Articles
Publication Date: 2025
International Ophthalmology (15732630)45(1)
To provide a narrative overview of the latest laboratory studies and clinical trials investigating the combination of bevacizumab with various supplements, including vitamin D, anti-oxidants, and other intravitreal injectable agents. We examine the potential benefits of these combinations in reducing vascular endothelial growth factor (VEGF) levels, improving clinical outcomes, and enhancing the overall treatment of retinal diseases. Bevacizumab, a widely used anti-VEGF agent, has demonstrated significant clinical benefits in the treatment of these retinal disorders by inhibiting abnormal blood vessel growth and reducing retinal edema. However, its use is associated with several limitations, including intraocular inflammation, systemic side effects, variability in patient responses, and the potential for drug resistance. To overcome these limitations, adjunctive treatment regimens may be necessary to enhance the efficacy and safety of bevacizumab. The retina, as one of the most metabolically active tissues in the body, is highly susceptible to hypoxia, leading to retinal ischemia and subsequent VEGF production. By exploring the synergies between bevacizumab and these supplements, we hope to identify novel therapeutic strategies that can improve patient outcomes and address the unmet needs in the management of retinal disorders. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
Publication Date: 2025
Scientific Reports (20452322)15(1)
Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children worldwide. In the present investigation, the circulating RNAs (circRNAs) HOTAIR, NEAT1, H19, PCAT1, and SNHG1 were selected as potential biomarkers for childhood ALL (pALL) based on their predicted interactions with miR-326, a recognized tumor suppressor implicated in pALL, along with comprehensive in silico analyses. Subsequently, the expression levels of the circRNAs were examined in 50 pALL samples and 20 healthy controls using RT-qPCR. Notably, HOTAIR was identified as a 95% specific biomarker of cancer susceptibility, exhibiting a substantial increase in expression within the bone marrow plasma and peripheral blood samples. 22 B-ALL patients with elevated relative expression levels of circHOTAIR (≥ 1.87) were then monitored at three distinct time intervals during chemotherapy. Results demonstrated a significant decrease in HOTAIR expression only among treatment-sensitive patients (P < 0.0001). This finding positions HOTAIR as a novel prognostic factor (AUC = 0.955), which may be used for monitoring the efficacy of chemotherapy in a non-invasive, cost-effective manner. Additionally, the regulatory inter-connection between HOTAIR and miR-326 was investigated by transfecting B-ALL RN-95 cells with exogenous miR-326. Data showed a time-dependent increase in cytoplasmic HOTAIR levels, alongside RAB35, resulting in a corresponding reduction in the cytoplasmic and exosomal miR-326 levels. While the results are preliminary due to the sample size, this study is the first to identify circHOTAIR as both a prognostic and diagnostic biomarker in B-ALL. Furthermore, it elucidates the role of HOTAIR as a sponge for miR-326, orchestrating its efflux from the cell via exosomes through RAB35. © The Author(s) 2025.
Publication Date: 2025
Annals Of Hematology (14320584)104(4)pp. 2417-2427
MiR-326 downregulation is strongly associated with multidrug resistance (MDR) and has been identified as an adverse prognostic biomarker for pediatric acute lymphoblastic leukemia (pALL). The choice to study miR-326 as a tumor suppressor in cancer biology, particularly its regulation of apoptosis, drug resistance, and stemness, stems from its strong association with MDR and potential as a therapeutic target in pALL. The current study aimed to investigate, for the first time, the molecular mechanisms underlying the role of miR-326 in ALL, using Gene Ontology annotation network and multilayer network analysis. Our findings revealed that miR-326 exhibits a multifunctional anti-tumor behavior, affecting various aspects of drug resistance, stemness, and apoptosis in cancer, particularly in the context of ALL. Quantitative real-time PCR demonstrated downregulation of the ABC transporter mRNAs ABCC1 and ABCB1 but not ABCA3 in B-ALL cells transfected with miR-326 mimic, as confirmed by bioinformatic data. Western blot analysis showed a possible cross talk between miR-326 and P53 through the upregulation of Mdm2 and P53 proteins. The heightened functional activity of P53 was subsequently validated through the observed augmentation in levels of P21 and CCND1, alongside the evident disruption in the expression levels of Bcl-2, Bcl-xl, and Bax genes. Subsequently, the ceRNA network between miR-326 and LncRNAs was exhibited and the impact of exogenous miR-326 on the expression levels of its molecular sponges, H19 and SNHG1 was examined using RT-qPCR. Future studies will explore the potential impact of miR-326 on its targets, and how this may influence the development of novel therapeutic strategies for ALL. © The Author(s) 2025.
Publication Date: 2025
Tissue and Cell (00408166)93
Chemotherapy remains a cornerstone in cancer therapy, but its effectiveness is often hindered by the development of drug resistance, a significant factor contributing to over 90 % of cancer-related deaths worldwide. A critical aspect of this resistance involves chronic endoplasmic reticulum stress, which activates the unfolded protein response (UPR), mainly through the activation of Activating Transcription Factor 6 (ATF6). Elevated ATF6 expression has been found to correlate with poor survival outcomes and increased resistance to chemotherapy across several malignancies. This study specifically investigates the role of ATF6 in cancer pathogenesis, focusing on its involvement in resistance mechanisms and the progression of the disease. Given the complex interactions between the UPR and other cellular pathways, including the DNA damage response (DDR), our findings emphasize the potential of targeting ATF6 and UPR and DDR pathways as a novel therapeutic strategy. This approach could potentially overcome chemoresistance and improve outcomes in cancer treatment. © 2025 Elsevier Ltd
Publication Date: 2024
International Journal Of Cancer Management (25384422)17(1)
Context: Adoptive T-cell therapy with chimeric antigen receptor (CAR) has shown tremendous progress in hematological cancers. However, some obstacles, such as high price tag, cytokine release syndrome, inability to penetrate solid tumors, and manufacturing complexity limit the wide application of this therapy. Natural killer (NK) cells can kill target cells via mechanisms similar to those of CD8+ cytotoxic T cells; therefore, CAR-NK cell therapy is a promising strategy for cancer treatment. Evidence Acquisition: In this manuscript, all articles published in English regarding CAR-NKs and their application for the treatment of different types of cancers were collected from several databases, including PubMed, Scopus, and Google Scholar, using related keywords such as "Cancer, CAR construction, NK cells, and CAR-NK cells". Results: Compared with CAR-T cells, CAR-NK cells have several advantages, including less toxicity, a high potential opportunity for universal off-the-shelf manufacturing, increased infiltration into solid tumors, overcoming resistant tumor microenvironment, and absence of graft-versus-host disease (GVHD). Conclusions: In this review, we discuss NK cell biology, the source of CAR-NK cells, CAR structure, advances, challenges, and ways to overcome these challenges in CAR-NK cell therapy. Furthermore, we have summarized and highlighted some preclinical and clinical studies in this field. © 2024, Samareh Salavati et al.
