Background and Objectives. The clinicopathological risk factors to predict recurrence of papillary thyroid cancer (PTC) patients remain controversial. Methods. PTC patients treated with thyroidectomy between January 1997 and December 2011 at the First Affiliated Hospital of Zhejiang University (Zhejiang cohort) were included. Multivariate Cox regression analysis was conducted to identify independent recurrence predictors. Then, the nomogram model for predicting probability of recurrence was built. Results. According to Zhejiang cohort (N = 1,697), we found that the 10-year event-free survival (EFS) rates of PTC patients with early-stage (TNM stages I, II, and III) were not well discriminated (91.6%, 89.0%, and 90.7%; P=0.768). The multivariate Cox model identified age, bilaterality, tumor size, and nodal status as independent risk factors for tumor recurrence in PTC patients with TNM stages I–III. We then developed a nomogram with the C-index 0.70 (95% CI, 0.64 to 0.76), which was significantly higher (P<0.0001) than the AJCC staging system (0.52). In the validation group, the C-index remained at a similar level. Conclusions. In this study, we build up a new recurrence predicting system and establish a nomogram for early-stage PTC patients. This prognostic model may better predict individualized outcomes and conduct personalized treatments.

Cuproptosis induction represents a promising alternative for immunotherapies and targeted therapies in breast cancer. This study aimed to investigate the prognostic and biological significance of cuproptosis-related genes in breast cancer. In the current study, we examined the transcriptional and clinical data of 13 cuproptosis-related genes in patients with breast cancer from TCGA database. We found that genes DLAT, SLC31A1, ATP7A and ATP7B were significantly related to the overall survival (OS) of breast cancer patients in univariate Cox regression analysis. Unlike lung or kidney cancers, SLC31A1 expression was upregulated in breast cancer samples compared with normal tissues, and predicted poor prognosis. Univariate and multivariate Cox regression analyses indicated that high SLC31A1 level was an independent prognostic factor for shorter OS. A nomogram integrating SLC31A1, age, T-, N-stage and clinical stage was constructed, and the calibration curves of the 1-, 3-, 5-, 10-year OS fitted well with the ideal model. Furthermore, we found that high SLC31A1 expression was related to deregulated immune response and metabolic pathways. Low SLC31A1 level predicted sensitivity to CTLA4 inhibitors but poor response to paclitaxel. Our study may provide novel insights for copper homeostasis and cuproptosis in breast cancer.

Diverse platinum drug candidates have been designed to improve inhibitory potency and overcome resistance for orthotopic tumors. However, the antimetastatic properties have rarely been reported. We herein report that homospermidineplatin (4a), a polyamine-Pt­(IV) prodrug, can potently inhibit tumor growth in situ and reverse cisplatin resistance as expected, and more importantly, 4a displays remarkably elevated antimetastatic activity in vivo (65.7%), compared to those of cisplatin (27.0%) and oxaliplatin (19.6%). The underlying molecular mechanism indicates that in addition to targeting nuclear DNA, 4a can modulate polyamine metabolism and function in a manner different from that of cisplatin. By upregulating SSAT and PAO, 4a downregulates the concentrations of Put, Spd, and Spm, which favors the suppression of fast-growing tumor cells. Moreover, the p53/SSAT/β-catenin and PAO/ROS/GSH/GSH-Px pathways are involved in the inhibition of 4a-induced tumor metastasis. Our study implies a promising strategy for the design of platinum drugs for the treatment of terminal cancer.

Multiple myeloma (MM) is an incurable hematological malignancy. Immunodeficiency results in the incapability of immunity to eradicate both tumor cells and pathogens. Immunotherapies along with antibiotics and other anti-infectious agents are applied as substitutes for immunity in MM. Immunotherapies including monoclonal antibodies, immune checkpoints inhibitors, affinity- enhanced T cells, chimeric antigen receptor T cells and dendritic cell vaccines are revolutionizing MM treatment. By suppressing the pro-inflammatory milieu and pathogens, prophylactic and therapeutic antibiotics represent anti-tumor and anti-infection properties. It is expected that deeper understanding of infection, immunity and tumor physio-pathologies in MM will accelerate the optimization of combined therapies, thus improving prognosis in MM.