Tamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients. The aim of the present study is to explore the effect of combining DEX and TAM on the inhibition of TAM-resistant LCC-2 cells (TAMR-1) through modulating the E2F3/SOX-2-mediated Wnt signaling pathway. The effect of the combination therapy on MCF-7 and TAMR-1 cell viability was assessed. Drug interactions were analyzed using CompuSyn and SynergyFinder softwares. Cell cycle distribution, apoptotic protein expression, gene expression levels of SOX-2 and E2F3, and cell migration were also assessed. Combining DEX with TAM led to synergistic inhibition of TAMR-1 cell proliferation and migration, induced apoptosis, reduced SOX-2 and E2F3 expression and was also associated with S and G2-M phase arrest. Therefore, combining DEX with TAM may present an effective therapeutic option to overcome TAM resistance, by targeting the E2F3/SOX-2/Wnt signaling pathway, in addition to its anti-inflammatory effect.

Wood dust is known to be a human carcinogen, with a considerable risk of lung cancer. The increased cancer risk is likely induced through its genotoxic effects resulting from oxidative DNA damage. This study aimed at assessing the genotoxicity of wood dust and demonstrating the role of sputum PCR as a screening tool for early prediction of lung cancer among wood workers. The study was carried out in the carpentry section of a modernized factory involved with the manufacture of wooden furniture in Greater Cairo, Egypt. Environmental assessment of respirable wood dust concentrations was done. Frequency of chromosomal aberrations (CA%) and sister chromatid exchanges (SCE%) in peripheral blood lymphocytes (PBL) was assessed and comet assays were performed in samples from among the study population (n = 86). Levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were measured. The polymerase chain reaction (PCR) was used to study hypermethylation of p16 and ̸or O-methylguanine-DNA methyltransferase (MGMT) gene promoters in sputum DNA. The concentrations of respirable wood dust exceeded the Egyptian and international permissible limits with highest levels generated by sawing operations. Laboratory investigations revealed statistically significantly higher frequencies of CA and SCE as well as increased comet tail length associated with significant decrement in the levels of SOD and GPx among exposed group. A statistically significant elevation in the extent of hypermethylation was detected for the p16 and MGMT gene promoters in the sputum DNA of studied wood workers. The study results support the conclusion that prolonged unprotected occupational exposure to wood dust is associated with possible genotoxicity and oxidative stress that might raise the risk for carcinogenesis including lung cancer.

Wood dust is known to be a human carcinogen, with a considerable risk of lung cancer. The increased cancer risk is likely induced through its genotoxic effects resulting from oxidative DNA damage. This study aimed at assessing the genotoxicity of wood dust and demonstrating the role of sputum PCR as a screening tool for early prediction of lung cancer among wood workers. The study was carried out in the carpentry section of a modernized factory involved with the manufacture of wooden furniture in Greater Cairo, Egypt. Environmental assessment of respirable wood dust concentrations was done. Frequency of chromosomal aberrations (CA%) and sister chromatid exchanges (SCE%) in peripheral blood lymphocytes (PBL) was assessed and comet assays were performed in samples from among the study population (n = 86). Levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were measured. The polymerase chain reaction (PCR) was used to study hypermethylation of p16 and ̸or O-methylguanine-DNA methyltransferase (MGMT) gene promoters in sputum DNA. The concentrations of respirable wood dust exceeded the Egyptian and international permissible limits with highest levels generated by sawing operations. Laboratory investigations revealed statistically significantly higher frequencies of CA and SCE as well as increased comet tail length associated with significant decrement in the levels of SOD and GPx among exposed group. A statistically significant elevation in the extent of hypermethylation was detected for the p16 and MGMT gene promoters in the sputum DNA of studied wood workers. The study results support the conclusion that prolonged unprotected occupational exposure to wood dust is associated with possible genotoxicity and oxidative stress that might raise the risk for carcinogenesis including lung cancer.