Chronic stress may influence cancer trajectories; however, the majority of current frameworks do not clearly define how organism‑level regulation interacts with tumor behavior. The present review summarizes mechanistic and translational evidence to propose a testable model in which cancer progression can, in selected contexts, be understood as over‑adaptation to sustained stress within a hierarchical neuro‑endocrine‑immune network. Within this framework, stress‑related signals converge in brainstem‑hypothalamic control circuits, and engage sympathetic, hypothalamic‑pituitary‑adrenal and vagal effector pathways, which may influence cellular programs, microenvironmental remodeling and systemic dissemination. The evidence is organized into three sections: Cellular adaptation, microenvironmental remodeling and systemic progression. This multiscale perspective provides a host‑context framework for understanding how chronic stress‑related physiology may interact with tumor‑intrinsic processes. Therapeutic implications are also discussed, including psychosocial support, exercise, mindfulness‑based interventions, vagal modulation and perioperative β‑blocker/COX‑2 strategies. At present, the strongest clinical evidence for these approaches supports improvements in symptoms, patient‑reported outcomes and selected biomarkers, whereas durable effects on tumor control or survival remain uncertain. Overall, this framework is presented as a conceptual and testable model intended to guide future research on host‑tumor interactions in cancer.

Proline‑ and glutamine‑rich splicing factor (SFPQ) is an RNA‑binding protein that is predominantly localized in the nucleus and plays a multifaceted regulatory role in the process of gene expression. The functions of SFPQ include the promotion or inhibition of gene transcription, pre‑mRNA splicing, mRNA processing, transport and localization, and translation. The primary impact of SFPQ on cellular processes is the regulation of cell cycle progression and apoptosis. In addition, SFPQ represents an important element of paraspeckles, exerting a notable influence on gene expression within the nucleus. The expression of SFPQ is altered in tumors, promoting the development and drug resistance of tumors in various ways, notably altering the prognosis of patients. In the present review, the fundamental physiological functions of SFPQ and its particular effects on tumorigenesis and development are discussed.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell invasion assay experiments shown in Fig. 3A, B and C on p. 2348, two pairs of data panels were overlapping, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. In addition, an independent investigation of the data in this paper undertaken by the Editorial Office revealed that flow cytometric data in Fig. 4A were shared with a paper that was published in the journal OncoTargets and Therapy featuring no authors in common (which was received at that journal one month after the submission of the above paper to International Journal of Molecular Medicine), and flow cytometric data in Fig. 5C were shared with a different paper also having no authors in common that was subsequently submitted to the journal Oncology Reports. The authors have been contacted by the Editorial Office to offer an explanation for the issues described above, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 42: 2343‑2352, 2018; DOI: 10.3892/ijmm.2018.3842].

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑C motif chemokine ligand (CCL)2/CCR2 and CCL22/CCR4 that govern T‑cell trafficking and functional states. A map of organ‑specific cytokine programs that link therapeutic benefit and toxicity in the brain, lung, gastrointestinal tract, oral mucosa and liver is then provided, and actionable targets within inflammasome‑associated pyroptosis and fibrogenic cascades are highlighted. RT technical parameters, including fractionation, treatment volume, stereotactic body RT, Fast Linear Accelerator‑based Scanning Hybrid ultra‑high dose-rate delivery and proton therapy can differentially shape cytokine dynamics and modify the therapeutic window. The DNA damage response network with poly (ADP‑ribose) polymerase (PARP)1 as a central node represents a second hub that interfaces with antigen presentation and IFN signaling, supporting rational combinations with PARP inhibitors and immune checkpoint blockade. Finally, a translational algorithm with three pillars is proposed. The first pillar uses IFN‑related gene signatures and circulating cytokine profiles to stratify tumors by baseline IFN activity. The second pillar aligns RT timing with endogenous STING or IFN pulses and incorporates CCR2, CCR4 or colony stimulating factor 1 receptor blockade to counter myeloid cell‑mediated immunosuppression. The third pillar co‑manages treatment‑related toxicities by targeting the NLR family pyrin domain containing 3/gasdermin D axis or by using fibrosis‑modulating interventions. Furthermore, ongoing clinical trials of cytokine-directed agents combined with RT are summarized. This framework positions cytokines as measurable and modifiable variables for individualizing combined RT and immunotherapy.

Prostate cancer (PCa) is a leading cause of cancer‑related deaths among men, and its incidence is increasing worldwide. Current treatments include androgen deprivation therapy, surgery, radiotherapy, chemotherapy and immunotherapy, among others. Surgical treatment has a less effective therapeutic effect in patients with advanced PCa. However, drug‑based treatments often lead to the development of drug resistance, highlighting the need to adopt new treatment strategies. The present review summarizes the role of gut microbiota and its metabolites in the treatment resistance of advanced PCa, potential microbiome‑targeted therapies and future research directions, for developing novel therapeutic approaches to overcome drug resistance and improve prognosis.

BackgroundTecartus (brexucabtagene autoleucel) is an autologous CAR-T product targeting CD19, but there are many undetected and unreported adverse events (AEs).MethodsWe counted data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from Q4 2020 through Q4 2024 for proportionate analyses to assess the association between Tecartus and adverse events and important medical events (IMEs).ResultA total of 792 datasets related to Tecartus were collected. The following SOCs are significant signals: Nervous system disorders, Infections and infestations, Neoplasms benign, malignant and unspecified (incl cysts and polyps). The most common AEs are cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and neurotoxicity. With Tecartus, most AEs occur within one month, but AEs can still occur after one year of use.ConclusionBy analysing data from the real-world FAERS database, we identified additional disproportionately reported AEs, providing clinicians with more information about disproportionately reported AEs before and during treatment.

A 10-year-old spayed female mixed-breed dog was presented with a one-week history of inappetence and hyperthermia. Blood smear evaluation revealed the presence of rare atypical cells, raising suspicion for a circulating neoplasm. Spleen cytology, histopathology, and immunohistochemistry confirmed the diagnosis of hemophagocytic histiocytic sarcoma. The morphologic similarity between the atypical cells observed in the blood smear and those identified in the splenic cytology strongly suggests systemic dissemination of the disease.

Dedifferentiated liposarcoma (DDLPS) is a typically non-lipogenic malignant neoplasm that arises from progression of an underlying atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLPS) and is classically defined by amplification of chromosome 12q15, including MDM2 and frequently cyclin-dependent kinase 4 (CDK4). Detection of MDM2 amplification by fluorescence in situ hybridization (FISH) and/or MDM2 protein expression immunohistochemistry (IHC) has, therefore, become central to the diagnosis of DDLPS, particularly in small biopsies from the retroperitoneum. Rare exceptions to this paradigm have been described, but the clinicopathologic and molecular spectrum of MDM2 non-amplified DDLPS remains poorly characterized. We report a series of MDM2 non-amplified DDLPS to better define their diagnostic features, genomic alterations and clinical behaviour.

Pathology archives from 2010 to 2025 were queried for cases diagnosed as DDLPS. Inclusion criteria required a high-grade sarcoma arising in a histologically confirmed ALT/WDLPS background, absence of MDM2 overexpression by IHC and lack of MDM2 amplification by FISH and/or single nucleotide polymorphism array. Clinicopathologic features, immunophenotype, treatment and outcomes were reviewed.

Among 253 cases of DDLPS identified during the study period, four (1.6%) fulfilled criteria for MDM2-negative DDLPS. All tumours arose in the retroperitoneum or intra-abdominal soft tissues and demonstrated high-grade sarcoma morphology with an associated WDLPS component on resection. Despite the absence of MDM2 amplification, all cases showed strong CDK4 expression by IHC. Molecular analysis revealed recurrent alterations involving cell-cycle regulation, including CDK4 copy number gain in all cases and loss of CDKN2A in three. Two cases harboured TP53 alterations. Clinically, outcomes were heterogeneous, ranging from aggressive disease with rapid recurrence and death within months to prolonged disease-free survival exceeding 5 years.

MDM2 non-amplified DDLPS represents a rare subset of DDLPS that appear to be driven by alternative mechanisms of cell-cycle dysregulation, most commonly involving CDK4 gain and CDKN2A loss, with occasional TP53 alterations. Awareness of this variant is critical to avoid misclassification as other high-grade sarcomas, particularly on limited biopsies, and underscores the importance of integrating morphology, IHC and broad genomic profiling in diagnostically challenging retroperitoneal sarcomas.

The scope of gene fusions in melanocytic neoplasms is broader than previously recognized, extending well beyond the Spitz-lineage neoplasms where kinase fusions involving ALK, ROS1, NTRK1/2/3, RET, MET, BRAF, and MAP3K8 define biologically and morphologically distinct tumors. Emerging studies demonstrate that a meaningful proportion of conventional non-Spitz lineage melanomas harbor oncogenic fusions. Such fusions may impact clinical behavior, histopathologic presentation and provide opportunities for targeted therapy. The World Health Organization classification of skin tumors, 5th edition, now incorporates fusion status into taxonomy and risk stratification, yet some important questions remain for further investigation: fusion-associated neoplasms can mimic non-melanocytic neoplasm; Spitz-type fusions appear in non-Spitz lesions; and melanocytic differentiation may occur in some other fusion-driven lesions. Broad-panel next-generation sequencing (including RNAseq), together with targeted fluorescence in situ hybridization and immunohistochemistry enhances detection of known and novel fusion partners. Early clinical evidence of TRK, ALK, and ROS1 inhibitor efficacy underscores the translational promise of fusion testing and opens avenues for personalized therapy. This review synthesizes current knowledge on the genomics, histopathology, diagnosis, and therapeutic implications of fusion-driven melanocytic neoplasms, highlighting consensus points and remaining controversies.

Malignant effusions provide a critical window into metastatic biology. Malignant effusion-derived organoids (ME-PDTOs) hold promise for modeling metastasis and predicting drug response, but the evidence remains fragmented. This systematic review aims to synthesize current evidence on the validity of ME-PDTOs as metastasis models and their concordance with clinical drug responses.

We systematically reviewed literature from the past 15 years in strict accordance with PRISMA 2020 guidelines for study identification and selection. Data on genetic, transcriptional, functional, and clinical correlation were extracted. Given sample size limitations and heterogeneity, a descriptive, study-level analysis was performed. Predictive performance (sensitivity, specificity) was calculated with 95% confidence intervals using multiple methods.

Sixteen studies (87 ME-PDTOs from 84 patients) were included. ME-PDTOs retained key driver mutations and displayed transcriptomic enrichment of epithelial-mesenchymal transition and stemness pathways. Functionally, they demonstrated migratory, invasive, and in vivo metastatic capacity. For drug response, six studies provided 77 drug-patient pairs (predominantly lung cancer, 89.6%). In the two largest lung cancer studies, ME-PDTO sensitivity for predicting clinical efficacy ranged from 0.82 to 0.90, and specificity from 0.80 to 1.00, though confidence intervals were wide in smaller studies.

Current evidence suggests that ME-PDTOs can recapitulate key metastatic features and show a promising correlative trend with clinical drug responses in lung cancer. However, significant limitations exist: evidence is limited, heterogeneous, and subject to selection and measurement biases. Future standardized, prospective studies are needed to validate their clinical predictive utility and address translational challenges.

CRD420251107909.