The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-surgical Adhesions.

BACKGROUND: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, few improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered a blood pressure regulator. However, recent studies have indicated that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and wound healing. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion. METHODS: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion. RESULTS: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are used for targeting the RAS system, and some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including telmisartan, valsartan, and enalapril. CONCLUSION: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting the Renin-Angiotensin System may help to prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation.

The Therapeutic Potential of Targeting Autophagy in the Treatment of Cancer.

Autophagy is a mechanism by which unwanted cellular components are degraded through a pathway that involves the lysosomes and contributes to several pathological conditions such as cancer. Gastrointestinal cancers affect the digestive organs from the esophagus to the anus and are among the most commonly diagnosed cancers globally. The modulation of autophagy using pharmacologic agents offers a great potential for cancer therapy. In this review, some commonly used compounds, together with their molecular target and the mechanism through which they stimulate or block the autophagy pathway, as well as their therapeutic benefit in treating patients with gastrointestinal cancers, are summarized.

The Dilemma of TP53 Codon 72 Polymorphism (rs1042522) and Breast Cancer Risk: A Case-Control Study and Meta-Analysis in The Iranian Population.

OBJECTIVE: Mutations of TP53 as a tumor suppressor gene are frequently observed in different types of cancer. A codon 72 polymorphism located on exon 4 with two alleles encoding either Proline (CCC) or Arginine (CGC) has been indicated as a common variation in association with cancers. Controversial results have been reported regarding the association of allelic polymorphism of codon 72 of TP53 gene and breast cancer risk in Iranian patients. Therefore, a case-control study was designed. A meta-analysis was also carried out to provide evidence of association between this variation and breast cancer in Iran, based on all available published data. MATERIALS AND METHODS: In this case-control study, blood sample of 622 participants, including 308 breast cancer cases and 314 controls were collected. Genotyping for rs1042522 was conducted by Allele Specific polymerase chain reaction (AS-PCR). In order to set a meta-analysis study, PubMed, Scopus and ISI Web of Knowledge and Persian databases were searched to explore relevant studies, published up to September 2018, containing information on TP53 polymorphism and the risk of breast cancer in Iran. Statistical analysis was performed using SPSS 16.0 and MetaGenyo. RESULTS: All retrieved available data as well as the results of our current study were consisted of 1965 breast cancer cases and 1999 healthy controls. No significant difference was observed in allele frequencies between groups (P=0.90) in our study. The cumulative results did not also show any association between rs1042522 and breast cancer risk on the dominant (P=0.61) and recessive (P=0.89) models. CONCLUSION: These findings cannot support contribution of rs1042522 polymorphism to breast cancer risk in an Iranian population. Future larger studies may help confirm this finding with a greater power.