The level of urinary thiobarbituric acid (TBA) reactants in healthy human subjects due to malonaldehyde derivatives was measured to assess the lipid peroxidation status of the whole body. For each subject the TBA reactant level over a day varied over a 2-3 fold range while the daily level varied over a 1.5-3 fold range under normal life-style conditions. One of the factors causing an increase in the reactant level within a single day may be the subjects's physical activity, because the reactant level of each subject was higher in the afternoon or in the evening than in the morning. Remaining awake all night or hard exercise caused a dramatic increase in the reactant level over a day and in the daily reactant level. The reactant level within a single day for a subject was increased 5.5 fold and the daily level 3 fold by remaining awake all night, and the level within a day was increased 22 fold by hard exercise while the corresponding daily level was increased 7 fold. It is unlikely that food, alcohol and smoking greatly affect the reactant level. The results suggest that increased physical activity enhances lipid peroxidation in the whole body and thus the increased urinary excretion of malonaldehyde derivatives.

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Background Rating lymphocytes (TILs) are a prognostic marker in breast cancer and high TIL infiltration correlates with better patient outcomes. Meanwhile, parameters involving immune cells in peripheral blood have also been established as prognostic markers. High platelet-to-lymphocyte ratios (PLRs) and neutrophil-to-lymphocyte ratios (NLRs) are related to poor outcomes in breast cancer, but their mechanisms remain unknown. To date, TILs and these parameters have been examined separately. Methods We investigated the relationship between TILs and the peripheral blood markers, PLR and NLR, in the same patients, using surgical specimens from 502 patients with invasive breast carcinoma without preoperative chemotherapy. For analysis of triple-negative breast cancer (TNBC) patient outcomes, 59 patients who received preoperative chemotherapy were also examined. For immune cell profiling, multiplexed fluorescent immunohistochemistry (mfIHC) of CD3, CD4, CD8, FOXP3 and T-bet, was conducted. Results A positive correlation between PLR and TIL was observed in TNBC (P = 0.013). On mfIHC, tumors in patients with high PLR and NLR contained more CD3+CD4+FOXP3+ T-cells (P = 0.049 and 0.019, respectively), while no trend was observed in CD8+ T-cells. TNBC patients had different patterns of outcomes according to TIL and PLR, with the TIL-high/PLR-low group having the lowest rate of disease relapse and death, and the longest distant metastasis-free and overall survivals, while the TIL-low/PLR-high group had the shortest survivals. Conclusions Our data suggest that the combination of PLR with TIL assessment may enable more accurate prediction of patient outcomes with TNBC.

Background: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial. Methods: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied. Results: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade ( P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline ( P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions. Conclusion: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.

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