Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Among its genetic subtypes, KMT2A (formerly MLL)-rearranged ALL (KMT2Ar-ALL) is associated with poor outcomes. Immunotherapy approaches are being studied and used in KMT2Ar-ALL; however, there is evidence that leukemic cells can escape immune control. Our previous study identified Galectin-1, an immune checkpoint protein, as highly expressed in KMT2Ar-ALL, suggesting it as a potential therapeutic target. To date, the exact mechanism of Galectin-1 regulation in KMT2Ar-ALL is unknown. Therefore, the present study aimed to investigate the potential involvement of the mTOR signaling pathway in the regulation of Galectin-1 expression in KMT2Ar-ALL.

The study employed both in silico and in vitro approaches: gene expression data from B-cell acute lymphoblastic leukemia subtypes were analyzed bioinformatically, while four leukemia cell lines (RS4;11, SEMK2, SUP-B15, and NB-4) were treated with the mTOR inhibitor everolimus to evaluate its effect on Galectin-1 expression at the mRNA and protein levels, using qPCR and immunoblotting. Transcription factor binding on the LGALS1 promoter was assessed with computational tools.

Galectin-1 mRNA and protein were selectively upregulated in KMT2Ar-ALL cells, and inhibition of the mTOR pathway with everolimus modulated Galectin-1 expression in these cells. A novel putative transcription factor, SP1, was proposed, which may bind to the Galectin-1 promoter and can be regulated by the mTOR pathway.

Targeting mTOR signaling contributes to the regulation of Galectin-1 immune checkpoint activity in KMT2Ar-ALL. Inhibition of mTOR may represent a potential therapeutic strategy to overcome immune evasion in this leukemia subtype.

Methionine addiction is a fundamental and general hallmark of cancer termed the Hoffman effect. Methionine restriction using recombinant methioninase (rMETase) has shown synergistic efficacy with numerous types of chemotherapeutic agents against cancer cells and not normal cells. Methionine adenosyltransferase 2A (MAT2A) is a crucial enzyme converting methionine to S-adenosylmethionine (SAM). A MAT2A inhibitor, AG-270, has been proposed as a potential anti-cancer drug. The present study evaluated whether AG-270 is a cancer-specific agent by comparing its efficacy in combination with rMETase on cancer and normal cells.

The half-maximal inhibitory concentrations (IC₅₀) of rMETase and AG-270 were determined on HCT116 human colon-cancer cells and Hs-27 human normal fibroblasts in vitro. The efficacy of rMETase combined with AG-270, at their respective IC₅₀ values, on HCT116 and Hs-27 was also determined. Cell viability was evaluated using the WST-8 reagent.

The IC₅₀ values of rMETase were 0.35 U/ml for HCT116 and 1.14 U/ml for Hs-27. The IC₅₀ values of AG-270 were 4.38 μM for HCT116 and 6.55 μM for Hs-27. The combination of rMETase and AG-270, at their respective IC₅₀, had synergistic efficacy on both cancer and normal cells, reducing viability to approximately 20% in both cell lines (p<0.05).

AG-270 showed lack of cancer specificity in combination with rMETase when tested on both cancer and normal cells. The present results contrast with numerous chemotherapy agents, which in combination with rMETase are synergistic on cancer cells but not on normal cells. The present findings suggest that MAT2A inhibition affects crucial metabolic pathways in normal as well as cancer cell types and thus AG-270 may not be suitable as a cancer-specific therapeutic strategy.

Treatment of cancers known to be positive for the nuclear progesterone receptor (nPR), e.g., breast, ovarian, and endometrial cancers with PR modulators/antagonists, e.g., mifepristone, have not shown impressive improvement in palliative or longevity benefits. In contrast, several case reports showed considerable palliation and/or extension of life using mifepristone treatment for various advanced cancers devoid of the nPR. The aim of this study was to determine whether mifepristone therapy could provide improved quality of life in a patient with breast cancer considered terminal based on extensive brain and lung metastases in which the estrogen receptor (ER) was present in 99% of the cells but only 1% positive for the nPR.

A 64-year-old woman with stage IV breast cancer with very symptomatic brain and lung metastases who was considered terminal was first treated with letrozole. She failed to show any clinical improvement. Attempts to also treat her with abemaciclib and subsequently ribociclib were stopped after a very short course related to side effects. Mifepristone 200 mg daily tablets resulted in marked improvement in her fatigue, dyspnea on exertion, cognition, and her issues with balance. This was associated with a 75% reduction in the size of the lung lesions and no new metastatic lesions by position emission tomography two months after starting mifepristone. She lived eight months and still maintained good quality of life, but she died of a cerebral vascular accident.

Mifepristone provided marked palliative benefit in this patient with nPR-negative, metastatic breast cancer, suggesting potential therapeutic value in similar cases. Confirmation of efficacy will require larger studies focused on tumors with absent or minimal nuclear progesterone receptor expression.

Ovarian yolk sac tumors (YSTs) are highly uncommon in postmenopausal women and may show unusual morphological patterns, including neuroendocrine differentiation. Such presentations are exceptionally rare and poorly characterized.

We report the case of a 75-year-old woman presenting with a pelvic mass and diffuse peritoneal and hepatic involvement. Histopathological evaluation revealed a yolk sac tumor with mixed architectural features and focal chromogranin A expression, consistent with neuroendocrine differentiation. The disease was classified as FIGO stage IVB. The patient started first-line chemotherapy with a dose-adjusted combination of bleomycin, etoposide, and cisplatin, tailored to her age and overall condition.

This case illustrates a particularly rare and aggressive presentation of ovarian YST in a postmenopausal patient. Early recognition, accurate pathological characterization, and individualized treatment are essential, although prognosis remains poor in this setting. Reporting such cases is crucial to improve understanding and management of these exceptional tumors.

Cyclin-dependent kinase 1 (CDK1) is a regulator of the G₂-M transition whose dysregulation undermines cell-cycle fidelity and drives malignant growth. Although CDK1 has been implicated in tumorigenesis, its prognostic value varies by cancer type. Here we analyzed the prognostic landscape of CDK1 across human cancers and prioritized on therapeutic candidates for cancer types in which CDK1 is most strongly implicated.

We performed a pan-cancer analysis of CDK1 expression across 31 tumor types from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx), and tested associations with outcome by univariate Cox regression and Kaplan-Meier analysis. To translate these findings into therapeutic insights, we carried out structure-based virtual screening of a curated natural-product library against the CDK1 ATP-binding pocket and assessed predicted binding affinity.

CDK1 was broadly overexpressed across multiple malignancies and high CDK1 expression associated with poorer survival in several tumor cohorts. Adrenocortical carcinoma (ACC) showed one of the strongest and most consistent prognostic associations, with CDK1 expression rising with advancing stage. Structure-based screening nominated five natural compounds namely, Salvianolic acid C, Salvianolic acid A, Calceolarioside B, Chicoric acid, and Plantagoside, as promising CDK1 kinase inhibitors and drug candidates for ACC. These compounds demonstrated favorable CDK1 binding and possess reported biological and anticancer activities, supporting their translational potential.

Our findings highlight CDK1 as a prognostic marker and a therapeutic target across multiple cancers, with particular relevance in ACC. By integrating pan-cancer transcriptomic analysis with structure-based drug discovery, this study not only emphasizes the clinical significance of CDK1 in ACC but also proposes natural compound-derived inhibitors as promising candidates for future therapeutic development.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and lung metastasis is the major cause of death. Highly metastatic osteosarcoma cells are mechanically softer than low-metastatic cells, and calcium ions are known to regulate cytoskeletal organization and cell stiffness. We tested whether clinically available ion channel blockers could increase the stiffness of LM8 osteosarcoma cells and prevent lung metastasis in vivo.

We evaluated the actin cytoskeletal structure and polymerization in ion channel blocker-treated LM8 cells using actin staining. Cell stiffness was measured using atomic force microscopy. Metastasis-related cellular functions were analyzed using cell proliferation, wound healing, and cell adhesion assays. Furthermore, lung metastasis and tumor volume were measured in LM8-bearing mice treated with an ion channel blocker.

Treatment with ion channel blockers significantly increased actin staining intensity and stiffness in LM8 cells compared to that in untreated LM8 cells (p<0.05). The proliferation potential was significantly lower in the amlodipine-treated group (p<0.05). The ion channel blockers treatment group demonstrated significantly higher adhesion than the control group (p<0.05). The migration potential of the disopyramide- and lidocaine-treated groups were lower than that of the control group. Daily intraperitoneal administration of 20 mg/kg amlodipine for five weeks in LM8-bearing mice significantly reduced lung metastasis compared to that in the control group (p<0.05). No significant differences in tumor volume were observed after amlodipine administration.

Amlodipine could increase tumor cell stiffness and significantly reduce lung metastasis.

Triplet therapy, combining androgen deprivation therapy (ADT), darolutamide, and docetaxel has recently emerged as the standard first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC). Febrile neutropenia (FN) is a major clinical issue not only as a serious infection but also as a cause for early cessation or dose reduction of chemotherapy. However, little is known regarding the predictive factors for the development of FN in patients with mHSPC receiving triplet therapy.

This study enrolled 60 patients diagnosed with mHSPC across multiple institutions from 2023 to 2025. We examined clinical characteristics, treatment schedules, adverse events, and oncological outcomes. We focused particularly on the development of FN and used logistic regression analysis to investigate the predictive factors.

The median age was 72 years old, and 43 patients (73.3%) had high-volume disease at diagnosis. Nine patients (15%) developed FN. Multivariate logistic regression analysis identified older age [≥75, p=0.0161; hazard ratio (HR)=7.49], high-volume disease (p=0.0335), and shorter interval from ADT to docetaxel (<40 days) (p=0.0389; HR=7.86) as independent predictive factors of the development of FN. Notably, prolonged castration period prior to docetaxel (≥40 days) significantly reduced the risk of FN from 23.5% to 3.8% (p=0.0001). Patients who developed FN tended to have shorter castration-resistant prostate cancer progression-free survival (CRPC-PFS) compared to those who did not (p=0.0812; HR=3.2).

Older age and high-volume disease were independent risk factors for FN in patients with mHSPC receiving triplet therapy. A longer interval from ADT initiation to docetaxel (≥40 days) was associated with a significantly lower risk of FN, suggesting that extending the pre-docetaxel castration period is a practical, adjustable scheduling strategy to improve treatment safety. These findings may support treatment selection and proactive prevention of FN.

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide. This study aimed to clarify the oncogenic function of POM121 and its involvement in signaling pathways driving tumor progression.

POM121 expression was analyzed in six GC cell lines and one normal gastric epithelial cell line, as well as in clinical datasets. Functional consequences of POM121 knockdown were assessed in AGS and KATO-III cells using cell proliferation, migration, soft agar colony formation, proteomic profiling, and in vivo xenograft models. Phosphorylation of p70S6 kinase at Thr389 and Thr421/Ser424 was examined to determine downstream signaling.

POM121 was consistently found to be upregulated in GC tissues and cell lines. Silencing of POM121 significantly inhibited proliferation, migration, anchorage-independent growth, and tumorigenicity in vivo. Proteomic analysis revealed that suppression of POM121 attenuated phosphorylation of p70S6K at Thr389 and Thr421/Ser424, indicating impaired mTOR-p70S6K signaling.

POM121 promotes GC progression by enhancing proliferative and invasive phenotypes through p70S6 kinase-mediated signaling. These findings establish POM121 as a novel oncogene, prognostic biomarker, and potential therapeutic target in GC.

Uterine cancer is the fourth most frequently diagnosed cancer in women, and continues to present significant clinical challenges, particularly in older populations. Tumor progression is tightly linked to metabolic adaptations, and emerging evidence points to an association between dysregulated vitamin B2 (riboflavin, Rf) metabolism and cancer development. Rf is an essential precursor of the flavin cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are critical for cellular energy metabolism and redox balance. The aim of the study was to investigate whether uterine cancer tissues exhibit alterations in the expression of key regulators of flavin homeostasis - riboflavin transporters (RFVT1-3) and FAD synthase (FADS) - and to determine how these changes relate to intracellular flavin levels and to the expression of the FAD-dependent epigenetic enzyme lysine-specific demethylase 1 (LSD1).

Paired samples of tumor tissue and surrounding normal mucosa from eight patients with uterine cancer were analyzed to evaluate the expression of: RFVTs by both RT-PCR and western blot; and FADS, and the FAD dependent enzyme lysine specific demethylase 1 (LSD1) by RT-PCR. Furthermore, we evaluated flavin cofactors levels by HPLC.

Quantitative analyses revealed a significant up-regulation of RFVT1 and RFVT3 at both mRNA and protein levels in tumor tissues, accompanied by markedly increased intracellular levels of Rf (3fold) and FAD (2.5fold). FADS, the enzyme responsible for FAD production and delivery to client flavoproteins, was also significantly overexpressed and correlated with elevated LSD1 expression.

A coordinated mechanism where uterine cancer cells adaptively up-regulate RFVTs, FADS, and LSD1 to meet their metabolic demands was revealed. These results provide insights into the metabolic vulnerabilities of uterine cancer and propose Rf metabolism and flavin-dependent processes as potential therapeutic targets.

Prostate cancer (PCa) is a leading malignancy in men, with biochemical recurrence (BCR) indicating potential disease progression in up to 50% of patient's post-curative therapy. The liprin-α family gene PPFIA2 has emerged as a potential biomarker in PCa, yet its prognostic role in localized disease remains underexplored.

PPFIA2 expression was analyzed using high throughput data from TCGA-PRAD, CPC, Stockholm, and GSE54460 cohorts, with validation in an in-house cohort via immunohistochemistry (IHC). Kaplan-Meier and Cox regression analyses assessed its prognostic value for BCR and overall survival. In vitro, PPFIA2 knockdown effects were evaluated in LNCaP and C4-2 cell lines using CCK-8 and Transwell assays. Gene Set Enrichment Analysis (GSEA) explored biological pathways, and mutation profiles were analyzed using maftools.

High PPFIA2 expression was associated with earlier BCR across multiple cohorts. IHC confirmed elevated PPFIA2 protein levels in PCa tissues, correlating with poorer prognosis. PPFIA2 knockdown reduced proliferation and migration in PCa cell lines. GSEA revealed PPFIA2's activation of proliferation-related pathways and suppression of protein synthesis. High PPFIA2 expression was linked to a lower SPOP mutation frequency.

PPFIA2 is an unfavorable prognostic biomarker for localized PCa. Its oncogene effect highlights its potential for risk stratification and targeted therapy.