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.

Intermittent fasting during adjuvant chemotherapy may promote differential stress resistance in breast cancer patients.

BACKGROUND: Preclinical studies prove that short-term fasting secures healthy cells against chemotherapy side effects and makes malignant cells more vulnerable to them. This study aimed to examine the effects of intermittent fasting (IF) during adjuvant chemotherapy AC (doxorubicin, cyclophosphamide) protocol in breast cancer (BC) patients. METHODS: Forty-eight newly diagnosed human epidermal growth factor receptor 2-negative (HER2 negative) BC patients were divided equally into two groups (24 each). The first group was recruited to fast intermittently for three consecutive days around chemotherapy for 18 h a day from 12 am to 6 pm and eats through 6 h a day from 6 pm to 12 am with permission of drinking water during fasting hours (IF group). This IF was repeated every 3 weeks for four cycles. The second group is a non-fasting (NF) group that was allowed to eat regularly. Toxicity in the two groups was compared. Hematologic, metabolic, and inflammatory parameters were measured and compared. RESULTS: Toxicity related to the gastrointestinal tract (GIT) was reduced in the IF group. Hematologic parameters showed no significant variations between the two studied groups after cycle 4. There was a significant increase in median glucose and median insulin levels (P < 0.001 and P = 0.001, respectively) in the NF group between baseline and after cycle 4. In addition, there was a significant decrease in the median insulin level (P = 0.002) in the IF group between the two time points. CONCLUSION: IF throughout chemotherapy was well tolerated and decreased the toxicity of chemotherapy. Additionally, IF-improved metabolic profiles of patients may have a positive impact on the clinical efficacy of chemotherapy.

Oral and Extraoral Intermediate Tumors: Are MMP-9 and Ki-67 Biomarkers Correlated to Their High Recurrence Rates?

Intermediate tumors of the head and neck fall in the borderline category. They are clinically aggressive tumors with no malignant phenotyping. They are locally infiltrative and have high recurrence rate with less chances to metastasize. The standard care is surgical excision with wide margins. However, surgeons are challenged with the anatomic complexity of the head and neck, increasing the susceptibly of satellite cells being left behind. Ki-67 and MMP-9 are proliferative index and extracellular matrix degradation biomarkers, respectively. They are directly correlated to malignant tumors, whereas less associated with the benign ones. Our main objective was to correlate between Ki-67 and MMP-9 expressions and the recurrence rates in these borderline tumors. We performed a retrospective immunohistochemical study comparing the immunoexpression of Ki-67 and MMP-9. Tumors of interest were aggressive fibromatosis (AF, n=70), epithelioid hemangioendothelioma (EHE, n=25), hemangiopericytoma (HP, n=25), benign fibrous histiocytoma (BFH, n=80) and juvenile ossifying fibroma (JOF, n= 40). Our results revealed that AF followed by HP showed significant high levels of MMP-9 expression, with an average positive area percentage of 40% and 37.4% respectively, compared with other tumors (P<0.05). Ki-67 immunoreaction was significantly the lowest in AF (2.3%, P<0.05) and the highest in JOF (24.7%). To conclude, MMP-9 can be used as a possible target in these tumors as an adjuvant therapy to minimize recurrence rates.