Spinal cord injury (SCI) is an intractable and worldwide difficult medical challenge with limited treatments. Neural stem/progenitor cell (NS/PC) transplantation derived from fetal tissues or embryonic stem cells (ESCs) has demonstrated therapeutic effects via replacement of lost neurons and severed axons and creation of permissive microenvironment to promote repair of spinal cord and axon regeneration but causes ethnical concerns and immunological rejections as well. Thus, the implementation of induced pluripotent stem cells (iPSCs), which can be generated from adult somatic cells and differentiated into NS/PCs, provides an effective alternation in the treatment of SCI. However, as researches further deepen, there is accumulating evidence that the use of iPSC-derived NS/PCs shows mounting concerns of safety, especially the tumorigenicity. This review discusses the tumorigenicity of iPSC-derived NS/PCs focusing on the two different routes of tumorigenicity (teratomas and true tumors) and underlying mechanisms behind them, as well as possible solutions to circumvent them.

Purpose: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/ genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of earlystage breast cancer.Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via nextgeneration sequencing (NGS) techniques using large gene panels.Results: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2 þ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer.Conclusions: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Objective: To develop a prognostic signature for patients with bladder cancer (BC). Methods: We identified differentially expressed miRNAs between normal bladder tissue and bladder cancer in the TCGA-BCLA dataset and evaluated prognostic values of these miRNAs. Then, a 21-miRNA signature was constructed based on the results of Cox proportional hazards regression model. Furthermore, functional enrichment analyses were conducted to explore the potential effects of the target genes of these 21 miRNAs. Results: Seventy six differentially expressed miRNAs were identified, among which 21 miRNAs including hsa-let-7c, mir-143, mir-944, mir-192, mir-590, mir-490, mir-141, mir-93, mir-1-2, mir-200c, mir-133a-1, mir-1-1, mir-133b, mir-20a, mir-185, mir-19a, mir-19b-2, mir-19b-1, mir-17, mir-15a, and mir-133a-2 were demonstrated to be significantly correlated with the overall survival (OS) of bladder cancer patients using Kaplan-Meier survival analysis and Log-rank test. The results of Chi-square test and multivariable logistic regression analysis showed that the 21-miRNA signature was significantly associated with the diagnosis type and T stage of bladder cancer. Univariate and multivariable survival analyses indicated that the 21-miRNA signature was an independent factor in predicting the overall survival of patients with bladder cancer. The results of functional enrichment analysis suggested that the target genes of these 21 miRNAs were mostly enriched in critical cancer-related biological processes and pathways, and the PPI network suggested that 60 targeted genes interacted with a minimum of 30 genes were at the hub of the whole network. In addition, we performed a multivariate nomogram and decision curve analysis (DCA) to evaluate the clinical application of 21-microRNA signature. Conclusion: We introduced a 21-miRNA signature which was associated the prognosis of patients of bladder cancer, and inspirational ideas for the future basic and clinical exploration.

Mesenchymal stem cell (MSC) is an absorbing candidate for cell therapy in treating spinal cord injury (SCI) due to its great potential for multiple cell differentiation, mighty paracrine secretion as well as vigorous immunomodulatory effect, of which are beneficial to the improvement of functional recovery post SCI. However, the therapeutic effects of MSC on SCI have been limited because of the gradual loss of MSC stemness in the process of expanding culture. Therefore, in this study, we aimed to maintain those beneficial properties of MSC via three-dimensional spheroid cell culture and then compared them with conventionally-cultured MSCs in the treatment of SCI both in vitro and in vivo with the aid of two-photon microscope. We found that 3D human placenta-derived MSCs (3D-HPMSCs) demonstrated a significant increase in secretion of anti-inflammatory factors and trophic factors like VEGF, PDGF, FGF via QPCR and Bio-Plex assays, and showed great potentials on angiogenesis and neurite morphogenesis when co-cultured with HUVECs or DRGs in vitro. After transplantation into the injured spinal cord, 3D-HPMSCs managed to survive for the entire experiment and retained their advantageous properties in secretion, and exhibited remarkable effects on neuroprotection by minimizing the lesion cavity, inhibiting the inflammation and astrogliosis, and promoting angiogenesis. Further investigation of axonal dieback via two-photon microscope indicated that 3D-HPMSCs could effectively alleviate axonal dieback post injury. Further, mice only treated with 3D-HPMSCs obtained substantial improvement of functional recovery on electrophysiology, BMS score, and Catwalk analysis. RNA sequencing suggested that the 3D-HPMSCs structure organization-related gene was significantly changed, which was likely to potentiate the angiogenesis and inflammation regulation after SCI. These results suggest that 3D-HPMSCs may hold great potential for the treatment of SCI.