Biomimetic Self-Propelled Asymmetric Nanomotors for Cascade-Targeted Treatment of Neurological Inflammation.

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

Development and validation of an ultra-high sensitive next-generation sequencing assay for molecular diagnosis of clinical oncology.

Dramatic improvements in the understanding of oncogenes have spurred the development of molecular target therapies, which created an exigent need for comprehensive and rapid clinical genotyping. Next-generation sequencing (NGS) assay with increased performance and decreased cost is becoming more widely used in clinical diagnosis. However, the optimization and validation of NGS assay remain a challenge, especially for the detection of somatic variants at low mutant allele fraction (MAF). In the present study, we developed and validated the Novogene Comprehensive Panel (NCP) based on targeted capture for NGS analysis. Due to the high correlation between SNV/INDEL detection performance and target coverage, here we focused on these two types of variants for our deep sequencing strategy. To validate the capability of NCP in single-nucleotide variant (SNV) and small insert and deletion (INDEL) detection, we implemented a practical validation strategy with pooled cell lines, deep sequencing of pooled samples (>2000X average unique coverage across target region) achieving >99% sensitivity and high specificity (positive predictive value, PPV >99%) for all types of variations with expected MAF >5%. Furthermore, given the high sensitivity and that false positive may exist in this assay, we confirmed its accuracy of variants with MAF <5% using 35 formalin-fixed and paraffin-embedded (FFPE) tumor specimens by Quantstudio 3D Digital PCR (dPCR; Life Technologies) and obtained a high consistency (32 of 35 mutations detected by NGS were verified). We also used the amplification refractory mutation system (ARMS) to verify the variants with a MAF in a broad range of 2-63% detected in 33 FFPE samples and reached a 100% PPV for this assay. As a potential clinical diagnosis tool, NCP can robustly and comprehensively analyze clinical-related genes with high sensitivity and low cost.

[Clinical diagnosis and treatment of primary retroperitoneal schwannoma: a report of 109 cases].

OBJECTIVE: To evaluate the surgical efficacies of primary retroperitoneal schwannoma (PRS) and analyze its risk factors for survival and recurrence. METHODS: From January 1993 to December 2012, 109 patients diagnosed with primary retroperitoneal schwannoma were treated at our department. And their clinical data were retrospectively analyzed. RESULTS: The overall 1,3,5-year survival rates of benign PRS were all 100%. Univariate analyses revealed that tumor size and modus operandi of tumor resection were associated with recurrence rate. For malignant PRS, the overall 1,3,5-year survival and recurrence rates were 89.6%, 62.1%, 41.4% and 41.4%, 65.5%, 72.4% respectively. Univariate analyses revealed that tumor size, modus operandi of tumor resection and tumor grade were associated with survival rate. Tumor grade was associated with recurrence rate and it was also an independent prognostic factor. CONCLUSION: The major management of PRS is complete excision. Benign PRS has an excellent survival rate. And tumor size and modus operandi of tumor resection are associated with recurrence rate. The survival rate of malignant PRS is associated with tumor size, modus operandi of tumor resection and tumor grade. As an independent prognostic factor, tumor grade is associated with recurrence rate.

Prognostic factors predicting the postoperative survival period following treatment for primary retroperitoneal liposarcoma.

BACKGROUND: Liposarcomas, which represent 20% of all adult sarcomas, are the most common histological type of malignant soft tissue tumors. The aim of this study was to define the prognostic factors that predict the postoperative survival period for patients with primary retroperitoneal liposarcoma. METHODS: The clinical data and prognoses of 71 patients with primary retroperitoneal liposarcoma who were treated in the General Hospital of the People's Liberation Army of China between January 1, 2000 and December 31, 2007 were retrospectively reviewed and analyzed. RESULTS: The primary tumor from each patient was resected; 54.9% (39/71) were deemed R0 resections, 31.0% (22/71) were R1 resections and 14.1% (10/71) were deemed R2 resections (palliative operations). The median follow up was 68 months (range: 1-160 months). Of the patients who received an R1 or R2 resection of their primary tumor, 96.7% (59/61) had tumor recurrence. The 1-year, 3-year, and 5-year recurrence-free rates were 77.0%, 29.8% and 19.7%, respectively. As of April 2013, 53 of the 71 patients had died from tumor recurrence. The overall 1-year, 3-year, 5-year, and 10-year survival rates were 88.7%, 76.1%, 61.7%, and 30.4%, respectively. The factors that were significantly associated with prognosis in the univariate analysis were age (as a categorical variable) (P = 0.006), modus operandi (P = 0.000), histologic subtype (P = 0.000), tumor grade (P = 0.000), ascites (P = 0.000), postoperative metastasis (P = 0.000) and adjuvant therapy (P = 0.030). However, in the multivariate analysis, the modus operandi (P = 0.000), tumor grade (P = 0.006), ascites (P = 0.027), postoperative metastasis (P = 0.023) and age (as a categorical variable) (P = 0.002) were the only significant predictors of survival. CONCLUSIONS: Complete resection remains the most effective method for treating liposarcoma. High grade, old age (≥ 60 years old), postoperative metastasis, and ascites predict poor prognoses.

CREPT expression correlates with poor prognosis in patients with retroperitoneal leiomyosarcoma.

Retroperitoneal leiomyosarcomas (LMSs) are rare gynecological malignancies that display poor prognosis and high mortality. Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is involved in the regulation of many cell cycle-related proteins. However, its distribution and clinical significance in retroperitoneal LMS remains poorly understood. This study assessed the histological classifications of postoperative tumor samples from 71 cases of retroperitoneal LMS that were collected at The General Hospital of the People's Liberation Army from January 1998 to December 2012. We found that more than half of the patients displayed positive expressions of CREPT, Ki-67 and PCNA via immunohistochemical analysis. The expression of CREPT correlated with histological grade (P = 0.044), and the PCNA expression level correlated with the differentiation of tumor cells and histological grade (P < 0.001 and P = 0.009, respectively). Multivariate analysis showed that survival was associated with histological grade and the expression level of CREPT (P = 0.011 and P = 0.012, respectively). Kaplan-Meier analysis showed that the patients lacking CREPT expression exhibited significantly longer overall postoperative survival (median, 60.0 months) than the patients displaying CREPT expression (median, 33.0 months), and CREPT expression correlated with distant recurrence within 5 years after surgery (P = 0.004). Western blot analyses showed that CREPT was more strongly expressed in the retroperitoneal LMS tumor tissue than in paired control tissue. Based on the above data, we concluded that CREPT displays unique immunostaining for retroperitoneal LMS tissue and can be used to supplement other currently available retroperitoneal LMS markers.

[Expression of CD133 in primary retroperitoneal leiomyosarcoma and its relationship with Ki-67].

OBJECTIVE: To explore the correlation between CD133 and proliferative marker Ki-67 in primary retroperitoneal leiomyosarcoma and evaluate their prognostic values. METHODS: A total of 50 primary retroperitoneal leiomyosarcoma samples were collected at our hospital from January 2000 to December 2012. There were 9 males and 41 females. All samples were analyzed for CD133 and Ki-67 protein expression by PV6000 immunohistochemistry. Their median age was 49 (27-75) years. All cases were successfully followed up. RESULTS: CD133 expression was detected in 74.00% (37/50) of primary retroperitoneal leiomyosarcoma samples. The CD133-positive rates of histological grades I & II primary leiomyosarcoma were 7/13 and 76.70% (23/30) respectively. All grade III samples (n = 7) were CD133 positive. And the expression of CD133 had a positive correlation with tumor size, mitotic counts and histological grade (χ(2) = 4.925, 4.525, 10.080; P = 0.026, 0.033, 0.013). The survival time of CD133-positive patients with M (Q1, Q3) was 32 (17, 56) months versus 44 (26, 65) months for those negative ones. The expression of Ki-67 was detected in 84.00% (42/50) of primary retroperitoneal leiomyosarcoma samples and its expression showed a positive correlation with mitotic counts. The expressions of CD133 and Ki-67 were positively correlated in primary retroperitoneal leiomyosarcomas (P = 0.009). Log-rank test showed that positive expressions of CD133 and Ki-67 and 5-year patient survival rate were correlated (P = 0.021, 0.049). Multivariate analysis showed that CD133 and mitotic counts were independent prognostic indicators for primary retroperitoneal leiomyosarcomas (HR = 2.040, 2.422; P = 0.000, 0.018). CONCLUSIONS: CD133 plays an important role in the progression of primary retroperitoneal leiomyosarcomas so that it may be used as a marker for patient prognosis. Combined detection of CD133 and Ki-67 has a prognostic value in patients with primary retroperitoneal leiomyosarcoma.