Central neurocytoma is a rare intraventricular tumor with favorable prognosis following gross total resection (GTR). However, the role of Ki67-MIB1 values in the postoperative decision making-process of treatment, as well as the indication for adjuvant radiotherapy, remain debated. Medical record data of patients with confirmed diagnosis of central neurocytoma who underwent surgical resection at Department of Neurosurgery of "Ospedale del Mare" in Naples - Italy, between January and December 2022, were retrospectively reviewed. Inclusion criteria were adult patients (> 18 years old), minimum follow up 42 months, complete demographic, clinical, neuroradiological and histopathological data, type of management, complications and outcome, time to recurrence, follow-up duration. Five adult patients were enrolled according to the inclusion criteria. Most patients were women (80%), with mean age 24 years old. Main presenting symptoms were headache and visual deficit. Lesions always involved lateral ventricles, with extension to the third ventricle in all but one cases. Transcortical approach to the ipsilateral lateral ventricle with extension to the third ventricle was the main adopted surgical route. GTR was achieved in all cases without postoperative complications nor postoperative new onset neurological deficits. No patients required ventricular shunting procedures for hydrocephalus during the surveillance period. Follow-up ranged from 43 to 54 months. Ki67-MIB1 values ranged from 5% to 10%. No patients underwent adjuvant radiotherapy. Our findings suggest that GTR alone may be sufficient even in patients with moderately elevated Ki-67. A tailored, risk-adapted postoperative strategy is recommended rather than routine adjuvant treatment.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) induce regressions and extend progression-free survival (PFS) in ovarian cancer, especially in tumors with BRCA1 or BRCA2 mutations that impair homologous recombination repair. While recent studies have clarified the key roles of BRCA1, BRCA2, and PARP1 in replication fork stability, the downstream mechanisms that mediate PARPi-induced cytotoxicity and resistance remain incompletely understood. Here we delineate cell fate outcomes following PARPi treatment in homologous recombination-deficient high-grade serous ovarian cancer and identify actionable pathways to overcome acquired resistance. Our findings reveal that PARPi-induced DNA damage simultaneously triggers apoptosis, which primarily occurs through the BAX/BAK-dependent intrinsic apoptotic pathway, while also driving cellular senescence, as manifested by the expression of senescence-associated β-galactosidase, CDKN1A upregulation and a senescence-associated secretory phenotype. Notably, the PARPi-induced senescent cells persist as resistance develops and exhibit multinucleation, a hallmark of nuclear atypia, both in vitro and in patient-derived xenografts (PDXs). Building on the observation that the anti-apoptotic protein BCLX_L restrains pro-apoptotic BCL2 family members after PARPi treatment, we show that addition of the BCLX_L inhibitor A-1155463 to PARPi therapy diminishes resistance in multiple high-grade serous ovarian cancer cell lines in vitro and significantly enhances PARPi-induced tumor response in a PDX model with acquired PARPi resistance in vivo. Overall, these preclinical findings strongly support the potential of combining BH3 mimetics with PARPis to treat resistant ovarian cancer.

Although the etiology of cervical cancer has been partially established, its pathogenesis remains a key research focus. Specific studies on the genital tract microbiota of cervical cancer patients in Southern China are still scarce. To address this research gap, the present study collected genital tract microbial samples from 16 cervical cancer patients and 16 healthy women. Analysis of cervical cancer-specific microbiota was conducted via 16S rRNA gene sequencing. The study included 32 women (16 cervical cancer patients and 16 healthy controls) aged 45-65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal and cervical microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V3-V4), and a comparative bioinformatics analysis of the microbiome was performed. The study revealed a homogeneous microbial composition dominated by Lactobacillus in healthy women, whereas cervical cancer patients exhibited increased diversity with reduced Lactobacillus and enriched Prevotella. No significant differences were observed between sampling sites within each group. Functional predictions linked the cancer-associated microbiota to metabolic pathways and the AEROBACTIN-SYN-PWY pathway. In conclusion, our findings suggest that these specific key microbial taxa and their related metabolic pathways contribute to the pathogenesis of cervical cancer and may serve as promising targets for clinical treatment and intervention.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide, largely owing to its high metastatic potential. Contactin-5 (CNTN5), a glycosylphosphatidylinositol-anchored membrane protein, has been implicated in tumor-related processes; however, its role in NSCLC progression remains unclear. This study aimed to investigate the clinical relevance, biological function, and underlying mechanism of CNTN5 in NSCLC.

CNTN5 expression was evaluated using public databases and clinical NSCLC specimens. Gain- and loss-of-function assays were performed in NSCLC cell lines. Cell proliferation, migration, and invasion were assessed using CCK-8, wound healing, and Transwell assays, respectively. An experimental lung metastasis model was used to determine metastatic capacity in vivo. RNA sequencing and enrichment analysis were performed to explore the molecular mechanisms involved.

CNTN5 was upregulated in NSCLC tissues and was associated with poor prognosis. CNTN5 overexpression significantly enhanced NSCLC cell migration and invasion, while increased CNTN5 expression promoted lung metastatic colonization in vivo. Transcriptomic and protein analyses indicated that CNTN5 was associated with alterations in Hippo signaling pathway. In addition, CNTN5 increased YAP1 expression and promoted its nuclear translocation, while YAP1 silencing partially reversed the pro-migratory and pro-invasive effects induced by CNTN5. Co-immunoprecipitation analyses further supported an interaction between CNTN5 and PTPN13, accompanied by enhanced nuclear localization of YAP1.

CNTN5 promotes NSCLC progression, particularly invasion and metastasis, and is associated with unfavorable clinical outcomes. Mechanistically, CNTN5 enhances YAP1 nuclear translocation and activates YAP1-associated transcriptional programs, highlighting its potential as a prognostic biomarker and therapeutic target in NSCLC.

Although timolol ophthalmic solutions or hospital-compounded formulations have been used off-label for the treatment of superficial infantile hemangioma (IH), no topical timolol formulation has been developed specifically for this indication. This study was the first to develop a population pharmacokinetic (popPK) model for topical timolol maleate gel and to perform exploratory exposure-safety analyses. Data from Phase I-III clinical trials in healthy adults and infants with proliferative superficial IH were used to develop the popPK model. Potential covariate effects on the pharmacokinetics were investigated, and exploratory relationships between timolol exposure and safety outcomes were assessed. A total of 810 plasma concentration measurements from 138 subjects (24 healthy adults and 114 infants) were included in the popPK analysis. Timolol pharmacokinetics were well described by a one-compartment model with first-order absorption and elimination. No significant covariates influencing clearance were identified. No apparent associations were identified between timolol exposure and the evaluated safety outcomes. Overall, systemic exposure following administration of this topical timolol maleate gel formulation was limited, supporting its favorable safety profile in infants with superficial IH. These quantitative findings may help guide its rational clinical use.

Gastric cancer ovarian metastasis (GCOM) is an aggressive clinical entity whose evolutionary dissemination routes and molecular features remain incompletely defined.

We performed whole-exome sequencing and patient-level phylogenetic reconstruction of 81 spatially distinct tumour specimens from 17 patients with GCOM.

Ovarian metastases showed a higher tumour mutational burden than matched primary tumours and substantial inter-lesional genomic heterogeneity. Phylogenetic reconstruction supported two major evolutionary routes of ovarian dissemination: lymph node-dependent evolution, in which ovarian metastases were phylogenetically associated with lymph node-related lineages, and lymph node-independent evolution, in which ovarian and lymph node metastases diverged along separate branches. Putative driver-gene alterations were relatively enriched in the shared/truncal mutational fraction, and SCAF4 emerged as an understudied candidate metastasis-associated factor. In GC cells, SCAF4 depletion was accompanied by widespread alterations in RNA splicing and interferon-related transcriptional programs and enhanced proliferative, migratory, invasive, and clonogenic phenotypes.

These findings support a dual-route evolutionary framework for GCOM and nominate SCAF4 as a candidate metastasis-associated factor, providing a genomic basis for understanding the biological heterogeneity of ovarian dissemination in GC.

A multi-site genomic sequencing and phylogenetic reconstruction in matched gastric primaries and ovarian metastases was performed. Uncovered two distinct evolutionary routes for gastric cancer ovarian metastasis: lymph node-dependent and lymph node-independent evolutionary patterns. Genomic and functional analyses nominate SCAF4 as a candidate metastasis-associated factor.

Several testicular disorders have been described in rabbits, including neoplasms, cryptorchidism, abscesses, and torsions. Testicular torsion, characterized by rotation of the testicle around its vascular axis, may occur in either a scrotal or intra-abdominal position, leading to ischemia and necrosis, and is considered an acute condition requiring surgical intervention. The present study describes the case of a 13-month-old male rabbit presenting with abdominal pain and increased volume in the hypogastric region, with only one testicle identified within the scrotal sac. Ultrasonographic examination revealed an ectopic right testicle containing cystic structures, consistent with a cystic neoplasm. Based on the clinical and imaging findings, an exploratory laparotomy was performed, revealing an intra-abdominal testicle with cystic areas, extensive necrosis, and torsion of the spermatic cord, followed by surgical removal. Histopathological evaluation revealed a neoplasm composed of tissues differentiated toward multiple primordial germ layers, consistent with a teratoma. This report highlights the rare association between abdominal cryptorchidism, cystic testicular teratoma, and spermatic cord torsion in a pet rabbit, emphasizing that this association should be considered in rabbits presenting with abdominal pain and intra-abdominal enlargement.

To develop rituximab (RTX)-conjugated decreased nonspecific adhesivity receptor-targeted (DART) nanoparticles for CD20-targeted paclitaxel (PTX) delivery in non-Hodgkin lymphoma (NHL) and evaluate their targeting, therapeutic activity, formulation stability, and immune-associated cellular responses.

PTX-loaded PLGA-PEG nanoparticles were conjugated with RTX (RTX-DART/PTX) or control IgG (IgG-DART/PTX). Physicochemical properties and colloidal and frozen-storage stability were characterized. CD20-dependent cellular association and intracellular localization were evaluated in Raji lymphoma cells using flow cytometry, competitive blocking, and confocal microscopy. Cytotoxicity was assessed following short-term treatment and media replacement. Calreticulin (CRT) surface exposure and macrophage polarization-associated markers were evaluated in vitro. Anti-tumor efficacy was assessed in a systemic luciferase-expressing Raji xenograft model.

RTX-DART/PTX exhibited a size near 100 nm, low polydispersity, near-neutral surface charge, and 7-8% PTX loading. DART nanoparticles maintained their colloidal properties in serum incubation for up to 72 hours, while frozen storage at -20°C in 10% sucrose for 3 weeks preserved physicochemical properties and biological activity. RTX-DART showed greater CD20-dependent cellular association and intracellular localization than IgG-DART and free RTX blocking reduced nanoparticle association. Under short-exposure conditions, RTX-DART/PTX produced greater cytotoxicity than free PTX and IgG-DART/PTX. RTX-DART/PTX also enhanced CRT surface exposure, while PTX-containing treatments altered macrophage polarization-associated markers and IGF1 secretion in vitro. In vivo, RTX-DART/PTX reduced systemic tumor bioluminescence and improved survival relative to PBS and IgG-DART/PTX.

These findings support RTX-DART/PTX as a proof-of-concept CD20-targeted nanomedicine strategy for systemic NHL. Further validation in additional lymphoma models, immunocompetent or humanized systems, and pharmacokinetic and biodistribution studies is required.

TP53 mutations (TP53m) are uncommon in chronic-phase Ph-negative myeloproliferative neoplasms but become enriched in myelofibrosis (MF) and accelerated/blast phase myeloproliferative (AP/BP-MPN). Their prevalence, allelic distribution, and phase-stratified outcomes have not been systematically synthesized.

A PRISMA-guided systematic review of EMBASE and PubMed identified cohort studies of adult Ph-negative MPN with molecularly confirmed TP53m. Pooled proportions with 95% CI were generated using random-effects models; survival outcomes were summarized descriptively.

Eleven retrospective cohort studies (N =  603) met inclusion criteria. TP53m were uncommon overall (3%, 95% CI: 1-13; I ² =  97%) but substantially enriched in MF or AP/BP-MPN cohorts (10%, 95% CI: 4-24; I ² =  89%). Among TP53m patients, disease distribution included AP/BP-MPN (33%, 95% CI: 26-41), MF (31%, 95% CI: 15-54), ET (16%, 95% CI: 5-41), and PV (11%, 95% CI: 4-27). Single- and multi-hit TP53 were present in comparable proportions (52% vs. 48%), with a pooled mean VAF of 37.48% (95% CI: 30.73-44.24; I ² =  97%). Unfavorable karyotype was identified in 42%. Median OS was: 37.4-72 months in PV, 44.4-54.6 months in ET, 11.6-24.7 months in MF, and 4.5-6 months in AP/BP-MPN. In CP-MPN, multi-hit TP53 conferred worse OS (9.5-18.5 months) versus single-hit disease (38 months to not reached); this distinction was absent in AP/BP-MPN. Leukemic transformation occurred in 35% (95% CI: 16-60; I ² =  93%) across two reporting cohorts, and allo-HCT was utilized in only 16% (95% CI: 13-19; I ² =  12%).

TP53m Ph-negative MPN are enriched in advanced-phase disease, carry comparable proportions of single-hit and multi-hit allelic configurations with high clonal burden, and demonstrate a clinically important survival gradient. Allelic status is a key prognostic determinant in CP-MPN but loses significance in AP/BP-MPN where outcomes are uniformly dismal. Standardized molecular reporting and prospective clinical trials are needed.

The authors have confirmed clinical trial registration is not needed for this submission.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by excessive myeloid proliferation. The impaired clearance of senescent erythrocytes is a key pathological feature, yet its mechanisms remain unclear. Pro-phagocytic platelet-erythrocyte (P-RBC) complexes may represent a novel intercellular interaction involved in this process.

To investigate the levels of P-RBC complexes in MPN patients, their association with clinical characteristics and thrombotic risk, and their potential diagnostic value.

In this retrospective cohort study, 152 MPN patients (including polycythemia vera [PV], essential thrombocythemia [ET], and primary myelofibrosis [PMF]) and 152 healthy controls were enrolled. P-RBC complex levels in peripheral blood were measured using flow cytometry. Correlations with laboratory parameters, thrombotic events, and survival were analyzed.

P-RBC complex levels were significantly higher in MPN patients than in controls (2.76 ± 0.53% vs. 1.28 ± 0.37%, P < 0.001). Levels varied by subtype, with PMF patients showing the highest levels (3.28 ± 0.52%), followed by PV (2.76 ± 0.44%) and ET (2.49 ± 0.39%) (P < 0.001). P-RBC levels positively correlated with hemoglobin (r = 0.456), C-reactive protein (r = 0.291), and lactate dehydrogenase (r = 0.736) (all P < 0.001). Patients with thrombotic events had higher P-RBC levels than those without (3.04 ± 0.70% vs. 2.72 ± 0.48%, P = 0.009). Multivariate analysis identified P-RBC level as an independent risk factor for thrombosis (OR = 3.07, P = 0.012). Although survival was worse in the high-P-RBC group, the difference was not statistically significant (P = 0.194). ROC analysis showed excellent diagnostic performance for MPNs (AUC = 0.990), with 100.0% sensitivity and 91.4% specificity at a 1.80% cutoff.

P-RBC complexes are significantly elevated in MPN patients and correlate with disease subtype, inflammation, and thrombotic risk. They represent a promising novel biomarker for MPN diagnosis and risk stratification.