Background/Objectives: Vedolizumab (VDZ) is the new monoclonal drug targeting α4β7 integrin for patients with moderate/severe IBD. Between 30 and 45% of patients fail to respond to VDZ after 14–16 weeks of treatment. The aim of the study was to explore the genetic profile of vedolizumab-treated Arab IBD patients in Saudi Arabia to identify the potential biomarkers to differentiate the responders from non-responders. Methods: A cohort of 16 patients with IBD, including 4 with Crohn’s disease and 12 with ulcerative colitis, were recruited. Following 16 weeks of VDZ treatment, nine were found to be responders and seven non-responders. Blood samples were collected for the whole exome sequencing of DNA from all patients. The variants in the whole-exome sequencing data were analyzed with a variety of bioinformatics tools and databases, such as Polyphen2, Mutation Taster, CADD, FATHMM, Open Target Platform, TOPPFun, STRING, and GTEx. Results: More than 1.6 million variants from 16 samples were analyzed. The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders. NOD2, IL23, IL10, IL27, and TRAF1 were found to be the significant IBD risk factors in multiple genome-wide association studies, and their pro-inflammatory activity might contribute to the inherent resistance to VDZ. Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects. Conclusions: This investigation is the first to apply whole-exome sequencing to identify the potential drug response biomarkers for the IBD drug VDZ in Saudi Arabia.

Background: This study evaluated the effects of black seed oil (BSO), a simulated ketogenic metabolic condition consisting of a low-glucose medium supplemented with 5 mM β-hydroxybutyrate (BHB), and their combination in EMT6/P and EMT6/DOX cells. The in vivo effects of a ketogenic diet, BSO, and their combination were also investigated in tumor-bearing mice. Methods: Cytotoxicity of black seed oil (BSO), a simulated ketogenic metabolic condition consisting of low-glucose medium supplemented with 5 mM β-hydroxybutyrate (BHB), their combination, and doxorubicin (DOX) was evaluated in EMT6/P and EMT6/DOX cells using the MTT assay. Combination index (CI) analysis was used to determine the interaction between BSO and the simulated ketogenic metabolic condition. Caspase-3 activity, vascular endothelial growth factor VEGF expression, and P-glycoprotein (P-gp) expression were evaluated in EMT6/DOX cells. In vivo, mice bearing EMT6/P and EMT6/DOX tumors received a ketogenic diet, BSO, their combination, DOX, and control treatment, and tumor growth, tumor weight, tumor-free rate, and serum biochemical parameters were assessed. Results: BSO half-maximal inhibitory concentration IC50 was 14.5-fold higher in EMT6/DOX than in EMT6/P, and DOX IC50 was 39.5-fold higher. The simulated ketogenic metabolic condition consisting of a low-glucose medium supplemented with 5 mM BHB + BSO combination gave a CI of 0.1244 in EMT6/P and 0.0239 in EMT6/DOX, indicating synergism in both lines. The combination produced the highest caspase-3 activity (1.54-fold vs. control), the lowest VEGF level (268.34 pg/mL vs. 953.34 pg/mL in control), and the lowest P-gp level (1.6 ng/mL vs. 3.7 ng/mL in control) among the treatments tested. In vivo, the combination reduced tumor volume by 87.15% in EMT6/P and 58.12% in EMT6/DOX, and gave a tumor-free rate of 66.6% in EMT6/P and 50% in EMT6/DOX. No consistent treatment-related change was observed in liver enzymes, renal markers, or lipid profile compared with healthy controls. Conclusions: The combination of a simulated ketogenic metabolic condition and BSO showed synergistic cytotoxic activity in vitro, while the ketogenic diet and BSO combination produced enhanced antitumor activity in vivo. These effects were associated with increased caspase-3 activity and reduced VEGF and P-gp expression in EMT6/DOX cells, without evidence of hepatic, renal, or metabolic toxicity. These findings support further investigation of this combination in doxorubicin-resistant breast cancer.

Cancer is a widespread disease and a leading cause of death worldwide. This has increased interest in foods that contribute to lowering its incidence. Olive oil is a key component of the Mediterranean diet and contains numerous bioactive compounds, including oleuropein, hydroxytyrosol, oleocanthal, squalene, sterols, tyrosol, and oleacein, which possess various properties and benefits. This review examines the potential of these compounds as anticancer agents and their ability to manage various types of cancer. Chemical structure, mechanisms of action, and potential to work in combination with conventional treatments were discussed for each compound. Studies discussed in this review show promising anticancer effects of olive oil compounds with high potential to augment conventional treatments through the anticipated anticancer effect of the Mediterranean diet with olive oil. This review focused on in vitro and preclinical studies of using olive oil phytochemicals in cancer research. However, further clinical and experimental studies are needed to determine the optimal dosage of olive oil and better confirm its therapeutic efficacy.

Cisplatin resistance remains a significant challenge in the effective treatment of breast cancer, underscoring the need for novel combination-based therapeutic strategies. Background: This study investigated the anticancer effects of ellagic acid (EA) and metformin (MET), both individually and in combination, against parental and cisplatin-resistant breast cancer models. To our knowledge, this is the first study to evaluate the EA-MET combination in the context of cisplatin resistance in breast cancer. Methods: The in vitro antiproliferative and apoptotic effects of EA and MET were assessed using MTT and caspase-3 assays in parental (EMT-6/P) and cisplatin-resistant (EMT-6/CPR) cells. An in vivo study was also conducted to evaluate the anti-tumor effects of the treatment combinations in mice bearing EMT-6/P or EMT-6/CPR tumors. Liver enzymes and creatinine levels were measured to assess potential hepatic and renal toxicity. Results: In vitro combination index analysis indicated a synergistic interaction between EA and MET in EMT-6/P cells (CI = 0.45) and a strong synergistic interaction in EMT-6/CPR cells (CI = 0.29) under the tested conditions. In vivo, the addition of the combination to cisplatin resulted in significant tumor size reductions of 73.83% and 56.25% in EMT-6/P and EMT-6/CPR bearing mice, respectively, along with tumor regressions of 66.6% and 50%, respectively. Conclusions: Thecombination of metformin and ellagic acid shows promise as a potential treatment for cisplatin-resistant breast cancer. Further research is needed to elucidate the precise anticancer mechanisms underlying this combination.