Q192R polymorphism in the PON1 gene and nasal polyp in a Turkish population.

The pathogenesis of nasal polyps is not completely understood. Oxidative damage contributes to polyp formation in the nasal mucosa. The paraoxonase 1 (PON1) enzyme is an important liver enzyme with high antioxidant activity. In this study, we investigated the correlation between Q192R genotypic polymorphism of the PON1 enzyme and nasal-polyp disease. The study examined 62 nasal-polyp patients and 88 controls. PON1 Q192R polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism. The genotype distribution of the PON1 gene was significantly different between nasal-polyp patients (QQ = 69.35%, QR = 25.81%, RR = 4.83%) and healthy controls (QQ = 52.27%, QR = 44.31%, RR = 3.40%). Our results suggest that the PON1 QQ genotype (odds ratio [OR] = 2.066, P = .036) is associated with a higher risk of developing the nasal-polyp disease while QR genotype (OR = 0.437, P = .021) showed a lower risk.

Antidepressant and antipsychotic drugs differentially affect PON1 enzyme activity.

Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)-associated, calcium-dependent enzyme. In this study, the effects of Haloperidol, Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme was purified from human blood using two-step procedures, namely, ammonium sulfate precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction chromatography. The overall purification of human serum PON1 was obtained in a activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDS-polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and fluoxetine hydrocloride were effective inhibitors on purified human serum PON1 activity with IC50 of 0.187 and 3.08 mM values, respectively. The kinetics of interaction of haloperidol and fluoxetine hydrocloride with the purified human serum PON1 indicated uncompetitive inhibiton pattern with Ki of 4.15 and 0.007 mM, respectively.

AGR2 Gene Expression in Glioblastoma: A Novel Molecular Potential Target for Diagnosis and Treatment.

AIM: To assess anterior gradient protein 2 (AGR2) gene expression in patients with human glioblastoma (GBM) in comparison to levels in healthy brain tissues. MATERIAL AND METHODS: We evaluated the expression levels of AGR2 gene in 34 tissue samples: 29 of them were derived from patients with glioblastoma (GBM group) and 5 were derived from patients with mesial temporal lobe epilepsy (control group). Moreover, in order to demonstrate the AGR2 gene expression, we performed RNA isolation from tissue samples, cDNA acquisition from RNA via reverse transcription and the demonstration of gene expression via real-time polymerase chain reaction. We therefore confirmed findings of both groups. RESULTS: The mean age of the GBM and control groups were 53.1 ± 12.82 years and 40.4 ± 10.92 years respectively. AGR2 gene expression levels of the GBM group were significantly higher than those of the control group (p < 0.01). There were no significant differences of AGR2 gene expression levels across age groups, levels of glucose, urea, creatinine, white blood cell count (WBC), neutrophil, lymphocyte, hemoglobin, platelet, thyroid-stimulating hormone (TSH), T3 and T4 in GBM group (p > 0.05). CONCLUSION: AGR2 gene expression was significantly higher in patients with GBM. Thus, AGR2 gene can be considered as a potential therapeutic target.

Discoidin domain receptor 1 as a promising biomarker for high-grade gliomas.

Background: Two fundamental challenges in the current therapeutic approach for central nervous system tumors are the tumor heterogeneity and the absence of specific treatments and biomarkers that selectively target the tumor tissue. Therefore, we aimed to investigate the potential relationship between discoidin domain receptor 1 (DDR1) expression and the prognosis and characteristics of glioma patients. Materials and Methods: Tissue and serum samples from 34 brain tumor patients were evaluated for DDR1 messenger ribonucleic acid levels in comparison to 10 samples from the control group, and Kaplan-Meier survival analysis has performed. Results: DDR1 expression was observed in both tissue and serum samples of the patient and control groups. DDR1 expression levels in tissue and serum samples from patients were higher in comparison to the control group, although not statistically significant (P > 0.05). A significant correlation between tumor size and DDR1 serum measurements at the level of 0.370 was reported (r = 0.370; P = 0.034). The levels of DDR1 in serum showed a positive correlation with the increasing size of tumor. The results of the 5-year survival analysis depending on the DDR1 tissue levels showed a significantly higher survival rate (P = 0.041) for patients who have DDR1 tissue levels above cutoff value. Conclusions: DDR1 expression was significantly higher among brain tumor tissues and serum samples and its levels showed a positive correlation with the increased size of tumor. This study can be a starting point, since it investigated and indicated, for the first time, that DDR1 can be a novel therapeutic and prognostic target for aggressive high-grade gliomas.

Ubiquitin-specific Protease 8 Gene Expression in Sporadic Pituitary Adenomas.

OBJECTIVES: In sporadic pituitary adenomas, the role of Ubiquitin-specific protease 8 (USP8) is not clearly defined. Mutations in USP8 gene are known to influence formation of the corticotroph adenomas. However, it has not been clarified whether changes in expression of USP8 have an impact on other pituitary adenomas or not. In this study we addressed the changes in USP8 gene expression levels in pituitary adenomas (PA) relative to non-adenomatous brain tissue. MATERIAL AND METHODS: USP8 gene expression analysis was performed on a total of 43 tissue samples from human pituitary adenomas and on 16 tissue samples from non-pituitary brain tissues (control group). Adenomatous tissues and control tissues were assessed for quantification of RNA expression of USP8.The levels of USP8 gene expression were determined relative to those in control group. RESULTS: Overall, the USP8 gene expression levels in PA were 3.7 times higher than the control brain tissues (CBT) (p=0.002). However, after stratification, only the USP8 in the secretory PA were higher than CBT(p=0.002). CONCLUSIONS: Present findings support that USP8 gene expression levels may contribute to pitutary tumorigenesis and hormonogenesis..

HIV/AIDS awareness and attitudes of tour guides in Turkey.

The aim of this study was to ascertain Turkish tour guides' awareness and attitudes regarding HIV and AIDS. A sample of 516 tour guides registered in Turkey who verbally consented to participate in this study responded to an anonymous, self-administered questionnaire. The respondents typically exhibited a reasonable to excellent degree of knowledge about HIV and AIDS. However, the survey revealed some common misconceptions, indicating that tour guides require additional training in the mechanisms of HIV transmission. We also observed some differences in the level of HIV-related knowledge between different demographic groups. The knowledge level of male respondents was better than that of the female respondents. We also observed that knowledge levels increased with both age and work experience. These results are discussed within the framework of critical studies on HIV-related knowledge. Implications for the development of curricula and in-service training programmes for tour guide organisations and institutions are discussed.

Relationship Between CIP2A and Endometrium Cancer.

OBJECTIVE: To determine whether there is a relationship between endometrium cancer and the oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Balikesir University Medical Faculty Hospital, Balikesir, Turkey, from January 2013 to July 2018. METHODOLOGY: CIP2A was studied immunohistochemically and molecularly in paraffin blocks. The correlation between CIP2A expression and different endometrial pathologies were evaluated. In addition, the relationship between CIP2A expression in tumor tissue and clinicopathological prognostic parameters and also between Ki67, P53, HER2 with CIP2A expression were investigated. RESULTS: A higher expression of CIP2A was found in endometrium cancer tissues compared to normal endometrial tissues. In addition, CIP2A expression according to molecular and immunohistochemical results was associated with significant poor prognostic factors such as FIGO Stage, FIGO Grade, cervical involvement, myometrial invasion and HER2 positivity. CONCLUSION: CIP2A could be a promising and therapeutic target in endometrium cancer. Invention of the complex connections of CIP2A with other oncoproteins may lead to amazing and interesting developments in both early diagnosis and treatment. Key Words: CIP2A, Endometrium cancer, Expression, Oncoprotein.

URG4 expression in invasive breast carcinoma and its relation to clinicopathological characteristics.

BACKGROUND: Upregulated gene 4 (URG4) is a recently described oncogene that upregulates cell proliferation. Its overexpression has been identified in many malignancies, and it is thought to be related to tumour progression, angiogenesis, metastasis and the recurrence of many cancers. This is the first study to show its expression in breast cancer patients and its association with clinicopathological characteristics in these patients. METHODS: Fifty invasive ductal breast carcinoma cases and 25 control cases were included in the study. Tumourous tissues and control tissues were assessed molecularly for quantification of mRNA expression of URG4 and immunohistochemically for protein expression of URG4. RESULTS: The mean ages of the patients and controls were 54.3 ± 11.3 and 38.9 ± 9.7 years, respectively. The expression levels of URG4 mRNA in tumour tissues were higher compared to control breast tissues (p = 0.023). An immunohistochemical assessment suggested that URG4 is strongly expressed in normal breast tissues and lower-grade (grades I and II) ductal carcinomas of the breast, but it is weakly expressed in high-grade (grade III) ductal breast carcinomas. Additionally, the immunohistochemical and molecular expression results of URG4 were relevant to most prognostic parameters (tumour size, oestrogen and progesterone receptor status, HER2 status and Ki67 proliferative index) for breast cancer. However, unlike the immunohistochemical studies, the molecular studies revealed that there was no significant difference in URG4 expression for different grades of tumour tissues. CONCLUSION: The literature data suggest that URG4 overexpression is associated with poor prognosis in many types of cancer. Conversely, our results in breast cancer specimens indicate that URG4 overexpression in breast ductal carcinomas is significantly associated with good prognostic parameters. Nevertheless, these preliminary findings should be confirmed by further studies.

Effect of certain non-steroidal anti-inflammatory drugs on the paraoxonase 2 (PON2) in human monocytic cell line U937.

The paraoxonase gene family in humans consists of three members as PON1, PON2 and PON3. PON2 can be expressed in several tissues; however, it is not released from the cells in those tissues. PON2 is also expressed in macrophages. Firstly, the commonly used NSAIDs diclofenac sodium and tenoxicam were applied on U937 cell line, the in vitro human monocyte cell line. Than PON2 specific Lactonase activity and paraoxonase family specific arylesterase were determined. Use of Diclofenac sodium in 0.845 mM dose during 6-12 h of incubation and Tenoxicam in 0.74 mM dose during 6 h of incubation resulted in a significant decline in the lactonase activity. Diclofenac sodium didn't make any change in the arylesterase activity. On the other hand, tenoxicam decreased arylesterase activity during the use of 12 h, in 0.74 mM and 1.48 mM dose.