The differences between EBV-positive and EBV-negative aggressive NK-cell leukemia (ANKL) remain po orly understood. Herein, we sought to investigate the clinicopathologic and molecular differences between EBV-positive and EBV-negative ANKL.

We retrospectively analyzed 14 ANKL cases (9 EBV-positive, 5 EBV-negative), assessing clinicopathologic, cytogenetic, and mutational features. In addition, we searched the published literature to further analyze the distribution of genetic variation between EBV-positive (n=116) and EBV-negative-ANKL (n=14). Lastly, we assessed the utility of p53 immunohistochemistry to screen for EBV-negative-ANKL.

Demographically, EBV-negative-ANKL patients were older (median age 64 vs. 37 years) and showed longer survival (median 13 vs. 1 month) than EBV-positive counterparts. Morphologic and immunophenotypic features were similar between groups. All EBV-negative cases assessed in our cohort harbored TP53 mutations (3/3). Combining our data with all reported ANKL cases with comprehensive mutational assessment of TP53, JAK/STAT and epigenetic modifier genes in the literature we find TP53 mutations or copy number alterations present in 82% of EBV-negative-ANKL (14/17) but in only 25% (29/116) of EBV-positive cases. In contrast, EBV-negative-ANKL showed less JAK/STAT and epigenetic modifier gene mutations compared to EBV-positive ANKL. Given the high frequency of TP53 genetic alteration, we show that p53 immunohistochemistry overexpression is present in all but one EBV-negative-ANKL case assessed thus far.

Our findings suggest that EBV-negative-ANKL is a distinct subtype of ANKL, highly enriched for TP53 genetic alterations and showing different epidemiologic and prognostic features compared to EBV-positive-ANKL. In addition, p53 immunohistochemistry may serve as a screening tool for EBV-negative-ANKL.

P21 is a key cyclin-dependent kinase inhibitor linked to cellular senescence. However, its spatial expression patterns within tumor compartments and their relationship with tumor aggressiveness remain poorly characterized in head and neck squamous cell carcinoma (HNSCC). This study investigated the spatial distribution of P21 across distinct tumor regions and evaluated its association with tumor aggressiveness, including stage and adverse pathological features, in HNSCC.

Formalin-fixed, paraffin-embedded tissues from patients with HNSCC were assessed using immunohistochemistry for P21. The intensity, percent positivity, and composite scores were quantified in the surface, center, and invasive-front regions. All variables were transformed using log (x+1), and spatial ratios comparing surface-to-center and invasive-front-to-center expressions were calculated. Non-parametric analyses were performed to compare early- and advanced-stage HNSCC, with additional subgroup analyses according to extracapsular extension (ECE), lymphovascular invasion (LVI), perineural invasion (PNI), and tumor subsites.

Advanced-stage HNSCC demonstrated significantly higher invasive-front-to-center log ratios for both percent positivity and composite P21 scores (p=0.0275), indicating relative enrichment of P21 expression at the invasive-front. Among advanced-stage HNSCC, PNI-positive cases showed the most pronounced increases in both surface-to-center and invasive-front-to-center spatial ratios (p<0.05), whereas no significant spatial differences were observed for ECE or LVI.

P21 expression demonstrated region-specific differences associated with tumor aggressiveness, with PNI-positive tumors showing the clearest enrichment of P21 expression at the invasive-front. These findings suggest that spatial, rather than absolute, P21 expression patterns may reflect progression-related phenotypes in HNSCC. Spatial profiling of P21 may provide exploratory insights into tumor biology and could help identify tumors with a higher invasive potential.

In Chinese culture, families often take primary control over disclosing a cancer diagnosis, balancing a desire to protect patients' emotional well-being with respect for their right to know. This dynamic can influence patients' psychological health and overall treatment experience.

To examine decision-making dynamics, communication strategies, and power structures involved in how Chinese families balance the delivery of information with patients' psychological protection when disclosing a cancer diagnosis.

This qualitative study used semistructured interviews with family members of adult patients with cancer in China. Purposive sampling ensured diversity in sex, age, and relationship to patients. Data collection and analysis were conducted simultaneously from June 1, 2024, to July 31, 2025, using thematic analysis.

Key themes related to how families managed cancer diagnosis disclosure. Interviews elicited family members' expectations, decision-making processes, and strategies for balancing protection and patient autonomy.

A total of 41 family members were interviewed (median [range] age, 38 [21-56] years; 24 females [58.5%]). Four themes were identified: (1) family negotiation and decision-making on diagnosis disclosure, (2) conflict and collaboration between families and health care professionals, (3) implementation of family-led initial disclosure strategies, and (4) dynamic adjustment of disclosure strategies with treatment progression. These themes illustrated how families continually balanced protection and autonomy in evolving clinical circumstances.

In this qualitative study, cancer diagnosis disclosure within Chinese families unfolded as a culturally embedded and fluid process, requiring ongoing negotiation and adjustment among family members. Given the continued prominence of families in medical decision-making in China, future interventions should aim to bridge the gap between family involvement in care and patient autonomy. While offering necessary family support, these strategies should also aim to steer the disclosure model toward one that elevates and protects the patient's voice, thereby moving closer to internationally accepted ethical standards.

Laparoscopic colorectal procedures are widely adopted for colorectal cancer surgery. The double-stapling technique for circular colorectal anastomosis carries leakage rates of 11.2-13.4% and elevates stricture risk. In 2024, we introduced an innovative intracorporeal linear isoperistaltic "overlap" colorectal anastomosis; preliminary data from ten patients confirmed its safety and feasibility. This study aims to assess the feasibility and safety of the colorectal "overlap" anastomosis technique for laparoscopic and robotic surgery on a larger group of patients.

An observational study was conducted from 2023 to 2025. A total of 100 patients with adenocarcinoma of the distal sigmoid colon, rectosigmoid junction, or upper rectum underwent laparoscopic or robotic colorectal surgery with intracorporeal "overlap" colorectal anastomosis. Demographic, intraoperative, and postoperative data, including complications, length of hospital stay, and 30-day readmission rates, were analyzed. Colonoscopy at 6 months assessed anastomosis configuration and patency.

The intracorporeal linear "overlap" colorectal anastomosis was performed in 100 patients (51 laparoscopic, 49 robotic-da Vinci Xi). Mean age was 67.0 ± 10.1 years and median body mass index (BMI) 26.9 kg/m² (interquartile range [IQR]: 24.4-30.4); 76 patients were classified as American Society of Anesthesiologists (ASA) II and 24 were ASA III. Per pTNM staging, 33 patients had stage I, 27 stage II, 38 stage III, and 2 stage IV. Median blood loss was 30.0 mL (20-50), operative time 240.0 min (210.0-282.5), lymph nodes harvested 13 (11-18), and time to bowel function recovery 48 h (24-48). No intraoperative complications, conversions, or technical deviations, anastomotic leaks, major complications (Clavien-Dindo grades ≥ III), strictures, or 30-day readmissions occurred. Median postoperative stay was 5 days (4-6).

The novel intracorporeal linear "overlap" colorectal anastomosis is safe and feasible and may be recommended as a reliable alternative to the conventional circular anastomosis in both laparoscopic and robotic colorectal surgery.

The efficacy of chemotherapy against malignant tumors is severely limited by multidrug resistance (MDR), of which the overexpression of P-glycoprotein (P-gp) is recognized as a key mechanism. Consequently, the development of potent, low-toxicity P-gp inhibitors represents a crucial direction in anticancer drug research. Based on our group's prior work on P-gp inhibitors and supported by molecular docking analysis, 21 novel tetrahydroisoquinoline derivatives were designed and synthesized in this study. Their ability to reverse MDR was assessed in the human esophageal carcinoma multidrug-resistant cell line Eca109/VCR. The most active compound 21 demonstrated a superior reversal fold (RF = 654) compared to the third-generation P-gp inhibitor TQ, as confirmed by colony formation and flow cytometry assays. Mechanistic investigations, including chemosensitization, intracellular fluorescent substrate accumulation, and molecular docking studies, verified that the MDR reversal effect of compound 21 is mediated through P-gp inhibition. This work provides a new strategic direction for developing tetrahydroisoquinoline-based sensitizers to overcome tumor drug resistance.

Benign prostatic hyperplasia (BPH) is the main cause of lower urinary tract symptoms (LUTS) in aging men. As the incidence of prostate cancer (PCa) increases with age, coexistence of BPO and PCa is a frequent issue. Radical prostatectomy might be considered as the best option for patients presenting with severe obstructive symptoms, allowing to simultaneously treat both diseases. However, not all patients are eligible or prefer surgery, therefore a large number of patients are referred to receive PCa radiotherapy (RT). Preexisting LUTS represent a well-known risk factor to develop severe genito-urinary (GU) toxicity. While improving urinary function before starting irradiation appears to be crucial, the development of new minimally invasive surgical therapies (MIST) for BPH creates new opportunities for treatment personalization in RT patients with LUTS.

Gastrointestinal stromal tumor (GIST) is a genomically-driven neoplasm with a genetic profile that determines the clinical course of the disease. However, currently available molecular data is limited due to the rarity of the disease and does not fully capture GIST clinical and biological heterogeneity.

To gain deeper insight into the molecular landscape of GIST, we performed a comprehensive multi-omic analysis (targeted panel, whole exome sequencing, whole transcriptomics) in a large real-world, multicenter cohort including 1,427 cases. Pathological review was undertaken in KIT/PDGFRA-wild type cases. Molecular findings were correlated with clinical data and insurance claims outcomes.

There is a complex spectrum of multi-layered genetic events that converge in three GIST molecular subgroups: KIT-mutant, PDGFRA-mutant, and KIT/PDGFRA-wild-type. These alterations can only be captured using next-generation sequencing technologies, and are associated with clinical features, biological aggressiveness, and patient outcomes. Mutations in alternative genes, whether actionable or not, are seldom present and unlikely to contribute to tumor progression. By contrast, the cooperative effect of novel somatic copy number alterations may be required for GIST evolution and progression, in addition to the core set of events involved in the current cytogenetic model of tumorigenesis.

This molecular landscape provides a broader molecular understanding of GIST and supports a widespread use of genetic profiling for patients' clinical management.

Mistletoe extract is a widespread complementary therapy mainly used for quality-of-life improvement in cancer patients. Advanced pancreatic cancer is associated with poor quality of life and better therapies for symptomatic relief are highly needed.

MISTRAL aimed to assess the impact of mistletoe extract on quality of life, body weight, observed costs and blood biomarkers in patients with advanced pancreatic cancer.

MISTRAL was an investigator-initiated, phase III, randomized, double-blind, placebo-controlled, parallel-group, superiority, multicenter, clinical trial with a nested biomarker study. Registration EudraCT 2014-004552-64, NCT02948309.

At 9 oncology centers, 290 participants were randomized to standard treatment (palliative chemotherapy or best supportive care) plus subcutaneous mistletoe extract or placebo. Main inclusion criteria were advanced pancreatic cancer, performance status 0-2, main exclusion criteria neuroendocrine pancreatic tumor. EORTC-QLQ-C30, EORTC-QLQ-PAN26, body weight, cost parameters and biomarkers were assessed from baseline up until 9 months.

No statistically significant differences for quality of life and weight were evident between treatment arms. Parameters for observed costs for supportive and inpatient care (days at hospital, parenteral nutrition infusions, nutritional supplement drinks, number of visits of palliative home care teams, symptom-relieving medication) were similar in both arms. Thus, calculation of costs was not performed. No effect on explored biomarkers (differential blood count, lymphocyte subpopulations, C-reactive protein, albumin and Ca19-9) was found except for a statistically significant increase of eosinophils in the mistletoe arm without association to clinical effect.

Since no benefit was observed, there is no clinical reason to recommend mistletoe extract in patients with advanced pancreatic cancer.

Acquired resistance to Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, remains a major therapeutic challenge in EGFR-mutant non-small cell lung cancer (NSCLC). Here, we report that cepharanthine (CEP), a natural bisbenzylisoquinoline alkaloid, effectively reverses gefitinib resistance through concurrent suppression of the AKT/P70S6K survival axis and activation of the Stimulator of Interferon Genes (STING)-mediated innate immune pathway. In gefitinib-resistant H1975 cells (EGFR L858R/T790M), CEP monotherapy significantly inhibited proliferation and induced mitochondrial apoptosis. Notably, CEP synergized with gefitinib to enhance therapeutic efficacy. RNA sequencing and functional validation revealed that CEP activates the STING/TANK-Binding Kinase 1 (TBK1)/Interferon Regulatory Factor 3 (IRF3) signaling cascade, resulting in robust production of T-cell chemoattractants C-X-C Motif Chemokine Ligand 9 (CXCL9), C-X-C Motif Chemokine Ligand 10 (CXCL10), and C-C Motif Chemokine Ligand 5 (CCL5). Critically, the STING inhibitor H-151 abolished CEP's antitumor effects in vitro. Our findings reveal a novel dual mechanism action of CEP and nominate it as a potential candidate for overcoming TKI resistance in NSCLC.

Apoptosis is a regulated process of programed cell death that removes damaged ells. GO-Y078, a new curcumin analog, has been studied in the oncology field and shown to exert anti-proliferative and anti-angiogenic effects in multiple tumor types. However, its detailed signaling mechanisms and functional effects in human cervical cancer have not been clarified. Herein, GO-Y078 was employed to examine the anti-cancer mechanism in cervical cancer cells. GO-Y078 reduced the cell viability and elicited chromatin condensation and apoptotic cells of human cervical SiHa and HeLa cancer cells. Active PARP and active caspase-9, -8, and -3 were involved in GO-Y078-stimulated apoptosis. GO-Y078 also elevated phosphorylation of mitogen-activated protein kinase (MAPK) pathway. Co-treatment with GO-Y078 and either the ERK inhibitor U0126 or the p38 inhibitor SB203580 significantly reduced GO-Y078-induced activation of caspase-9, -8, and -3. In conclusion, GO-Y078 is a potential therapeutic candidate that induces apoptotic cell death in cervical cancer cells through phosphorylation-dependent activation of MAPK signaling followed by caspase activation.