Association of the Polymorphism rs3918242 of the Matrix Metalloproteinase-9 Gene with Coronary Artery Disease in a Younger Population.

Coronary artery disease (CAD) is a complex disease resulting from the interaction of numerous so-called traditional risk factors and comorbid conditions on the one side (such as dyslipidemia, smoking, obesity, diabetes, hypertension) and genetic factors on the other. The evidence of a genetic contribution to the development of CAD, especially in the last 2 decades is consistent. It is important that a number of established gene polymorphisms in the younger CAD population are in the genes involved in the inflammatory response and tissue maintenance and remodeling processes. The aim of this study is to investigate the association of the rs3918242 polymorphism of the matrix metal-loproteinase 9 (MMP9) gene with the coronary artery disease in the younger population. In this observational genetic-association study of cases and controls, the demographic, clinical, laboratory and genetic data of the younger population in a group of selected 70 CAD patients aged up to 45 years were analyzed, of which 35 patients have negative and 35 have positive coronary angiography finding, and 43 are men and 27 are women. The analysis of the genotypic and allelic frequency determined an association of the polymorphism and the occurrence of the positive coronary angiographic findings in the population of patients under the age of 45. The carriers of the heterozygous genotype CT have almost 5 times higher probability of having a positive coronary angiography finding compared to the carriers of the reference homozygous genotype CC (p=0.012). Thus, this parameter could be used for clinical risk assessment for the development of CAD.

Effects of Serenoa repens Alcohol Extract on Benign Prostate Hyperplasia.

An increasing tendency has recently emerged for the use of phytotherapeutic agents as alternative to commercial pharmacological agents for the treatment of benign prostate hyperplasia (BPH). The purpose of this study is to evaluate the effects of Serenoa repens alcohol extract treatment on BPH patients' symptoms and major parameters during one-year follow-up. The study was performed on 70 men aged 40 - 79 years (mean 60.58) with symptomatic BPH that were divided into a group of 40 patients treated with Serenoa repens extract (SRT) and a control group of 30 patients that received no treatment and were observed only. The following parameters were determined at the time of diagnosis (baseline), and after 6 and 12 months: prostate size, serum prostate-specific antigen (PSA) and uroflowmetry parameters including maximum flow rate (MFR), average flow rate (AFR) and post-voiding residual volume (PVRV). In addition, the relevant patient symptoms were evaluated using the International Prostate Symptom Score (IPSS) system. The patients in the SRT group showed a statistically significant increment of the average MFR and AFR values and reduction of PV relative to the control group (p<0.05). The significant differences between the proportion of patients with prostate volume >40 ml in the SRE treated group vs. control group was observed (p<0.05). The mean IPSS score was highly significantly reduced in the SRT group (p<0.01). The mild improvements of the urine flow, prostate size and IPSS score during 12 months treatment with the Serenoa repens extract indicate possible efficiency of this phytotherapeutic agent in patients with BPH.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer.

INTRODUCTION: Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). OBJECTIVE: The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients' clinical outcome. MATERIALS AND METHODS: In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. RESULTS: UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. CONCLUSIONS: The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Correlation of hTERT Expression with Cervical Cytological Abnormalities and Human Papillomavirus Infection.

Telomerase Reverse Transcriptase (TERT) is the main catalytic sub-unit of telomerase, a reverse transcriptase enzyme. Telomerase expression is regulated at many levels, with numerous studies suggesting that up-regulation of human TERT gene (hTERT) at transcriptional level results in immortal cell phenotype associated with cancer. The aim of this study is to determine the correlation between hTERT expression and different cervical precursor lesions, as well as with cervical cancer in patients with confirmed Human papillomavirus (HPV) infection. The study included molecular analyzes on cervical samples from 214 women and matched Papanicolaou (Pap) test results. HPV detection and genotyping was performed by polymerase chain reaction (PCR) and genotyping. Quantitative real-time PCR (qRT-PCR) was performed using TaqMan probes and were calculated relative to the reference gene. Results showed significantly increased hTERT mRNA expression levels in high-grade and low-grade lesions compared to normal control samples (p<0.01) associated with 6.31 fold higher risk for developing ASC-US and 9.20 for LSIL. Strong correlation between HPV infection and hTERT expression in the high-grade lesions and cervical cancer was also observed. hTERT relative expression values showed 98% specificity and 100 % sensitivity as indicator of cervical lesions particularly for the ACS-H, HSIL and cervical cancer. In conclusion, hTERT expression correlate with the cytological grade of the cervical lesions and HPV infection and has a potential to be used as a diagnostic and prognostic marker.

Molecular Biology and Genetic Mechanisms in the Progression of the Malignant Skin Melanoma.

Malignant skin melanoma is a tumor deriving from transformed skin melanocytes as a result of complex interactions between genetic and environmental factors. This melanoma has a potential to metastasize early and very often it is resistant to the existing modalities of the systemic therapy. As in any other neoplasms, certain types of melanoma may skip certain stages of progression. The progression from one stage to another is accompanied by specific biological changes. Several key changes in the melanoma tumorogenesis influence the regulation of the cell proliferation and vitality, including the RAS-RAF-ERK, PI3K-AKT, and p16INK4/CDK4/RB pathways. A key role in the dissreguarity of the RAS-RAF-ERK (MAPK) pathway in the malignant melanoma development have been demonstrated by many studies. To date, the molecular genetic alterations during melanoma development have been partially known. In the pathogenesis of the malignant melanoma, there are mutations of various genes such as NRAS, BRAF, and PTEN and mutations and deletions of CDKN2A. In the past years, great advance has been made in the insights of the molecular aspects of the melanoma pathogenesis. However, this field yet poses a challenge to discover new details about the melanoma molecular characteristics. The research results are focused towards the improvement of the melanoma patients prognosis by introducing personalized targeted therapy.

High frequency of the HRAS oncogene codon 12 mutation in Macedonian patients with urinary bladder cancer

Point mutations at codon 12 of the HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) oncogene are one of the best defined and widely studied molecular genetic events in transitional cell carcinoma (TCC) of the urinary bladder. The aim of this study was to use the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of paraffin-embedded tissue-derived DNA to determine the frequency of the HRAS oncogene G ->T codon 12 mutation in TCC patients being treated at the University Urology Clinic in Skopje, Republic of Macedonia. DNA isolated from paraffin-embedded tissue (PET) surgically removed TCC specimens of 62 (81.58 percent) out of 76 patients were successfully amplified, the remaining 14 (18.42 percent) showing compromised DNA integrity. The codon 12 mutation of the HRAS oncogene was found in 24 (38.71 percent) out of 62 successfully tested TCC urinary bladder samples. No significant relationship between the mutation frequency and the histopathological grade of tumor differentiation was detected (chi² = 0.044; p = 0.978). The relatively high frequency of mutations found in our study was comparable with some of the previously reported data obtained by this and/or other PCR-based methods. This highly sensitive and specific PCR-RFLP analysis was demonstrated to be a suitable method for the detection of mutations at codon 12 of the HRAS oncogene in PET samples of urinary bladder TCC.