Browsing by Author "Wali, Adil Farooq"

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Comparative Efficacy of Immune Checkpoint Inhibitors and Therapeutic Vaccines in Solid Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
(Vaccines, 2025) Babiker, Rasha; Wali, Adil Farooq; El-Tanani, Mohamed; Rabbani, Syed Arman; Rangraze, Imran; Satyam, Shakta Mani; Patni, Mohamed Anas; El-Tanani, Yahia
Background: Immune checkpoint inhibitors (ICIs) and therapeutic vaccines have emerged as promising immunotherapeutic strategies for solid tumors. However, their comparative efficacy in improving overall survival (OS) remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of ICIs and therapeutic vaccines in improving OS in patients with solid tumors. Methods: A comprehensive search was con ducted across PubMed, Cochrane Library, Embase, and Clinical Trials.gov for randomized controlled trials (RCTs) published between 1 January 2010 and 31 December 2024. Studies comparing ICIs or therapeutic vaccines against control treatments (placebo, standard of care, or active comparators) in adults with solid tumors were included. The primary out come was OS, and data were pooled using RevMan (web). Risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Thirteen RCTs involving 10,991 participants were included. A total of 5722 of them were treated with therapeutic vaccines or checkpoint inhibitors. Therapeutic vaccines demonstrated insignificant improvement in OS, with a pooled mean difference of 1.89 months (95% CI: −0.54–4.31; P = 0.13), although with homo geneity (I2 = 0%). ICIs showed a statistically significant OS benefit, with a pooled mean difference of 1.32 months (95% CI: 0.62–2.02; P = 0.0002) and low heterogeneity (I2 = 12%). Conclusions: Therapeutic vaccines provide a larger but less consistent benefit, whereas ICIs offer modest but more consistent survival advantage. These findings support the need for personalized immunotherapy approaches as well as further research to identify predictive biomarkers and optimize treatment strategies by acquiring deep insights into the TMEdynamic and behaviors.
Epigenetic Alterations in Hepatocellular Carcinoma: Mechanisms, Biomarkers, and Therapeutic Implications
(Pharmaceuticals, 2025) Wali, Adil Farooq; Ansari, Abid Reza; Mir , Prince Ahad; El-Tanani , Mohamed; Babiker , Rasha; Hussain, Md Sadique; Uppal, Jasreen; Zargar, Asma Ishrat; Mir, Reyaz Hassan
Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, continues to pose a significant global health burden due to its high mortality rate. In addition to genetic alterations, epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA (ncRNA) dysregulation, play critical roles in HCCinitiation and progression. Notably, miR-375 and miR-483-5p are among the most dysregulated miRNAs in HCC, with their altered expression levels closely associated with tumor stage and patient survival. These epigenetic modifications offer promising therapeu tic avenues due to their reversibility and dynamic nature. Furthermore, specific epigenetic signatures such as CDH1 promoter hypermethylation and HOTAIR overexpression are being explored as potential biomarkers for early detection and treatment response. In this chapter, we review recent advances in the epigenetic landscape of HCC and discuss their diagnostic and therapeutic implications, highlighting their potential to improve patient outcomes through personalized medicine approaches
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 MohamedShehata
Abstract: 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.
Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis
(Medicina, 2025) Rangraze, Imran; Wali, Adil Farooq; El-Tanani , Mohamed; Patni , Mohamed Anas; Rabbani, Syed Arman; Babiker, Rasha; Satyam, Shakta Mani; El-Tanani, Yahia; Rizzo, Manfredi
Background and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several cancers while taking into account the impact of metformin use. Materials and Methods: As of 15 October 2024, the literature for Medline, Embase, and WebofScience was systematically searched. ROBINS-I and the RoB 2 tool were used for assessing the risk of bias in observational studies and randomized controlled trials (RCTs), respectively. The strength of the evidence with respect to the GRADE criteria was checked. Random effects meta-analyses were conducted alongside sensitivity analyses, subgroup analyses, and meta-regressions. By utilizing funnel plots as well as Egger’s test and trim-and-fill analysis, publication bias was evaluated. Results: In total, 65 studies were included in the final analyses: Metformin intake was linked to a lower risk of cancer (RR 0.72; 95% CI: 0.64–0.81, I2 = 45%). Significant reductions were observed in breast cancer (RR 0.68; 95% CI: 0.55–0.83) and colorectal cancers (RR 0.62; 95% CI: 0.51–0.76). Evidence certainty fluctuated from moderate to low, though analyses confirmed the results. Plofs funded the publication bias, but adjustment in trim-and-fill did not change the outcome significantly. Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational studies. There is a need for large RCTs
PI3K/AKT/mTOR Pathway in Breast Cancer Pathogenesis and Therapy: Insights into Phytochemical-Based Therapeutics
(Nutrition and Cancer, 2025) Wali, Adil Farooq; Talath, Siajunisa; El Tanani, Mohamed; Rangraze, Imran Rashid; Babiker, Rasha; Shafi, Sadat; Bansal, Ruby
Breast cancer (BC) is listed as the most prevalent cancer form in women worldwide, with major subtypes classified by hormone receptor (HR) and HER2 status including, HR+/HER2– (~65–70%), HER2+ (~15–20%), Triple-Negative-HR–/HER2– (~10–15%) and rare sybtypes (<5%). Scientific evidence has revealed that PI3K/AKT/mTOR signaling cascade plays an important role in the development and progression of BC, contributing to key cellular processes including cell growth, proliferation, angiogenesis, and metastasis. Dysregulation of the components of this cascade including functional loss of Phosphatase and TENsin homolog (PTEN), PI3K hyperactivation, and gain-of-function of AKT, are frequently observed in BC subtypes, making it a promising target for therapeutic intervention. A myriad of studies have documented the potential of phytochemicals, including curcumin, chrysin, fisetin, genistein, resveratrol and lycopene as modulators of the PI3K/AKT/mTOR axis. These phytochemicals exhibit multifaceted mechanisms of action, including inhibition of key kinases, induction of apoptosis, suppression of angiogenesis, and reversal of resistance to chemotherapy. This review aims to provide a detailed overview about the role of PI3K/AKT/mTOR alteration in BC development and the current research on phytochemicals that modulate the PI3K/AKT/mTOR pathway in BC. We documented the molecular mechanisms through which these compounds exert their effects, their potential synergistic interactions with conventional therapies, and the challenges and prospects for their clinical application. The evidence presented underscores the promise of phytochemicals as novel, less toxic adjuncts to traditional BC therapies, warranting further exploration and development for clinical use
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, Manfredi
The 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.