Artificial intelligence (AI) is increasingly influencing cancer diagnostics, with ongoing advancements into more refined and advanced applications. This review examines current applications of AI in cancer diagnosis. AI has demonstrated considerable success in screening and diagnosis of a range of cancer types, including breast, colorectal, and skin cancer, but challenges with specificity and false-positive rates remain. Within radiology and histopathology, AI shows promise in identifying cancers and augmenting clinician performance. Natural language processing and AI-driven clinical documentation tools can expedite diagnosis by reducing administrative burden and extracting clinically meaningful data from unstructured records. Additionally, AI models using unimodal and multimodal data can improve patient prognostication and risk stratification. Despite these advances, challenges relating to deployment, bias, interpretability, accountability and real-world efficacy persist. Prospective validation and careful implementation are required to ensure safe, equitable, and effective adoption of AI in cancer diagnostics.

Mammary tumors in sheep are exceedingly rare, with all reported cases being benign to noninvasive and slow growing. Here, we describe a squamous cell carcinoma (SCC) with widespread metastases presumptively arising from the mammary parenchyma in a 3.5-y-old ewe. Following a history of chronic mastitis and severe swelling of the udder, the udder was removed surgically and submitted for examination. Three weeks after surgery, because of poor prognosis, the animal was euthanized and autopsied. The udder had no cutaneous lesions but had parenchymal disorganization and extensive areas of necrosis delimiting large, fluid-filled cavities. Two cord-like masses extended from the mammary gland into the pelvic cavity and subcutis of the right hindlimb. Numerous nodules were observed within the mammary and abdominal lymph nodes, peritoneum, lungs, and heart. Histologically, mammary and extramammary lesions consisted of neoplastic squamous epithelial cells, often surrounding keratinized cores. Neoplastic cells had diffuse cytoplasmic immunolabeling for pancytokeratin, confirming their epithelial lineage. Non-keratinized neoplastic cells were positive for p63 and, infrequently, for cytokeratin 19, suggesting mammary histogenesis. Considering the lack of a primary extramammary mass and the tumoral immunophenotype, a presumptive diagnosis was made of primary mammary SCC with metastasis to multiple organs. The aggressive clinical behavior of this neoplasm contrasts with that of reported ovine mammary neoplasms and cutaneous SCCs.

Chimeric antigen receptor (CAR)-T-based strategies target the B-cell maturation antigen (BCMA) expressed on the surface of malignant plasma cells in patients with multiple myeloma (MM). Idecabtagene vicleucel (ide-cel), an anti-BCMA CAR-T therapy, has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). Notably, the extent of CAR-T cell expansion correlates with objective response rates and complete responses, indicating that monitoring CAR-T cells is critical for predicting clinical outcomes in these patients. Although several tools are available to monitor CAR-T cells in patient blood samples, they remain costly, prompting us to develop novel fluorescent and soluble BCMA reagents for CAR-T cell labeling. BCMA is a type III transmembrane protein, and we found that a recombinant construct consisting of the BCMA extracellular domain fused to green fluorescent protein (GFP) failed to traffic through the Golgi apparatus and was not secreted. Incorporation of the interferon-α2 signal peptide restored intracellular trafficking and enabled efficient secretion of soluble BCMA-GFP and BCMA-mCherry fusion proteins. These reagents specifically labeled anti-BCMA CAR-T cells. Overall, our results establish a cost-effective method to generate soluble BCMA probes and provide accessible tools for monitoring CAR-T cells in translational settings.

No comparative analysis of the infrequently occurring B-cell neoplasms (BCNs) in the oral cavity has yet been reported in patients with non-immunosuppressiveness or immunosuppressiveness. To identify any differences in clinicopathological findings between patients with non-immunosuppressiveness and those with immunosuppressiveness, we compared the clinicopathological characteristics of oral-cavity BCNs in these patient groups. The clinical characteristics of 39 patients were analyzed from hospital records, including 24 with non-immunosuppressiveness and 15 with immunosuppressiveness. Histological and immunohistochemical evaluation was performed using formalin-fixed paraffin-embedded tissue sections. Comparisons between the two groups were conducted using cross-tabulations and the chi-squared or Fisher exact test. In patients with non-immunosuppressiveness, diffuse large B-cell lymphoma (DLBCL) was the most common type (14/24, 58%), followed by mucosa-associated lymphoid tissue lymphoma (MALT-L, 4/24, 17%). In patients with immunosuppressiveness, EBV-positive mucocutaneous ulcers (EBV-MCU) were the most common type (9/15, 60%), followed by DLBCL (3/15, 20%) and polymorphic/lymphoplasmacytic infiltration (3/15, 20%). Macroscopic findings showed 21 masses (88%) and 3 ulcers (13%) in patients with non-immunosuppressiveness and 11 ulcers (73%) and 4 masses (27%) in patients with immunosuppressiveness. Immunohistochemistry revealed that BCNs in patients with non-immunosuppressiveness expressed EBER in only 1 case (1/22, 5%), whereas those in patients with immunosuppressiveness expressed EBER in all cases (15/15, 100%). Our macroscopic findings and EBV status allowed us to distinguish BCNs between patients with non-immunosuppressiveness and those with immunosuppressiveness.

4-[4-(Bis(2-(nitrooxy)ethyl)amino)phenyl]butanoic acid (NPB), a phenylbutyrate-derived nitric oxide (NO) donor, has been developed as a potential anticancer agent for pancreatic cancer. In the present study, we investigated the cytotoxic effects of NPB under cellular stress conditions and examined its effects on autophagy-related pathways and hypoxia-inducible factor-1α (HIF-1α) signaling. NPB-induced cell death was enhanced under nutrient-deprived conditions in PANC-1 cells. In addition, NPB induced greater cell death under hypoxic conditions than under normoxic conditions in PANC-1 cells, whereas in BxPC-3 cells, NPB-induced cell death was slightly but significantly lower under hypoxic conditions than under normoxic conditions. Using GFP-LC3-RFP-LC3ΔG reporter cells, NPB suppressed starvation-induced autophagic flux. In pancreatic cancer cells, NPB decreased DAPGreen fluorescence, an indicator of autophagy-related vesicular activity, and increased propidium iodide-positive cells under hypoxic conditions. Western blot analysis showed that NPB induced the accumulation of p62 and LC3 under both normoxic and hypoxic conditions. Under hypoxic conditions, NPB also reduced HIF-1α expression. Under cobalt chloride (CoCl₂)-induced HIF-1α-accumulating conditions, NPB and the NO donor NONOate suppressed HIF-1α expression, whereas OH-PB, a non-NO-releasing analog, showed little effect. Furthermore, the proteasome inhibitor MG132 restored HIF-1α accumulation in NPB-treated cells. Time-course analysis under CoCl₂-treated conditions showed that NPB reduced HIF-1α expression concomitantly with p62 accumulation. These findings suggest that NPB induces pancreatic cancer cell death, particularly under nutrient-deprived and hypoxic conditions, accompanied by impairment of autophagy-related pathways and NO-dependent, proteasome-associated reduction of HIF-1α.

Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.

Patient-derived organoids (PDOs) have emerged as physiologically relevant cancer models that preserve key genetic, histological, and functional features of the tumors from which they are derived. In parallel, CRISPR-based perturbation technologies have transformed functional genomics by enabling scalable interrogation of gene function. Their integration provides a powerful framework for identifying cancer dependencies, modeling oncogenic evolution, and investigating mechanisms of drug response and resistance in patient-relevant settings. This review examines how CRISPR knockout, CRISPR interference/activation, and precision editing approaches have been applied in PDO systems to uncover context-specific vulnerabilities, reconstruct mutational trajectories, and study tumor heterogeneity. We further compare pooled and arrayed screening formats and discuss what is uniquely enabled by performing CRISPR screens in organoids rather than conventional 2D models. Particular emphasis is placed on the technical and analytical constraints of organoid-based screening, including variable editing efficiency, clonal bottlenecks, biological heterogeneity, and limited scalability. We argue that the major value of organoid-based CRISPR screening lies in its ability to identify functionally actionable cancer vulnerabilities in a patient-contextualized model, while also introducing methodological challenges that must be addressed for robust clinical translation.

Circulating tumor DNA (ctDNA) monitoring may detect resistance to KRAS^G12C inhibitors earlier than conventional imaging. However, in the specific context of KRAS^G12C inhibitors, the temporal relationship between molecular, radiologic, and clinical progression remains poorly characterized. A 66-year-old woman with KRAS^G12C/STK11/KEAP1-mutant lung adenocarcinoma received second-line adagrasib after progression on chemo-immunotherapy. Serial ctDNA monitoring by droplet digital PCR and targeted next-generation sequencing was performed. Baseline KRAS^G12C ctDNA (6205.3 copies/mL) declined to 3.2 copies/mL after 7 weeks, indicating initial response. However, ctDNA levels rose to 21.1 copies/mL at month 4 and 315.2 copies/mL at month 6. Concurrent NGS revealed three emergent KRAS mutations (G12D, G13D, Q61H), confirming polyclonal resistance. Notably, CT and MRI imaging remained stable by RECIST criteria throughout this period. Significant clinical deterioration, requiring prolonged hospitalization, occurred approximately 8 weeks after initial ctDNA rise. The patient died 2 months after detection of resistance mutations. In this case, NGS ctDNA detected three acquired KRAS resistance mutations in addition to the original G12C, during a prolonged period of radiographic stability, illustrating polyclonal evolution under adagrasib pressure. These findings suggest that longitudinal liquid biopsy monitoring may provide early detection of resistance in KRAS^G12C-mutant NSCLC.

To investigate the expression profile of IL-6 in patients with acute promyelocytic leukemia (APL) and its role in modulating the ability of hPMSCs to regulate the differentiation of NB4 cells.

Peripheral blood samples were obtained from newly diagnosed APL patients and healthy controls. IL-6 levels were measured using flow cytometry-based (FCM) multiplex immunoassays. A co-culture system of hPMSCs and NB4 cells was established. The effects of hPMSCs on ATRA-induced differentiation, proliferation, and phagocytic activity of NB4 cells were evaluated by Wright-Giemsa staining, FCM, CCK-8 assays, and phagocytosis assays. Western blot analysis was performed to investigate the signaling mechanisms by which IL-6 regulates CD73 expression in hPMSCs. To determine whether the regulatory effects of hPMSCs are mediated by CD73, interventions using a CD73 inhibitor and CD73-knockdown hPMSCs were conducted.

IL-6 levels were significantly elevated in the peripheral blood of APL patients and showed a positive correlation with both risk stratification and the severity of retinoic acid syndrome (RAS). hPMSCs enhanced ATRA-induced differentiation of NB4 cells while suppressing their proliferation and phagocytic function. Moreover, inhibition or knockdown of CD73 markedly attenuated the pro-differentiation effect of hPMSCs on NB4 cells. NB4 cells exhibited high surface expression of adenosine receptors. IL-6 was found to upregulate CD73 expression in hPMSCs through activation of the PI3K/AKT signaling pathway.

IL-6 enhances the pro-differentiation capacity of hPMSCs toward NB4 cells by upregulating CD73 expression, offering a potential new strategy for the clinical treatment of APL.

BACKGROUND Thoracic SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient undifferentiated tumor (SMARCA4-UT) is a rare and highly aggressive thoracic malignancy. It predominantly affects male smokers and typically arises in the mediastinum, where rapid tumor growth and early metastasis contribute to a poor prognosis. Recent evidence suggests that this tumor exhibits biological heterogeneity and variable responses to therapy, underscoring the need for further clinical characterization. CASE REPORT A 67-year-old man presented with dyspnea and superior vena cava syndrome. Computed tomography revealed a 7-cm mass in the anterior and superior mediastinum with suspected lymph node and bone metastases. Histological examination demonstrated a sheet-like proliferation of large atypical cells with rhabdoid features and necrosis. Immunohistochemical analysis showed loss of SMARCA4 (Brahma-related gene 1 [BRG1]) expression, positivity for cluster of differentiation 34 (CD34) and sex-determining region Y-box 2 (SOX2), weak epithelial membrane antigen expression, preserved integrase interactor 1 (INI1) expression, and negativity for other epithelial markers, fulfilling the diagnostic criteria for SMARCA4-UT. Despite palliative radiotherapy and combination immunotherapy with nivolumab and ipilimumab, the tumor rapidly progressed. The patient developed grade 4 drug-induced pneumonitis; transient stabilization was achieved, but his condition deteriorated. He died 6 months after disease onset. Autopsy revealed widespread metastases with minimal therapeutic effect, highlighting the aggressive clinical course and treatment resistance. CONCLUSIONS SMARCA4-UT is a highly aggressive tumor requiring comprehensive immunohistochemical evaluation for accurate diagnosis. This case highlights the limited efficacy of immune checkpoint inhibitors in a PD-L1-negative setting and underscores the need for more effective therapeutic strategies.