High Diagnostic and Prognostic Value of miRNAs Compared with the Carcinoembryonic Antigen As A Traditional Tumor Marker.

Early diagnosis and accurate prognosis are significant important challenges against effective treatment of cancer and improving patient's condition. Hitherto, many research works have tended to focus on the carcinoembryonic antigen (CEA) to detect cancers and estimate the survival rates of patients with multiple cancer types, including colorectal, breast, non-small cell lung, and pancreas cancer. Limited sensitivity and specificity of this traditional tumor marker make it an inappropriate biomarker to diagnose cancer, especially in the early stages while several lines of research have introduced miRNAs as reliable indicators of tumor initiation, development, and therapy response. Indeed, miRNAs have unique properties that provide considerable benefits, such as discriminating benign diseases from malignancies, predicting cancer development and progression, checking sensitivity to treatment, and initial detecting of tumors. This review summarizes the relationships between miRNAs and CEA, the diagnostic significance of CEA in combination with miRNAs, and the distinct advantages of miRNAs over CEA as tumor biomarkers. Advancement in our current understanding of miRNAs is very essential to discover new and effective biomarkers for diagnostic, prognostic, and therapeutic goals of cancer patients.

Application of Molecular Docking for the Development of Improved HIV-1 Reverse Transcriptase Inhibitors.

INTRODUCTION: Inhibition of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV) by low molecular weight inhibitors is still an active area of research. Here, protein-ligand interactions and possible binding modes of novel compounds with the HIV-1 RT binding pocket (the wild-type as well as Y181C and K103N mutants) were obtained and discussed. METHODS: A molecular fragment-based approach using FDA-approved drugs were followed to design novel chemical derivatives using delavirdine, efavirenz, etravirine and rilpivirine as the scaffolds. The drug-likeliness of the derivatives was evaluated using Swiss-ADME. The parent molecule and derivatives were then docked into the binding pocket of related crystal structures (PDB ID: 4G1Q, 1IKW, 1KLM and 3MEC). Genetic Optimization for Ligand Docking (GOLD) Suite 5.2.2 software was used for docking and the results analyzed in the Discovery Studio Visualizer 4. A derivative was chosen for further analysis, if it passed drug-likeliness and the docked energy was more favorable than that of its parent molecule. Out of the fifty-seven derivatives, forty-eight failed in drug-likeness screening by Swiss-ADME or at the docking stage. RESULTS: The final results showed that the selected compounds had higher predicted binding affinities than their parent scaffolds in both wild-type and the mutants. Binding energy improvement was higher for the structures designed based on second-generation NNRTIs (etravirine and rilpivirine) than the first-generation NNRTIs (delavirdine and efavirenz). For example, while the docked energy for rilpivirine was -51 KJ/mol, it was improved for its derivatives RPV01 and RPV15 up to - 58.3 and -54.5 KJ/mol, respectively. CONCLUSION: In this study, we have identified and proposed some novel molecules with improved binding capacity for HIV RT using a fragment-based approach.

Detection of JC Polyomavirus tumor antigen in gastric carcinoma: a report from Iran.

BACKGROUND AND OBJECTIVES: Factors contributing to development of gastric cancer are still under investigation. The JC Virus (JCV), as an oncogenic virus, has been indicated to play a possible role in gastric carcinogenesis. Theoretically, tumor antigen (T-Ag), the viral transforming protein, is capable of binding and inactivating tumor suppressor proteins p53 and pRb, there by promoting cancer development although such a role in gastric cancer is still controversial and additional data is needed to reach a definite conclusion. The prevalence of the virus varies in different geographic regions, therefore, we aimed to investigate JCV presence in cancerous gastric tissues of Iranian patients. MATERIALS AND METHODS: Thirty-one paired samples were included in this study (total of 62 samples). T-Ag sequences were investigated using real-time PCR in formalin fixed paraffin embedded (FFPE) tissue samples from the tumor site and relevant adjacent non-cancerous tissues (ANCT). In positive samples, JCV copy number (viral load) was also measured using real-time PCR. To evaluate T-Ag protein expression, immunohistochemistry examination was performed using an anti-T-Ag specific antibody. RESULTS: JCV sequences were detected in 17 out of 31 gastric cancer tissue samples (54.84%) and in 10 out of 31 of the non-cancerous adjacent gastric mucosa (32.25%) (Odds ratio of 2.4). Viral load in tumoral and adjacent tissue samples was not statistically different (p=0.88). Immunohistochemical study confirmed presence of JC T-Ag in the nuclear compartment. CONCLUSION: We showed the presence of the JC virus in gastric carcinoma tissue samples in our geographic region. This finding provides supportive data for a possible contribution of JCV in gastric cell transformation to malignancy. However, we highly recommend additional investigations to further explore JC virus and gastric cancer in order to reach a conclusion.

Bee venom induces apoptosis and suppresses matrix metaloprotease-2 expression in human glioblastoma cells

Abstract Glioblastoma is the most common malignant brain tumor representing with poor prognosis, therapy resistance and high metastasis rate. Increased expression and activity of matrix metalloproteinase-2, a member of matrix metalloproteinase family proteins, has been reported in many cancers including glioblastoma. Inhibition of matrix metalloproteinase-2 expression has resulted in reduced aggression of glioblastoma tumors in several reports. In the present study, we evaluated effect of bee venom on expression and activity of matrix metalloproteinase-2 as well as potential toxicity and apoptogenic properties of bee venom on glioblastoma cells. Human A172 glioblastoma cells were treated with increasing concentrations of bee venom. Then, cell viability, apoptosis, matrix metalloproteinase-2 expression, and matrix metalloproteinase-2 activity were measured using MMT assay, propidium iodide staining, real time-PCR, and zymography, respectively. The IC50 value of bee venom was 28.5 µg/ml in which it leads to decrease of cell viability and induction of apoptosis. Incubation with bee venom also decreased the expression of matrix metalloproteinase-2 in this cell line (p < 0.05). In zymography, there was a reverse correlation between bee venom concentration and total matrix metalloproteinase-2 activity. Induction of apoptosis as well as inhibition of matrix metalloproteinase-2 activity and expression can be suggested as molecular mechanisms involved in cytotoxic and antimetastatic effects of bee venom against glioblastoma cells.