ABSTRACT
Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific combination of gold nanoparticles (GNPs) and Newcastle disease virus (NDV) to enhance the antitumor effect of breast cancer in both in vitro and in vivo models. Two human breast cancer cell lines (MCF-7 and AMJ-13) and a normal epithelial cell line (HBL-100) were used and treated with NDV and/or GNPs. The MTT assay was used to study the anticancer potentials of NDV and GNP. The colony formation assay and apoptosis markers were used to confirm the killing mechanisms of NDV and GNP against breast cancer cell lines. p53 and caspase-9 expression tested by the qRT-PCR technique. Our results showed that combination therapy had a significant killing effect against breast cancer cells. The findings demonstrated that NDV and GNPs induced apoptosis in cancer cells by activating caspase-9, the p53 protein, and other proteins related to apoptosis, which holds promise as a combination therapy for breast cancer.
Subject(s)
Breast Neoplasms , Metal Nanoparticles , Oncolytic Virotherapy , Oncolytic Viruses , Animals , Humans , Female , Oncolytic Virotherapy/methods , Caspase 9/genetics , Gold , Tumor Suppressor Protein p53/genetics , Cell Line, Tumor , Breast Neoplasms/therapy , Apoptosis , Immunotherapy , Newcastle disease virusABSTRACT
Introduction: Morphine has been a crucial analgesic agent used perioperatively in various surgical procedures. Genetic factors can lead to morphine dose requirement interpatient variability. Our objective was to determine the contribution of genetic polymorphisms in human µ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 to the variation of the perioperative morphine consumption in women undergoing laparoscopic cholecystectomy. Methods: This is a prospective cohort study that included 102 adult Arab females undergoing laparoscopic cholecystectomy. The exposures were carrying the genetic variants of OPRM1, ABCB1 and rs2952768. Our primary outcome was total morphine or morphine equivalent dose required perioperatively. The secondary outcomes were pain score during the first 24 hours and adverse drug reactions. A standardized, general anaesthesia was used for all subjects. In addition to the genetic factors, we also investigated non-genetic factors influencing post-operative pain sensitivity and morphine consumption. Results: Both (rs1799971, A>G) in OPRM1 and (rs2952768, T>C) showed statistically significant association with intra-operative total morphine dose requirements. Patients carrying the "G" allele in OPRM1 had a significantly higher total morphine mean rank dose compared to the AA genotype [62.9 vs 47.1, p=0.008]. Furthermore, patients homozygous for the rs2952768 (T>C) minor allele "CC" had a higher mean rank compared to the other genotypes [72.7 vs 50.1, p=0.046]. Conclusion: OPRM1 (rs1799971) and rs2952768 are associated with variation of intra-operative morphine consumption in laparoscopic cholecystectomy. Clinical Trial Identifier: This study was registered at ClinicalTrials.gov, NCT04621864. https://clinicaltrials.gov/ct2/show/NCT04621864.