Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer.

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH+, CD87+CD276+, and EGF+Axl+) in smokers. A number of CTCs and CSCs in patients with SCLC have been shown to be resistant to chemotherapy (CT). High cytotoxic activity and resistance to apoptosis of reprogrammed CD3+CD8+ T-lymphocytes (rTcells) in relation to naive CD3+CD8+ T-lymphocytes was demonstrated in a smoking patient with SCLC (Patient G) in vitro. The target for rTcells was patient G's blood CSCs. Reprogramming of CD3+CD8+ T-lymphocytes was carried out with the MEK1/2 inhibitor and PD-1/PD-L1 pathway blocker nivolumab. The training procedure was performed with a suspension of dead CTCs and CSCs obtained from patient's G blood. The presented data show a new avenue for personalized SCLC diagnosis and targeted improvement of chemotherapy based on the use of both CTCs and CSCs.

Spiperone Stimulates Regeneration in Pulmonary Endothelium Damaged by Cigarette Smoke and Lipopolysaccharide.

BACKGROUND: Endothelial dysfunction and destruction of the pulmonary microcirculation are important pathogenic factors in chronic obstructive pulmonary disease (COPD). In COPD, bronchial obstruction is associated with endothelial dysfunction. Thus, new pharmacological treatment options aimed at restoring the pulmonary endothelium represent a clinical need in COPD therapy. Notch1 has been shown to protect cells against apoptosis, inflammation, and oxidative stress caused by cigarette smoke extract (CSE). Therefore, drug which effect on Notch1 may be a potential therapeutic target for COPD in the future. METHODS: In this study, we assessed the potential of spiperone to mediate regeneration of pulmonary endothelium in model of pulmonary emphysema induced by a CSE and lipopolysaccharide (LPS) in female C57BL/6 mice. RESULTS: Spiperone increased the number of capillaries as well as the expression of the CD31 in the alveolar tissue compared to the controls. Moreover, application of spiperone prevented alveolar wall destruction (DI), and reduced the area of emphysema. Lastly, we demonstrated that spiperone positively influenced mobilization and migration of endothelial progenitor cells (EPC, CD45-CD34+CD31+), CD309+-endothelial cells, and angiogenesis precursors (CD45-CD117+CD309+) into the lung. Spiperone administration significantly reduced the number Notch1 positive CD309+-endothelial cells and Notch1+ EPCs. CONCLUSION: Overall, our results suggest that spiperone mediates endothelial regeneration in an animal model of COPD. Thus, it could represent a novel therapeutic approach for treatment of emphysema associated with COPD.