Anti-CD44 Monoclonal antibody, clone JN8 [PE]

Background:The aim of the study was to evaluate the role of different immunohistochemical and radiomics features in patients with small cell lung cancer (SCLC). Methods:Consecutive patients with histologically proven SCLC with limited (n= 47, 48%) or extensive disease (n= 51, 52%) treated with radiotherapy and chemotherapy at our department were included in the analysis. The expression of different immunohistochemical markers from the initial tissue biopsy, such as CD56, CD44, chromogranin A, synaptophysin, TTF-1, GLUT-1, Hif-1 a, PD-1, and PD-L1, and MIB-1/KI-67 as well as LDH und NSE from the initial blood sample were evaluated. H-scores were additionally generated for CD44, Hif-1a, and GLUT-1. A total of 72 computer tomography (CT) radiomics texture features from a homogenous subgroup (n= 31) of patients were correlated with the immunohistochemistry, the survival (OS), and the progression-free survival (PFS). Results:The median OS, calculated from diagnosis, was 21 months for patients with limited disease and 13 months for patients with extensive disease. The expression of synaptophysin correlated with a better OS (HR 0.546 95% CI 0.308-0.966,p= 0.03). The expression of TTF-1 (HR 0.286, 95% CI: 0.117-0.698,p= 0.006) and a lower GLUT-1 H-score (median = 50, HR: 0.511, 95% CI: 0.260-1.003,p= 0.05) correlated with a better PFS. Patients without chromogranin A expression had a higher risk for developing cerebral metastases (p= 0.02) and patients with PD 1 expression were at risk for developing metastases (p= 0.02). Our radiomics analysis did not reveal a single texture feature that correlated highly with OS or PFS. Correlation coefficients ranged between -0.48 and 0.39 for OS and between -0.46 and 0.38 for PFS. Conclusions:The role of synaptophysin should be further evaluated as synaptophysin-negative patients might profit from treatment intensification. We report an, at most, moderate correlation of radiomics features with overall and progression free survival and no correlation with the expression of different immunohistochemical markers.

Gold nanoparticles (AuNPs) have been widely documented as tumor radiosensitizers via enhanced energy deposition of ionizing radiation. However, the sensitization efficiency of AuNPs is still far from satisfactory owing to the irradiation on nontarget tissues and the tumor radio-resistance. To address these issues, we report herein the rational design and development of hyaluronic acid-modified Au-Ag alloy nanoparticles (Au-Ag@HA NPs) with effective tumor radiosensitization by receptor mediated tumor targeting as well as microenvironment-activated hydroxyl radicals (center dot OH) generation. In our work, Au-Ag@HA NPs were synthesized by the coreduction of HAuCl4 and AgNO3 in the presence of trisodium citrate, followed by surface modification of HA to the Au-Ag alloy NPs. HA modification affords the alloy NPs with specific targeting to 4T1 breast cancer cells overexpressing CD44 receptor, while the introduction of Ag atom imparts the alloy NPs with superior multienzyme-like activities to the monometallic AuNPs for efficient tumor catalytic therapy. More importantly, the ionizing radiation and peroxidase-like activity of Au-Ag@HA NPs boost the production of center dot OH and the release of toxic Ag+ in the tumor sites, thereby leading to effective tumor therapeutic outcome. This work provides a promising treatment paradigm for radiation/nanozyme/Ag+ combined therapy against cancer and will advance the design and development of multifunctional nanoplatforms for synergetically enhanced tumor therapy.