Faculty of Medicine and Surgery
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Item Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies(Cancer Letters, 2024) El-Tanani, Mohamed; Rabbani , Syed Arman; Babiker, Rasha; Rangraze, Imran; Kapre, Sumedha; Palakurthi, Sushesh Srivastsa; Alnuqaydan, Abdullah M.; Aljabali, Alaa A.; Rizzo, Manfredi; El-Tanani, Yahia; Tambuwala, Murtaza M.This comprehensive review delves into the pivotal role of the tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights into the intricate interplay between cancer cells and their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular and acellular elements, not only fosters tumor progression but also profoundly affects the efficacy of conventional and emerging cancer therapies. Through nuanced exploration, this review illuminates the multifaceted nature of the TME, elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, and the establishment of physical barriers to drug delivery. Moreover, it investigates innovative therapeutic approaches aimed at targeting the TME, including stromal reprogramming, immune microenvironment modulation, extracellular matrix (ECM)-targeting agents, and personalized medicine strategies, highlighting their po tential to augment treatment outcomes. Furthermore, this review critically evaluates the challenges posed by the complexity and heterogeneity of the TME, which contribute to variable therapeutic responses and potentially unintended consequences. This underscores the need to identify robust biomarkers and advance predictive models to anticipate treatment outcomes, as well as advocate for combination therapies that address multiple facets of the TME. Finally, the review emphasizes the necessity of an interdisciplinary approach and the integration of cutting-edge technologies to unravel the intricacies of the TME, thereby facilitating the development of more effective, adaptable, and personalized cancer treatments. By providing critical insights into the current state of TME research and its implications for the future of oncology, this review highlights the dynamic and evolving landscape of this field.Item Advancements in non-invasive biomarkers for detection and monitoring of breast cancer recurrence(SCIENCE PROGRESS, 2025) El-Tanani, Yahia; El-Tanani, Mohamed; Rabbani, Syed Arman; Babiker, Rasha; Satyam, Shakta ManiBreast cancer recurrence remains a major cause of mortality, with up to 30% of early stage patients relapsing as incurable metastatic disease. Conventional surveillance with imaging and serum markers (CA15–3, CEA) lacks the sensitivity and specificity to detect minimal residual disease. This narrative review examines non-invasive biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and exosomes and the technologies enhancing their performance. Droplet digital PCR and next-generation sequencing detect ctDNA at allele frequencies below 0.1%, identifying molecular relapse a median of 10–12 months before radiologic progression. Microfluidic and affinity-based platforms isolate CTCs with over 75% sensitivity in metastatic settings. Nanoengineered sensors and standardized workflows improve exosome isolation, revealing miRNA and protein signatures predictive of recurrence. Proteomic and metabolomic profiling iden tify dysregulated metabolic pathways and protein networks, offering functional insights that complement molecular assays. Integrative multi-omics approaches merge genomic, transcriptomic, proteomic and metabolomic data; machine-learning frameworks detect subtle patterns and correlations, enabling dynamic, personalized surveillance. By detect ing molecular and functional biomarkers early, clinicians can tailor therapy, monitor treatment response and intervene promptly. Challenges include low analyte abundance, assay variability, high costs and lack of standardized protocols, limiting clinical adoption. Prospective validation in large cohorts is critical. We highlight ongoing clinical trials such as ctDNA-guided adjuvant therapy and CTC-driven stratification studies that aim to establish clinical utility. Non-invasive biomarker platforms could shift breast cancer fol low-up from reactive detection to proactive intervention, ultimately improving survival and quality of life through personalized, real-time monitoring.Item Repurposing Anthelmintic Drugs for COVID-19 Treatment: AComprehensive Meta-Analysis of Randomized Clinical Trials on Ivermectin and Mebendazole(Antibiotics, 2025) Satyam, Shakta Mani; El-Tanani, Mohamed; Patni, MohamedAnas; Rehman, Abdul; Wali, Adil Farooq; Rangraze, Imran Rashid; Babiker, Rasha; Rabbani, Syed Arman; El-Tanani, Yahia; Rizzo, ManfrediThe COVID-19 pandemic necessitated the urgent exploration of therapeutic options, including drug repurposing. Anthelmintic drugs such as ivermectin and mebendazole have garnered interest due to their potential antiviral and immunomod ulatory properties. However, conflicting evidence from randomized clinical trials (RCTs) necessitates a comprehensive meta-analysis to determine their efficacy and safety in COVID 19 management. Objective: This meta-analysis evaluates the clinical efficacy of ivermectin and mebendazole in treating COVID-19 by analyzing their impact on viral clearance, symptom resolution, hospitalization duration, and safety profiles. Methods: A systematic search of Scopus, PubMed, Embase, and the Cochrane Library was conducted following PRISMA guidelines to identify RCTs published up to February 2025. Eligible studies in cluded adult patients with confirmed COVID-19 who received ivermectin or mebendazole compared with a placebo or standard of care. Data extraction and risk of bias assessment were performed using the Cochrane Risk of Bias Tool. Statistical heterogeneity was eval uated using the I2 statistic, and pooled effect sizes were calculated for primary clinical outcomes. Results: Twenty-three RCTs (n = 12,345) were included, with twenty-one studies on ivermectin and two on mebendazole. The pooled analysis suggested no statistically significant improvement in viral clearance (p = 0.39), hospitalization duration (p = 0.15), or symptom resolution (p = 0.08) with ivermectin or mebendazole. However, individual stud ies indicated potential benefits, particularly for mebendazole, in reducing viral load and inflammation. Both drugs exhibited favorable safety profiles, with no significant increase in adverse events. Conclusions: The promising propensities observed in selected studies underscore the potential of ivermectin and mebendazole as adjunct therapies for COVID-19. With well-established safety profiles, immunomodulatory effects, and affordability, these drugs present strong candidates for further exploration. Advancing research through well-designed, large-scale RCTs will help unlock their full therapeutic potential and expand treatment options in the fight against COVID-19.Item Impact of Lifestyle Modifications on Cancer Mortality: A Systematic Review and Meta-Analysis(Medicina, 2025) Rabbani , Syed Arman; Patni, Mohamed Anas; El-Tanani, Mohamed; Rangraze, Imran Rashid; Wali, Adil Farooq; Babiker, Rasha; Satyam, Shakta Mani; El-Tanani, Yahia; Almetwally, Abdelrahman Adel MohamedShehataAbstract: Background and Objectives: Cancer survival poses significant challenges in oncol ogy, with lifestyle modifications increasingly recognized as crucial in modifying patient outcomes post-diagnosis. This meta-analysis aims to systematically evaluate the impact of various lifestyle interventions on cancer survival across different types of cancer. Methods: Acomprehensive literature search of electronic databases including PubMed, Scopus and Cochrane was performed to identify relevant studies up to 30 November 2024. Relevant studies were chosen and data were extracted and analyzed using SPSS Version 29.0 soft ware. Results: Our systematic review included data from 98 studies involving a total of 1,461,834 cancer patients to evaluate the impact of lifestyle factors on cancer survival. Out of these, 64 studies were included in the meta-analysis. Our meta-analysis demonstrates that adherence to specific dietary patterns significantly improves cancer-specific outcomes. The Healthy Eating Index (HEI) diet was associated with a reduction in cancer-specific mortality (pooled log HR: −0.22; 95% CI: [−0.32, −0.12]; p < 0.001). Similar benefits were observed with the Mediterranean diet (aMED), which also reduced cancer mortality and recurrence (pooled log HR: −0.24; 95% CI: [−0.40, −0.07]; p < 0.001), and the Dietary Approaches to Stop Hypertension (DASH) diet (pooled log HR: −0.22; 95% CI: [−0.33, −0.12]; p < 0.001). Additionally, general dietary improvements were beneficial for breast cancer-specific mortality across 17 cohort studies (pooled log HR: −0.15; 95% CI: [−0.25, −0.06]; p < 0.001). Engaging in any form of physical activity post-diagnosis was associated with significant improvements in cancer-specific mortality or recurrence (pooled log HR: −0.31; 95% CI: [−0.38, −0.25]; p < 0.001). Participants who ceased smoking after diagnosis exhibited more favorable cancer outcomes (pooled log HR: −0.33; 95% CI: [−0.42, −0.24]; p <0.001), with smoking cessation notably reducing cancer-specific mortality among lung cancer survivors (pooled log HR: −0.34; 95% CI: [−0.48, −0.20]; p < 0.001). Additionally, reducing alcohol intake post-diagnosis significantly improved cancer outcomes (pooled log HR: −0.26; 95% CI: [−0.33, −0.19]; p < 0.001). Alcohol moderation in gastrointestinal tract cancer survivors specifically decreased both cancer-specific mortality and recurrence (pooled log HR: −0.22; 95% CI: [−0.29, −0.15]; p < 0.001). Conclusions: Lifestyle modifica tions after cancer diagnosis significantly improve cancer-specific outcomes. Specific dietary patterns, increased physical activity, smoking cessation, and reduced alcohol intake are all associated with lower cancer-specific mortality. Integrating these lifestyle changes into oncology care may enhance patient survival and quality of life.
