Post-endoscopy gastric cancer (PEGC), defined as gastric cancer diagnosed after a negative upper gastrointestinal endoscopy, is considered a key indicator of endoscopic quality. Although international studies estimate that PEGC accounts for 5-11% of gastric cancer cases, evidence from Latin America remains scarce.

We conducted a retrospective multicentre observational study across three tertiary hospitals in Bogotá, Colombia (2024-2025). Adult patients with histologically confirmed gastric neoplasms were included. PEGC was defined as cancer diagnosed between 6 and 36 months after a negative endoscopy. Clinical characteristics, tumour location, and hospital outcomes were compared between PEGC and non-PEGC cases.

Amongst 599 patients, 71 met criteria for PEGC, corresponding to a frequency of 11.9% (95% CI: 9.5-14.7). Helicobacter pylori positivity was 67.1% overall and 70.4% amongst PEGC cases. PEGC was associated with higher rates of palliative management (23.9% vs 2.8%; OR 10.77; 95% CI: 5.09-22.77; p<0.001) and increased in-hospital mortality (16.9% vs 7.0%; OR 2.70; 95% CI: 1.33-5.46; p=0.004).

PEGC was frequent in this Colombian cohort and associated with adverse hospital outcomes, highlighting missed diagnostic opportunities and the need to strengthen endoscopic quality standards in high-burden regions. These findings support the incorporation of PEGC rate as a quality indicator for upper gastrointestinal endoscopy in high-incidence regions.

Vobramitamab duocarmazine is an investigational antibody-drug conjugate (ADC) targeting B7 homolog 3 (B7-H3) with a cytotoxic duocarmycin-based DNA-alkylating payload. This study evaluated its safety and antitumor activity in advanced solid tumors.

In this phase 1/2 trial (CP-MGC-018-01/NCT03729596), vobramitamab duocarmazine was evaluated at 0.5-4.0 mg/kg intravenously every 3 weeks. The multicohort tumor-expansion phase focused on metastatic castration-resistant prostate cancer (mCRPC), lung, breast, melanoma, and squamous head and neck carcinomas. Primary end points were safety and tolerability. Secondary end points included pharmacokinetics, immunogenicity, and antitumor activity.

Across vobramitamab duocarmazine-treated patients, 97.9% (140 of 143) experienced treatment-related adverse events (TRAEs) of all grades; the grade ≥3 TRAE rate was 65.0% (93 of 143). With two dose-limiting toxicities in patients receiving 4.0 mg/kg (grade 4 afebrile neutropenia and grade 3 fatigue), the recommended dose for expansion was 3.0 mg/kg. Among all patients treated at 3.0 mg/kg, the rate of grade ≥3 TRAEs was 65.3% (79 of 121) and the confirmed objective response rate (ORR) was 7.2% (seven of 97), with a 6.3-month median duration of response (DOR). Among patients with mCRPC receiving 3.0 mg/kg, the confirmed ORR was 8.3% (two of 24), with a 5.3-month median DOR; the confirmed prostate-specific antigen with a ≥50% decline from the baseline response rate was 43.9% (18 of 41), with a 6.2-month median DOR.

Vobramitamab duocarmazine demonstrated modest antitumor activity across tumor types, with the most pronounced activity in mCRPC. Treatment was limited by toxicity, particularly pleural effusions and fatigue, which restricted dosing duration. Study treatment was discontinued to refocus on mCRPC in a randomized phase 2 study (TAMARACK/NCT05551117), which was later discontinued after assessment of the vobramitamab duocarmazine safety and efficacy profile.

The diagnosis of an ectodermal dysplasia (ED) is often made by dermatologists. Some of the more than 50 distinct ectodermal dysplasias, however, are still largely unknown and their pathogenesis is poorly understood. Since we recently discovered that variants of the Interferon Regulatory Factor 6 (IRF6) gene IRF6 may cause ED, we have further investigated the link between this gene and maldevelopment of tissues originating from the embryonic ectoderm. Disease characterization in two previously reported subjects and one newly identified patient (mosaic status) included systematic clinical and genetic evaluation, assessment of all available patient records and dental radiographs, hearing tests and immunostaining of skin samples. Structural models of native and mutant IRF6 were analysed to elucidate the pathogenesis. IRF6-associated ED, a combination of natal teeth (irregularly), absent sweat glands, hidradenitis suppurativa-like symptoms, onychodysplasia, agenesis of numerous deciduous and permanent teeth, and sensorineural hearing impairment, was linked to amino acid substitutions in a region between the DNA-binding domain and the protein-binding domain of IRF6, which has not yet been assigned a function. Genotype-phenotype correlations from a total of five patients and immunohistochemical data support the assumption that IRF6-associated ED is based on a gain-of-function mechanism. Thus, IRF6 variants are not only the cause of Van der Woude syndrome and popliteal pterygium syndrome, two diseases with cleft lip/palate as common features, but are most likely responsible also for a new, challenging syndrome without orofacial clefting. Our results facilitate accurate and early diagnosis in affected individuals and may pave the way for specific treatment.

The perivascular epithelioid cell family of neoplasms in the lung encompass lymphangioleiomyomatosis, angiomyolipoma, angioleiomyoma, and perivascular epithelioid cell tumor (PEComa). They share the unique attribute of immunoreactivity for both melanocytic and muscle markers. Some are primary pulmonary neoplasms, while others, such as lymphangioleiomyomatosis, are now thought to represent metastatic, indolent tumors from uterine sites of origin. The clinical and morphologic appearances vary considerably, but a genetic link with tuberous sclerosis complex is a common feature. Considerable advances in our understanding of tumor biology, management, and treatment have been made over the last 2 decades, particularly for lymphangioleiomyomatosis. This review will highlight those advances and our current understanding of pulmonary PEComa-related lesions.

Recurrence rates in patients with resected pancreatic ductal adenocarcinoma (PDAC) remain high, posing a significant clinical challenge. Pre-operative neutrophil-to-lymphocyte ratio (NLR) has shown promise as a prognostic marker in various cancers. NLR's role in PDAC recurrence has not been widely explored. This study aims to investigate the effect of pre-operative NLR on post-operative PDAC recurrence.

A retrospective analysis was performed on patients who underwent surgery with curative intent for PDAC between 2015 and 2024. Patients were divided into two groups (high and low) using an NLR threshold of 3. Primary outcome was disease recurrence. The predictive value of NLR was compared using receiver operating characteristic curves and univariable and multivariable Cox regression models.

125 Patients were included; high NLR group n = 53 and low NLR group n = 72. Both groups were well balanced across all baseline characteristics. NLR is a strong predictor of recurrence compared to platelet-to-lymphocyte ratio (PLR) (AUC: NLR 0.716 vs. PLR 0.593, p = 0.022). The high NLR group had a significantly greater recurrence rate compared to the low NLR group (62.3% vs. 31.9%, p = 0.002) and a significantly greater local recurrence rate (43.4% vs. 19.4%, p = 0.004). A high NLR remains a significant negative prognosticator for recurrence in univariable (hazard ratio [HR] 2.540, p < 0.001) and multivariable analysis (HR 2.817, p < 0.001).

A high pre-operative NLR (> 3) was associated with significantly greater risk of recurrence, especially local recurrence. NLR may be used within risk stratification models to identify patients at risk of PDAC recurrence.

Colorectal cancer (CRC) is a prevalent malignancy with a complex genetic basis. Recent genome-wide association studies (GWAS) have identified a susceptibility locus at 3p21.31, however, the functional SNP(s) underlying the association between the 3p21.31 region and CRC remain to be elucidated. In this study, we identified rs2101247 as the potential functional SNP and further demonstrated that rs2101247 is significantly associated with the expression of the nearby long non-coding RNA (lncRNA) RP11-708J19.2 (ENSG00000271161.1). Functional experiments showed that RP11-708J19.2 is upregulated in CRC tumor tissues, and its knockdown reduces cell viability while promoting apoptosis in SW1116 and HCT116 cell lines. Mechanistically, RP11-708J19.2 interacts directly with the deacetylase SIRT7, modulating histone H3K18 acetylation (H3K18ac). Specifically, RP11-708J19.2 knockdown leads to a significant upregulation of H3K18ac levels, implicating a SIRT7-mediated epigenetic pathway in CRC progression. Our findings elucidate a novel functional SNP-lncRNA axis that contributes to CRC pathogenesis, providing potential biomarkers for early detection and therapeutic targets for intervention.

As a major cause of cancer-related death, lung adenocarcinoma (LUAD) remains a significant health challenge. Parthanatos plays a crucial role in tumor progression, influencing cancer cell survival and therapy resistance. This study constructed a parthanatos-based prognostic model and explored its associated biological processes.

Data on LUAD transcriptomics and parthanatos-related genes were collected from publicly databases and related literature. Differential expression analysis and weighted gene co-expression network analysis were employed to identify candidate genes. Univariate Cox regression analysis and machine learning algorithms were employed to screen prognostic genes and construct the risk model. Gene expression patterns and intercellular communication within distinct cell types were explored by single-cell sequencing. Lastly, prognostic gene expression in tissue samples was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting.

PPP1R14B, MIF, ALG3, C11orf24, and MZT2A were identified as prognostic genes. The risk model had good predictive performance. The risk score effectively stratified patients into high- and low-risk groups with significantly divergent overall survival (p< 0.0001). Prognostic genes were involved in vital processes such as DNA replication, protein metabolism, and immune response. Single-cell analysis highlighted expression variations across cell types, particularly in epithelial cells, with strong communication from myeloid cells and fibroblasts. RT-qPCR confirmed the high expression of prognostic genes in LUAD. Importantly, PPP1R14B expression was particularly significant, and it potentially influenced the LUAD malignant phenotype.

This study constructed and validated a risk model for LUAD associated with parthanatos, providing new insights into the pathological mechanisms of LUAD and highlighting potential therapeutic targets.

The ubiquitin domain-containing protein 1 (UBTD1) is involved in protein homeostasis and cell cycle regulation, and emerging evidence suggests its role in tumor biology. However, its function in ovarian cancer (OC) remains unclear. OC is highly lethal due to late diagnosis, metastasis, and platinum resistance. This study is aimed at investigating the role of UBTD1 in OC by integrating single-cell transcriptomics, mutation and HRD-related analyses, tumor microenvironment evaluation, and experimental validation.

We examined UBTD1 expression, prognosis, somatic mutation features, and immune microenvironment characteristics utilizing public databases, such as the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Single-cell RNA-seq data were analyzed using Seurat, hdWGCNA, and CopyKAT to characterize UBTD1-associated malignant-cell states and inferred CNV burden. Based on the median UBTD1 expression, TCGA-OV samples were divided into high and low expression groups to compare mutation spectra, DNA repair pathway activity, stromal scores, and immune cell infiltration. Functional assays were performed in A2780 and SK-OV-3 cell lines following lentiviral shRNAs-mediated UBTD1 knockdown. RNA sequencing and rescue experiments were used to explore downstream pathways.

Integrated single-cell and TCGA-OV analyses revealed that UBTD1-low tumors were enriched for genomic instability-related features, including increased inferred CNV burden and higher tumor mutation burden. By comparison, UBTD1-high tumors showed increased stromal scores and modest enrichment of selected immune-cell populations, including macrophages and neutrophils. Experimentally, UBTD1 was upregulated in OC and associated with poor prognosis. UBTD1 knockdown inhibited malignant phenotypes, enhanced cisplatin sensitivity, promoted apoptosis, and suppressed TNF/AP-1/FOS-related signaling. FOS overexpression partially reversed the effects of UBTD1 silencing.

UBTD1 expression defines distinct mutation and microenvironmental states in OC and functionally promotes malignant phenotypes, potentially through TNF/AP-1/FOS-related signaling.

Sialic acid-binding immunoglobulin-like lectin 10 (SIGLEC10), a member of the SIGLEC family, is selectively expressed on multiple immune cell subsets and plays a key role in immune regulation through the recognition of sialylated ligands. Recent studies suggest that SIGLEC10 functions as an emerging immune checkpoint that contributes to the regulation of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME).

Immunohistochemistry was performed to assess SIGLEC10 expression in a CRC cohort comprising 202 patients, and the association between SIGLEC10 expression and patient survival and prognosis was evaluated. Immunofluorescence staining and flow cytometry were used to characterize the localization and phenotypic features of SIGLEC10-expressing cells within tumor tissues. The Cancer Genome Atlas (TCGA) and RNA sequencing (RNA-seq) datasets were analyzed to investigate SIGLEC10-associated tumor immune signaling pathways. Additionally, single-cell datasets from Tumor Immune Single-cell Hub 2 (TISCH2) were used to further investigate the regulatory mechanisms of SIGLEC10^high TAMs within the TME. Finally, the therapeutic potential of SIGLEC10 as an immunotherapeutic target in CRC was evaluated.

High SIGLEC10 expression predicts poor prognosis in CRC patients and serves as an independent prognostic factor. SIGLEC10 is predominantly expressed in CD68⁺ macrophages and is associated with TAMs phenotypes. Functional enrichment analyses indicate that SIGLEC10^high TAMs are involved in the regulation of multiple inflammatory and tumor immune signaling pathways. Immune infiltration and differential analyses suggest that SIGLEC10^high TAMs may facilitate tumor immune evasion by promoting increased infiltration of immune cells and recruiting various immune chemokines. Single-cell analyses reveal that SIGLEC10^high TAMs may remodel the TME through TNFSF13B-mediated regulation of multiple immune cell populations, including B cells. Finally, SIGLEC10 exhibits considerable potential as an immunotherapeutic target for CRC.

This study highlights SIGLEC10 as an independent prognostic factor in patients with CRC and its potential as a promising target for immunotherapy in CRC.

Currently, specific therapy for alpha-1 antitrypsin deficiency (AATD) consists solely of augmentation therapy with alpha-1 proteinase inhibitors, including Glassia (Alpha₁-PI). The real-world experience and impact of Alpha₁-PI have not been well characterized. The aim of this retrospective cohort study was to describe the characteristics and healthcare resource utilization (HCRU) of patients with AATD receiving Alpha₁-PI.

De-identified records from adults with diagnosed AATD (aged ≥18 years) who had ≥2 in/outpatient claims and ≥12 months of continuous enrollment before and after the index date were evaluated as sub-cohorts, with analysis focusing primarily on patients receiving Alpha₁-PI. Outcomes included baseline demographics, clinical characteristics, AAT testing rates, treatment patterns, and HCRU, with descriptive statistics calculated for continuous variables and categorical measures.

249 patients were identified as Alpha₁-PI users, of which 159 (63.8%) were new users. At baseline, the most common comorbidities were any chronic pulmonary disease (95.2%), hypertension (59.4%), and emphysema (46.2%). AAT testing rates during the study period were 49.4% and 56.6% among anytime and new Alpha₁-PI users, respectively. During 12 months of follow-up, new Alpha₁-PI users achieved a mean of 22.3 (standard deviation, 16.2) prescription claims. In total, 103 (64.8%) patients adhered to treatment (proportion of days covered ≥80%). Seventy-four new users (46.5%) persisted in using Alpha₁-PI, whilst 45 (28.3%) discontinued and started another augmentation therapy. Most patients required outpatient visits (99.2%).

Claims-based adherence may be misclassified because an infusion claim does not confirm administration, and some Alpha₁-PI claims may bundle multiple infusions. As a result, proportion of days covered and observed treatment patterns may be overestimated and may reflect reimbursement patterns rather than actual use.

Patients with AATD had a high burden of comorbidities, treatment discontinuations and switching, and HCRU, demonstrating an unmet need when utilizing Alpha₁-PI for augmentation therapy.