Prostate cancer progression toward an aggressive, therapy‑resistant disease state remains a major clinical challenge, indicating a need to identify novel molecular drivers of such progression and actionable therapeutic targets. The present study analyzed the role of dynein heavy chain domain 1 (DNHD1), a previously uncharacterized regulator of malignancy, in prostate cancer. Integrative transcriptomic analyses across The Cancer Genome Atlas and independent clinical cohorts revealed that DNHD1 is markedly upregulated in advanced‑stage prostate cancer and positively correlated with increasing Gleason scores. Elevated DNHD1 expression was associated with poor overall survival and disease‑free survival, which supports its clinical relevance as a prognostic biomarker. Functional analyses demonstrated that DNHD1 promoted tumor cell proliferation, colony formation, migration and invasion in vitro. Molecular correlation modeling and pathway analyses revealed histone deacetylase 6 (HDAC6) as a key downstream effector of DNHD1. DNHD1 expression was positively correlated with and regulated HDAC6 expression in clinical datasets. Gain‑of‑function and loss‑of‑function experiments further revealed that HDAC6 is required for DNHD1‑mediated oncogenic phenotypes in prostate cancer, positioning HDAC6 as a functional mediator downstream of DNHD1. The DNHD1‑HDAC6 axis was associated with cilium assembly‑related pathways, suggesting a previously unrecognized association between ciliary regulation and prostate cancer progression. HDAC6 inhibition with tubastatin A effectively suppressed DNHD1‑driven tumor growth and motility, as well as increased acetylated α‑tubulin and decreased androgen receptor signaling. These findings indicated a potential therapeutic vulnerability within the DNHD1‑HDAC6 axis. They implied that in prostate cancer, the DNHD1‑HDAC6 axis, a novel regulatory pathway, promotes aggressiveness and that HDAC6 is a targetable mediator of DNHD1‑driven malignancy. This axis can be considered a prognostic indicator and mechanistic foundation for developing targeted therapeutic strategies for advanced prostate cancer.

Cervical cancer is a malignant tumor that threatens women's health and radiotherapy represents a major therapeutic approach for its treatment; however, radioresistance frequently leads to treatment failure. The present study aimed to investigate whether loperamide (LOP), a µ‑opioid receptor agonist commonly used as an antidiarrheal agent, could enhance the radiosensitivity of cervical cancer cells by regulating ferroptosis. A Cell Counting Kit‑8 assay was used to evaluate the cytotoxicity of LOP in SiHa and HeLa cells, and EdU and colony formation assays were performed to assess cell proliferation. In addition, wound‑healing and Transwell assays were performed to detect cell migration. Flow cytometry was applied to measure cell apoptosis and intracellular reactive oxygen species (ROS) levels, and colorimetric assays were used to determine malondialdehyde (MDA) and glutathione (GSH) contents. The mRNA and protein expression levels of the ferroptosis‑related markers GSH peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were analyzed using reverse transcription‑quantitative PCR and western blotting. The results showed that LOP significantly inhibited the viability of SiHa and HeLa cells, and exerted a synergistic effect with radiotherapy (combination index <1) to suppress cell proliferation and migration. Combined treatment with LOP and radiotherapy markedly increased apoptosis and ROS accumulation, elevated MDA levels and reduced GSH levels. Moreover, the combination treatment significantly downregulated the expression of GPX4 and SLC7A11. These findings indicated that LOP enhances the radiosensitivity of cervical cancer cells, with ferroptosis induction via inhibition of the GPX4/SLC7A11 axis as a contributing mechanism. Both apoptosis and ferroptosis were induced by the combination treatment, suggesting that the radiosensitizing effect may involve multiple cell death pathways. These observations provide a basis for further investigation into LOP as a potential radiosensitizing agent in cervical cancer.

Pituitary prolactinoma is the most prevalent subtype of functional pituitary adenoma, for which dopamine agonists (DAs) have been established as the universal first-line therapeutic regimen in clinical practice. Approximately 10-25% of patients exhibit poor therapeutic responsiveness to DAs, presenting with persistent hyperprolactinemia and uncontrolled tumor growth, while the molecular mechanisms underlying this drug resistance phenotype remain incompletely characterized.

In the present study, GH3 rat pituitary tumor cells were employed as the in vitro experimental model to investigate whether the DNA methyltransferase inhibitor decitabine could modulate cellular sensitivity to dopamine agonists, and to further elucidate the associated potential molecular basis. Transcriptome sequencing coupled with systematic bioinformatics analysis was conducted on GH3 cells after decitabine intervention to screen candidate differentially expressed genes, from which Trim7 was selected as the key target for subsequent functional validation.

Functional assays demonstrated that Trim7 overexpression significantly enhanced cabergoline-induced apoptosis in GH3 cells. A concomitant reduction in cell proliferation was also observed in the Trim7 overexpression group compared with the empty vector control, although this difference did not reach statistical significance.

Collectively, these data establish a significant correlative relationship between Trim7 upregulation and improved dopamine agonist sensitivity in GH3 cells. Complementary loss-of-function experiments are still required to define the definitive causal role of Trim7 in this regulatory axis. The present findings provide preliminary evidence for the involvement of epigenetic regulation in dopamine agonist resistance, and suggest that Trim7 may serve as a promising potential therapeutic target for future intervention strategies in drug-resistant prolactinomas.

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare primary hepatic neoplasm characterized by the coexistence of hepatocellular and cholangiocellular differentiation within the same tumor. The diagnosis is challenging because imaging characteristics may resemble those of hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC), depending on the dominant histologic component. We present a case of cHCC-CC demonstrating discrete regions with imaging features of both HCC and ICC, along with elevation of both alpha-fetoprotein and carbohydrate antigen 19-9. Recognition of discrete imaging features of HCC and ICC in the same mass should raise suspicion for cHCC-CC when evaluating primary liver neoplasms. Accurate diagnosis of cHCC-CC is important for prognostication and to guide clinical decision-making.

Bladder cancer (BC), a highly prevalent malignancy of the urinary tract, imposes a considerable clinical burden because of its high recurrence rates and a substantial risk of disease progression. Accumulating evidence suggests that microbiome dysbiosis is associated with the initiation and progression of BC through potentially bidirectional interactions. Recent advances in high-throughput sequencing technologies have facilitated a more comprehensive characterization of the urinary microbiome, thereby revealing its potential involvement in the pathogenesis of BC. This review summarizes the proposed mechanisms through which microbial communities may contribute to BC carcinogenesis, including chronic inflammation, microbial metabolite production, and epigenetic regulation. We further critically evaluate the established mechanisms of Bacillus Calmette-Guérin (BCG) immunotherapy-a standard intravesical immunotherapy for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC)-and examine the emerging application of microbiome profiling as a source of candidate noninvasive biomarkers and potential correlates or modulators of immune checkpoint inhibitor (ICI) response. Additionally, we elucidate the associations between microbiota heterogeneity and immunotherapy response, offering novel insights into microbiome-targeted therapeutic strategies for BC.

Epstein-Barr virus positive plasma cell neoplasms in immunocompetent hosts typically behave like aggressive lymphomas, often classified as plasmablastic lymphoma. We evaluated six sinonasal neoplasms in elderly males with unusually indolent courses at Mayo Clinic.

A single-center, retrospective review of plasmablastic lymphoma cases identified six cases with unusually favorable outcomes. We analyzed clinical presentations, pathologic features, and treatment outcomes.

All patients were male with age range 61-80 years. Five patients had Ann Arbor stage IE disease and one had Stage IV; all lacked B symptoms, and LDH was normal in five. Histologic evaluation revealed mixed mature plasma cell and plasmablastic features in three cases and pure plasmablastic morphology in three. All cases demonstrated EBER and CD138 positivity with monotypic light chain restriction (3 κ, 3 λ). Four patients recieved systemic chemotherapy, one had local radiation alone, and one was observed. No patients died of this disease within the follow-up period.

These neoplasms show less aggressive behavior than typical plasmablastic lymphoma, suggesting this sinonasal disease represents a distinct indolent subset of EBV positive PCNs.

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

Fibroblast growth factor receptor (FGFR) signaling is a major oncogenic pathway in multiple cancer types and an important determinant of therapeutic response and resistance. However, its role in coordinating apoptotic susceptibility with tumor immune escape remains insufficiently integrated. This review summarizes how FGFR signaling regulates mitochondrial apoptosis through the RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, PLCγ-PKC/Ca²⁺, and JAK-STAT pathways. These signaling networks converge on BCL-2 family proteins, BH3-only regulators, FOXO-dependent transcription, BAX/BAK activation, mitochondrial outer membrane permeabilization, cytochrome c release, and caspase activation. Non-canonical mechanisms involving redox homeostasis, metabolic stress, c-Myc regulation, and autophagy further determine whether FGFR inhibition produces transient adaptation or irreversible cell death. FGFR alterations may also shape the immune contexture of selected tumors by influencing inflammatory signaling, PD-L1 regulation, antigen-presentation pathways, tumor-stromal interactions, and susceptibility to immune-mediated elimination. These effects are strongly dependent on tumor lineage, genomic background, bypass receptor tyrosine kinase signaling, mitochondrial priming, and the local immune microenvironment. We further synthesize preclinical and emerging clinical evidence for combining FGFR-targeted therapies with immune checkpoint blockade and discuss the biomarkers and limitations that may determine therapeutic benefit. By linking apoptotic regulation, immune evasion, and therapeutic resistance, this review provides a framework for mechanism-based treatment strategies in FGFR-aberrant cancers.

While immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized the treatment of skin cancers, a significant proportion of patients with advanced melanoma and cutaneous squamous cell carcinoma (cSCC) exhibit primary or acquired resistance. Identifying non-redundant inhibitory pathways is crucial for the next generation of immunotherapy. As a unique checkpoint, VISTA (PD-1H) maintains immune tolerance through a distinct pH-sensitive mechanism. In the acidic tumor microenvironment (TME), protonated histidine residues enhance VISTA's binding affinity, allowing it to act as a localized guardian of immune privilege in both melanoma and cutaneous squamous cell carcinoma. By integrating molecular insights with bioengineering innovations, VISTA-directed rational combinations demonstrate significant preclinical potential to overcome immune resistance and achieve durable responses in refractory malignancies.

Tumor immunoediting is a dynamic process of interaction between the host immune system and tumor cells and encompasses three sequential phases: elimination, equilibrium, and escape. It plays a central regulatory role in melanoma initiation, progression, and therapeutic response. Currently, increasing attention has been directed toward the complexity of the melanoma tumor microenvironment, in which functional dysregulation of immune cell subsets, imbalance of cytokine networks, and alterations in the metabolic milieu collectively drive the process of immunoediting. However, most existing studies have focused on individual phases or isolated factors, and a comprehensive understanding of the entire immunoediting process and its systematic associations with tumor heterogeneity and resistance to immunotherapy remains insufficient. This review summarizes recent advances in tumor immunoediting within the melanoma tumor microenvironment, with particular emphasis on the regulatory mechanisms through which individual components of the immune microenvironment influence different phases of immunoediting, providing a theoretical basis for optimizing melanoma immunotherapy and identifying novel therapeutic targets.

Solitary fibrous tumor (SFTs) of the head and neck (H&N) are rare mesenchymal neoplasms with varied clinical behavior. Since 2019, advances in immunohistochemistry, particularly nuclear STAT6 expression, have improved diagnostic accuracy. A comprehensive update is needed to reassess clinical presentation, diagnosis, and outcomes.

The aim of this systematic review was to evaluate the clinical presentation, diagnosis, management, and outcomes of solitary fibrous tumor of the head and neck reported between June 2019 upto 10th June 2025. The review includes pooled analysis of demographics, tumor characteristics, histopathologic and immunohistochemical features, treatment approaches, recurrence rates, and follow-up outcomes among patients diagnosed with H&N SFTs.

Eligible studies were English-language case reports, case series, and observational studies that reported solitary fibrous tumor arising in the head and neck region in humans. Exclusion criteria included non-English publications, non-H&N SFTs, editorials, review articles, and studies without individual patient data. Two independent reviewers performed screening and full-text assessment based on PRISMA guidelines, resolving discrepancies by consensus. Of 503 identified studies, 103 met inclusion criteria (36.1%).

The review included 103 studies comprising 281 patients with head and neck SFTs. The median age was 47 years (range: 6 months-84 years); 53% were female. Common sites included the oral cavity (27.5%), orbit (18.5%), and sinonasal region (13.3%). Most patients presented with painless swelling. Histologically, tumor demonstrated spindle cell morphology; 99.1% were STAT6-positive. Surgical excision was the primary treatment in 96.4% of cases, with negative margins achieved in 85%. Recurrence occurred in 10.3%, primarily associated with positive margins, increased mitotic activity, and nuclear atypia. Adjuvant radiotherapy was administered in 5.3% of cases. Distant metastases were rare (<5%). The average follow-up period was 25 months.

Head and neck SFTs exhibit indolent behavior but carry a risk of recurrence, especially in tumors with high-risk histologic features. STAT6 immunohistochemistry is highly sensitive and should be considered the gold standard for diagnosis. Complete surgical excision with negative margins is essential for optimal outcomes. This review underscores the need for long-term follow-up in patients with H&N SFTs to detect late recurrences or metastasis.

The online version contains supplementary material available at https://doi.org/10.1007/s12663-026-02990-1.