PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)

Phosphoproteomic analysis revealed differential phosphorylation of proteins linked to cancer progression, including TCOF1, IRF2BP2, and HDGFRP2. These findings demonstrate that even low-dose exposure to BDE-209 can modulate cellular signaling and promote malignancy-associated phenotypic changes, underscoring its potential role in worsening cancer prognosis and highlighting the broader health risks posed by persistent environmental contaminants.

Our findings reveal a mechanistic pathway towards enhancing radionuclide uptake in vivo, with clinical relevance for RAI therapy and identifying survival indicators of recurrent disease.

Analyses in SCLC cell lines and mouse models shows that depletion of DNAPKcs leads to proteasomal degradation of MYC via GSK3β pathway. We show that DNAPKcs upregulation contributes to immunotherapy resistance and DNAPKcs inhibition represents a promising therapeutic strategy to induce antitumor immunity and potentiate immunotherapy efficacy in immunologically suppressed SCLC.

Among these hub proteins, five proteins (NPM1, TOP2A, EZH2, PRKDC, and HNRNPK) were identified as clinically relevant when cross-referenced with the Human Protein Atlas database and the literature, highlighting their potential as diagnostic and therapeutic targets. These findings highlight the potential of nanoMIP-based snapshot imprinting as an alternative to 'classical' approaches for identifying potential protein targets for diagnostic and therapeutic applications.

This study provides veterinary pathologists with descriptive guidance on the pathology associated with human CAR T-cell therapy in immunodeficient mice. Additional molecular data and detailed information related to each construct are necessary to further investigate the translatability of such liabilities to the clinical setting.

APL mice had significantly higher levels of thrombin-antithrombin complexes compared with AML mice. These leukemia mouse models can be used to understand how the hemostatic system is dysregulated in leukemia.

The genomic landscape of OCA is marked by frequent TERT promoter mutations and distinct mutational patterns associated with patient gender and tumor metastatic status. These findings highlight potential molecular subtypes, reveal pathways potentially driving metastasis (eg, involving MEN1/TSC2), and identify novel sex-specific alterations (MST1R, PRKDC), offering avenues for improved development of targeted therapeutic strategies for OCA.

The therapeutic relevance of these findings was substantiated in vivo, where DML administration significantly prolonged survival in an M-NSG mouse xenograft model engrafted with NB4 leukemia cells. These results systematically establish that DML induces apoptosis in myeloid leukemia cells directly through PERK/eIF2α/ATF4/CHOP signaling pathway in response to ER stress.

H3-7/15 × 19-CAR-T cells significantly improved the therapeutic efficacy of traditional CAR-T cells, including CD19- and H3-CAR-T cells, acting in pancreatic cancer- and non-small cell lung cancer-derived xenograft tumor models based on NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju (NCG) mice. In summary, H3-7/15 × 19-CAR-T cells possess potential for clinical transformation and represent a new strategy for treating solid tumors.

In humanized models, engraftment of human immune cells can result in distinctive syndromes, including xenogeneic graft-versus-host disease, post-transplant lymphoproliferative disorders, and chimeric myeloid cell hyperactivation syndrome, which can impact study outcomes and lead to mortality and morbidity. This review is intended as a resource for comparative pathologists to become familiar with these widely used immunodeficient mice, so they can interpret strain-specific lesions and recognize experimental confounders in these mouse models.

Further, we showed that in this model the xenograft response to both therapeutic treatments can be assessed using FLIM and OCT. Overall, this work presents an optimized mouse model suitable for assessing the effect of combined TIL immunotherapy and OV on GBM in translational studies.

These findings highlight the pivotal role of DNA-PKcs status in shaping the DNA damage response and radiosensitivity of glioblastoma cells. Targeting compensatory repair pathways in DNA-PKcs-deficient tumors may offer novel strategies for radiosensitization in glioblastoma therapy.