Percorrer por autor "Alzoubi, Karem H."
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- Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model studyPublication . Hassanein, Mai M.; Hagyousif, Yousra A.; Zenati, Ruba A.; Al-Hroub, Hamza M.; Khan, Farman Matloob; Abuhelwa, Ahmad Y.; Alzoubi, Karem H.; Soares, Nelson C.; El-Huneidi, Waseem; Abu-Gharbieh, Eman; Omar, Hany; Zaher, Dana M.; Bustanji, Yasser; Semreen, Mohammad H.Background: Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments. Methods: We conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). Results: Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis. Significance: This in vivo study highlights TNBC's metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.
- Molecular signatures of xenograft colorectal cancer in mice treated with topotecan: A mass spectrometry-based studyPublication . Hagyousif, Yousra A.; Zenati, Ruba A.; Soares, Nelson C.; Al-Hroub, Hamza M.; Khan, Farman Matloob; Qaisar, Rizwan; Hamoudi, Rifat; El-Awady, Raafat; Abuhelwa, Ahmad Y.; Ramadan, Wafaa; El-Huneidi, Waseem; Abu-Gharbieh, Eman; Alzoubi, Karem H.; Bustanji, Yasser; Semreen, Mohammad H.Background: Colorectal cancer (CRC) is one of the most common cancers worldwide, yet it continues to have a low survival rate, largely due to the lack of effective treatments. Metabolomics offers new insight into disease diagnosis and biomarkers discovery. The aim of the study is to identify serum biomarkers in a CRC xenograft mouse model treated with topotecan using advanced metabolomics techniques to enhance our understanding and management of the disease. Methods: The therapeutic potentials of the anticancer drug topotecan on metabolomic alterations in CRC were explored using the UHPLC-ESI-QTOF-MS platform. A comprehensive metabolomic analysis was conducted to compare four different animal groups: HCT-116 CRC xenograft mice treated with topotecan (treated group), vehicle-control HCT-116 xenograft mice (untreated CRC xenograft mice), positive controls (healthy mice injected with topotecan), and negative controls (healthy mice). Results: The study identified 53 altered metabolites across all four groups (p-value < 0.05). Independent T-test revealed that 15 metabolites were statistically significant among vehicle controls and negative controls. Additionally, 20 metabolites showed significant differences between the potential responders to topotecan and the vehicle controls. Moreover, only one metabolite was statistically significant between the positive and negative controls. Conclusion: The findings provide a detailed characterization of metabolic alterations associated with topotecan treatment in CRC. These insights contribute to a better understanding of the drug's mechanism of action, which may help predict CRC patients' response to topotecan and guide the development of personalized therapeutic strategies.
- Untargeted Multiomics of LNCaP Cell Line Treated with a Novel DNA Minor Groove Binder and/or Doxorubicin Using Mass SpectrometryPublication . Zenati, Ruba A.; Soares, Nelson C.; Alniss, Hasan Y.; Al-Hroub, Hamza M.; El-Awady, Raafat; Abuhelwa, Ahmad Y.; Ramadan, Wafaa S.; Aleidi, Shereen M.; El-Huneidi, Waseem; Abu-Gharbieh, Eman; Alzoubi, Karem H.; Bustanji, Yasser; Semreen, Mohammad H.Prostate cancer (PCa) remains a major global health concern, ranking among the most prevalent cancer in men worldwide. Despite the availability of various therapeutic options, the clinical efficacy of current anti-PCa agents is often compromised by drug resistance and adverse effects. DNA minor groove binders offer a potential therapeutic alternative, owing to their selective mechanism of action and favorable safety profiles. In the present study, we utilized a multiomics strategy to investigate the molecular impact of novel compound MGB4. LNCaP cells were treated with doxorubicin, MGB4, or a combination of both, followed by LC-MS/MS-based untargeted proteomics and metabolomics analyses. One-way ANOVA (p-value <0.05) revealed 55 significantly dysregulated proteins and 57 altered metabolites across treatments. Our findings indicate that both MGB4 and doxorubicin impacted key cellular pathways, including inhibition of translation and alterations in sphingolipid and amino acid metabolism, while doxorubicin and the combination therapy also reduced spermine and spermidine metabolism. Notably, the combined treatment exhibited synergistic effects, significantly impacting purine metabolism and reducing metabolite levels more than individual therapies. This study provides key molecular insights into MGB4 and doxorubicin's mechanisms, supporting MGB4 as a potential prostate cancer drug candidate.