The tumor microenvironment (TME) is increasingly recognized as a critical modulator of the initiation, progression, metastasis, and therapeutic resistance

Treatment trends of retinoblastoma (RB) have gradually evolved from eye enucleation and external radiation to local treatment. Combined treatment with an oncolytic virus and chemotherapy is currently a new method in RB treatment. To investigate the therapeutic effect of oncolytic adenovirus SG600 in combination with vincristine (VCR) on retinoblastoma in vitro, the cell viability, cell cycle effects and apoptotic activity of HXO-RB₄₄ cells treated with SG600, VCR or SG600 plus VCR were measured using a cell counting kit-8-based procedure and flow cytometry. Western blot analysis for Akt, p-Akt, p-p53 and p-Rb protein was performed to investigate the underlying mechanisms of combined therapy. The combination therapy exerted a synergistic antitumor effect via a type of G₂/M and S phase arrest rather than the induction of apoptosis. The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells. An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB₄₄ after co-treatment might be associated with cell cycle block. Western blot examination revealed that VCR might enhance SG600 replication. These results suggest that viro-chemo combination therapy is a feasible and potentially promising approach for the treatment of retinoblastoma.

Background: Ocular adnexal B-cell lymphoma (OABL) is a rare subtype of non-Hodgkin lymphoma. The molecular characteristics of OABL remain poorly understood. We performed an integrated study to investigate the proteotranscriptome landscape and identify novel molecular characteristics and biomarkers of OABL. Methods: Integrated quantitative proteome and transcriptome were performed on 40 OABL 12 idiopathic orbital inflammation, 6 reactive lymphoid hyperplasia, and 13 aesthetic orbital plastic surgery specimens. Complete clinicopathologic and prognostic data of the patients were recorded. Results: We identified high global protein-mRNA concordance as a novel characteristic of OABL. High concordance was related to OABL recurrence. By integrated expression profile, motif enrichment and trend analysis, we found that alternative splicing is inflammation-independently dysregulated in OABL. After portraying the aberrant alternative splicing event landscape, we demonstrated the oncogenic role of ADAR, a core splicing regulator that regulates the splicing of Rho GTPase and cell cycle members. We found that ADAR regulates cell proliferation and Rho GTPase inhibitor sensitivity of lymphoma. We identified DNAJC9 as a potential biomarker for OABL in proteomic analyses. Immunohistochemistry and immunofluorescent staining showed the nuclear staining of DNAJC9 was significantly higher in extranodal marginal zone lymphomas compared with inflammation specimens. Conclusions: These results provide an integrated gene expression profiling and demonstrate that high global protein-mRNA concordance is a prognosis-related molecular characteristic of OABL. We portray the alternative splicing events landscape of OABL, and reveal the oncogenic role of ADAR. We identified strong nuclear staining of DNAJC9 as a promising pathology diagnostic biomarker for extranodal marginal zone lymphomas.

Background: Orbital computed tomography (CT) is commonly used for the diagnosis and digital evaluation of orbital diseases. Yet, this approach requires longer scanning time, increased radiation exposure, and, especially, difficult patient positioning that can affect judgment and data processing. According to high-quality research on orbital imaging, computer-assisted surgery, and artificial intelligent diagnostic development, the correction of a coordinate system is a necessary procedure. Nevertheless, existing manual calibration methods are challenging to reproduce and there is no objective evaluation system for errors. Purpose: To establish a method for automatic calibration of orbital CT images and implementation of quantitative error evaluation. Material and Methods: A standard three-dimensional (3D) orbit model was manually adjusted, and optimized orbital models were reconstructed based on the initial registration of the skull-bound directed bounding box and the registration of the mutual information method. The calibration error was calculated based on the signed distance field. Seventeen cases of orbital CT were quantitatively evaluated. Results: A new method for automatic calibration and quantitative error evaluation for orbital CT was established. The calibrated model error with ±2 mm accounted for 81.61% ± 6.91% of the total models, and the error of ±1 mm accounted for 53.49% ± 7.07% of the total models. Conclusion: This convenient tool for orbital CT automatic calibration may promote the related quantitative research based on orbital CT. The automated operation and small error are beneficial to the popularization and application of the tool, and the quantitative evaluation facilitates other coordinate systems.

Ocular adnexal lymphoma (OAL) is the most common orbital malignancy in adults. Advanced tools for precise diagnosis and prognosis of OAL are in demand. Here, the nanoparticle-enhanced laser desorption/ionization mass spectrometry was applied for the construction of OAL-associated serum metabolic patterns (SMPs) from 239 participants (104 OAL and 135 non-OAL). Through machine learning, the diagnostic performance with an area-under-the-curve (AUC) of 0.901 was achieved for OAL based on SMPs. Furthermore, a diagnostic metabolic panel was constructed with an AUC of 0.875. Moreover, a prognosis scoring system was built and its desirable prediction efficacy for progression-free survival of OAL was confirmed ( P < 0.05). Specifically, the decreased serum alanine level was found to play both vital roles in the diagnosis and prognosis of OAL, and we demonstrated that uptake of alanine promotes glycolysis and cell growth in lymphoma cells. Our study highlights the value of the serum metabolite biomarkers in the clinical management of OAL.