Objective To investigate the radiosensitizing effect of 17AAG-cypate micelles on human non-small cell lung cancer A549 cells and its possible mechanism.Methods (1) A single-hit multi-target model formula was used to analyze the radiosensitizing effects of 17AAG-M and 17AAG-cypate-M.(2) The effects of 17AAG-cypate-M on the viability of A549 cells under laser and X-ray irradiation were analyzed by MTT assay.(3) The effect of the drugs on the cell senescence was observed by β-galactosidase staining assay.(4) The effects of different treatment conditions on DNA damage repair were analyzed by γ-H2AX immunofluorescence staining assay.(5) The expression of p-Erk1/2 and p-Akt was measured by Western blot.The paired t test was used for analyzing the differences between groups.Results Compared with the X-ray irradiation group,the X-ray+17AAG-cypate-M group had a lower mean lethal dose and a sensitization enhancement ratio greater than 1,indicating that 17AAG-cypate-M had a radiosensitizing effect.Compared with the 17AAG-M group,the 17AAG-cypate-M group showed significantly lower cell viability (P<0.01),a significantly higher percentage of aging cells (P<0.01),and significantly further delayed DNA damage repair (P<0.01).And the 17AAG-cypate-M group had lower expression of p-Erk1/2 and p-Akt than the 17AAG-M group.Conclusions Compared with 17AAG-M,17AAG-cypate-M has a higher radiosensitizing effect on A549 cells.The mechanism might be inducing the cell senescence,delaying DNA damage repair,and inhibiting the expression of p-Erk1/2 and p-Akt.

Background and objective The aim of this study is to determine the effcacy and feasibility of a novel folate receptor (FR)-based circulating tumor cell (CTC) detection method in the diagnosis of lung cancer. CTCs were col-lected from 3 mL of blood based on negative enrichment by immunomagnetic beads and then labeled by a conjugate of a tumor-speciifc ligand folate and an oligonucleotide.Methods Atfer washing off redundant conjugates, the bound conjugates were removed and analyzed by quantitative polymerase chain reaction.Results The CTC levels of 97 patients with lung cancer were signiifcantly higher than that of the controls (18 patients with benign lung diseases;P<0.001). With a threshold of 8.7 Folate units, the method showed a sensitivity of 82.5% and a speciifcity of 72.2% in the diagnosis of lung cancer, especially a sensitivity of 86.8% in stage I disease. Compared with the existing clinical biomarkers such as neuron-speciifc enolase (NSE), carcinoembryonic antigen (CEA), and CYFAR21-1, the method showed the highest diagnostic effciency in lung cancer (area under the curve, 0.859; 95%CI: 0.779-0.939) and stage I lung cancer (area under the curve, 0.912; 95%CI: 0.829-0.994). For future work, the CTC levels of 5 lung cancer patients higher than 8.7 Folate units/3 mL in their postoperation.Conclusion FR-positive CTCs were feasible diagnostic biomarkers in patients with lung cancer, as well as in early-stage tumors.

Extracellular vesicles (EVs) are tiny biological nanovesicles ranging from approximately 30-1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids. The classification of EVs includes exosomes, microvesicles, and apoptotic bodies, dependent on various factors such as size, markers, and biogenesis pathways. The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways. EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication, contributing to organ development and the progression of cancer. This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche, and cellular communication among different germ layers in developmental biology. In addition, it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles. All such discoveries have been facilitated by tremendous technological advancements in EV-associated research, especially the microfluidics systems. Their pros and cons in the context of characterization of EVs are also extensively discussed in this review. This review also deliberates the role of EVs in normal cell processes and disease conditions, and their application as a diagnostic and therapeutic tool. Finally, we propose future perspectives for EV-related research in stem cell and cancer biology.
Biomarkers/metabolism* ; Cell-Derived Microparticles/metabolism* ; Exosomes ; Extracellular Vesicles/metabolism* ; Humans ; Neoplasms/metabolism*