Chemo-Phototherapy with Carfilzomib-Encapsulated TiN Nanoshells Suppressing Tumor Growth and Lymphatic Metastasis.

The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.

MicroRNA-488 inhibits proliferation and motility of tumor cells via downregulating FSCN1, modulated by Notch3 in breast carcinomas.

As important modulators in multiple physiological processes, microRNAs (miRNAs) have been reported in various malignant tumors, including breast cancer. The current study investigated the function of a new tumor suppressor microRNA, miR-488, and its molecular mechanism of metastasis in breast cancers. CCK8 and transwell assays revealed that the upregulated miR-488 level significantly inhibited the proliferation and migration of breast cancer cells. As a potential downstream gene, the mRNA and protein level of FSCN1 was suppressed by increased miR-488 and vice versa. Luciferase assay showed that miR-488 directly bind to the 3'UTR of FSCN1 and suppressed the translation process of FSCN1. The promoter region of miR-488 was directly bound by Notch3 and promoted the expression of miR-488 transcriptionally. Immunohistochemistry results revealed that in patients with breast cancer, the expression of Notch3 and were negatively correlated with the FSCN1 levels significantly. Therefore, the current finding predicted miR-488 as a tumor suppressor molecule in breast cancer, and demonstrated that Notch3/miR-488/FSCN1 axis is established and involved in regulating the metastasis of breast cancers, providing novel therapeutic targets for patients with breast cancers.

Predictive Value of Preoperative Multidetector-Row Computed Tomography for Axillary Lymph Nodes Metastasis in Patients With Breast Cancer.

Introduction: Axillary lymph nodes (ALN) status is an essential component in tumor staging and treatment planning for patients with breast cancer. The aim of present study was to evaluate the predictive value of preoperative multidetector-row computed tomography (MDCT) for ALN metastasis in breast cancer patients. Methods: A total of 148 cases underwent preoperative MDCT examination and ALN surgery were eligible for the study. Logistic regression analysis of MDCT variates was used to estimate independent predictive factors for ALN metastasis. The prediction of ALN metastasis was determined with MDCT variates through receiver operating characteristic (ROC) analysis. Results: Among the 148 cases, 61 (41.2%) cases had ALN metastasis. The cortical thickness in metastatic ALN was significantly thicker than that in non-metastatic ALN (7.5 ± 5.0 mm vs. 2.6 ± 2.8 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of >3 mm (OR: 12.32, 95% CI: 4.50-33.75, P < 0.001) and non-fatty hilum (OR: 5.38, 95% CI: 1.51-19.19, P = 0.009) were independent predictors for ALN metastasis. The sensitivity, specificity and AUC of MDCT for ALN metastasis prediction based on combined-variated analysis were 85.3%, 87.4%, and 0.893 (95% CI: 0.832-0.938, P < 0.001), respectively. Conclusions: Cortical thickness (>3 mm) and non-fatty hilum of MDCT were independent predictors for ALN metastasis. MDCT is a potent imaging tool for predicting ALN metastasis in breast cancer. Future prospective study on the value of contrast enhanced MDCT in preoperative ALN evaluation is warranted.