Tumor mutational burden (TMB) and PD-L1 are established biomarkers for guiding immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC). As ICI use expands into early-stage disease, we explored the feasibility of using TMB, which can be determined via a comprehensive genomic profiling assay along with EGFR and ALK genomic alterations, as a biomarker for outcomes in both neoadjuvant and adjuvant settings. TMB-high status (≥10 mut/Mb) showed a numerically higher, but not statistically significant, rate of pathological complete response among patients receiving neoadjuvant ICI and significantly associated with more favorable time to recurrence in patients receiving adjuvant ICI, particularly among patients with PD-L1 expression <50%. TMB should be considered in future early-stage NSCLC ICI clinical trials to further validate these results.

Proton beam therapy (PBT) has proven to be highly effective in treating pediatric medulloblastoma, offering both excellent therapeutic outcomes and reduced side effects. However, factors influencing tumor response following PBT remain poorly defined, including the optimal interval time between surgery and PBT initiation (ISP).

To investigate the expression of Golgi membrane protein 1 (GOLM1) in oral squamous cell carcinoma (OSCC) and its effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in OSCC cells and the underlying mechanisms.

We present a case of human epidermal growth factor receptor 2 (HER2)-overexpressing, alpha-fetoprotein (AFP)-producing metastatic gastric adenocarcinoma diagnosed in the USA. Both HER2 overexpression and AFP production are independently associated with poor prognosis in gastric cancer, and their co-expression is rare. This gastric cancer subtype has been reported mainly in Asian populations, with fewer cases in Western countries. Due to its rarity, optimal treatment strategies are not well-established, and clinicians typically treat with standard cytotoxic chemotherapy regimens. Our patient presented with a visceral crisis denoted by impending liver failure, prompting the urgent initiation of first-line systemic therapy with fluorouracil, leucovorin, oxaliplatin and trastuzumab. This resulted in rapid clinical improvement, normalisation of liver function tests and tumour markers, and radiographic response with approximately 50% reduction in hepatic metastatic disease burden. This case underscores the aggressive behaviour and rarity of HER2-positive, AFP-producing gastric cancer, highlighting the critical need for prompt diagnosis and initiation of systemic therapy.

To determine the pre-specified long term efficacy (survival and swallowing function) and safety of medial retropharyngeal lymph node (MRLN) region sparing radiotherapy for non-metastatic nasopharyngeal carcinoma.

It remains unclear what factors differentiate patients who present with early rather than late pulmonary metastases after resection of a soft-tissue sarcoma, and how their outcomes differ. The purpose of this study was to compare the survival of patients with early and late sarcoma metastases in the lungs, and to compare the differences between the two groups.

Prostate cancer is the most prevalent cancer in men worldwide. As new treatments become available, costs also increase, and patients from lower-middle-income countries do not have access to those treatments due to cost restriction and governmental approval. However, several non-survival-prolonging treatments (nspTx) continue to be offered to patients with metastatic castration-resistant prostate cancer (mCRPC).

Gliomas exhibit significant prognostic heterogeneity, and single-omics data/existing technologies struggle to balance multi-omics integration efficiency, prediction accuracy, and clinical adaptability-hindering the clinical translation of precise prognostic assessment. Focussing on glioblastoma (GBM) and lower-grade glioma (LGG), this study proposes an integrated solution: three-step multi-omics feature selection combined with the limited random forest (FRF) model, using TCGA-derived transcriptomic, genomic, epigenomic and clinical survival data. Prognosis-related features are first screened using univariate Cox regression, refined by random forest-based feature importance for dimensionality reduction and then integrated into a multi-omics matrix through sample matching. The FRF model balances efficiency and accuracy by limiting decision tree number and depth, optimising node splitting criteria, and adding a dual-weighted correction mechanism. Results show that FRF achieves an AUC of 0.96 for GBM, outperforms logistic regression (LR) and support vector machine (SVM) across all LGG metrics, and reduces training time to minutes-meeting the 2-h clinical prognostic demand. Ablation experiments confirm that the multi-omics model improves performance by 11.63% compared with the optimal single-omics model, with core features consistent with glioma molecular mechanisms. This resolves the challenge of rapid integration and precise prediction, providing an efficient tool for glioma prognostic assessment and supporting multi-omics clinical translation.

Systemic therapy, including immune checkpoint inhibitors, has improved survival in advanced hepatocellular carcinoma (HCC); however, its efficacy remains limited in patients with macroscopic vascular invasion (MVI), a subgroup with an extremely poor prognosis. Although combining immunotherapy with local treatments such as hepatic arterial infusion chemotherapy (HAIC) and radiation therapy (RT) is considered a promising approach, robust supportive evidence from routine clinical practice is lacking.

Deciphering the mechanisms underlying antitumor immunity is critical for improving cancer immunotherapy efficacy. Here, we identify WFDC21P (lnc-DC) as a positive regulator of antitumor immunity through promoting the activation of the RNA-sensing retinoic acid-inducible gene-I (RIG-I) pathway in triple-negative breast cancer (TNBC). WFDC21P directly binds to RIG-I-interacting protein G3BP1 and is required for a rapid assembly of functional G3BP1-RIG-I-double-stranded RNAs condensates via phase separation, which enables robust activation of RIG-I. WFDC21P is downregulated in TNBC tissues and correlates with less CD8+ T cell infiltration in tumors and worse outcome of patients. WFDC21P knockdown in TNBC cells markedly dampens RIG-I activation and reduces the expression of IFN-stimulated genes, including MHC-I and PD-L1. In syngeneic tumor models, WFDC21P expression not only suppresses tumor growth by augmenting the infiltration and cytotoxic function of CD8+ T cells but also improves the response to immune checkpoint blockade, thus providing a compelling combination immunotherapy strategy for treating triple-negative breast cancer.

This study presents a nationwide infrastructure for the collection and utilization of gynecologic cancer biospecimens, established through the Korea Biobank Project. We comprehensively describe the biobanking strategy, quality control protocols, and development of secondary resources to support future translational and discovery-based research.

Neuroblastomas are heterogeneous pediatric tumors of the sympathetic nervous system for which treatments are still limited. Fundamental and applied approaches have been enabled thanks to the generation of patient-derived tumoroids (PDT), ex vivo 3D structures used as avatars of the original tumor. We generated neuroblastoma PDT and quantified the spatial distribution of CD133+ cancer stem cells using immunohistochemistry. We observed that those cells tend to aggregate in the PDT. In order to better understand the set of rules needed for generating such structures, we implemented a multiscale agent-based neuroblastoma tumoroid model. Model rules specify single cell's fate based on their intracellular content, which dynamically evolves according to a stochastic gene regulatory network. The state of this network can be modulated by cell-to-cell signaling through neighbor cell fate decisions and, possibly, spatial location. We first observed that in the absence of any spatial rules for inter-cellular interactions, no spatial structure emerged. The addition of simple rules (signaling by cell-to-cell contact or differential cell adhesion) only marginally improved the quantitative agreement to the experimental dataset. In sharp contrast, the addition of short-range pro-stem cell diffusive signaling among stem cells produced very realistic 3D PDT-like structures. This works highlights the power of our multiscale approach to discard too simplistic rules and to propose a minimal set of hypotheses required to reproduce qualitatively and quantitatively experimentally observed spatial structures. In the case of neuroblastoma-derived PDT, short-range spatial diffusion of stem-to-stem cell signaling proved to play a key role in successfully reconstructing the spatial structure.

The distinct roles of GSK3 isoforms (GSK3α/β) in tumorigenesis and immune modulation remain poorly characterized across malignancies. We integrated multi-omics data from TCGA, GTEx, and single-cell RNA-seq to analyze GSK3α/β expression patterns in 31 cancers. Functional clustering, survival analysis (Cox regression), immune infiltration, and in vitro validation (AML cell lines treated with CHIR-99021) were performed. Integrated multi-omics analysis of 31 malignancies revealed divergent dysregulation of GSK3 isoforms: GSK3α was upregulated in 19 solid tumors but suppressed in AML, while GSK3β was elevated in 23 cancers and high-risk AML subtypes (FAB-M0/M1, P = 0.0013). GSK3β outperformed GSK3α as a pan-cancer diagnostic biomarker, achieving superior AUC in 9 tumors. Prognostically, high GSK3α predicted poor OS in ACC (HR = 8.80, P = 0.0047) and MESO (HR = 2.75, P < 0.0067), whereas GSK3β independently stratified cytogenetic-risk AML (HR = 4.22, P = 0.007). Immune profiling uncovered isoform-specific TME modulation: GSK3α correlated with protumorigenic immune infiltration (Treg/Th17, r = 0.38), contrasting GSK3β's broad negative associations with cytotoxic effectors (r = -0.27). Functional validation in AML THP-1 cells demonstrated that the GSK3 inhibitor CHIR-99021 (10 μM) significantly suppressed proliferation, induced apoptosis, and caused S-phase cell cycle arrest, concomitant with downregulation of c-Myc. These findings establish GSK3β as a key regulator of oncogenic programs in AML. This study provides a comprehensive pan-cancer atlas of GSK3 isoform-specific functionality, nominating GSK3β as a high-priority therapeutic target.

Most studies regarding quality of life in patients with non-functioning pituitary adenoma are based on general questionnaires that might not capture disease-specific aspects, making further exploration of patients' experiences with non-functioning pituitary adenoma necessary. This study aimed to describe how patients that have undergone surgery due to non-functioning pituitary adenoma experience the effects of the disease on their life.

The actin-binding protein CAPG (Capping Actin Protein, Gelsolin Like) is implicated in oncogenesis, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study combined bioinformatic analysis of TCGA/GEO datasets, immunohistochemistry on clinical samples, and functional in vitro assays to define CAPG's significance in PDAC. We found CAPG significantly overexpressed in PDAC tissues (n = 179 tumor vs. 171 normal, p < 0.05), with levels correlating with advanced tumor stage (T3 vs. T1) and predicting poorer overall (p = 0.0085) and disease-free (p = 0.015) survival. In vitro, siRNA-mediated CAPG knockdown in PANC-1 and AsPC-1 cells markedly inhibited proliferation (CCK-8 assay) and migration (wound healing assay), and significantly sensitized cells to gemcitabine-induced apoptosis. Mechanistically, CAPG knockdown was associated with reduced ERK1/2 phosphorylation and Cyclin D1 expression, and ERK1/2 inhibition phenocopied the anti-proliferative and chemosensitizing effects. Our results establish CAPG as a negative prognostic biomarker in PDAC, demonstrate its critical role in driving proliferation and migration-potentially via modulating ERK pathway activity-and highlight its promise as a therapeutic target whose inhibition can enhance chemotherapy efficacy.

Inositol plays a crucial role in follicular development by regulating insulin signaling and ovarian function. However, its precise mechanism of action remains unclear. This study investigated the effects of myo-inositol (MI) and D-chiro-inositol (DCI) on the development of murine ovarian follicles in vitro. Follicles treated with DCI exhibited larger diameters than controls on Day 6 (275.20 ± 12.54 μm; p = 0.037) and Day 8 (277.47 ± 11.47 μm; p = 0.048), indicating a modest, marginally significant effect that was not maintained by Day 10. The rate of follicular antrum formation was significantly higher in the DCI-treated group on Day 6 (p < 0.05); however, no significant differences were observed on Days 8 and 10. In contrast, MI treatment did not affect follicular survival, diameter, or antrum formation compared with controls. Estradiol concentrations and the expression levels of follicle-stimulating hormone receptor and aromatase genes did not differ significantly among groups. Together, these data provide in vitro evidence that DCI can facilitate the transition from the secondary (preantral) to the early antral stage under these culture conditions. Given the small experimental sample size, the use of healthy murine follicles cultured under a high FSH concentration, and the absence of a PCOS-like ovarian milieu, these findings should be interpreted cautiously and cannot be directly generalized to infertility treatment in women with PCOS. Future studies using PCOS animal models and human follicle systems are needed to clarify translational relevance of these findings.

Genes encoding subunits of the mitochondrial tricarboxylic acid cycle enzyme complex succinate dehydrogenase (SDH) are a leading cause of the neuroendocrine tumour syndrome hereditary paraganglioma-pheochromocytoma. Pathogenic variants of SDHD and SDHAF2 confer a remarkable parent-of-origin tumour risk, in which paternally inherited variants cause tumours but maternally inherited variants do not. Formulated to explain this observation, the Hensen hypothesis proposes that loss of an (unknown) imprinted gene(s), together with the remaining wildtype SDH gene, is a prerequisite for tumour formation; in effect a three-hit hypothesis. This study had three objectives, first, as a test of the Hensen model, second, as a potential model for a disease for which no mouse or cell model currently exists, and finally, as a test of chromosome (Ch.) configuration to interrogate large genomic regions carrying an unknown phenotypic modifier. We crossed a gene knockout line (Sdhc, mouse Ch.1) to a Robertsonian chromosome line, Rb(1:7), harbouring the homologous gene imprinting centre (human Ch.11p15, mouse Ch.7) implicated in human tumourigenesis, to create a metacentric chromosome with characteristics of human chromosome 11. We developed 7 cohorts combining Sdhc (mouse Ch.1) wildtype or knockout with distinct configurations of Rb(1:7), confirming both paternal and maternal inheritance of Sdhc. We noted significant weight gain, and in heterozygote Sdhc KO-Rb/wt mice high levels of immune activation. Thyroid abnormalities, including lesions with papillary thyroid carcinoma-like features, were common (30-50%) in Sdhc knockout mice with both heterozygous and homozygous Rb chromosomes, regardless of mode of inheritance. We also observed a single case of bilateral pheochromocytoma in which loss of Sdhc was not the driver. While our findings did not recapitulate features of the Hensen Model, this study does suggest that chromosomal structure, even in the form of a seemingly innocuous single Robertsonian configuration, can dramatically impact clinical phenotype.

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer, with limited treatment options due to the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression. This characteristic renders TNBC resistant to hormone-based and HER2-targeted therapies, leaving cytotoxic chemotherapy as the predominant strategy and highlighting the urgency for novel interventions. In this study, we investigated the mechanism of action of GL24, a potent 4-(phenylsulfonyl)morpholine-based small molecule with selective tumor suppression effects on metastatic TNBC cells, while being ineffective against TNBC cells derived from the primary tumor site, using gene co-expression analysis. By considering the distinct phenotypic responses induced by GL24, we tailored our co-expression analysis approach, selecting gene pairs that exhibited differential co-expression in effective cells while excluding gene pairs that also showed differential patterns in non-effective cells. Constructing a co-expression network from these differential pairs, followed by enrichment analysis and functional annotation, revealed specific gene interactions and molecular pathways associated with GL24-mediated TNBC inhibition. These insights supported the previously established findings that showed convergence on apoptosis based on differentially expressed genes, while also providing complementary information by highlighting pathways involved in metabolic alterations, proliferation, and migration or invasion. This expanded understanding advances the knowledge of the mechanisms of GL24 in combating TNBC.

There are still many gaps in the understanding of melanoma subtypes in Mexico. Currently, there is a growing search for prognostic markers and potential therapeutic targets for melanoma treatment. Nestin has been identified as a marker of angiogenesis, invasiveness, and shortened survival in various tumor types, and therefore we evaluated nestin expression in two types of melanoma tissue to investigate its possible clinical and pathological associations.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease with increasing prevalence. Squamous papilloma of the esophagus is a rare benign lesion, with prevalence estimates of 0.014%-0.45% and association in EoE has not been reported. Our aims were to determine the prevalence of papilloma in a large cohort of EoE adults and clinical features of EoE associated with papilloma. We performed a retrospective chart review of EoE adults at two academic centers from 2002 to 2013 using current EoE consensus guidelines. Extracted data included patient demographics, clinical features, endoscopic findings, and histological information. Papilloma findings were confirmed by review by a senior gastrointestinal pathologist. A subset of papilloma biopsies was stained for human papilloma virus (HPV) and cell proliferation via ki-67 staining. In a cohort of 454 EoE patients, 41 patients (9%) presented with a papilloma. 46% were male, median age of 42 years (ranging 18-82). The median size of papilloma was 3 mm (range 1-5 mm); 63% were in the mid/proximal esophagus. Features of age, disease duration, eosinophil count, and atopy did not differentiate EoE patients with/without papilloma. Patients with papilloma were more likely to be female, have endoscopic exudates and edema. Papillomas stained negative for HPV and normal ki-67 staining. (1) The prevalence of papilloma in EoE adults was 9%, which represents a 24-fold increase than estimates in the general population. (2) Female gender and inflammatory endoscopic features were more common in EoE patients with papillomas. (3) The clinical significance of papilloma in EoE is unknown and merits further investigation.