Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.

Metal nanoparticles as a promising technology in targeted cancer treatment.

Traditional anticancer treatments have several limitations, but cancer is still one of the deadliest diseases. As a result, new anticancer drugs are required for the treatment of cancer. The use of metal nanoparticles (NPs) as alternative chemotherapeutic drugs is on the rise in cancer research. Metal NPs have the potential for use in a wide range of applications. Natural or surface-induced anticancer effects can be found in metals. The focus of this review is on the therapeutic potential of metal-based NPs. The potential of various types of metal NPs for tumor targeting will be discussed for cancer treatment. The in vivo application of metal NPs for solid tumors will be reviewed. Risk factors involved in the clinical application of metal NPs will also be summarized.

CD8+ cytotoxic and FoxP3+ regulatory T lymphocytes serve as prognostic factors in breast cancer.

BACKGROUND: There is conflicting evidence regarding the prognostic value of cytotoxic T cell infiltration in breast cancer. The aims of this study were to detect the expression levels and localization of FoxP3 and CD8 in invasive ductal carcinoma of the breast and to investigate the correlations among FoxP3+ regulatory T cells (Tregs), CD8+ cytotoxic T lymphocytes (CTLs), clinicopathological features, and prognosis in patients with breast cancer. METHODS: Immunohistochemistry was used to detect the expression levels and localization of FoxP3 and CD8. One-sample t-test, one-way analysis of variance, and Kaplan-Meier log-rank tests were used to analyze correlations between the expression levels of CD8 and FoxP3; Kaplan-Meier Log-rank test was used to analyze clinicopathological features to explore the prognostic significance of CD8 and FoxP3 in patients with breast cancer. RESULTS: FoxP3 expression in the tumor bed was higher than that in the stroma, while CD8 was primarily expressed in the stroma. CD8 expression was associated with favorable prognostic factors. However, FoxP3 expression and an increased ratio of total FoxP3+ Tregs to CD8+ CTLs were significantly correlated with unfavorable prognostic factors. Additionally, an increased ratio was associated with molecular subtypes (ER+Her2+, ER+Her2-, ER-Her2+, and ER-Her2-) of breast cancer. Overexpression of FoxP3 and a high FoxP3+/CD8+ ratio were correlated with poor overall survival (OS) and disease-free survival (DFS). However, CD8 expression only affected OS in patients with breast cancer. CONCLUSIONS: Tumor-infiltrating lymphocytes are localized variously depending on the subtype. CD8+ CTLs were associated with a good prognosis, while FoxP3+ Tregs were associated with adverse outcomes in patients with breast cancer. CD8+ CTLs and FoxP3+ Tregs are potential predictive prognostic factors for patients with breast cancer.

Comparison of the Retinal Straylight in Pseudophakic Eyes with PMMA, Hydrophobic Acrylic, and Hydrophilic Acrylic Spherical Intraocular Lens.

Purpose. To investigate the intraocular straylight value after cataract surgery. Methods. In this study, 76 eyes from 62 patients were subdivided into three groups. A hydrophobic acrylic, a hydrophilic acrylic, and a PMMA IOL were respectively, implanted in 24 eyes, 28 eyes, and 24 eyes. Straylight was measured using C-Quant at 1 week and 1 month postoperatively in natural and dilated pupils. Results. The hydrophilic acrylic IOLs showed significantly lower straylight values than those of the hydrophobic acrylic IOLs in dilated pupils at 1 week and 1 month after surgery (P < 0.05). However, the straylight values of the hydrophilic acrylic IOLs were the lowest among the three IOL groups. No significant difference was observed in straylight between 1 week and 1 month postoperatively in each group with natural and dilated pupils (P > 0.05). Moreover, no significant difference was found in straylight between natural and dilated pupils in each group at 1 week and 1 month postoperatively (P > 0.05). Conclusions. Although the hydrophobic acrylic IOL induced more intraocular straylight, straylight differences among the 3 IOLs were minimal. Pupil size showed no effect on intraocular straylight; the intraocular straylight was stable 1 week after surgery.

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.