Oral squamous cell carcinoma (OSCC) remains a significant health burden with limited therapeutic options and high mortality. Sesbania grandiflora, a medicinal plant rich in phytochemicals, has been traditionally used for its medicinal properties and is emerging as a potential anticancer agent.

This study aimed to investigate the anticancer mechanisms of S. grandiflora against OSCC using an integrated approach, combining network pharmacology, molecular docking, ADME profiling, and in vitro validation.

Network pharmacology was employed to identify hub genes and pathways associated with S. grandiflora bioactives. Molecular docking was performed to evaluate binding interactions of D-glucuronic acid, a major phytoconstituent, with key cancer-related targets. ADME profiling assessed drug-likeness and pharmacokinetic properties. in vitro assays, including MTT, flow cytometry, and Western blotting, were conducted on KB oral cancer cells to validate mechanistic insights.

Key hub genes identified included AKT1, BCL2, PIK3CA, MTOR, and CASP8, which were enriched in pathways such as the PI3K-Akt, p53, HIF-1, and EGFR-mediated apoptosis pathways. Molecular docking revealed strong and stable interactions of D-glucuronic acid with target proteins, supporting its multi-targeted activity. ADME analysis indicated favorable pharmacokinetic properties, including high GI absorption, BBB permeability, and minimal CYP450 inhibition. Experimental validation demonstrated significant cytotoxicity (IC₅₀: 250-300 µg/mL), dose-dependent G1-phase cell cycle arrest, downregulation of BCL-2, and upregulation of BAX, confirming the induction of apoptosis.

S. grandiflora exerts anticancer effects through modulation of PI3K-AKT-mTOR and apoptotic pathways. D-glucuronic acid emerges as a promising bioactive compound, supporting further in vivo studies and clinical exploration for OSCC management.

Colorectal cancer is the third most prevalent cancer and the second leading cause of cancer-related deaths worldwide. Limitations of current treatments include adverse effects and drug resistance, highlighting the need for new chemotherapeutic agents. This study evaluated the cytotoxic activity of crude methanolic extract of the parotid gland secretions of Ingerophrynus philippinicus (PGSE), a toad endemic to the Philippines, against human colorectal carcinoma cell line (HCT-116) and identified its bioactive compounds.

Crude methanolic extract of parotid gland secretions was prepared and evaluated for antiproliferative activity using the MTT assay. An Annexin V/PI assay was used to assess apoptosis and necrosis. The presence of bufadienolides was determined using Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Double Tandem Mass Spectrometry (UPLC-QTOF-MS/MS).

The extract exhibited cytotoxic activity against HCT-116 cells in a dose-dependent manner with an IC50 of 4.462 ± 2.141 μg/mL. The Annexin V/PI assay revealed that treated cells predominantly underwent late apoptosis (89.52% ± 2.25%), with smaller proportions of early apoptosis (6.16% ± 2.49%), and necrosis (4.32% ± 0.29%). The UPLC-QTOF-MS/MS analysis identified three bufadienolides (bufalin, bufotalin, and bufotalinin) in the PGSE.

PGSE demonstrates potent cytotoxic activity against colorectal cancer cells, primarily through apoptosis, and contains bufadienolides with known antineoplastic activity. These findings support its potential as a source of bioactive compounds for anticancer research.

Cervical cancer remains a major global health burden and is predominantly associated with human papillomavirus (HPV) infection. However, a subset of tumors develops independently of HPV, and their molecular characteristics are not fully understood. This study aimed to synthesize and compare the frequency of somatic mutations across key oncogenic pathways, p53, PI3K-Akt-mTOR, AMPK, and Ras-Raf-MAPK, in HPV-associated and HPV-independent cervical cancers.

A systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251044316). Comprehensive searches were performed in PubMed, EMBASE, LILACS, Web of Science, Scopus, CINAHL, and Cochrane Central from January 2016 to March 2025 using controlled descriptors related to cervical cancer, somatic mutations, and HPV status. Eligible studies included observational designs reporting cervical cancers with molecular HPV testing and somatic mutation profiling. Data extraction was conducted independently by multiple reviewers and validated by a senior author. Study quality was assessed using STROBE criteria. Extracted variables encompassed sample characteristics, HPV status, sequencing method, genes assessed, and mutation frequencies.

Eleven studies comprising 3,479 cervical cancer samples met the inclusion criteria, including 468 (13.4%) HPV-independent tumors. HPV-independent cancers demonstrated higher frequencies of TP53 and CDKN2A mutations, reaching up to 50% and 37.5%, respectively. Alterations in the PI3K-Akt-mTOR pathway, particularly PIK3CA and PTEN, showed heterogeneous patterns, with some studies reporting higher prevalence in HPV-independent tumors and others in HPV-associated tumors. Mutations in ERBB3, NTRK1, ITGB3, TSC2, and TERT were more frequent in HPV-associated cancers, while NTRK3 and RICTOR alterations appeared more common in HPV-independent tumors, although these findings were generally reported in isolated studies. Inconsistencies were also observed for STK11 (AMPK pathway) and KRAS (Ras-Raf-MAPK pathway). Considerable methodological variability limited cross-study comparability.

HPV-independent cervical cancers may represent a distinct molecular subgroup, particularly regarding the p53 pathway; however, study heterogeneity limits firm conclusions. Further standardized genomic studies are needed.

Immune checkpoint inhibitors have shown limited efficacy in bladder cancer due to the immunosuppressive tumor microenvironment. To address this challenge, we developed a β-lapachone-loaded iron-based carbon nanozyme (C-MIL@Lapa) that synergistically induces ferroptosis and immunogenic cell death (ICD). Carbonized MIL-100(Fe) (C-MIL) serves as both a drug carrier and a nanozyme with dual peroxidase and glutathione oxidase activities. In tumor cells, β-lapachone generates endogenous H₂O₂ via NQO1-mediated redox cycling, which is then converted into cytotoxic hydroxyl radicals by C-MIL. This cascade reaction causes glutathione depletion and lipid peroxidation, leading to ferroptosis. Meanwhile, ferroptotic cell death releases damage-associated molecular patterns that trigger ICD, activating dendritic cells and CD8⁺ T cell-mediated antitumor immunity. In vitro and in vivo results demonstrated that C-MIL@Lapa significantly inhibited bladder cancer growth and remodeled the tumor immune microenvironment. This work provides a nanozyme-based strategy for synergistic ferroptosis-immunotherapy of bladder cancer with promising clinical potential.

To describe the clinical presentation and histopathology of a meibomian gland epithelioma that clinically resembled squamous cell carcinoma in a steer.

A 15 year-old Hereford-Lowline cross steer presented for evaluation of an approximately 2 × 4 cm ulcerated, pedunculated eyelid mass arising from the right inferior eyelid margin.

Excision of the mass followed by adjunctive cryotherapy was performed. The mass was submitted for histopathologic analysis.

Histopathologic evaluation revealed the mass to be consistent with a meibomian gland epithelioma, a neoplastic proliferation of the basal/reserve cells of the meibomian gland. The steer recovered routinely from the procedure with no evidence of regrowth of the mass at 13 months post-operatively.

Meibomian gland epitheliomas are one of the most common eyelid tumors of dogs; however, this is the first known report of a histologically confirmed meibomian gland epithelioma in cattle. Clinically, the mass resembled the appearance of squamous cell carcinoma, a common eyelid tumor in Hereford cattle. The clinical misclassification of a benign eyelid mass as squamous cell carcinoma could lead to unnecessary aggressive management such as enucleation, exenteration, or culling. This case confirms the importance of histopathologic analysis of excised tissues to reach an accurate diagnosis and appropriate treatment and follow-up plans.

Recent years have seen substantial advances in lung cancer management, with therapeutic options expanding rapidly through the integration of targeted therapies, immunotherapies, antibody-drug conjugates, and novel, immune-engaging agents. Although outcomes have improved for selected patients with non-small cell lung cancer and small cell lung cancer, the increasing number of regimens has amplified clinical complexity, with persistent evidence gaps, limited head-to-head comparisons, and underrepresentation of key subgroups in trials. Emerging genomic tools and novel therapeutic modalities provide opportunities to further improve patient outcomes but also add to the challenges of clinical decision-making. To address these issues, a multidisciplinary panel of oncology experts, primarily based in the United States, convened to review current evidence gaps, controversies, and unmet needs in the management of lung cancer. Key areas were identified in treatment selection and sequencing as well as the management of high-risk subtypes, highlighting the need for prospective, head-to-head clinical trials. Findings from this panel will inform a 2026 follow-up conference in which a modified Delphi method will be used to develop formal consensus recommendations to provide actionable guidance for practicing clinicians.

Poly(ADP-ribose) polymerase inhibitors (PARPi) are commonly used in tumors with homologous recombination deficiency (HRD) but are associated with an increased risk of therapy-related myeloid neoplasms (tMN). Clonal hematopoiesis (CH) driven by DNA damage response (DDR) mutations is the origin of most tMN. Here, to better understand the causes of tMN following PARPi therapy, we studied the relationship between PARPi use and CH. We observed a high frequency of DDR CH following PARPi therapy, largely explained by prior carboplatin exposure. Among patients with serial blood sampling, DDR CH expanded during carboplatin and to a lesser extent, during PARPi treatment. Surprisingly, this expansion was largely reduced in patients with germline HRD. We validated these findings in a mouse model of Trp53-mutated CH. Our findings suggest that the increased risk of tMN following PARPi is largely influenced by prior oncologic therapies, including carboplatin, and may vary by germline HRD status.

To examine whether changes in the expression of 40 preselected mammalian target of rapamycin complex 1 (mTOR) pathway-related genes were associated with changes in fatigue scores during external beam radiation therapy (EBRT) to treat prostate cancer.

A total of 26 men completed the Functional Assessment of Cancer Therapy-Fatigue subscale and provided whole blood samples at baseline and at the midpoint of EBRT. Microarray gene expression data were analyzed using the limma package in R. Associations between changes in gene expression and changes in fatigue scores were computed using linear models and empirical Bayes moderation, with adjustment for radiation fraction.

After adjusting for radiation fraction, changes in the expression of 24 of 40 preselected genes were significantly associated with changes in fatigue during EBRT (false discovery rate < .05).

Findings suggest that mTOR-related genes may play a role in radiation therapy-related fatigue; validation of these implicated genes in an independent cohort is warranted.

BackgroundSelexipag, an oral IP prostacyclin receptor agonist, improves outcomes in pulmonary arterial hypertension (PAH); however, real-world hemodynamic data and the relationship between adverse events (AEs) and treatment response are limited.ObjectivesThe aims of this study were to evaluate the efficacy and safety of selexipag in a Japanese cohort and assess whether treatment-emergent adverse events, particularly headache and diarrhea, were associated with subsequent hemodynamic responses.DesignWe conducted a retrospective observational study at the National Cerebral and Cardiovascular Center in Japan.MethodsWe retrospectively analyzed consecutive patients with PAH initiating selexipag at our institution between 2016 and 2022. Baseline and follow-up right heart catheterization, 6-minute walk distance (6MWD), and B-type natriuretic peptide (BNP) were assessed at 26, 52, and 104 weeks. AEs requiring treatment were recorded.ResultsOf the 97 included patients, 94% received dual or triple PAH therapies at baseline. At 52 weeks, selexipag was associated with reductions in pulmonary vascular resistance (-1.36±4.70 Wood units; p=0.036) and mean pulmonary artery pressure (mPAP; -4.27±9.61 mmHg; p=0.001) and an increase in 6MWD (+26.6±53.8 m; p=0.003), without significant changes in cardiac index or BNP. The proportion of patients at low ESC/ERS 3-strata risk increased from 63% to 78% (p=0.017). AEs occurred in 62% of patients, most commonly headache (42%) and diarrhea (29%). Headaches, typically developing during dose escalation, might be associated with a better prognosis through greater mPAP reduction.ConclusionSelexipag initiation improved pulmonary hemodynamics, exercise capacity, and risk profile, without new safety signals. Headache, a common prostacyclin-related AE, may indicate treatment responsiveness and predict therapeutic outcomes. Careful titration to the maximally tolerated dose with vigilant AE management may optimize outcomes.

The global COVID-19 pandemic has profoundly affected healthcare. Puerto Rico (PR) faces a growing shortage of healthcare specialists that, compounded by the COVID-19 pandemic, has disrupted access to epilepsy care. This study assessed the impact of the pandemic and the exodus of healthcare specialists on epilepsy care from the perspective of healthcare providers.

We conducted a systematic search to identify neurologists practicing in PR during the study period using multiple sources, including government databases, professional associations, and publicly available online directories, with license verification performed through the Puerto Rico Department of Health. In addition, we distributed a survey on epilepsy care from January through May 2023 to obtain responses from actively practicing healthcare providers.

In our cross-referenced search (N = 163), 23.9% of neurologists identified in PR appeared to be inactive or were untraceable, suggesting possible migration from the island. Active neurologists were unevenly distributed, with the highest concentrations in the metropolitan area and notably fewer practitioners in western and southern municipalities. Among the survey respondents providing epilepsy care, 75% were neurologists, and 58.3% provided both outpatient and inpatient care to people with epilepsy (PWE). Barriers to care included fear of viral infection (66.7%) and lack of access to technology (50%). Among PWE, COVID-19 infection was reported by 75% of healthcare providers, and one-third noted unmet patient care needs in their practices.

The pandemic has exacerbated existing barriers to care for PWE and the shortage of healthcare specialists in PR, underscoring the need to reform public policy and improve access to services across the island.