GSTP1 polymorphism,cigarette smoking and cervical cancer risk in Korean women

Previous studies have suggested that glutathione S-transferase (GST) genotypes may play a role in determining susceptibility to cervical cancer, though the data have often been conflicting. The objective of this study was to examine the effect of GSTP1 polymorphism on cervical carcinogenesis. The studied subjects, patients who were pathologically diagnosed with invasive cervical cancer yielding positive results for human papillomavirus (HPV) (n=342), were compared to healthy, normal, female controls (n=707). DNA from peripheral blood samples from studied subjects whose GSTP1 specific sequences had been determined by PCR with allele-specific primers were reviewed in comparison with the normal controls. The genetic susceptibility of GSTP1 (11q 13.1) in cervical carcinogenesis was determined by examining the effect of gene and environmental factors by the different histopathologic types of invasive cervical cancers. In assessing polymorphism GSTP1, the percentages of individuals homozygous for the A allele, homozygous for the G allele, and heterozygous for the two alleles were 66.8%, 3.9%, and 29.3%, respectively, in the control group, and 64.3%, 4.1%, and 31.6%, respectively, among in women with cervical cancer. Compared with GSTP1 G allele positive (GA or G/G), the odds ratio (OR) (95% confidence interval) for GSTP1 A/A was 1.0 (0.7 - 1.4) for invasive cervical cancer. However, the risk increased with GSTP1 A/A among ever smokers (3.9, 1.7 - 8.9, p-value=0.0012) compared with GSTP1 G allele positive among nonsmokers. In particular, this risk was higher among women with squamous cell carcinoma (4.7, 2.0 - 10.8, p=0.0003). Polymorphism of GSTP1 among smoking women was associated with a higher risk of developing cervical cancer.     

Proper cut-off value of free to total PSA ratio for detection of prostate cancer in Korean men

To assess whether the free-to-total prostate specific antigen (PSA) ratio (F/T PSA ratio) would enhance prostate cancer detection in Korean men with serum total PSA levels between 4 and 20 ng/ml. Methods: A total of 240 consecutive patients whose serum PSA levels were between 4 and 20 ng/ml were enrolled in this two-year study. All patients underwent ultrasound-guided transrectal biopsies of the prostate gland. The F/T PSA ratio was measured using the Roche immunoassay. Results: Of the 240 patients, 202 (84%) had benign histologies, while 38 (16%) had prostate cancer. The two patient groups were well matched for age. The mean F/T PSA ratio showed a statistically significant difference between the two groups: in the benign histology group it was 0.14 (0.04 - 0.37), and 0.10 (0.08 - 0.20) in the prostate cancer group (p < 0.05). Out of the 183 patients with a PSA level between 4-10 ng/ml, the mean F/T PSA ratios were 0.14 and 0.11 in the benign histology (n=158) and prostate cancer groups (n=25), respectively (p < 0.05). From the 57 patients with a PSA level between 10 - 20 ng/ml, the mean F/T PSA ratios were 0.14 and 0.10 in the benign histology (n=44) and prostate cancer groups (n=13), respectively (p < 0.05). Overall, when the cut-off value of the F/T PSA ratio was 0.10, the sensitivity and specificity were 75.0% and 76.5%, while for the cut-off value of 0.15 they were 83.3% and 39.7% respectively. Conclusion: Our data demonstrated the usefulness of the free to total PSA ratio in distinguishing benign prostate disease and cancer disease, hence eliminating unnecessary biopsies. It is recommended that a cut-off value for the F/T PSA ratio of 0.10 be applied to Korean men which this is lower than the value used in Western countries.     

Evaluation of a Selective Transport Medium for Gastric Biopsy Specimens To Be Cultured for Helicobacter pylori

Since the means of culturing Helicobacter pylori may not be available in some laboratories, prolonging the survival of this organism during transportation is a major concern in terms of improving detection rates. A selective transport medium was evaluated for the preservation of H. pylori from 254 gastric biopsy specimens collected from a rural area in China where culturing is not feasible. Gastric biopsy specimens were inoculated in sterile broth consisting of brain heart infusion (BHI) broth, horse serum, and yeast extract supplemented with vancomycin, amphotericin B, and nalidixic acid (VAN). Of the 254 biopsy specimens, 238 were identified by histology to have H. pylori infection. Total rates of recovery of H. pylori from the H. pylori-positive gastric biopsy specimens stored in the BHI-VAN broth ranged from 76 to 46% after storage of specimens for 5 to 9 days. In conclusion, the selective medium is useful for prolonging the survival of H. pylori in gastric biopsy specimens for which immediate culture is not feasible.     

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.     

Expression of E-cadherin and alpha-, beta-, gamma-catenin proteins in endometrial carcinoma

Loss of the cell adhesion molecule E-cadherin is suggested to promote tumor invasion and distant metastasis in tumor development. Recently, it has been proposed that E-cadherin function requires its linkage to the cytoskeleton through catenins. We evaluated the expression of E-cadherin and alpha-, beta-, gamma-catenins in tissues of human endometrial carcinoma, analyzed the patterns of cell adhesion molecules' expression in endometrial carcinoma and investigated the relationship between the statuses of cell adhesion molecules and various clinicopathological factors. This study investigated the immunohistochemical expression of E-cadherin and alpha-, beta-, gamma-catenins in 33 paraffin embedded formalin fixed tissues of endometrial carcinomas. Aberrant E-cadherin, and alpha-, beta-, gamma-catenin expression was observed in 33.3 (11 of 33), 27.3 (9 of 33), 18.2 (6 of 33), and 51.5 (17 of 33) % of the specimens, respectively. Statistically significant correlation was found between aberrant expression of E-cadherin and lymph node metastasis and cell types other than endometrioid adenocarcinoma. Aberrant pattern of gamma-catenin expression was also correlated with deep myometrial invasion. However, alpha-, and beta-catenin expression was not correlated with any clinicopathological parameters. Using the Kaplan-Meier method and log-rank comparison test, abnormal expression of E-cadherin was correlated closely with poor survival (p < 0.05), but cases with loss of both E-cadherin and catenin expression predicted even poorer survival than cases with only one or no aberrant expression in E-cadherin and catenins. We revealed aberrant expression of these cell adhesion molecules among patients with endometrial carcinoma. Aberrant expression of E-cadherin was correlated with lymph node metastasis and cell types other than endometrioid adenocarcinoma, while aberrant expression of gamma-catenin was related with deep myometrial invasion. The expression of E-cadherin might be a possible prognostic factor for endometrial cancer while the expression of catenins may help predict patient's survival.     

Mechanisms of nitric oxide interplay with Rho GTPase family members in modulation of actin membrane dynamics in pericytes and fibroblasts

Migration of pericytes such as hepatic stellate cells is fundamentally important for diverse biological and pathological processes including tumor invasion and fibrosis. In prototypical migratory cells such as fibroblasts, the small GTPases Rac1 and RhoA govern the assembly of lamellipodia and stress fibers, respectively, cytoskeletal structures that are integral to the cell migration process. The gaseous signaling molecule nitric oxide (NO) influences growth factor chemotactic responses, although this occurs primarily in cell-type-specific ways and through cell biological effects that are poorly characterized. In this study, we use complementary molecular and cell biological approaches to delineate important roles for Rac1, RhoA, and NO in migration of the human hepatic stellate cell line LX2 and primary rat hepatic stellate cells. Both platelet-derived growth factor (PDGF) and Rac1 overexpression drove migration through formation of actin-positive filopodia spikes in LX2 as compared to the formation of lamellipodia in fibroblasts. NO inhibited PDGF- and Rac1-driven migration in LX2 by abrogating filopodia formation and inhibited migration of fibroblasts by attenuating lamellipodial protrusions. Additionally, RhoA conferred resistance to NO inhibition of migration and restored chemotactic responses to PDGF in the absence of functional Rac1 in LX2. In conclusion, these studies identify novel crosstalk between small GTPases, cytoskeletal structures, and NO in pericyte-specific pathways, providing counterbalances in the chemotactic responses to growth factors.     

Role of L3T4-bearing T-cell populations in experimental murine chlamydial salpingitis.

A role for both the cellular and humoral components of the immune response has been established for chlamydial infection. The significance of helper (L3T4) T cells was evaluated by using a Chlamydia trachomatis murine salpingitis model for upper genital tract chlamydial infection. Mouse oviducts were inoculated with C. trachomatis by using the mouse pneumonitis agent (MoPn) or control medium. Mice depleted of L3T4-bearing lymphocytes had significantly higher (P less than 0.05) numbers of organisms recovered at day 7 postinoculation. The rate of hydrosalpinx formation was significantly higher in the mice depleted of L3T4-bearing lymphocytes (27 of 31 [87%] ) than in the infected undepleted group (8 of 16 [50%] ) (P less than 0.01). The geometric mean antichlamydial immunoglobulin G titers at day 54 postinoculation were significantly higher in the L3T4-depleted mice (mean titer, 2,030) than in the undepleted group (mean titer, 776; P less than 0.05). The rate of fertility was lower in the L3T4-depleted group (2 of 31 [6%]) than in the infected, undepleted mice (2 of 16 [13%]), but this difference did not reach statistical significance. In conclusion, the greater persistence of organisms in the oviduct and higher rates of hydrosalpinx formation in mice depleted of L3T4-bearing cells suggests that these cells play a role in the clearing of organisms following infection and thus in reducing the degree of oviduct obstruction and damage.     

Effect of Carbohydrate Source on Kanagawa-Type Hemolysis of Vibrio parahaemolyticus

Almost all strains of Vibrio parahaemolyticus produced Kanagawa-type hemolysis on media of high salt content in the presence of fermentable carbohydrates.     

Lifestyle Risk Score: handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions

Recent studies consider lifestyle risk score (LRS), an aggregation of multiple lifestyle exposures, in identifying association of gene-lifestyle interaction with disease traits. However, not all cohorts have data on all lifestyle factors, leading to increased heterogeneity in the environmental exposure in collaborative meta-analyses. We compared and evaluated four approaches (Naïve, Safe, Complete and Moderator Approaches) to handle the missingness in LRS-stratified meta-analyses under various scenarios. Compared to “benchmark” results with all lifestyle factors available for all cohorts, the Complete Approach, which included only cohorts with all lifestyle components, was underpowered due to lower sample size, and the Naïve Approach, which utilized all available data and ignored the missingness, was slightly inflated. The Safe Approach, which used all data in LRS-exposed group and only included cohorts with all lifestyle factors available in the LRS-unexposed group, and the Moderator Approach, which handled missingness via moderator meta-regression, were both slightly conservative and yielded almost identical p values. We also evaluated the performance of the Safe Approach under different scenarios. We observed that the larger the proportion of cohorts without missingness included, the more accurate the results compared to “benchmark” results. In conclusion, we generally recommend the Safe Approach, a straightforward and non-inflated approach, to handle heterogeneity among cohorts in the LRS based genome-wide interaction meta-analyses.Subject terms: Genetics, Risk factors