Colorectal Cancer: Risk Factors, Novel Approaches in Molecular Screening and TreatmentAnbari, Ghanadi
Int J Mol Cell Med (2025) 14 (1), 576-605
Abstract: By 2040 the burden of colorectal cancer will increase to 3.2 million new cases per year and 1.6 million deaths per year. This highlights the importance of improving preventive measures and treatment strategies. This piece concisely overviews the latest therapeutic and diagnostic approaches for colorectal cancer. In 2019, factors such as low milk intake, smoking, insufficient calcium consumption, and alcohol use had a significant impact on colorectal cancer DALYs worldwide. A comprehensive search was conducted in December 2023 using keywords related to drugs, therapeutic agents, colorectal cancer, diagnostic methods, epidemiology, and novel therapeutic approaches in the PubMed and Scopus databases. Initially, 325 articles were identified based on titles, abstracts, and publication dates. After removing duplicates, 170 unique articles were included. Medications like Nimotuzumab, Cetuximab, and Panitumumab target the Epidermal Growth Factor Receptor (EGFR), which EGF activates. HER2, activated by ligands, is the focus of drugs like Trastuzumab and Pertuzumab. The PD-1/PD-L1 and CTLA-4 pathways, as the immune checkpoints, which involve T cells, are targeted by medications like Ipilimumab. Adoptive cell therapy, including CAR-T cell therapy, TCR modification, and enhancing T cell activity through tumor-infiltrating lymphocytes, is used to combat cancer cell growth. In medical advancements, adoptive cell transfer therapy (ACT) and exosomes in the tumor immune microenvironment (TME) are notable treatment methods that boost the immune system. HIF1A-AS1, CRNDE-h, NEAT1, ZFAS1, and GAS5, along with IGFBP-2, have demonstrated significant CRC diagnostic capacity. Compared to CRC patients with low HIF1A-AS1 expression, individuals with high expression levels were linked to a worse 5-year survival rate.© The Author(s).
Alveolar epithelial type 2 cell specific loss of IGFBP2 activates inflammation in COVID-19Pujadas, Chin, Sankpal
et alRespir Res (2025) 26 (1), 111
Abstract: The coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, our understanding of SARS-CoV-2-induced inflammation in alveolar epithelial cells remains very limited. The contributions of intracellular insulin-like growth factor binding protein-2 (IGFBP2) to SARS-CoV-2 pathogenesis are also unclear. In this study, we have uncovered a critical role for IGFBP2, specifically in alveolar epithelial type 2 cells (AEC2), in the immunopathogenesis of COVID-19. Using bulk RNA sequencing, we show that IGFBP2 mRNA expression is significantly downregulated in primary AEC2 cells isolated from fibrotic lung regions from patients with COVID-19-acute respiratory distress syndrome (ARDS) compared to those with idiopathic pulmonary fibrosis (IPF) alone or IPF with a history of COVID-19. Using multicolor immunohistochemistry, we demonstrated that IGFBP2 and its selective ligands IGF1 and IGF2 were significantly reduced in AEC2 cells from patients with COVID-ARDS, IPF alone, or IPF with COVID history than in those from age-matched donor controls. Further, we demonstrated that lentiviral expression of Igfbp2 significantly reduced mRNA expression of proinflammatory cytokines-Tnf-α, Il1β, Il6, Stat3, Stat6 and chemokine receptors-Ccr2 and Ccr5-in mouse lung epithelial cells challenged with SARS-CoV-2 spike protein injury (S2; 500 ng/mL). Finally, we demonstrated higher levels of cytokines-TNF-α; IL-6 and chemokine receptor-CCR5 in AEC2 cells from COVID-ARDS patients compared to the IPF alone and the IPF with COVID history patients. Altogether, these data suggest that anti-inflammatory properties of IGFBP2 in AEC2 cells and its localized delivery may serve as potential therapeutic strategy for patients with COVID-19.© 2025. The Author(s).
Targeted proteomics of serum IGF-I, -II, IGFBP-2, -3, -4, -5, -6 and ALSAlbrethsen, Drici, Slot Vilmann
et alClin Chem Lab Med (2025)
Abstract: The insulin-like growth factors (IGFs) regulate growth in humans. IGF-I and IGF binding protein (IGFBP)-3 are biomarkers in children with growth disorders. We investigate a targeted proteomics method for absolute quantitation of eight IGF protein family members in human serum, including the peptide hormones IGF-I and -II, and the six binding proteins IGFBP-2, -3, -4, -5, -6 and acid labile subunit (ALS).Serum preparation was optimized for targeted proteomics of IGF related proteins on a clinical LC-MS/MS platform (UHPLC coupled with Triple-Q MS). We created quality controls, standards and internal standards and 289 serum samples from healthy children and adolescents were measured in ten batches over two months. The method was compared to WHO reference standards, clinical and research immunoassays, and relative proteomics profiling.The sensitivity and reproducibility were sufficient for most but not all IGF protein family members. Targeted proteomics correlated well with clinical immunoassays for IGF-I (R2=0.88) and for IGFBP-3 (R2=0.46), (p<0.001). The correlation between targeted proteomics and non-clinical immunoassays for IGF-II, IGFBP-2, -4, -5, -6 and ALS varied between proteins.We present a method for parallel quantification of IGF-I, IGFBP-3, 5 and ALS for clinical verification studies, whereas targeted proteomics of the five remaining IGF related proteins (IGF-II, IGFBP-2, -4, and -6) require further examination. The sensitivity of our new IGF-I method suggests a possible diagnostic role for targeted proteomics of IGF-I in the management of children with extremely low levels of circulating IGF-I.© 2025 Walter de Gruyter GmbH, Berlin/Boston.
Post-lactation mass recovery and metabolic hormone dynamics in adult female Weddell sealsKirkham, Avery, Beltran
et alGen Comp Endocrinol (2025) 365, 114706
Abstract: Weddell seal (Leptonychotes weddellii) females lose substantial body mass across an intensive, nutritionally restricted lactation period and then must rapidly recover mass during the short Antarctic summer. In this study, we examined endocrine dynamics associated with mass loss across lactation and subsequent realimentation in Weddell seals, comparing patterns between seals that recently gave birth and demographically similar non-reproductive females (skip females) in McMurdo Sound, Antarctica. Postpartum seals near weaning (∼35 days postpartum, n = 64) and skip females (n = 32) were handled during early austral summer (November/December) and rehandled in late summer (January/February). Body mass, body composition (% lipid), and a suite of metabolic hormones (growth hormone (GH), insulin-like growth factor (IGF)-I, cortisol, total thyroxine (tT4), free thyroxine (fT4), and total triiodothyronine (tT3) and IGF binding protein (IGFBP)-2 and -3) were measured. Postpartum seals gained mass after weaning (0.98 ± 0.56 kg·day-1 (mean ± SD)), primarily as lean tissue rather than lipid, while their serum concentrations of tT4 and fT4, IGF-I, and cortisol increased. Their circulating GH and IGFBP-2 concentrations decreased and correlated negatively with mass. Skip females had greater body masses and lipid stores than postpartum seals at the end of the lactation period in early summer, but they lost mass (-1.03 ± 0.35 kg·day-1) and lipid stores over summer while their serum cortisol concentrations increased. Overall, body mass and composition of postpartum and skip females converged across summer. This convergence, likely driven in large part by contrasting endocrine profiles between the groups, may allow female Weddell seals to reach an advantageous seasonal body mass "set point" by onset of winter.Published by Elsevier Inc.
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