Objective: To determine whether the creatinine/cystatin C (Cr/CysC) ratio, which is influenced by muscle mass, can be used as a predictive marker of the adverse effects of chemotherapy. Methods: This single-centre, retrospective, observational study assessed patients with lung cancer. Serum Cr and CysC levels were measured once within 1 month prior the commencement of chemotherapy. Results: A total of 25 patients with lung cancer were enrolled in the study: 22 received first-line therapy; three received second-line therapy. A significant difference was noted regarding the Cr/CysC ratios between patients with nonsmall-cell lung cancer (NSCLC) and those with small-cell lung cancer (0.78 versus 0.92, respectively). A significant difference was also noted in the Cr/CysC ratios of patients with NSCLC with toxicity grades <3 and ≥3 (0.84 versus 0.70, respectively). Similar findings were observed in patients with NSCLC who received platinum-based combination therapy (toxicity grade < 3, 0.85; toxicity grade ≥3, 0.69). Conclusion: The Cr/CysC ratio could serve as a useful predictive marker for chemotherapy-related adverse effects in patients with NSCLC.

Silent information regulator 2 (SIR2) is a highly conserved protein, the mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1 is involved not in only longevity due to caloric restriction but in a variety of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration. However, accumulating evidence shows that SIRT1 is overexpressed in various types of malignant cells, and its inhibitors suppress the growth of tumor cells. The relationship between SIRT1 and metastasis remains to be clarified. Here, we examined the effect of SRT1720, a SIRT1 activator, on lung metastasis of breast cancer cells. 4T1 breast cancer cells were subcutaneously implanted into syngeneic BALB/c mice and SRT1720 was administered alone or with an antitumor agent, cisplatin. As expected, cisplatin decreased the lung metastasis score, whereas SRT1720 increased metastasis irrespective of cisplatin. In the primary tumors, cisplatin suppressed the mRNA level of angiopoietin-like protein 4 (angptl4), a lung metastasis-promoting gene product of breast cancer, but SRT1720 reduced the effectiveness of cisplatin. The results obtained with animal experiments were in accordance with those in human cancer cells; SRT1720 significantly increased the amount of VEGF secreted from MDA-MB-231 cells. Moreover, a transendothelial cell migration assay showed that SRT1720 promotes the migration of MDA-MB-231 cells across an endothelial cell layer despite the presence of cisplatin. These findings imply that SRT1720 promotes the pulmonary metastasis of breast cancer cells and SIRT1 may be an important target for suppressing metastasis to the lung.

Background/Aim: Little information is available about the association between peripheral T-lymphocyte expression of programmed cell death protein 1 (PD1) and the efficacy of immune checkpoint inhibitor therapy in patients with non-small cell lung cancer (NSCLC). We analyzed the PD1 and cytotoxic T-lymphocyte associated protein 4 (CTLA4) expression in peripheral blood T-lymphocytes of patients with NSCLC receiving immune checkpoint inhibitor therapy. Patients and Methods: Patients with NSCLC who were scheduled to receive treatment with immune checkpoint inhibitors were prospectively enrolled in this study between November 2017 and November 2018. Peripheral blood samples were obtained within 1 week before or after the initiation of treatment with an immune checkpoint inhibitor. Results: Flow cytometry was conducted in 19 patients. Patients were treated with nivolumab, pembrolizumab, or atezolizumab. The group with a high percentage of PD1⁺CD4⁺ T-lymphocytes relative to the total CD4⁺ T-lymphocyte count had a longer progression-free survival [median=6.0 (95% confidence intervaI=0.5-not estimated) months] than the group with a low percentage of PD1⁺CD4⁺ T-lymphocytes [median=1.1 (95% confidence intervaI=0.4-5.0) months; p=0.034, log-rank test]. However, no significant associations were detected with the percentages of CTLA4⁺CD4⁺, PD1⁺CD8⁺ or CTLA4⁺CD8⁺ T-lymphocytes in the peripheral blood. Conclusion: A high percentage of peripheral CD4⁺PD1⁺ T-lymphocytes was associated with a longer progression-free survival in patients receiving treatment with an immune checkpoint inhibitor. The systemic immune system may have an influence on the efficacy of immune checkpoint inhibitor therapy in patients with NSCLC.

Immune checkpoint inhibitors have significantly improved the prognosis in patients with non-small cell lung cancer, compared with cytotoxic agents. However, the prediction of treatment response is often difficult, even after assessing the tumor programmed death-ligand 1 expression. We conducted this observational study to analyze the association between the differentiation of peripheral CD4 + T cells and the efficacy of immune checkpoint inhibitor therapy. We enrolled patients who were diagnosed with non-small cell lung cancer and received immune checkpoint inhibitor therapy between 2020 and 2022. Blood samples were collected at the start of immune checkpoint inhibitor therapy, and the expressions of PD-1, CCR7, and CD45RA in peripheral CD4 + T cells were analyzed by flow cytometry. The association between the findings of flow cytometry and survival after the initiation of the immune checkpoint inhibitor therapy was evaluated. Forty patients with non-small cell lung cancer were enrolled. The Cox proportional hazards model showed that an increased proportion of CD45RA-CD4 + T cells was associated with a reduced risk of progression after adjustment for performance status, tumor programmed death-ligand 1 expression level, mutation status of the epidermal growth factor receptor gene, and combined therapy with cytotoxic agents. The present study showed that the proportion of peripheral CD45RA- CD4 + T cells was associated with progression-free survival after the initiation of immune checkpoint inhibitor therapy, independent of several clinical factors.

Background: Physical activity (PA) is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD) patients. Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging. We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients. Methods: Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer. We assessed the SIRT1 and related genes mRNA expression levels in the peripheral blood mononuclear cells (PBMCs) of the subjects. We carried out respiratory function testing, blood gas analysis, the 6-minute walk test, and measurement of the cross-sectional area of the erector spinae muscles (ESMCSA) by chest computed tomography. We analyzed the association of PA with the results of each of the examinations. Results: The mean age was 72±9 years, and the mean forced expiratory volume in 1 second was 1.4±0.56 L (52%±19% predicted). Our findings revealed a correlation between the daily PA and ESMCSA. The SIRT1 and Forkhead box O (FOXO)1 mRNA expression levels in PBMCs were positively correlated with moderate-PA time (r=0.60, p=0.008 for SIRT1 and r=0.59, p=0.01 for FOXO1).