Sonic hedgehog (Shh) pathways have been shown to involve in many cellular processes including cancer cell proliferation and growth. Our studies show that triacetyl-resveratrol (TCRV)interacts with the Gli-DNA zinc finger complex which is a downstream target of Shh pathway. TCRV is a derivative of natural polyphenol compound resveratrol, grape polyphenol with cancer preventative activities in several cancers. TCRV interacted actively and specifically with Gli-DNA zinc finger complex through binding at the site targeted by the affinity (-8.0 Kcal/mol) with the VAL159, ARG162, HIS170, LEU184, GLU185, ASN186, DA14 AND DA15 residues. These studies could be helpful to understand the mechanism of TCRV and its chemo-theraputive effects for the prevention and treatment of cancers.

Cancer Drug resistance is a medical concern that requires extensive research and a thorough understanding in order to overcome. Remarkable achievements related to this field have been accomplished and further work is needed in order to optimize the cure for cancer and serve as the basis for precise medicine with few or no side effects.

Background: Lipomodelling has been increasingly used recently for the correction of defects and asymmetry following oncologic breast cancer treatment [1]. The current evidence on the efficacy of breast reconstruction using lipomodelling after breast cancer treatment is inadequate and the evidence raises no major safety concerns [2]. Objective: We have audited our outcome results against the NICE guideline criteria for both safety and efficacy. Data was collected retrospectively of all the lipomodelling cases performed in Northumbria Healthcare NHS Foundation Trust between 04/2011-04/2013. Methods: A total of 36 patients was included in the study, the average amount of fat injected was 113.91 mls per session, Cytori technique gave the least complication rate 11% vs Coleman and body jet techniques 44% and 45% respectively. Results: We met the NICE guideline criteria in; number of sessions for each patient, the duration of hospital stays and we documented the amount of fat harvested and injected in each patient. We didn’t fulfil the guidelines in: volume change; as no definite tool was used other than clinical assessment; 80% were very good and good aesthetic outcome compared to NICE’s 87%, while the aesthetic outcome was absent in 8% compared to NICE’s 2.7%. Regarding the safety, we met the NICE’s guidelines in local recurrence rates <1%, and local infection rate<1%, as well as pneumothorax and fat embolism (0%). However; we had a high liponecrosis rate 13% vs 3%, and liponecrotic cysts (8.33% vs 7%), these were more frequent with Bodyjet technique. Conclusion: Lipomodelling is a safe procedure following breast cancer surgery, which can be carried out at District general hospitals levels with comparable outcomes.

Gentisic Acid (GA) is an endogenously synthesized quinonoid phenolic acid in plants, where it functions as an immune molecule against viral plant pathogens via modifying microRNAs. In mammalians, GA is both consumed from exogenous sources (from fruits and vegetables) and produced endogenously as an endogenous siderophore and as a byproduct of tyrosine catabolism. Besides the edible plants, aspirin is also an important source of GA, since its catabolism produces GA. Noteworthy, humans with variant alleles of CYP2C9 which are incapable to produce GA during aspirin catabolism do not benefit from aspirin in reduction of adenomas in the large bowel. In past, GA was succesfully used in the treatment of rheumatological diseases in humans with high biosafety. GA has an affinity to connective tissue proteins and a higher retention of exogenous GA was demonstrated in humans with cancer. GA has both direct and indirect strong antioxidant effects as a free radical scavenger molecule and as an agonist of NRF2 (Nuclear factor erythroid-derived 2-like 2), an important transcription factor which regulates synthesis of antioxidant molecules. GA blocks cancer promotion in animal models in association with reduction of free radical products and stimulating antioxidant molecules. GA also exerts prominent antiinflammatory effects while stimulating elements of acquired immunity, lymphocytes; which likely occur due to its strong efficacies to block cyclooxygenases, 12-lipoxygenase and acting as a ligand of GPR35/CXCR8. GA also specifically inhibit protumorigenic signaling of Fibroblast Growth Factor (FGF) and cyclin dependent kinase-1 (CDK1). Sulfonated derivative of GA (2,5-dihydroxyphenylsulfonate, dobesilic acid) blocks subcutaneous growth of C6 glioma; and GA also acts as an agonist of Vasoactive Intestinal Polypeptide (VIP) pathway, which suppresses invasion of glioma cells in vitro. GA also inhibits OAT3/ SLC22A8, which involves efflux of chemotherapeutics from the brain which may help to achieve therapeutic concentrations of anticancer agents in brain tumors. In future, combined aspirin-GA preparates may be tested for potential activity in cancer prevention and treatment.