Factors Affecting the Practices of Cervical Cancer Screening among Female Nurses at Public Health Institutions in Mekelle Town, Northern Ethiopia, 2014: A Cross-Sectional Study

Objective. In Ethiopia, the age-adjusted incidence rate of cervical cancer is high, 35.9 per 100,000 women. Despite this fact, cervical cancer screening coverage in Ethiopia is very low. The objective of this study is to assess the magnitude and factors affecting the practices of cervical cancer screening among female nurse in Mekelle Town, Tigray, Northern Ethiopia, 2014. Methods. This study used a cross-sectional design. Bivariate and multivariate logistic regression was used to evaluate factors associated with cervical cancer screening practice. Results. A total of 225 female nurses participated in the study. The magnitude of cervical cancer screening practice among these nurses was 10.7%, within the past five years of the survey. Attitude and work place of the respondents were significantly associated with a history of cervical cancer screening practices with an adjusted odds ratio (AOR) of 3.023, 95% CI (1.134–8.059), and 3.424, 95% CI (1.080–10.853), respectively. Conclusion. The study showed that the magnitude of the cervical screening practice is very low among nurse health professionals. Negative attitude and workplace were identified to be the predictors of decision for cervical cancer test.

Molecular Docking Study Characterization of Rare Flavonoids at the Nac-Binding Site of the First Bromodomain of BRD4 (BRD4 BD1)

ε-N-Acetylation of lysine residues (Kac) is one of the most frequently occurring posttranslational modifications (PTMs) which control gene transcription and a vast array of diverse cellular functions. Bromodomains are epigenetic regulators involved in posttranslational modification. In silico docking studies were carried out to evaluate the binding potential of selected rare flavonoids on to Nac binding site of BD1 domain of BRD4 BET family proteins. Rare flavonoids like 3-O-acetylpinobanksin, naringenin triacetate, and kaempferol tetraacetate were found to occupy the WPF shelf and at the same time they exhibited a better binding affinity with multiple crystal structures of first bromodomain BRD4 (BRD4 BD1) when compared with the known inhibitors.

CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival

Aim. The analysis of the association of CXCR4 expression in gastric cancer (GC) and bone marrow (BM) with clinical characteristics. Patients and Methods. 65 patients with GC were investigated. Immunohistochemistry, immunocytochemistry, NMR-spectroscopy, and zymography were used. Results. CXCR4 was expressed in 78.5% of GC specimens and correlated with tumor hypoxia (P<0.05), VEGF expression (P<0.01), and gelatinases activity (P<0.05). CXCR4-positive cells in GC were detected in 80% of patients with disseminated tumor cells (DTCs). Overall survival (OS) of patients with CXCR4-positive tumors was poorer than that of patients with CXCR4-negative tumors (P=0.037). The CXCR4-positive cells in BM were found in 46% of all patients and in 56% of patients with DTCs. CXCR4 expression in BM was not associated with OS. Risk of unfavourable outcome is increased in patients with CXCR4-positive tumors (P<0.05). CXCR4 expression in BM was positively associated with DTCs, especially in patients with M0 category. Risk of unfavourable outcome is increased in patients with M0 category and with both CXCR4-positive BM and DTCs (P=0.03). Conclusions. CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. CXCR4 expression in BM is associated with DTCs.

Validation of Microcirculatory Parameters Derived from the Standard Two-Compartment Model with Murine Xenografts Model

The purpose of this study was to validate DCE-MRI parameters such as blood flow (F), permeability surface area product (PS), fractional intravascular space (v1), and fractional extracellular extravascular space (v2), obtained using a standard two-compartment model against other established analysis methods and histological indices. DCE-MRI datasets of 28 mice implanted with various human cancer xenografts were acquired and analyzed. Statistically significant correlations were found between the parameters derived from the standard two-compartment model (v1, v2, F, and PS) with the histological markers of intravascular and interstitial space and with the corresponding flow and permeability estimates obtained by the initial slope method and Patlak plot, respectively.

Hepatocellular Carcinoma Is the Most Frequent Final Diagnosis of Focal Liver Lesions Identified in a Cross-Sectional Evaluation of Patients with Chronic Liver Disease in Saudi Arabia

Background. Hepatocellular carcinoma (HCC) is a frequent diagnosis in patients with chronic liver disease (CLD) and a newly identified liver lesion, although benign diseases may also be responsible for this finding. Objective. To evaluate the characteristics of focal liver lesions in a population of patients with CLD not under surveillance for HCC in the Middle East. Methods. We performed a cross-sectional study evaluating 77 patients with CLD and a focal liver lesion identified during ultrasonography. Patients’ characteristics were analyzed on the basis of the final diagnosis (HCC versus benign lesions). Results. The most frequent diagnosis was HCC (64.9%). These patients were older (median age 64 versus 55 years, P=0.003) and cirrhotics (80.0% versus 51.9%, P=0.018), with multinodular lesions (58.0% versus 29.6%, P=0.031) and portal vein thrombosis (24.0% versus 0%, P=0.001) compared to patients with benign lesions. Prevalence of elevated alpha-fetoprotein (>10 ng/mL) was similar in both groups (80.0% versus 88.9%, P=0.198). Cirrhosis (odds ratio: 3.283) and multinodularity (odds ratio: 2.898) were independently associated with HCC. Conclusions. HCC is the most common diagnosis in Middle-Eastern patients with CLD and a liver lesion identified outside HCC surveillance programs, especially in cirrhotic patients. In these patients, elevated alpha-fetoprotein does not differentiate HCC from benign lesions.

AgCu Bimetallic Nanoparticles under Effect of Low Intensity Ultrasound: The Cell Viability Study In Vitro

The effects of metallic nanoparticles as cytotoxicity or antibacterial activity are widely known. It is also obvious that ultrasound is one of the most widely used therapeutic modalities in medicine. The effect of application of therapeutical ultrasonic field in the presence of metallic nanoparticles AgCu <100 nm modified by phenanthroline or polyvinyl alcohol was examined on human ovarian carcinoma cells A2780. Metallic nanoparticles were characterized by electron microscopy and by measuring of zeta potential. The cell viability was tested by MTT test. The experimental results indicate a significant decrease of cell viability, which was affected by a combined action of ultrasound field and AgCu nanoparticles. The maximum decrease of cells viability was observed for nanoparticles modified by phenanthroline. The effect of metallic nanoparticles on human cell in presence of ultrasound exposure was found—a potential health risk or medical advantage of targeted therapy in the future.

Association between Latitude and Breast Cancer Incidence in Mainland Australian Women

Aim. To investigate whether breast cancer incidence increases with increasing latitude in mainland Australian women. Methods. A cross-sectional study of female breast cancer and cutaneous melanoma incidence 2002–2006 by 5-year age group and local government area. Latitude, Accessibility/Remoteness Index of Australia (ARIA), and Index of Relative Socioeconomic Disadvantage (IRSD) were assigned to local government areas. Latitude was grouped into bands (≤27°S; >27–30°S; >30–33°S; >33–36°S, and >36°S), and IRSD was divided into quintiles and ARIA into four categories. Breast cancer rates were age standardized using the direct method. The joint effects of latitude, age, IRSD, and ARIA on incidence of breast cancer and cutaneous melanoma were assessed using multiple logistic regressions. Results. At latitudes south of 30°S, rates of breast cancer were over double that north of 27°S (76.4 versus 160.2–176.5). Age-adjusted odds ratios of breast cancer were increased in all latitudes south of 30°S compared with north of 27°S within each IRSD and ARIA category (all P<0.001). After adjusting for age, IRSD, and ARIA, the odds ratio of breast cancer south of 30°S was 1.92 (95% CI 1.84–2.09; P<0.001), whereas cutaneous melanoma was 0.65 (95% CI 0.61–0.68; P<0.001) times north of 30°S. Discussion. Increasing latitude is positively associated with breast cancer and negatively associated with cutaneous melanoma incidence. These findings support suggestions that increased risk of breast cancer might be explained by lower ultraviolet radiation-induced vitamin D synthesis.

Impact of Immunochemotherapy-Related Hepatic Toxicity on the Outcome of HCV-Positive Diffuse Large B-Cell Lymphoma Patients

We conducted this prospective study which included 28 de novo CD20-positive DLBCL patients to assess the clinical outcome, treatment response, and hepatic toxicity in DLBCL patients who received rituximab-CHOP as a first line treatment in relation to HCV infection status. We included 7 patients with positive HCV infection (group A) and 21 patients with negative HCV infection (group B). HCV infection was not a significant risk factor for prognosis (1-year event-free survival rates, 71.4% versus 81%, P=0.53; overall survival rates, 85.7% versus 90.5%, P=0.72, for groups A and B, resp.). CR rate was 71.4% (5/7) in group A and 76.2% (16/21) in group B (P=0.8). Of the 7 patients who were HCV positive, 2 (28.6%) had enzyme flare (grade 2), compared with 1 of the 21 (4.8%) patients who were HCV negative (P=0.15). Two (28.6%) of the 7 positive HCV infection patients had viral reactivation (≥1 log10 IU/mL increase in the viral load). No patient required discontinuation of immunochemotherapy owing to hepatotoxicity in either group. In conclusion, HCV infection might not influence the clinical course in DLBCL patients who receive rituximab-CHOP. Close monitoring of hepatic function and viral load is recommended.

BAY 61-3606, CDKi, and Sodium Butyrate Treatments Modulate p53 Protein Level and Its Site-Specific Phosphorylation in Human Vestibular Schwannomas In Vitro

This study is done to evaluate the effect of spleen tyrosine kinase inhibitor (BAY 61-3606), cyclin-dependent kinase inhibitor (CDKi), and sodium butyrate (Na-Bu) on the level and phosphorylation of p53 protein and its binding to murine double minute 2 (MDM2) homologue in human vestibular schwannomas (VS). Primary cultures of the tumor tissues were treated individually with optimum concentrations of these small molecules in vitro. The results indicate modulation of p53 protein status and its binding ability to MDM2 in treated samples as compared to the untreated control. The three individual treatments reduced the level of total p53 protein. These treatments also decreased Ser392 and Ser15 phosphorylated p53 in tumor samples of young patients and Ser315 phosphorylated p53 in old patients. Basal level of Thr55 phosphorylated p53 protein was present in all VS samples and it remained unchanged after treatments. The p53 protein from untreated VS samples showed reduced affinity to MDM2 binding in vitro and it increased significantly after treatments. The MDM2/p53 ratio increased approximately 3-fold in the treated VS tumor samples as compared to the control. The differential p53 protein phosphorylation status perhaps could play an important role in VS tumor cell death due to these treatments that we reported previously.

miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model

Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660). We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.