Gastric cancer (GC) remains a leading cause of cancer-related mortality, with chemoresistance posing a critical barrier to effective treatment. Tumor-associated macrophages (TAMs), particularly the immunosuppressive M2-polarized subset, are emerging as pivotal mediators of chemoresistance within the tumor microenvironment (TME). TAMs promote resistance through multifaceted mechanisms, including activation of pro-survival signaling pathways, induction of epithelial-mesenchymal transition (EMT), and enhancement of angiogenesis. For instance, M2-like TAMs secrete CXCL5, which activates the PI3K/AKT/mTOR axis in GC cells, thereby conferring resistance to 5-fluorouracil (5-FU). Similarly, TMEM, a transmembrane protein overexpressed in cisplatin-resistant GC, drives M2 polarization of TAMs via the Wnt/β-catenin pathway, further amplifying drug resistance and tumor progression. Clinical studies reveal that high TAM infiltration correlates with poor chemotherapy response and reduced survival in GC patients. This review synthesizes current evidence on TAM-driven chemoresistance in GC, highlighting the molecular interplay between TAMs, tumor cells, and stromal components. It underscores the potential of TAM-centric therapies-including checkpoint inhibitors, epigenetic modulators, and combination regimens-to overcome resistance and improve clinical outcomes. By integrating preclinical insights and clinical data, this work provides a roadmap for developing precision therapies that exploit TAM biology to enhance chemosensitivity in GC.
S. Abdul-Rahman, Abdulkareem Shareef, S. Jyothi et al.· Cell Biology International· 0 citations
Vision restoration is a vital yet challenging objective in ophthalmology, as traditional therapies cannot reverse irreversible retinal damage. This issue is of significant concern, considering that millions globally are afflicted by untreatable degenerative conditions such as retinitis pigmentosa (RP) and age-related macular degeneration. Stem cell treatments and retinal organoid (RO) technology have emerged as revolutionary methodologies. ROs derived from pluripotent stem cells (PSCs) autonomously form three-dimensional (3D) laminar structures that mimic the natural human retina, providing exceptional platforms for disease modeling, pharmacological screening, and cellular replacement. Clinical studies indicate that retinal pigment epithelium (RPE) transplantation enhances visual function. In contrast, PSC-derived mesenchymal stem cells (MSCs), retinal progenitor cells (RPCs), and RPE grafts have neuroprotective and regenerative capabilities in preclinical and early-phase trials. Notwithstanding this advancement, several challenges remain, including suboptimal cell survival, insufficient functional synaptic integration, immunological rejection, tumorigenic potential, and the absence of standardized production processes. This article presents three unique contributions, diverging from previous reviews that focus solely on positive outcomes: (1) a comprehensive assessment of advancements and challenges in PSCs, MSCs, RPCs, and RPE; (2) a methodical examination of the disparity between structural engraftment and genuine functional integration; and (3) a cohesive discourse on innovative strategies such as optogenetics, 3D bioprinting, and extracellular vesicle-based therapies. We consolidate recent clinical discoveries, highlight persistent obstacles, and provide a roadmap for the future. Growing evidence suggests that, despite significant obstacles, effective retinal regeneration is gradually becoming a reality.
B. Jaber, M. Abd, S. Younis et al.· International Immunopharmaco...· 0 citations
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