Chromogranin A (CgA) as poor prognostic factor in patients with small cell carcinoma of the cervix: results of a retrospective study of 293 patients.

BACKGROUND: Small cell carcinoma of the cervix (SCCC) is a very rare tumor. Due to its rarity and the long time period, there is a paucity of information pertaining to prognostic factors associated with survival. The objective of this study was to determine whether clinicopathologic finings or immunohistochemical presence of molecular markers predictive of clinical outcome in patients with SCCC. METHODOLOGY AND FINDINGS: We retrospectively reviewed a total of 293 patients with SCCC (47 patients from Cancer Center of Sun Yat-sen University in china, 71 patients from case report of china journal, 175 patients from case report in PubMed database). Of those 293 patients with SCCC, the median survival time is 23 months. The 3-year overall survival rates (OS) and 3-year disease-free survival rates (DFS) for all patients were 34.5% and 31.1%, respectively. Univariate and multivariate analysis showed that FIGO stage (IIb-IV VS I-IIa, Hazard Ratio (HR) = 3.08, 95% confidence interval (CI) of ratio = [2.05, 4.63], P<0.001), tumor mass size (≥ 4 cm VS <4 cm, HR = 2.37, 95% CI = [1.28, 4.36], P = 0.006) and chromogranin A (CgA) (Positive VS Negative, HR = 1.81, 95% CI = [1.12, 2.91], P = 0.015) were predictive of poor prognosis. CgA stained positive was found to be highly predictive of death in early-stage (FIGO I-IIa) patient specifically. CONCLUSIONS: Patients with SCCC have poor prognosis. FIGO stage, tumor mass size and CgA stained positive may act as a surrogate for factors prognostic of survival. CgA may serve as a useful marker in prognostic evaluation for early-stage patients with SCCC.

Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study.

The term "minimal hepatic encephalopathy" (MHE) refers to a population of individuals who have no recognizable clinical symptoms but perform abnormally on neuropsychological and neurophysiological tests. Research shows that MHE patients have impairments in cognition affecting their daily lives that should be treated. This study explored the neural basis of spatial working memory impairment in MHE patients using behavioral test and BOLD-fMRI. Twelve normal controls, twelve cirrhosis patients without MHE and twelve MHE patients took part. The memory quotient of the MHE group (Wechsler Memory Scale-Chinese revised: WMS-CR) was lower than the normal control group and the cirrhosis-without-MHE group, and primarily concerned short-term memory and transient memory. Performance accuracy was lower for the MHE group than the control group and the cirrhosis-without-MHE group, and mean reaction time was prolonged. The fMRI data highlighted a neural network consisting of: bilateral prefrontal cortex (PFC), bilateral premotor area (PreMA), supplementary motor area (SMA) and bilateral parietal areas (PA), which was activated in the n-back task. The load effect of BOLD-fMRI response appeared in all regions of interest (ROI) for the normal control group, but only appeared in PreMA and PA, and did not vary with n-back load in PFC or SMA for the MHE group. Activation intensities for all ROIs were higher for the normal control group than the MHE group, especially in 2-back load. In conclusion, these results demonstrate that MHE patients have debilitated spatial working memory, and that impairments of bilateral PFC, PMA, SMA, and PA commonly lead to spatial working memory dysfunction. Furthermore, PFC impairment may form the neural basis of spatial working memory impairment.

[Clinical significance of counting follicles in diagnosis of polycystic ovary syndrome by the three-dimensional ultrasound imaging with sonography based automated volume calculation method].

OBJECTIVE: To investigate clinical significance of counting follicles classification by three-dimensional imaging with sonography based automated volume calculation (SonoAVC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS: Eighty cases with PCOS were counted classified follicles and determined ovarian volume by three-dimensional (3D) imaging with SonoAVC method matched with 60 infertile women with fallopian tube or male factors as control. Main clinical, biological and other ultrasonographic markers were assessed during the early follicular phase, and the relationship between the follicle number range per ovary or the volume per ovary and the major hormonal features of PCOS was studied. RESULTS: Three-dimensional ultrasound imaging with SonoAVC method provides a new path for objective quantitative assessment of follicle count, ovarian volume, total follicle numbers. The volume of (11 ± 8) ml, total numbers of 27 ± 14 follicle and number of 22 ± 19 follicle with diameter of ≥ 2 - < 6 mm in PCOS patients were significantly higher than (6 ± 4) ml in ovarian volume, 6 ± 4 in total follicles and 2 ± 3 in follicle with diameter of ≥ 2 - < 6 mm in controls (P < 0.05), while follicles were similar for the ≥ 6 - ≤ 9 mm range (P > 0.05). Total follicle numbers and follicles ≥ 2 - < 6 mm had significantly positive relationships with ovarian volume (r = 0.600, 0.618, P < 0.01) and level of testosterones (r = 0.364, 0.291, P < 0.05), follicles ≥ 2 - < mm also had significantly positive relationships with total follicle number (r = 0.916, P < 0.01). The follicles within the ≥ 6 - ≤ 9 mm range was significantly and negatively related to ovarian volume and total follicle numbers (r = -0.618, -0.263, all P = 0.001), but no significantly related to the major hormonal features of PCOS. The ovarian volume was significantly positively related with luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio (r = 0.282, P = 0.010) but negatively related to FSH level (r = -0.226, P = 0.042). CONCLUSIONS: Ovarian volume, total follicle numbers and follicles ≥ 2 - < 6 mm in PCOS patients were significantly higher than those in controls. The larger ovarian volume might produce more total follicle and follicles ≥ 2 - < 6 mm. The higher level of testosterone might produce more total follicle probably, which mainly result in more follicles ≥ 2 - < 6 mm. These morphologically ultrasonographic characteristics could reflect pathophysiological changes in PCOS. Obviously, it has important clinical significance to count follicles in patients with PCOS by the three-dimensional ultrasound imaging with SonoAVC method.

[Transfection of hBcl-2 gene protects the liver against ischemia/reperfusion injury in rats during liver transplantation].

OBJECTIVE: To study the effect of hBcl-2 gene transfer on rat liver against ischemia-reperfusion injury, and explore the feasibility of this approach to reduce ischemia-reperfusion injury in liver transplantation. METHODS: We constructed the replication-deficient recombinant adenoviruses Adv-EGFP and Adv-Bcl-2 and transfected them into 293 cells and packaged into adenovirus particles for amplification and purification. The empty plasmid vector virus was constructed similarly. Male SD rats were randomized into Adv-Bcl-2-transfected group, Adv-EGFP-transfected group, ischemia-reperfusion group, and sham-operated group, and liver allograft transplantation model was established by sleeve method. In the transfected groups, the recombinant viruses were administered by perfusion through the portal vein, and the ischemia-reperfusion and sham-operated groups received no treatment. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of bcl-2 in the liver tissue of each group, and at 0, 60 and 180 min after reperfusion, serum AST, LDH, and MDA levels were measured. Histological changes of the liver cells were evaluated by HE staining. RESULTS: Bcl-2 mRNA and protein expressions in Adv-Bcl-2-transfected group, as compared with those in Adv-EGFP-transfected group and control group, were significantly increased (P<0.01); the serum levels of AST, LDH and MDA in Adv-Bcl-2-transfected group were significantly lower than those of Adv-EGFP-transfected group and ischemia-reperfusion group (P<0.05 or 0.01). Compared with the sham-operated group, Adv-Bcl-2 treatment group showed lessened edema and vacuolar degeneration of the liver cells without patches or spots of necrosis. In ischemia-reperfusion and Adv-EGFP group, HE staining revealed hepatic lobular destruction and extensive liver cell swelling, enlargement, vacuolar degeneration, edema and occasional focal necrosis. CONCLUSION: Adv-Bcl-2 transfection can induce the expression of bcl-2 gene to reduce ischemia-reperfusion injury of the liver graft in rats.

[Impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics of a new contrast agent targeted to choriocarcinoma cells in vitro].

BACKGROUND & OBJECTIVE: At present, the investigation of microbubble contrast agents is a hot spot. Although these contrast agents can increase the ultrasound detection rate of tumor vessels, they lack tissue specificity. This study was to evaluate the impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells (JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors. METHODS: The objects were divided into three groups: the uneven microbubble group (n=10), the uniform microbubble group (n=10) and the tiny microbubble group (n=10). The rosette formation rate was counted. JARs were calculated by flow cytometry (FCM). The shape of the rosette was recorded. The targeted contrast agent was prepared by mixing SonoVue microbubbles of different uniformity with rabbit anti-human chorionic gonadotrophin (HCG) antibody. The binding rates of the contrast agent to JARs before and after PBS rinse were analyzed. RESULTS: The binding rate was significantlylower in the uneven microbubble group (60.4+/-1.5)% than in the uniform microbubble group (84.3+/-5.5)% and the tiny microbubble group (90.6+/-6.8)% (P<0.05). The binding rates of different microbubbles to JARs before and after PBS rinse were different. The uniform microbubbles were the most stable ones, with the binding rate of (84.3+/-5.5)% and (82.4+/-3.7)% before and after PBS rinse (P>0.05). The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 72.9%, 81.03% and 88.5% in the uneven microbubble group, the uniform microbubble group and the tiny microbubble group, respectively (P<0.05). CONCLUSIONS: The binding capacity of the targeted SonoVue microbubbles to JARs is related to instantaneous uniformity of the microbubble, which is determined by the shaking method before preparation. Improving instantaneous uniformity of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.

[Binding of targeted microbubble contrast agent to choriocarcinoma cells in vitro].

OBJECTIVE: To observe the cell binding characteristics of SonoVue microbubbles targeting choriocarcinoma cells and provide evidence for clinical ultrasonic localization of the tumor utilizing the microbubbles. METHODS: The targeted microbubbles were prepared by conjugating anti-HCG antibody with the SonoVue microbubbles and added in choriocarcinoma cells or endometrial stromal cells to compare the cell binding rate of the agents under optical microscope and with flow cytometry. RESULTS: Flow cytometry demonstrated a binding rate of 77.6% between the SonoVue microbubbles and anti-HCG antibody. Light microscopy showed that the total rosette formation rate of the choriocarcinoma cells exposed to the targeted microbubble bearing anti-HCG antibody reached (87.8-/+6.3)%, significantly higher than that of the endometrial stromal cells [(9.4-/+1.7)%, P<0.05]. The binding rate of the targeted microbubbles with the choriocarcinoma cells before and after PBS washing were (85.4-/+4.7)% and (83.1-/+3.8)% (P>0.05), respectively, suggesting strong stability of the binding. The binding rate was 81.0% according to the results of flow cytometry. CONCLUSION: The targeted microbubbles as a contrast agent can efficiently bind to the choriocarcinoma cells in vitro with a stability sufficient to resist the blood flow.

[Changes in the sonographic appearance of the endometrium after different premenopausal tamoxifen therapies].

OBJECTIVE: To assess the effect of different schemes of premenopausal tamoxifen therapy on the endometrium. METHODS: Totally 109 normal premenopausal women positive for high-risk factors of breast cancer were divided into two groups, namely periodic and consecutive tamoxifen treatment groups. Endometrial thickness as examined by vaginal sonography was assessed in relation to duration of tamoxifen use and time from discontinuation of the drug. RESULTS: After one year of tamoxifen use, the mean endometrial thickness in periodic treatment group was 6.5-/+1.4 mm, and 10.2-/+2.0 mm in consecutive treatment group. Endometrial thickness increased with the duration of tamoxifen use at the rate of 0.51 mm/year in the periodic treatment group, and 0.73 mm/year in consecutive treatment group. After discontinuation of tamoxifen, the endometrial thickness in the former group decreased by 1.29 mm/year, and by 1.33 mm/year in the latter. CONCLUSIONS: Endometrial hyperplasia is obviously milder in premenopausal women receiving periodic tamoxifen treatment who are at risk for breast cancer than that in women with consecutive treatment. After discontinuation of the drug, the endometrial thickness decreases at a roughly equal slow rate in the two groups.