Control of the spider-like interference structure in photoelectron momentum distributions of a helium atom in a few-cycle nonlinear chirped laser pulse.

We investigate theoretically the photoelectron momentum distributions (PMDs) of the helium atom in the few-cycle nonlinear chirped laser pulse. The numerical results show that the direction of the spider-like interference structure in PMDs exhibits periodic variations with the increase of the chirp parameter. It is illustrated that the direction of the spider-like interference structure is related to the direction of the electron motion by tracking the trajectories of the electrons. We also demonstrate that the carrier-envelope phase can precisely control the opening of the ionization channel. In addition, we investigate the PMDs when a chirp-free second harmonic (SH) laser pulse is added to the chirped laser field, the numerical results show that the interference patterns can change from only spider-like interference structure to both spider-like and ring-like interference structures.

Overexpression of Stat3 increases circulating cfDNA in breast cancer.

PURPOSE: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs). METHODS: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay. RESULTS: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers. CONCLUSION: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.

Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066.

Doxorubicin (Dox) is widely used in the treatment of triple-negative breast cancer cells (TNBCs), however resistance limits its effectiveness. Cancer stem cells (CSCs) are associated with Dox resistance in MCF-7 estrogen receptor positive breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) may functionally shift non-CSCs towards CSCs. However, whether Stat3 drives the formation of CSCs during the development of resistance in TNBC, and whether a Stat3 inhibitor reverses CSC-mediated Dox resistance, remains to be elucidated. In the present study, human MDA-MB-468 and murine 4T1 mammary carcinoma cell lines with the typical characteristics of TNBCs, were compared with estrogen receptor-positive MCF-7 cells as a model system. The MTT assay was used to detect cytotoxicity of Dox. In addition, the expression levels of CSC-specific markers and transcriptional factors were measured by western blotting, immunofluorescence staining and flow cytometry. The mammosphere formation assay was used to detect stem cell activity. Under long-term continuous treatment with Dox at a low concentration, TNBC cultures not only exhibited a drug-resistant phenotype, but also showed CSC properties. These Dox-resistant TNBC cells showed activation of Stat3 and high expression levels of pluripotency transcription factors octamer-binding transcription factor-4 (Oct-4) and c-Myc, which was different from the high expression of superoxide dismutase 2 (Sox2) in Dox-resistant MCF-7 cells. WP1066 inhibited the phosphorylation of Stat3, and decreased the expression of Oct-4 and c-Myc, leading to a reduction in the CD44-positive cell population, and restoring the sensitivity of the cells to Dox. Taken together, a novel signal circuit of Stat3/Oct-4/c-Myc was identified for regulating stemness-mediated Dox resistance in TNBC. The Stat3 inhibitor WP1066 was able to overcome the resistance to Dox through decreasing the enrichment of CSCs, highlighting the therapeutic potential of WP1066 as a novel sensitizer of Dox-resistant TNBC.