Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC.

Introduction: Previous studies reported an association between immune checkpoint inhibitor infusion timing and the treatment effect in metastatic NSCLC. The present study assessed the association between durvalumab infusion timing and survival outcomes in patients with locally advanced NSCLC. Methods: Patients receiving durvalumab after chemoradiotherapy for locally advanced NSCLC at a single institution were retrospectively analyzed, and the association of the proportion of durvalumab infusions greater than or equal to 20% versus less than 20% after 3 PM with progression-free survival (PFS) and overall survival was assessed. Results: A total of 82 patients were included, with a median age of 69 years (interquartile range, 62-74 years); of these, 67 patients (82%) were of male sex, and 78 patients (95%) had a history of smoking. The median number of durvalumab infusions per patient was 16 (interquartile range, 8-24). Patients with at least 20% of their durvalumab infusions after 3 PM (n = 12/82, 15%) had a significantly shorter PFS than those who did not (median: 7.4 mo versus not available [NA]; hazard ratio [HR], 2.43; 95% confidence interval [CI]: 1.11-5.34, p = 0.027), whereas overall survival was shorter among the former compared with the latter group (median: 22.4 versus NA; HR, 1.80; 95% CI: 0.73-4.42, p = 0.20). In addition, both backward stepwise multivariable analysis and propensity score-matching analysis revealed that receiving at least 20% of durvalumab infusions after 3 PM was significantly associated with worse PFS (HR, 2.54; 95% CI: 1.03-5.67, p = 0.047; and HR, 4.64; 95% CI: 1.95-11.04; p < 0.001, respectively). Conclusions: The time of day of durvalumab infusions may impact survival outcomes in patients with locally advanced NSCLC.

Assessment of a cancer genomic profile test for patients with metastatic breast cancer.

Comprehensive cancer genomic profile (CGP) tests are being implemented under Japanese universal health insurance system. However, the clinical usefulness of CGP test for breast cancer patients has not been evaluated. Of the 310 patients who underwent CGP testing at our institution between November 2019 and April 2021, 35 patients with metastatic breast cancer whose treatment strategy was discussed by our molecular tumor board within the study period were investigated after exclusion of 2 cases that could not be analyzed. The turn-around time, drug accessibility, and germline identification detection were evaluated. The subtype was luminal in 20 patients (57.1%), triple-negative in 12 patients (34.3%), and luminal-HER2 in 3 patients (8.6%). Actionable gene mutations were detected in 30 patients (85.7%), and 7 patients (20.0%) were recommended for clinical trial participation, with the drug administered to 2 patients (5.7%). Three patients (8.6%) died due to disease progression before the test results were disclosed. We report the results of an initial assessment of the utility of CGP testing for patients with metastatic breast cancer under Japanese universal health insurance system. Conducting CGP tests at a more appropriate time could provide patients with greater benefit from treatments based on their specific gene mutations.

Tomato endo beta-mannanase: A candidate of potential tomato allergen protein detected with human monoclonal antibody established from a patient suffered from Japanese cedar pollinosis.

Peripheral blood lymphocytes from a patient allergic to Japanese cedar pollens were transformed by Epstein-Barr virus infection. Some transformed B-lymphoblastoid cells (BLCs) secreted IgM class antibodies to cedar pollen extracts and tomato fruit extracts. One stable human-mouse hybridoma clone Y-22-3-3 secreting IgM class monoclonal antibody to tomato fruit extracts was established by cell fusion of BLCs with mouse myeloma cells. Western blot analysis of tomato extracts showed Y-22-3-3 monoclonal antibody recognized a tomato protein with a molecular weight of 40 kDa. The CBB-stained 40 kDa protein from antibody-affinity chromatography was analyzed by MALDI-TOF/TOF, and identified as tomato endo-beta-mannanase, which was previously reported as one of the potential candidates for tomato allergens.

Removal of carotene-like colored compounds by liquid-liquid extraction during polycyclic aromatic hydrocarbons analysis of plant tissue.

Plants contain a wide variety of chemicals, some of which may have similar chromatographic behavior to polycyclic aromatic hydrocarbons (PAHs). During solid phase extraction (SPE) with Si-gel for instance, the co-elution of carotene-like colored compounds with PAHs has been observed. In this paper, liquid-liquid extraction was applied for the separation and subsequent analysis of PAHs from plant extracts. PAHs containing 2-6 rings, which include naphthalene, phenanthrene, pyrene, benzo[a]pyrene and benzo[ghi]perylene, were used as representative target chemicals. Carotene-like compounds extracted from Komatsuna (Brassica campestris) shoot by acetone followed by Si-gel treatment were incorporated as undesired components in the model matrix. Results showed the feasibility of employing either acetonitrile or 2% (w/v) KOH-methanol as solvents for high PAHs recovery and low extraction of colored fraction. For acetonitrile, 86.9-93.5% of each PAH could be recovered after three extraction cycles (relative standard deviation, RSD<1.6%) with only about 10% co-extraction of colored fraction. For 2% KOH-methanol, PAHs recoveries ranging from 79.3% to 83.1% after five cycles (RSD<1.5%) were achieved while the percent extraction of colored fraction was also low at 10%. The relatively higher selectivity of the solvents for PAHs over the colored fraction as well as the solubility of the matrix solution in the solvent may have contributed to these results. On this basis, liquid-liquid extraction is very useful for the pre-treatment of plant extracts for PAHs analysis.