Colonoscopy is a key screening method for colorectal cancer (CRC), but its effectiveness is limited. Computer-aided detection (CADe) and computer-aided diagnostics (CADx), as part of an artificial intelligence (AI) system, improve the detection and optical characterization of lesions. This review maps and analyzes the evidence on the application of AI in colonoscopy, with a focus on the detection, segmentation, and characterization of colon neoplasms, available platforms, architectural models and implementation. The review was conducted in accordance with JBI and PRISMA-ScR guidelines, using the PCC framework. Meta-analyses, randomized controlled trials, systematic and narrative reviews, observational studies, guidelines, and consensus documents on the use of AI systems in different phases of colonoscopy were searched. CADe significantly improves adenoma detection and reduces the number of missed lesions. CADx, segmentation, depth of invasion assessment, and detection of learned lesions remain limited and heterogeneous. CADe has strong evidence for improving ADR, whereas current evidence for CADx remains insufficient to support a "resect-and-discard" strategy. Further cost-effectiveness studies are needed. Commercial platforms vary in their features and level of clinical validation. Colonoscopy using AI is a current topic with rapid development. This scoping review comprises heterogeneous literature covering clinical applications, technical aspects, the potential benefits and limitations of AI in improving colonoscopy performance and reducing the burden of colorectal cancer. Further trials involving diverse patient populations across different countries are needed to validate and extend the current evidence.

In total, 37-39% of prepubertal patients present with cancer cells in their testes at the time of diagnosing a hematologic malignancy, and elimination of cancer cells from immature testicular tissue (ITT) remains unsuccessful. Treating testicular single-cell suspensions (TCSs) with chemotherapy before generating testicular organoids (TOs) for in vivo maturation after transplantation could be considered to safely restore fertility with cryo-stored ITT. Five different enzymatic digestion protocols (E1 to E5) were compared but did not show significant differences. For subsequent experiments, E3 using 1.4 mg/mL DNase I and 0.5 mg/mL Liberase was chosen based on the highest recovery of viable testicular cells per mg of tissue and lowest enzymatic concentrations. TCSs were contaminated with a human leukemia HL-60 cell line at concentrations of 4 or 10% and exposed for 24 h to cisplatin (1 µM or 3 µM) or carboplatin (10 µM or 30 µM) prior to TO generation and compared to controls. After eighteen days, hematoxylin and eosin staining showed the development of TOs with forming seminiferous tubules (STs) and interstitium in all conditions. Chemotherapy-treated TOs showed altered germ cell (GC) (DDX4⁺) and somatic (ACTA2⁺, CYP11A1⁺) cell-type-specific location. CD43⁺ HL-60 cells were located outside forming STs in untreated TOs, while in chemotherapy-treated TOs, HL-60 cells were found inside and outside STs. Cancer cell numbers were significantly reduced in 30 µM carboplatin, showing a 3.7-fold reduction, whereas 10 µM carboplatin, 1 µM and 3 µM cisplatin did not demonstrate a statistically significant reduction. DDX4⁺ GC numbers were not statistically reduced after cisplatin or carboplatin exposure. Chemotherapy did not significantly reduce somatic cell numbers. As substantial residual cancer cell contamination remained, it is unlikely that short-term cisplatin/carboplatin treatment as a stand-alone purging strategy will achieve adequate decontamination for a safe fertility restoration approach. Future research should focus on exploring other chemotherapeutic drugs and/or combinations and elucidating the mechanism of chemotherapy-induced altered TO generation.

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignancy for which cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is central to treatment in appropriately selected patients. Recurrence remains common even after complete macroscopic cytoreduction. Current HIPEC regimens are protocolized at the institutional and population levels but are not individualized using site-specific molecular or functional tumor biology. We performed a narrative review of clinical, genomic, epigenetic, immune, microenvironmental, and patient-derived organoid evidence relevant to DMPM, CRS/HIPEC, and treatment resistance. Recurrence is multifactorial, with plausible contributions from spatial, histologic, genomic, epigenetic, immune, stromal, and pharmacokinetic heterogeneity. Three primary reports provide direct DMPM organoid evidence, including preliminary demonstrations of patient-specific drug response and discordant responses among anatomically distinct implants. However, these platforms differ biologically, and predictive thresholds, analytical reproducibility, turnaround time, and microenvironmental modeling remain unvalidated. Multi-site organoid pharmacotyping integrated with molecular profiling is therefore a plausible strategy for studying HIPEC resistance. Translation requires a staged pathway encompassing analytical validity, blinded clinical validity, and clinical-utility testing. Precision HIPEC should presently be considered an investigational, validation-ready framework rather than a standard of care.

Non-small cell lung cancer is one of the leading causes of cancer-related mortality. The effectiveness of treatment is limited by several factors, including significant tumoral heterogeneity, rapid development of drug resistance, high metastatic potential, and a complex tumor microenvironment. In recent years, natural products have emerged as valuable resources for the discovery of novel antitumor strategies against non-small cell lung cancer. These compounds possess diverse chemical properties, target multiple pathways, are abundant in nature, and exhibit relatively low toxicity. The utilization of existing medications with established pharmacokinetic profiles and safety records, combined with shorter development timelines, shows promise for advancing lung cancer treatment research. A growing body of evidence indicates that both naturally occurring compounds and commercially available drugs exert effects that extend beyond traditional cytotoxic mechanisms. These agents influence processes such as ferroptosis, oxidative stress, metabolic reprogramming, autophagy, apoptosis, epithelial-mesenchymal transition (EMT), tumor immune microenvironments, and epigenetic networks, suggesting that their activities can be leveraged for a robust multi-target antitumor strategy. Accordingly, this review summarizes research advances on natural products and repurposed marketed drugs for non-small cell lung cancer; outlines their potential for combination with chemotherapy, targeted therapy, radiotherapy and immunotherapy; and discusses future directions for clinical translation.

Progressive resistance exercise training (RET) enhances skeletal muscle mass in healthy postmenopausal women (HEAs) and breast cancer survivors (BCSs) undergoing endocrine therapy. MicroRNAs (miRNAs) are recognized as key epigenetic regulators of exercise-induced adaptations, functioning as tumor suppressors, oncomiRs, and modulators of skeletal muscle homeostasis. Nevertheless, the impact of RET on circulating miRNA profiles in this population remains largely unexplored. This study aimed to explore the effects of a 12-week progressive RET program on plasma miRNAs associated with tumor biology and skeletal muscle regulation in HEAs and BCSs. Five HEAs and five BCSs undergoing endocrine therapy completed a 12-week supervised progressive RET program (3 sessions/week, 60-80% 1RM). Plasma samples were collected before and after intervention, and candidate miRNA expression was quantified by qRT-PCR, normalized to hsa-miR-16-5p, and analyzed using the 2^-ΔΔCt method. At baseline, no significant differences were observed between HEA and BCS in tumor suppressor miRNAs (miR-let-7f-5p, miR-125a-5p, miR-342-3p), oncomiRs (miR-21-5p, miR-155-5p, miR-221-3p), or skeletal muscle-related miRNAs (miR-206-3p, miR-486-5p) (p > 0.05). The only exception was miR-375-3p, which showed increased expression in HEA vs BCS (p = 0.037). After 12 weeks of RET, The BCS group showed increases in miR-125a-5p (p = 0.050) and miR-342-3p (p = 0.048) with significant group × time interactions that remained significant after Benjamini-Hochberg False Discovery Rate (BH-FDR) correction (FDR-adjusted p = 0.042 for both). Both groups displayed a nominal increase in miR-375-3p (p = 0.042), which did not remain significant after FDR correction. No significant changes were detected for miR-let-7f-5p or the analyzed oncomiRs in either group. Both miR-206-3p and miR-486-5p exhibited upward trends in the BCS group (p > 0.05). In this exploratory study, 12-week RET program was associated with selective changes in plasma miRNA expression in the HEA and BCS groups, suggesting that this training regimen may act as an epigenetic modulator of circulating miRNAs involved in tumor suppression and skeletal muscle homeostasis.

De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2- disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2- tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23-0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48-1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination.

Vernonia calvoana (VC), a commonly used medicinal plant in West Africa, has been shown by our research team to inhibit the proliferation of OVCAR-3 ovarian cancer cells through mechanisms involving oxidative stress, DNA damage, and S-phase cell cycle arrest. The objective of the current study was to elucidate the intrinsic apoptotic mechanisms triggered by VC fraction seven (VCF7). OVCAR-3 cells were treated with VCF7 (0, 8, 16, and 32 μg/mL) for a duration of 48 h. Apoptosis was assessed using Annexin V/Propidium Iodide (PI) staining followed by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was assessed through JC-1 staining and confocal microscopy, while chromatin condensation was analyzed using DAPI staining. DNA fragmentation was examined by agarose gel electrophoresis. Caspase 3 activity was measured using flow cytometry. Protein expression levels of p53, Bcl-2, cytochrome c, caspase-9, and caspase-3 were determined by Western blot analysis, and mRNA expression levels of p53 and Bcl-2 were evaluated using qRT-PCR. VCF7 induced apoptosis in a concentration-dependent manner. Analysis using Annexin V/PI indicated an increase in apoptotic cell populations from 10.5% to 30%, along with a rise in necrotic cells from 7% to 50% across treatment concentrations. A modest, concentration-associated decrease in mitochondrial membrane potential was recorded (0.96-, 0.88-, and 0.85-fold at 8, 16, and 32 μg/mL, respectively; p < 0.05). DAPI staining validated the concentration-dependent chromatin condensation and nuclear fragmentation. The analysis of DNA fragmentation showed progressive internucleosomal degradation, appearing as a smear pattern with distinct fragments at elevated concentrations, indicative of concurrent apoptotic and necrotic cell death. The activation of caspase-3 reached a peak of 28% at 16 μg/mL. Western blot analysis indicated an upregulation of p53, a downregulation of Bcl-2, an increase in total cytochrome c protein levels, and an increased expression of caspase-9 and caspase-3 in a concentration-dependent manner. These findings were corroborated at the transcriptional level by qRT-PCR, which showed increased p53 mRNA and decreased Bcl-2 mRNA expression. Taken together, these results underscore the potential of VCF7 as a promising plant-derived anticancer agent and support the need for further preclinical and clinical studies in ovarian cancer.

Neuro-endocrine-related cancers overexpress ELAVL4 (HuD), a neuron-specific RBP implicated in post-transcriptional regulation. HuD plays a role in tumor cell survival; its knockdown in cancer cells and tumors leads to reduced growth and viability. In this review, we addressed HuD's role in several molecular pathways that contribute to the development of cancer. For example, cancer cells that have high levels of HuD are able to better withstand stressful tumor microenvironments because HuD stabilizes certain mRNAs, which promotes tumor development, modulates oxidative and metabolic stress, enhances autophagy, and impairs apoptosis. We discussed future studies on HuD in cancer, which should focus on its diverse roles in various cancer types and the molecular aspects. Furthermore, assessing HuD's contribution to the efficacy of immunotherapy requires an understanding of how it affects immune responses in malignancies. The development of targeted therapies, such as RNA-based approaches and small molecules, offers intriguing avenues for precision cancer management. The transition of HuD-directed therapies from preclinical models to clinical trials is anticipated to be accelerated by ongoing advancements in RNA-targeted drug discovery, structural biology, medicinal chemistry, and targeted drug delivery, even though no HuD-specific therapies have yet entered standard clinical practice.

Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy because of recurrence, treatment resistance, and limited therapeutic efficacy in advanced disease. This study investigated the anticancer effects and molecular mechanisms of jaceidin (JAC), a naturally occurring flavonoid derivative, in human OSCC cells. SCC-1 and SCC-47 cells were treated with JAC, and cell viability, colony formation, cell cycle distribution, apoptosis, and apoptosis-related signaling pathways were examined. JAC reduced OSCC cell viability and colony formation in a dose- and time-dependent manner. It also induced G2/M cell cycle accumulation and decreased the expression of cyclin D1, cyclin E1, phosphorylated cdc2, and CDK2/4/6. Apoptosis analyses showed that JAC promoted caspase-dependent apoptotic signaling, as evidenced by increased cleavage of caspase-3, caspase-8, caspase-9, and PARP. JAC modulated death receptor-associated signaling, characterized by increased Fas, TRADD, and DR5 expression and caspase-8 cleavage, while the decoy receptors DcR2 and DcR3 were also upregulated. JAC also promoted mitochondrial apoptotic signaling by increasing Bax, Bak, and Bim expression while decreasing Mcl-1. In addition, JAC attenuated AKT and ERK1/2 phosphorylation, and pharmacological inhibition with LY294002 or U0126 further enhanced JAC-induced apoptotic signaling. Furthermore, JAC reduced survivin expression and attenuated survivin-mediated apoptotic resistance. These findings suggest that JAC suppresses OSCC cell survival in association with modulation of AKT/ERK-survivin signaling and caspase-dependent apoptosis.

Non-small-cell lung cancer (NSCLC) treatment is hampered by its complex pathogenesis and high heterogeneity. N6-methyladenosine (m⁶A) represents the most common post-transcriptional modification regulating RNA stability and function in eukaryotes. This methylation is catalyzed by methyltransferase complexes, with METTL14 being the core catalytic subunit. Abnormal expression of lncRNA MSTRG.292666.16 is related to poor prognosis of NSCLC. However, the mechanism by which it regulates NSCLC progression through m⁶A modification remains unclear. We employed cell function experiments, molecular mechanism analysis, RNA interaction experiments, and a nude mouse tumor model to explore the roles of METTL14-mediated MSTRG.292666.16 m⁶A modification in NSCLC and the potential MAPK signaling pathway involved. METTL14 was significantly upregulated in NSCLC cell lines and promoted m⁶A modification of MSTRG.292666.16 by forming a stable association with it. METTL14 knockdown significantly inhibited the viability, migration and invasion of A549 cells and promoted apoptosis, whereas MSTRG.292666.16 overexpression reversed these effects. Mechanistically, METTL14 upregulated the expression of MSTRG.292666.16 through m⁶A modification, thereby activating the MAPK pathway (manifested as elevated levels of MAPK8IP3 and p-ERK1/2). The use of a selective p38 MAPK inhibitor SB203580 stimulated the tumor-suppressive effect of METTL14 knockdown, whereas the activator U-46619 reversed it. In vivo experiments confirmed that METTL14 knockdown significantly inhibited tumor growth, whereas MSTRG.292666.16 overexpression partially restored the malignant phenotype of the tumor, which was associated with MAPK pathway activation. This study revealed that METTL14-dependent m⁶A modification of MSTRG.292666.16 may act as an upstream driver to activate the MAPK cascade and facilitate NSCLC progression. These findings clarify a key epitranscriptomic regulatory mechanism driving NSCLC development and offer preliminary molecular clues for exploring potential therapeutic targets in subsequent clinical NSCLC research.