Emad Jafarzadeh

Examining the relationship between per-and polyfluoroalkyl substances and breast, colorectal, prostate, and ovarian cancers: a meta-analysis

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used widely in industrial and commercial applications. Concerns exist about their potential link to cancer risk as possible endocrine-disrupting chemicals. We conducted a meta-analysis to evaluate the dose-response relationship between PFAS, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS) exposure and risk of breast, prostate, colorectal, and ovarian cancers. We systematically searched major databases through May 2022 and identified 13 observational studies for inclusion. Using random-effects models, we calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) comparing the highest versus lowest PFAS exposure categories. Additionally, we analyzed the dose-response correlation between PFAS and cancer risk in a subset of studies. The study revealed no substantial correlation between exposure to PFASs and the incidence of breast cancer (BC) (OR

Targeting Cancer Stem Cells and Hedgehog Pathway: Enhancing Cisplatin Efficacy in Ovarian Cancer With Metformin

ABSTRACTOvarian cancer (OC) remains a leading cause of gynaecological cancer deaths due to late diagnosis and the emergence of resistance to platinum‐based chemotherapy, like cisplatin (Cis). Here, we investigated the potential of metformin (Met), a drug commonly used for type 2 diabetes, to overcome Cis resistance in OC. Our findings revealed a synergistic effect of Met with Cis in inhibiting cell viability, proliferation and colony/sphere formation capacity in both cisplatin‐sensitive (A2780) and ‐resistant (A2780/CDDP) ovarian cancer cell lines. This synergistic action triggered apoptosis through DNA damage, S‐phase cell cycle arrest and modulation of autophagy. Met also significantly decreased the expression of pluripotency transcription factors (Oct‐4, Sox2 and Nanog), indicating its potential to target cancer stem cells (CSCs). Furthermore, the combination therapy downregulated multidrug resistance protein 1 (MDR1) and excision repair cross‐complementation group 1 (ERCC1) expression, thereby sensitising resistant cells to Cis‐induced cytotoxicity. Additionally, the combination treatment suppressed the Hedgehog (Hh) signalling pathway, which is an important factor in inhibiting CSCs. Our study highlights the potential of the Met signalling pathway to synergise with Cis, overcoming therapeutic resistance in OC by targeting diverse cellular processes, including CSCs, and warrants further investigation in preclinical models.