Targeted gene therapy for cancer: the impact of microRNA multipotentiality.

Cancer is a life-threatening disease and its management is difficult due to its complex nature. Cancer is characterized by genomic instability and tumor-associated inflammation of the supporting stoma. With the advances in omics science, a treatment strategy for cancer has emerged, which is based on targeting cancer-driving molecules, known as targeted therapy. Gene therapy, a form of targeted therapy, is the introduction of nucleic acids into living cells to replace a defective gene, promote or repress gene expression to treat a disease. MicroRNAs (miRNAs) are non-coding RNAs (ncRNAs) that regulate gene expression and thus are involved in physiological processes like cell proliferation, differentiation, and cell death. miRNAs control the actions of many genes. They are deregulated in cancer and their abnormal expression influences genetic and epigenetic alterations inducing carcinogenesis. In this review, we will explain the role of miRNAs in normal and abnormal gene expression and their usefulness in monitoring cancer patients. Besides, we will discuss miRNA-based therapy as a method of gene therapy and its impact on the success of cancer management.

The potential preventive effect of dietary phytochemicals In Vivo.

INTRODUCTION: Chemoprevention refers to using specific substances during oncogenesis. Curcumin and catechins are both polyphenol types of phytochemicals present in curcuma longa and green tea. The effect of curcumin is synergistic with epigallocatechin gallate, the most abundant polyphenol in tea. AIM: To evaluate and compares the chemopreventive effect of both green tea and curcumin (each individually and in combination) through induction of hamster buccal pouch carcinoma. MATERIALS AND METHODS: Squamous cell carcinoma was chemically induced in fifty Syrian golden hamsters divided into 5 groups (10 each). The first group was used as a normal control group. The second group received the carcinogenic agent only. The other three groups received green tea, curcumin, and a combination of both, respectively. Flow cytometry, immunofluorescence, and immunohistochemical assays were used to evaluate apoptosis, proliferation, and angiogenesis. ANOVA test was used to analyze the results between the study groups. RESULTS: The cells of the positive control group (B) resulted in 11.57% apoptosis. In the study groups, treatment of the cells with green tea (C), and curcumin (D) and both of them (E) showed increased apoptosis. The fluorescent image in group B showed an increase of the red fluorescence in the nucleus and cytoplasm of the squamous cell carcinoma cells while groups C, D, and E showed a decrease of the red fluorescence in the nuclei of the squamous cell carcinoma cells. The microvessel density was higher in the positive control group as compared to the treated groups. CONCLUSIONS: The combination of green tea and curcumin has a significant chemopreventive effect against oral carcinogenesis.

Following cytotoxic nanoconjugates from injection to halting the cell cycle machinery and its therapeutic implications in oral cancer.

BACKGROUND: The concept of personalized therapy has been proven to be a promising approach. A popular technique is to utilize gold nanoparticles (AuNPs) as drug delivery vectors for cytotoxic drugs and small molecule inhibitors to target and eradicate oral cancer cells in vitro and in vivo. Both drug and nanocarrier designs play important roles in the treatment efficacy. In our study, we standardized the nanosystem regarding NPs type, size, surface ligands and coverage percentage leaving only the drugs mode of action as the confounding variable. We propose that similarly constructed nanoparticles (NPs) can selectively leverage different conjugated drugs irrelevant to their original mode of action. If proven, AuNPs may have a secondary role beyond bypassing cancer cell membrane and delivering their loaded drugs. METHODS: We conjugated 5- fluorouracil (5Fu), camptothecin (CPT), and a fibroblast growth factor receptor1-inhibitor (FGFR1i) to gold nanospheres (AuNSs). We followed their trajectories in Syrian hamsters with chemically induced buccal carcinomas. RESULTS: Flow cytometry and cell cycle data shows that 5Fu- and CPT- induced a similar ratio of S-phase cell cycle arrest as nanoconjugates and in their free forms. On the other hand, FGFR1i-AuNSs induced significant sub-G1 cell population compared with its free form. Despite cell cycle dynamics variability, there was no significant difference in tumor cells' proliferation rate between CPT-, 5Fu- and FGFR1i- AuNSs treated groups. In our in vivo model, FGFR1i-AuNSs induced the highest tumor reduction rates followed by 5Fu- AuNSs. CPT-AuNSs induced significantly lower tumor reduction rates compared with the 5Fu- and FGFR1i- AuNSs despite showing similar proliferative rates in tumor cells. CONCLUSIONS: Our data indicates that the cellular biological events do not predict the outcome seen in our in vivo model. Furthermore, our results suggest that AuNSs selectively enhance the therapeutic effect of small molecule inhibitors such as FGFR1i than potent anticancer drugs. Future studies are required to better understand the underlying mechanism.