Vepdegestrant is an investigational, orally administered PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader being evaluated for the treatment of ER+/HER2- advanced breast cancer, with promising results in prior studies of Western and Japanese patients. Vepdegestrant had not been previously evaluated in Chinese patients.

The optimal timing of immune checkpoint inhibitor (ICI) initiation in advanced gastric cancer (GC) remains unclear. In this study, we evaluated the association between ICI initiation timing, tumor response, and survival outcomes in a real-world setting for GC.

Adjuvant cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve outcomes in hormone receptor-positive (HR+), HER2-negative early breast cancer, though trial results have been heterogeneous. Menopausal status and endocrine therapy backbone may contribute to variability in treatment effect. We performed a meta-analysis evaluating whether menopausal status influences the efficacy of adjuvant CDK 4/6 inhibition.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by unfavorable clinical outcomes. Identifying novel biomarkers and therapeutic targets is essential for advancing HCC management. Although DBF4 zinc finger B (DBF4B) has been associated with the progression of various cancers, its specific role in HCC remains poorly understood.

to reassess the prognostic value of positive surgical margins (PSM) after partial nephrectomy (PN) in terms of relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and cancer-specific mortality (CSM) within a large cohort spanning changing surgical eras, including the progressive adoption of minimally invasive approaches.

Transarterial radioembolization (TARE) is an established locoregional therapy for advanced hepatocellular carcinoma (HCC). Prognosis depends on both tumor progression and hepatic function. Despite multiple scoring systems, predicting therapeutic benefit remains challenging.

BLABEL was set up to collect data on the first-line treatment patterns and 5-year disease-evolution of non-muscle invasive bladder cancer (NMIBC) in Belgium. The primary objective was to describe treatment regimens following diagnosis, with patient and disease characteristics and 5-year disease evolution as secondary objectives.

The role of contrast-based imaging (CBI) at diagnosis in early breast cancer remains debated. More sensitive baseline staging may identify synchronous disease that would otherwise present as early ipsilateral or contralateral events. We examined whether CBI at diagnosis is associated with differences in early locoregional outcomes.

Immune escape is a hallmark of cancers, which affects the efficacy of immunotherapy. Herein, this study analyzed the significance of GATA1/FGL1 in the immune escape of cervical squamous cell carcinoma (CESC) to deepen the understanding of immune escape-associated molecular mechanisms. In silico analysis predicted the correlations of FGL1 with CESC prognosis and CD8+ T cell infiltration as well as the relation between FGL1 and GATA1. After FGL1 and/or GATA1 gain- and loss-of-function, CC cells were co-cultured with CD8+ T cells. The sensitivity of CC cells to CD8+ T cells was assessed, as well as the secretion of perforin, GzmB, IFN-γ, and TNF-α. Also, CD8+ T cell proliferation and apoptosis were measured. The binding of GATA1 to the FGL1 promoter was validated through luciferase and ChIP assays. GATA1-knockdown U14 cells were transplanted into immunocompetent C57BL/6 mice in combination with or without CD8α mAb to ascertain the impacts of GATA1 on tumor growth and immune escape in CESC in vivo. Knockdown of either FGL1 or GATA1 markedly enhanced the sensitivity of CC cells to CD8+ T cell‑mediated cytotoxicity and increased the secretion of perforin, GzmB, IFN‑γ, and TNF‑α. It also promoted CD8+ T cell proliferation while reducing their apoptosis. These effects of GATA1 knockdown were partially negated by FGL1. In vivo, GATA1 knockdown prominently diminished the tumor growth and increased the infiltration and cytotoxic effects of CD8+ T cells. Collectively, GATA1 knockdown facilitates CD8+ T cell responses and suppresses immune escape in CESC by downregulating FGL1.

Myeloid cells play crucial roles in cancer progression, influencing tumor growth, metastasis, and response to immunotherapy. The mechanisms shaping their diverse functions in the tumors remain poorly understood and may offer therapeutic opportunities. Here, we identify the lipid-presenting molecule CD1d as a regulator of tumor progression and myeloid heterogeneity in the tumor microenvironment. Using several mouse models of breast cancer, we demonstrate that genetic deletion or antibody-mediated targeting of CD1d leads to reduced tumor growth, altered immune infiltration, and improved efficacy of anti-PD-1 immunotherapy. Specifically, CD1d targeting reshapes the intratumoral myeloid compartment, enhancing proinflammatory programs and resulting in accumulation of inflammatory monocytes. The CD1d-dependent control of myeloid cell functional differentiation is cell-intrinsic and conserved in human and mouse. Through single-cell RNA sequencing, we define the transcriptional landscape associated with CD1d deficiency and derive a gene signature that correlates with clinical outcomes and response to immunotherapy in breast cancer patients. Thus, CD1d could provide a potential target to alter tumor-infiltrating myeloid populations and enhance immunotherapy responses.

Cancer originates from the uncontrolled proliferation of normal cells. Previous studies have demonstrated that CDC25B, a cell cycle-regulating phosphatase, is overexpressed in various tumors, including hepatocellular carcinoma, and its expression level may serve as a prognostic biomarker. The present study investigated the upstream miRNA regulators of CDC25B and demonstrated that their interactions can inhibit hepatocellular carcinoma progression. Here, stable hepatocellular carcinoma cell lines overexpressing or knocking down CDC25B were established using lentiviral vectors. The effects of CDC25B expression on the invasive phenotype of hepatocellular carcinoma cells were analyzed using plate cloning, scratch assays, and Transwell assays, and a subcutaneous tumor xenograft model in mice was established to evaluate the impact of CDC25B on tumor growth in vivo. Furthermore, dual-luciferase reporter assays were used to validate the targeted regulatory relationship between miR-200a-3p and CDC25B, while miR-200a-3p mimics and inhibitors were employed to elucidate the specific downstream mechanisms. We found that high expression of CDC25B significantly enhanced the epithelial-mesenchymal transition process, thereby accelerating the proliferation, invasion, and migration of hepatocellular carcinoma cells, whereas CDC25B knockdown exerted the opposite effects. In vivo tumorigenicity experiments in nude mice confirmed that overexpression of CDC25B promoted tumor growth. In addition, the dual-luciferase reporter assay confirmed that miR-200a-3p specifically targets and downregulates CDC25B expression, thereby inhibiting hepatocellular carcinoma progression.

Keratinocyte carcinoma (KC) places a considerable and growing burden on healthcare systems. Given the KC population's heterogeneity, tailored clinical pathways are needed to accommodate diverse management needs. This study applied machine learning (ML)-based phenomapping to identify distinct real-world subgroups within a national KC population using demographic and medical history variables. The study included KC patients treated in publicly-funded, office-based dermatology practices and registered in the Danish Skin Cancer Registry (2014-2022). In 106,490 KC patients, 7 ML-derived clusters were identified. One cluster (22.2%; n=23,590) consisted primarily of young, well educated high-income medically noncomplex females presenting with low-risk basal cell carcinomas (BCCs). Four clusters (55.2%; n=58,736) comprised patients with a greater dermatological disease burden, characterized by facial BCCs, multiple BCCs, a greater proportion of squamous cell carcinomas (SCCs), a history of skin cancer or previous actinic keratosis-related treatment. The remaining 2 clusters (22.7%; n=24,164) comprised highly comorbid patients with a greater proportion of SCCs, a high number of KCs on the head and neck and high immunosuppressive drug exposure. ML-derived phenomapping of a national KC population identified distinct, clinically relevant KC subgroups, providing a basis for tailored clinical pathways with differentiated resource needs.

Tracheal resection/reconstruction is among the most technically demanding procedures in thoracic surgery, traditionally requiring open approaches with complex airway management. The emergence of robotic-assisted surgery combined with venovenous extracorporeal membrane oxygenation (VV-ECMO) offers a minimally invasive alternative providing enhanced surgical precision, reduced postoperative morbidity and optimal apnoeic operative conditions. We report a robotic tracheal resection/reconstruction under VV-ECMO in a 65-year-old patient with a tracheal mucoepidermoid carcinoma following endoscopic debulking with incomplete margins. Key surgical highlights include a percutaneous VV-ECMO enabling complete apnoeic conditions, lymph node dissection to initiate progressive tracheal exposure, preserving the vagus nerve and tracheal vascularization, an original fluorescence-guided transillumination technique for intraoperative resection margin identification, and end-to-end anastomosis using three continuous V-Loc sutures. The patient was discharged on postoperative Day 7 with no major complications. Resection was finally complete, and anastomotic integrity was confirmed at two-month bronchoscopy. Given the rarity of this tumour and the steep learning curve of robotic airway surgery, a step-by-step video tutorial was necessary to establish a reproducible, didactic framework for this combined approach.

To determine whether immunohistochemical B7-H3 expression is associated with magnetic resonance imaging (MRI)-derived tumour volume, peritumoral brain oedema volume, and oedema index in adult gliomas.

To evaluate the association between intravaginal therapy with carboxymethyl-β-glucan (CMBG) and polycarbophil and cytological regression of atypical squamous cells of undetermined significance (ASCUS) and cervical intraepithelial neoplasia grade 1 (CIN 1), compared with standard follow-up.

Type 2 diabetes mellitus (DM) is implicated in cancer development and associated with poor survival in patients with cancer. However, the impact of DM on the outcome of small cell lung cancer (SCLC) remains unknown. This study investigated the correlation between DM and clinical outcomes and long-term prognosis of patients with extensive-stage small cell lung cancer (ES-SCLC).

Meningiomas exhibit marked biological heterogeneity that is not fully captured by current histopathological grading. Increasing evidence suggests that mitochondrial metabolism contributes to tumor aggressiveness; however, the molecular mechanisms regulating mitochondrial function in meningiomas remain poorly defined. Here, we investigated the role of mitochondrial transcription factor A (TFAM)-driven mitochondrial biogenesis and translation in meningioma progression. We performed integrative transcriptomic, immunohistochemical, and mitochondrial DNA analyses in a well-characterized cohort of 91 meningiomas, comprising World Health Organization grade 1 (G1) and grade 2 (G2) tumors with long-term clinical follow-up. RNA sequencing identified enrichment for mitochondrial metabolic pathways, including oxidative phosphorylation and ATP metabolism, that was preferentially activated in G2 meningiomas. TFAM and its upstream regulator PGC1α were significantly upregulated at both mRNA and protein levels in G2 tumors and exhibited a positive correlation, consistent with enhanced mitochondrial biogenesis. Although mitochondrial DNA copy number did not differ significantly between grades, G2 meningiomas showed a trend toward increased mitochondrial mass. Notably, G2 meningiomas demonstrated marked enrichment of mitoribosomal genes, including MRPL15, MRPL35, MRPL42 and MRPS22, whose expression correlated positively with TFAM and PGC1α expression levels. Network analysis identified TFAM as a central hub linking mitochondrial biogenesis, translation, and metabolic pathway activation. These findings were independently validated using a publicly available meningioma transcriptomic dataset. Together, our results reveal a TFAM-centered mitochondrial regulatory program that integrates mitochondrial biogenesis, translational capacity, and oxidative metabolism in higher-grade meningiomas. This mitochondrial translational axis represents a previously unrecognized mechanism underlying meningioma progression and highlights potential metabolic vulnerabilities for therapeutic intervention.

Anal intraepithelial neoplasia (AIN) is a premalignant lesion caused by human papillomavirus. Surgical excision is the preferred treatment, but recurrence rates are high, and the risk of progression to squamous cell carcinoma of the anus (SCCA) remains.

The clinicopathological and therapeutic landscape of lung neuroendocrine tumors (NETs) is continuously evolving. Although systemic chemotherapy has historically represented a management cornerstone, the available data are predominantly retrospective and outdated. A critical review of the current literature and public clinical trial registries was performed to evaluate the role of chemotherapy and targeted cytotoxic delivery systems in lung NETs. Given the nature of the review, the evidence was synthesized descriptively. In early-stage disease, the clinical utility of perioperative (neoadjuvant and adjuvant) chemotherapy remains uncertain and lacks universal standardization. In the advanced or metastatic setting, traditional platinum/etoposide regimens demonstrate suboptimal efficacy in controlling well-differentiated carcinoids. Conversely, oral alkylating agents (temozolomide) and combination schedules such as CAPTEM (capecitabine/temozolomide) or temozolomide paired with cabozantinib offer promising response and disease control rates. Future strategies are moving away from unselected systemic cytotoxicity toward targeted delivery and chemo-immunotherapy platforms, leveraging peptide-drug conjugates (PDCs like PEN-221), antibody-drug conjugates (ADCs), and bispecific T-cell engagers (BiTEs) directed against emerging surface targets such as DLL3 (e.g., tarlatamab) and TROP2. There is an urgent, unmet clinical need for prospective, multicenter clinical trials and international registries. Dissecting the complex molecular landscape of lung NETs will be essential to identify predictive biomarkers and actionable therapeutic targets, ultimately transitioning clinical management from empirical, extrapolated choices to robust, evidence-based, stage-specific standards of care.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. Cigarette smoke extract (CSE) is a major environmental factor driving NSCLC progression, yet the underlying molecular mechanisms remain incompletely understood. Protein arginine methyltransferase 6 (PRMT6) is implicated in various malignancies, including NSCLC, and epithelial-mesenchymal transition (EMT) contributes to metastasis and poor prognosis in this disease. However, the role of PRMT6 in CSE-induced NSCLC progression has not been elucidated.