Biological impact of advanced glycation endproducts on estrogen receptor-positive MCF-7 breast cancer cells.

Diabetes mellitus potentiates the risk of breast cancer. We have previously described the pro-tumorigenic effects of advanced glycation endproducts (AGEs) on estrogen receptor (ER)-negative MDA-MB-231 breast cancer cell line mediated through the receptor for AGEs (RAGE). However, a predominant association between women with ER-positive breast cancer and type 2 diabetes mellitus has been reported. Therefore, we have investigated the biological impacts of AGEs on ER-positive human breast cancer cell line MCF-7 using in vitro cell-based assays including cell count, migration, and invasion assays. Western blot, FACS analyses and quantitative real time-PCR were also performed. We found that AGEs at 50-100μg/mL increased MCF-7 cell proliferation and cell migration associated with an enhancement of pro-matrix metalloproteinase (MMP)-9 activity, without affecting their poor invasiveness. However, 200μg/mL AGEs inhibited MCF-7 cell proliferation through induction of apoptosis indicated by caspase-3 cleavage detected using Western blotting. A phospho-protein array analysis revealed that AGEs mainly induce the phosphorylation of extracellular-signal regulated kinase (ERK)1/2 and cAMP response element binding protein-1 (CREB1), both signaling molecules considered as key regulators of AGEs pro-tumorigenic effects. We also showed that AGEs up-regulate RAGE and ER expression at the protein and transcript levels in MCF-7 cells, in a RAGE-dependent manner after blockade of AGEs/RAGE interaction using neutralizing anti-RAGE antibody. Throughout the study, BSA had no effect on cellular processes. These findings pave the way for future studies investigating whether the exposure of AGEs-treated ER-positive breast cancer cells to estrogen could lead to a potentiation of the breast cancer development and progression

Cupping Therapy (Al-Hijamah): An Exploratory Study of Healthcare Professionals Controversial Beliefs and Conceptions, Kingdom of Saudi Arabia

Background: Cupping therapy (Al-Hijamah) is a traditional therapy, supported and practised by people around the world since ancient times. Cupping therapy related to complementary and alternative medicine is associated with controversial, false beliefs and misconceptions. Objective: This study aimed at exploring controversial beliefs and conceptions about cupping therapy among healthcare professionals, Riyadh, Kingdom of Saudi Arabia (KSA). Methods: A cross-sectional study involving 241 healthcare professionals was carried out from January to June 2016. All participants requesting license for practicing cupping therapy underwent one week Al-Hijamah training course at National Center for Complementary and Alternative (NCCAM). Prior to training course, all subjects completed a 23-item predesigned questionnaire related to controversial beliefs and misconceptions concerning cupping therapy. All participants gave written informed consent. Results: Healthcare professionals who participated in the study (n=241) were 93 physicians, 56 physiotherapists, 61 nurses and 31 other specialists. Saudi participants represented 46.1%. 60.6% were adult males with mean clinical experience of 13.0±9.37 years. "Al-Hijamah gets rid of bad blood" was the commonest controversial belief reported by 68.1% of participants. A proportion of participants (31.5%) reported "Al-Hijamah is absolutely safe" and "Al-Hijamah is effective in the treatment of all diseases". The least controversial beliefs reported by 12%, 8.7% and 2.9% of participants were "Cupping can be used for all patients and all diseases”, "Cupping like a blood donation is not different" and "The scarification of cupping (in wet cupping) must be deep", respectively. Conclusion: The explored controversial beliefs and misconceptions related to cupping therapy may impact knowledge, attitude and practice of cupping practitioners. Therefore, all healthcare professionals need to be regularly exposed to a training course targeting these beliefs and misconceptions concerning cupping therapy prior to giving them license for practicing this traditional modality. Continuing research in cupping mechanisms of action is another prioritized area which can provide scientific explanations underlying its efficacy and outcome together with alleviating its false beliefs and misconceptions