of DNA followed by polymerase chain reaction(PCR) of the highly polymorphic CAG repeat of the androgen receptor gene.Results The average X-inactivation levels of the mutant allele decreased while the degree of proteinuria increased,so there was a negative correlation between the degree of proteinuria and the X-inactivation ratios of the mutant allele in blood cells(r=-0.543,P=0.002).However,there was no correlation between the degree of proteinuria and the X-inactivation ratios of the mutant allele in skin fibroblasts(r=-0.131,P=0.701).Conclusions X-inactivation ratios might explain partially the diverse phenotypes in XLAS female patients,which suggested that the prognosis of XLAS female might be predicted via analysis of the X-inactivation in peripheral blood cells.

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Female ; Healthy Volunteers ; Humans ; Male ; Pregnenediones ; pharmacokinetics ; Tablets

Objective To investigate the viability of analysis of hemodynamic changes with color Doppler flow imaging in the prediction of acute rejection in transplanted liver.Methods Sixty-eight patients enrolled in the study were categorized into three groups:transplanted liver without acute rejection [rejection activity index(RAI) 0-3,n =24],transplanted liver with mild acute rejection (RAI 4-5,n =23),transplanted liver with moderate and severe acute rejection (RAI 6-9,n =21).All the patients were confirmed by pathology.The color Doppler flow imaging were performed in all the patients within 24 hours and 1 week after biopsy.Results In transplanted liver with moderate and severe acute rejection,the peak systolic velocity of portal vein (PV-PSV) was (31.4 ± 14.1)cm/s,significantly lower than that in transplanted liver without acute rejection,which was (45.1 ± 17.7)cm/s (P ＜0.05).A week later after steroid therapy,the PV-PSV in transplanted liver with moderate and severe rejection was increased to (46.7 ± 21.8)cm/s(P ＜0.05).Patients with acute rejection were associated with the decrease of the PVPSV (P ＜0.05).Conclusions The decrease of PV-PSV may have some clinical value in evaluation the acute rejection in transplanted liver.

Anti-Arrhythmia Agents ; therapeutic use ; Cardiomyopathies ; drug therapy ; etiology ; Child, Preschool ; Female ; Humans ; Moricizine ; therapeutic use ; Tachycardia ; complications ; drug therapy ; Treatment Outcome

Objective To evaluate DWI in the assessment of viability of hepatic alveolar echinococcosis (HAE) by comparing DWI with PET-CT results. Methods 18-fluorodeoxy glucose(18F-FDG) PET-CT and DWI(b values=0, 800 s/mm2) were retrospectively analyzed in 8 patients with clinically verified HAE. The metabolic activity of HAE lesions in both techniques were determined by two independent radiologists respectively. Kappa test was assessed between the results of two observers. Results Sixteen lesions (composed of 14 HAE and 2 cystic echinococcosis, CE) were detected. (1)Eight lesions (≥2 cm) showed perilesional hyper-signal intensity on DWI, mainly around the lesion bounding by normal liver parenchyma. One patient (≥2 cm) had oral drug therapy for three years, and the lesion showed discontinuous perilesional hyper-signal intensity on DWI after the therapy. Five lesions (<2 cm) were depicted as nodular high signal on DWI.(2)Eight lesions (≥2 cm) showed perilesional increased FDG uptake on PET-CT, while 5 lesions (<2 cm) displayed as“hot pot”. One patient (leison≥2 cm) who had oral drug therapy for three years showed hepatic defect without any FDG uptake in post-treatment PET-CT. Two CE lesions showed negative results on both DWI and PET-CT. The Kappa value of 0.880 indicated a good coincidence between DWI and PET-CT in depicting the metabolic activity of HAE (P=0.006). Conclusions This preliminary study showed the value of DWI in assessing HAE viability. DWI should be routinely used as one of the techniques in the evaluation of HAE.

Objective To establish the reference value of liver virtual touch tissues quantification (VTQ) values in healthy subjects. Methods Liver stiffness was measured with Siemens Acuson S2000 ultrasound system in totally 300 healthy subjects. The first one hundred healthy subjects received VTQ measurements in four parts (superficial and deep parts of right lobe, superficial and deep parts of left lobe). Then the achievement rate in different part of liver was calculated to choose the suitable measuring position. On the other hand, the reproducibility was analyzed with intraclass correlation coefficient (ICC). The last two hundred healthy subjects received VTQ measurements in the suitable position only. The reference value of VTQ was calculated using (x-)±1.96s. Results It was stable to measure liver stiffness with VTQ technique. The achievement rate was high in right lobe, and the deep parts of right lobe was the best measuring position. There was significant difference of VTQ value between males and females (P＜0.001), while the VTQ value was similar in different age groups. The reference value was 0.79-1.57 m/s in males and 0.74-1.40 m/s in females. Conclusion Liver VTQ value in healthy subjects are different between males and females.