Elevated Serum Vitamin B12 Levels as a Potential Biomarker for Solid Tumors in Jordanian Patients: A Retrospective Case–Control Study Sahar Kamal Otoom, Lobna Gharaibeh, Anas Abed, Ibrahim Aldeeb International Journal of Breast Cancer, 2026 Background Vitamin B12 deficiency is classically associated with anemia and neurological dysfunction. However, recent studies suggest that elevated plasma vitamin B12 may indicate increased short‐term cancer risk. This association remains largely unexplored in Middle Eastern populations, including Jordan, where cancer rates are rising and diagnosis often occurs at advanced stages due to limited screening. Objective This study is aimed at investigating the association between serum vitamin B12 levels and the risk of colorectal, breast, and lung cancers in a Jordanian population, evaluating differences by cancer type and stage. Methods A retrospective case–control study was conducted at King Abdullah University Hospital, Jordan, from January 2018 to December 2022. The study enrolled 260 patients diagnosed with colorectal, breast, or lung cancer and 260 matched healthy controls. Data collected included sociodemographic factors, clinical characteristics, and serum vitamin B12 levels. Results Serum vitamin B12 levels were significantly higher in cancer patients compared with controls (579.23 ± 468.72 vs. 492.70 ± 174.36 pg/mL; p = 0.005). High vitamin B12 levels (> 800 pg/mL) occurred in 15.8% of cancer patients versus 1.5% of controls ( p < 0.001). Vitamin B12 levels varied significantly by cancer type, being highest in lung cancer patients (669.53 ± 566.59 pg/mL) compared with breast (594.86 ± 468.9 pg/mL) and colorectal cancer patients (439.62 ± 291.89 pg/mL; p = 0.024). There was a strong positive correlation between vitamin B12 levels and cancer stage, peaking in Stage IV cancers, r = 0.629, p = 0.001. Conclusion Elevated serum vitamin B12 levels are significantly associated with solid cancers in Jordanian patients, particularly pronounced in lung cancer and advanced stages. These findings do not imply a causal relationship, but rather suggest that serum vitamin B12 may function as a potential biomarker for cancer detection and disease monitoring in resource‐limited settings.
Anticancer Activity of Alectinib through Hydroxypropyl-βCyclodextrin Complexation: In Vitro Evaluation on A549 Lung Cancer Cells Muathe Najim, Israa Al-Ani, Ibraheem Al-Deeb, Bashar J. M. Majeed, Tha'er Ata, et al. Drug Research, 2026 Alectinib is an effective inhibitor of anaplastic lymphoma kinase utilized in the treatment of anaplastic lymphoma kinase-positive non-small-cell lung cancer. Nonetheless, its limited solubility in water restricts its therapeutic effectiveness. This research seeks to improve the anticancer efficacy of alectinib through the formation of an inclusion complex with hydroxypro-pyl-β-cyclodextrin. The alectinib–hydroxypro-pyl-β-cyclodextrin complex was synthesized via the kneading method and characterized according to established studies. In vitro assays, such as cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), colony formation, scratch wound healing, and tube formation assays, were conducted to assess the antiproliferative, antimigratory, and antiangiogenic activities of the complex in comparison to free alectinib. The alectinib–hydroxypro-pyl-β-cyclodextrin complex exhibited markedly increased cy-totoxicity, diminished colony formation, inhibited cell migration, and impaired tube formation compared to free alectinib. The findings indicate that hydroxypro-pyl-β-cyclodextrin complexation enhances the solubility and anticancer efficacy of alectinib, presenting a viable strategy for improving its therapeutic potential in the treatment of non-small-cell lung cancer. Alectinib, in conjunction with hydroxypropyl-β-cyclodextrin, was evaluated for its effects on A549 cells, which are representative of non-small-cell lung cancer. This study focused on its anticancer activity and its influence on cell migration. Angiogenesis refers to the physiological process through which new blood vessels form from pre-existing vessels.
In Vitro and In Vivo Evaluation of Alectinib-Loaded Dendrimer Nanoparticles as a Drug Delivery System for Non-Small Cell Lung Carcinoma Mahmood R. Atta, Israa Al-Ani, Ibrahim Aldeeb, Khaldun M. AlAzzam, Tha’er Ata, et al. Pharmaceutics, 2025 Background/Objectives: Alectinib, a second-generation tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer (NSCLC), exhibits suboptimal oral bioavailability, primarily attributable to its inherently low aqueous solubility and limited dissolution kinetics. This study aimed to enhance Alectinib’s solubility and therapeutic efficacy by formulating a G4-NH2-PAMAM dendrimer complex. Methods: The complex was prepared using the organic solvent evaporation method and characterized by DSC, FTIR, dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with the G4-NH2-PAMAM dendrimer complex. Cytotoxicity against NSCLC cell line A549 was assessed using MTT assays, clonogenic assay, and scratch-wound assay. Xenograft effect was investigated in the H460 lung cell line. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: Alectinib exhibited an encapsulation efficiency of 59 ± 5%. In vitro release studies demonstrated sustained drug release at pH 6.8 and faster degradation at pH 2.5. Anticancer activity in vitro showed comparable efficacy to free Alectinib, with 98% migration inhibition. In vivo tumor suppression studies revealed near-complete tumor regression (~100%) after 17 days of treatment, compared to 75% with free Alectinib. Pharmacokinetic analysis indicated enhanced absorption (shorter Tmax), prolonged systemic circulation (longer half-life), and higher bioavailability (increased AUC) for the dendrimer-complexed drug. Conclusions: These findings suggest that the G4-NH2-PAMAM dendrimer system significantly improves Alectinib’s pharmacokinetics and therapeutic potential, making it a promising approach for NSCLC treatment.
Quality of Life Assessment of Breast Cancer Patients Undergoing Chemotherapy in Jordan: A Cross-Sectional Study Sijood Janabi, Lobna Gharaibeh, Ibrahim Aldeeb, Ali Abuhaliema International Journal of Breast Cancer, 2025 Purpose: Breast cancer patients are subjected to many hardships during chemotherapy which negatively affects the patient’s quality of life. The current study was conducted to identify aspects with low scores and produce untoward effects on the quality of life. Results: The results of the study showed that the social functioning domain achieved high quality of life mean score of 76.68 ± 32.94 while emotional functioning attained 38.18 ± 29.61. The most apparent symptoms detected were insomnia and fatigue followed by pain and loss of appetite. Regarding EORTC‐BR45, higher score and better quality of life were observed in the body image domain with a mean score of 60.72 ± 37.19, while the future perspective domain achieved low quality of life of 35.41 ± 42.9, and the most obvious symptom for patients was upset by hair loss. Conclusion: The results of the study showed the impact of chemotherapy on the lives of patients and highlighted the aspects that need greater focus by healthcare providers in Jordan. In addition to providing treatment, emotional and psychological support are necessary to improve the quality of life for these women.
Anti-angiogenic effects of Moringa oleifera silver nanoparticles on endothelial cells: in vitro and ex vivo studies Rolla Al-Shalabi, Vuanghao Lim, Ibrahim Al-Deeb, Melissa Kilus, Nozlena Abdul Samad Exploration of Targeted Anti Tumor Therapy, 2025 Aim: Angiogenesis, invasion, and tube formation are critical processes in tumor progression and metastasis. The use of nanoparticles derived from natural products presents a promising approach for targeted cancer therapy. This study evaluates the anti-angiogenic and anti-invasive effects of Moringa oleifera silver nanoparticles (MO-AgNPs) as a therapeutic strategy against these processes. Methods: The anti-angiogenic and anti-invasive activities of MO-AgNPs were investigated using a series of in vitro and ex vivo models. These included the rat aortic ring assay, endothelial tube formation assay, cell invasion assay using endothelial cell lines (Ea.hy926), and a three-dimensional (3D) co-culture spheroid model to simulate tumor microenvironment behavior. Comparisons were made with known inhibitors: quercetin (15.11 μg/mL) and suramin (100 μg/mL). Results: MO-AgNPs at 12 μg/mL significantly inhibited Ea.hy926 cell invasion by 62.10% and significantly suppressed endothelial tube formation, comparable to the effect of quercetin. In the ex vivo aortic ring assay, MO-AgNPs reduced microvessel sprouting by 83.824 ± 0.081%, surpassing the inhibition achieved by suramin. Additionally, in the 3D spheroid model, MO-AgNPs at concentrations of 12 μg/mL and 6 μg/mL, as well as quercetin, significantly reduced spheroid diameter by day 14, indicating suppressed invasive potential and angiogenic support. Conclusions: MO-AgNPs exhibit strong anti-angiogenic and anti-invasive effects across various tumor-relevant models, highlighting their potential as a therapeutic agent against tumor progression and angiogenesis-related diseases. These results support further investigation of MO-AgNPs as a novel nanotherapeutic for cancer treatment.
Anti-Angiogenic effects of Ocimum basilicum ethanolic extract: In vitro and ex vivo evidence of endothelial inhibition Ibrahim Aldeeb, Qasem Abdallah, Amin Malik Shah Abdul Majid, Melissa Kilus, Nozlena Abdul Samad Nutricion Clinica Y Dietetica Hospitalaria, 2025 Background: Angiogenesis and inflammation are two linked processes that exacerbate solid malignancies such as colorectal cancer. Bearing this in mind, it was important to study the anti-angiogenic properties of a well-known anti-inflammatory herb, Ocimum basilicum Lamiaceae (OB). Although many studies have explored the OB cytotoxic properties against a panel of cell lines, to the best of our knowledge, this is the first study that aims to investigate the in vitro and ex vivo anti-angiogenic properties of OB. Methods: Ethanolic extract of Ocimum basilicum leaves (OBL70) was prepared in 70% ethanol. Its half-maximal (IC50) inhibitory concentration on HT29 and EA.hy926 cells were evaluated using viability assay. Its antiangiogenic activities were investigated through ex vivo rat aorta ring assay, migration assay, invasion assay, and tube formation assay. Results and Conclusion: OBL70 demonstrated selective cytotoxicity against EA.hy926 endothelial cells and HT29 cells with IC50 value of 79.78± 2.35 and >100 µg/ml respectively. At 100 µg/ml, 7 days exposure to OBL70 significantly inhibited rat aortic formation of new blood vessels by 77.46 ± 9.3% while the percentage of EA.hy926 survival after 96h exposure was reduced to 71.6± 4.1 %. In addition, OBL70 inhibited EA.hy926 migration by 59.1 % ± 1.17 and 49.5 % ± 3.79 at 12 and 24 h. OBL70 also decreased the number of endothelial cell invasion through the Matrigel by 31.51 ± 2.37%. Notably, at both 200 and 100 µg/ml, OBL70 was able to stop tube formation totally. These significant findings suggest promising potential for translation into anti-angiogenic therapeutic agent.
In Vitro Potentiation of Doxorubicin Cytotoxicity Utilizing Clarithromycin Loaded-PEGylated Liposomes Islam Alfreahat, Hamdi Nsairat, Ibrahim Deeb Aldeeb, Ali Al-Samydai, Walhan Alshaer Technology in Cancer Research and Treatment, 2025 Background Doxorubicin (DOX) is a potent chemotherapeutic agent for breast cancer, but its effectiveness is often diminished by resistance mechanisms, particularly through p-glycoprotein (P-gp) mediated drug efflux. Clarithromycin (CAM), a macrolide antibiotic, inhibits multiple metabolic pathways including CYP3A and P-gp, potentially countering DOX resistance. Objective This study aimed to evaluate the potentiation of DOX and its effectiveness against the MCF-7 breast cancer cell line by encapsulating both DOX and CAM in PEGylated liposomes. Methods PEGylated liposomes containing DOX and CAM were prepared using the thin film hydration method. The physicochemical properties of the liposomes, including average particle size, polydispersity index (PDI), and zeta potential, were characterized. Encapsulation efficiencies for CAM and DOX were assessed, and stability of the liposomes was evaluated over 9 days at room temperature. Cell viability was measured using an IC 50 assay, and P-gp expression levels were determined by ELISA. Results The CAM/DOX-PEGylated liposomes exhibited optimal average particle size (238 ± 26.7 nm), PDI (0.29 ± 0.107), and zeta potential (−20.9 ± 2.17 mV). These liposomes maintained good stability regarding size and charge over 9 days. Encapsulation efficiencies were 81.05% for CAM and 78.13% for DOX. The IC50 value for CAM/DOX-PEGylated liposomes was 0.13 µM, representing a significant reduction compared to the physical mixture of CAM and DOX (0.25 µM) and free DOX (0.21 µM) against MCF-7 cells. ELISA analysis showed a reduction in P-gp expression of approximately 5% with CAM/DOX-PEGylated liposomes compared to 1.61% with free DOX. Conclusion The results indicate that CAM encapsulated in PEGylated liposomes enhances the effectiveness of DOX against breast cancer cells, likely through the inhibition of p-glycoprotein. This approach may offer a promising strategy to overcome DOX resistance and improve chemotherapy outcomes.
Investigating the Therapeutic Potential of Cisplatin- and Rutin-Loaded Nanoliposomes against Colorectal Cancer Cells Abdulazeez M. Al-Mashhadani, Ali Al-samydai, Ibrahim Al-Deeb, Simone Carradori, Hanan Azzam, et al. Anti Cancer Agents in Medicinal Chemistry, 2025 Introduction: Colorectal cancer is an important cause of cancer-related mortality, necessitating innovative therapies to improve efficacy and reduce side effects. This study explores the potential of Cisplatin and Rutin-loaded nanoliposomes (Cis-NLs and Rut-NLs) for anti-colorectal cancer activity. Methods: Cis-NLs and Rut-NLs were prepared using thin-film hydration, achieving encapsulation efficiencies of 95.5% and 62.5%, respectively. Drug release studies revealed controlled profiles, with Cis-NLs showing a complete release (100%) and Rut-NLs reaching 23.48% over 48 hours. Stability assessments demonstrated minimal changes in size, polydispersity index (PDI), and zeta potential over three months. Encapsulation efficiency decreased slightly for Cis-NLs (92.87%) and significantly for Rut-NLs (26.55%). Several tests were performed to evaluate the biological activity of this combination on colorectal cancer cells and HDF cells to check its selectivity. Results: In vitro cytotoxicity studies on HT29 colorectal cancer cells revealed IC50 values of 1.72 µg/mL for free Cisplatin, 2.35 µg/mL for Cis-NLs, >100 µg/mL for free Rutin, and 63.33 µg/mL for Rut-NLs. A combination of Cis-NLs and Rut-NLs reduced the IC50 to 2.2 µg/mL. Selective toxicity evaluation using human dermal fibroblasts showed an IC50 of 79.24 µM for cisplatin, reduced to 63.3 µM in Cis-NLs, with Rut-NLs demonstrating negligible toxicity. Discussion: Wound healing assays confirmed significant inhibition of cell migration, with wound closure reduced from 62.41% in controls to 34.35% in treated groups. Utilizing nanotechnology, liposomal formulations were synthesized to enhance drug delivery and therapeutic synergy. Conclusion: These results highlight the potential of Cisplatin and Rutin-loaded nanoliposomes as a combination therapy for colorectal cancer.
