Charupong Saengboonmee

Abnormal pH and viscosity are defining features of the tumor microenvironment, offering valuable targets for cancer diagnostics and therapy. Here, we introduce Cy7-TCF-Mpip, a triple-functional near-infrared (NIR) probe that integrates pH responsiveness, viscosity sensitivity, and photodynamic activity within a single heptamethine cyanine scaffold. Cy7-TCF-Mpip exhibits substantial fluorescence enhancement under acidic and high-viscosity conditions, as well as NIR absorption/emission (724–870 nm), and efficient singlet oxygen generation (ΦΔ up to 0.065) upon 660 nm irradiation. The probe selectively accumulates in hepatocellular carcinoma and cholangiocarcinoma (CCA) cells, responding dynamically to changes in hypoxia-induced acidity and cellular viscosity. Upon light activation, Cy7-TCF-Mpip induces potent, ROS-mediated photodynamic cytotoxicity with minimal dark toxicity and preferential phototoxicity toward CCA cells compared with nonmalignant cholangiocytes under the tested conditions. In vivo, the probe significantly suppresses tumor growth in a CCA xenograft model after local 660 nm light irradiation, with no observable body-weight loss or obvious behavioral abnormalities under the tested conditions. Overall, Cy7-TCF-Mpip represents a compact and versatile NIR theranostic platform for image-guided photodynamic therapy of primary liver cancers.

Introduction: Cholangiocarcinoma (CCA) is a highly metastatic bile duct cancer with the highest global incidence in Northeastern Thailand. Most patients are diagnosed at advanced stages, necessitating the identification of novel prognostic markers and therapeutic targets. High mobility group A1 (HMGA1) is a non-histone chromosomal protein that orchestrates the transcription of genes involved in tumor progression, and its overexpression has been implicated in multiple malignancies. Aims: This study aimed to investigate the clinical significance and oncogenic roles of HMGA1 in CCA progression. Methods: HMGA1 expression was evaluated in a hamster CCA model and human CCA tissues using immunohistochemistry. The functional effects of HMGA1 on cell growth, migration, and invasion, along with the underlying molecular mechanisms were investigated in vitro using human CCA cell lines. Results: HMGA1 upregulation was detected as an early event in the cholangiocarcinogenesis of a hamster model. In the human cohort (n = 81), high HMGA1 expression significantly correlated with histological type ( p =0.014), metastatic stage ( p =0.004) and shorter overall survival ( p =0.024). In vitro , siRNA-mediated suppression of HMGA1 remarkably inhibited cell proliferation. While HMGA1 silencing increased cleaved caspase-3, it resulted in only a modest increase in the apoptotic cells. Instead, this caspase activation was primarily associated with a marked reduction in cell migration and invasion through the modulation of epithelial-mesenchymal transition (EMT) markers, and cytoskeletal remodeling in a cell line-specific manner. Conclusions: These retrospective and preclinical findings suggest that HMGA1 is a critical driver of CCA progression and a valuable prognostic indicator. HMGA1 promotes neoplastic transformation and aggressiveness of CCA. Targeting HMGA1 may serve as a potential therapeutic strategy to attenuate CCA progression, warranting further clinical validation.

Hydroxyflavone-modified aza-BODIPY derivatives were developed as metal-free photosensitizers integrating photodynamic therapy (PDT) with singlet oxygen-triggered carbon monoxide (CO) release for neuroblastoma treatment. The compounds exhibit near-infrared absorption, efficient singlet oxygen generation, and light-controlled CO release via hydroxyflavone decarbonylation. Among the series, AF-I demonstrated superior phototherapeutic activity compared with the non-CO-releasing analogue and reference PDT/CO systems under identical conditions. Mechanistic studies indicate that PDT serves as the primary cytotoxic pathway, while localized CO release functions as a sensitizing component that enhances oxidative stress-induced apoptosis. AF-I retained improved phototoxicity under hypoxic conditions, suggesting partial preservation of PDT efficacy when oxygen availability is limited. Zebrafish biodistribution studies revealed limited blood-brain barrier penetration, supporting potential application in extracranial neuroblastoma. This work establishes a metal-free strategy for integrating controlled gasotransmitter release with PDT and provides a molecular framework for next-generation light-activated combination phototherapeutics.

Cyclin D-CDK4/6 is a component of mammalian cell-cycle machinery that drives cell proliferation. Small-molecule inhibitors of CDK4/6 have been approved for treatment of breast cancer patients. In addition to halting cell-cycle progression, inhibition of CDK4/6 can affect other tumor cell-intrinsic and -extrinsic functions. Here, we examined the impact of CDK4/6 inhibition on the CD155–CD226–TIGIT pathway that operates at the interface of tumor cells and the immune environment. We demonstrate that inhibition of CDK4/6 upregulates the expression of surface CD155 protein in cancer cells and downregulates an immuno-inhibitory receptor TIGIT in tumor-infiltrating lymphocytes. We observed these effects in human breast cancer cell lines, in mouse mammary carcinoma allograft models, in freshly resected human breast tumors and in paired pre-/on-treatment biopsies of breast cancers from patients undergoing monotherapy with a CDK4/6 inhibitor. We propose that inhibition of CDK4/6, through its tumor cell-intrinsic and -extrinsic effects, may shift the balance from the immunoinhibitory CD155–TIGIT to the immunostimulatory CD155–CD226 interaction, and through this mechanism may augment the antitumor immunity. Our results suggest that coadministration of CDK4/6 inhibitors and anti-TIGIT antibodies may further promote CD155–CD226-signaling and may have a strong synergistic antitumor effect.

This study aimed to investigate the effects of glucosamine, a glucose analogue mainly transported via glucose transporter (GLUT) 2, on the progression of cholangiocarcinoma (CCA) cells. Differential expressions of GLUTs in CCA and normal bile ducts were analyzed using a public transcriptomic dataset. The effects of glucosamine on CCA cell viability and proliferation were examined using an MTT assay and flow cytometry. Molecular mechanisms were investigated using Western blots and lectin blots. GLUT2 expression was significantly decreased in CCA compared with the normal bile duct tissues. Glucosamine significantly reduced CCA cell viability in a dose-dependent manner (p < .05), while flow cytometry showed increased G1 cell cycle arrest and apoptosis in glucosamine-treated cells (p < .05). Glucosamine significantly suppressed high-mannose type N-glycosylation in CCA cells, as shown in concanavalin A lectin blots and the Western blots of glycoprotein 130 (p < .05), leading to a reduced epidermal growth factor receptor (EGFR) expression and STAT3 phosphorylation. Cell viability and high-mannose type N-glycosylation could be partially rescued by high-glucose supplementation, confirming that disrupting high-mannose type N-glycosylation and EGFR/STAT3 signaling are part of the underlying mechanisms. Glucosamine exerted anti-cancer effects on CCA cells, suggesting its potential for further study as a repurposing drug for CCA.

Glucose metabolism is crucial for cancer cell survival and proliferation. Hepatocellular carcinoma (HCC) cells exhibit distinct metabolic adaptations that support tumor progression under nutrient‐limited conditions. The study examines the impact of glucose availability and GPD2‐mediated metabolic adaptation on HCC progression, as well as how these processes are modulated by glucose transport inhibitors and metformin. Cell proliferation and migration of HCC cells (HepG2 and Huh7) and lung cancer cells (A549) were examined under different glucose concentrations using MTT, colony formation, and scratch assays. The impacts of glucose transporter 1 (GLUT1) inhibitors and metformin were also evaluated. Gene and protein expression data were analyzed from TCGA/CPTAC datasets, and GPD2 expression was validated by immunohistochemistry. High glucose enhanced proliferation and migration of liver cancer cells. Unlike A549, HepG2 and Huh7 cells maintained growth under glucose deprivation, indicating metabolic plasticity. GPD2 was markedly upregulated in HCC tissues and correlated with poor survival. Metformin suppressed cell proliferation and migration in a dose‐dependent manner, with stronger effects under low‐glucose conditions. Mechanistically, metformin downregulated Cyclin D1 and XIAP, induced Caspase‐3 cleavage, and reduced the EMT marker, Slug. Correlation analyses revealed positive associations between GPD2 and CCND1 or SNAI2, indicating a link between GPD2 and cell cycle and EMT signaling. In conclusion, HCC cells utilize GPD2‐mediated metabolic adaptation to sustain growth under glucose‐limiting conditions. GPD2 represents a prognostic biomarker and therapeutic target in HCC. Metformin effectively inhibits HCC progression by disrupting GPD2‐linked pro‐survival and EMT pathways.

Aberrant glycosylation in meningioma (MG) suggests the potential use of glycobiomarkers for diagnosis, monitoring, and prognosis. Using lectin-based glycomics, Dolichos biflorus agglutinin (DBA) is an effective tool for detecting the glyco-biomarker DBA-binding glycan (DBAG) in patient sera. Using an in-house enzyme-linked lectin assay, the level of serum DBAG in MG patients (44.10 AU/mL) was significantly higher than that of healthy controls (10.21 AU/mL), with 86.4% sensitivity and 90.0% specificity. The MG patients with WHO grade II-III (77.35 AU/mL) had higher serum DBAG levels than those with grade I (35.92 AU/mL). Lectin histochemistry staining of MG tissues showed that tumor cells were positive for DBAG in 149 of 150 cases, indicating the tumor origin of serum DBAG. Functional analyses using MG cell lines, IOMM-Lee and HKBMM, suggested the involvement of DBAG in MG progression. The serum DBAG levels in other brain tumors (BT) were also measured. Data showed that serum DBAG levels were higher in malignant BTs (67.44 AU/mL) compared to benign BTs (50.43 AU/mL). In conclusion, DBA can be used to detect a serum glycobiomarker for MG and brain tumors. DBAG was involved in MG cell viability and migration, suggesting its potential as a target for future MG therapy.