Objective To investigate the clinical features and prognosis of patients with first-episode liver metastasis of different molecular subtypes of breast cancer and risk factors for liver metastasis of breast cancer.Methods A retrospective analysis was performed for 122 breast cancer patients with first-episode liver metastasis from January 2009 to January 2014.According to the cell surface receptors of breast cancer,these patients were divided into the four molecular subtypes of Luminal A,Luminal B,human epidermal growth factor receptor 2 (HER2) overexpression,and triple-negative breast cancer (TNBC).The association of patients' age at initial diagnosis,body mass index (BMI),menstruation status,clinical TNM (cTNM) stage,levels of lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) at recurrence,liver metastasis,and treatment condition with the patients' prognosis were analyzed.The chi-square test and Fisher's exact test were used for categorical data,the Kaplan-Meier method was used for survival analysis,the log-rank test was used for univariate analysis of influencing factors,and the Cox regression model was used for multivariate analysis.Results Among the 122 patients,12 had Luminal A subtype,61 had Luminal B subtype,30 had HER2 overexpression subtype,and 19 had TNBC subtype.In the patients with Luminal A,Luminal B,HER2 overexpression,and TNBC subtypes,the median disease-free survival (DFS) was 32,23,16,and 10 months,respectively (P =0.001),the median overall survival (OS) was 54,35,26,and 13 months,respectively (P =0.003),and the median OS after liver metastasis was 30,16,10,and 9 months,respectively (P =0.019).In HER2-positive patients,the application of trastuzumab in the past significantly prolonged the patients' DFS by 11 months and OS by 18 months (P ＜ 0.05).The results of the multivariate analysis showed that cTNM stage,molecular subtype,and targeted therapy were independent influencing factors for DFS of breast cancer patients with liver metastasis (P ＜ 0.05),and that BMI,increased LDH at recurrence,cTNM stage,molecular subtype,salvage chemotherapy,radiotherapy,and targeted therapy were independent influencing factors for OS of breast cancer patients with liver metastasis (P ＜ 0.05).The patients with TNBC,HER2 overexpression,and Luminal B subtypes exhibited worse prognosis and had a risk of recurrence 15.97,8.81,and 4.76 times higher than those with Luminal A subtype.The risk of death in the patients with TNBC,HER2 overexpression,and Luminal B subtypes was 8.42,6.02,and 3.86 times that in those with Luminal A subtype.Conclusion The prognosis of breast cancer patients with first-episode liver metastasis is associated with the increase in LDH when liver metastasis occurs,BMI,cTNM stage,and molecular subtype.Compared with the patients with Luminal subtypes,those with HER2 overexpression and TNBC subtypes tend to develop liver metastasis in early stage and have a shorter OS.Salvage chemotherapy,targeted therapy,and radiotherapy can significantly improve the prognosis of patients with liver metastasis.

OBJECTIVETo identify novel lncRNAs involved in cerebellar neurogenesis using neuronal specific Nbs1-deficient (Nbs1(CNS-del)) mouse model.

METHODSMicroarray analysis was performed to identify differentially expressed lncRNAs between Nbs1(CNS-ctr) and Nbs1(CNS-del) mice. Expression profiles of lncRNA Gm15577 and coding gene Negr1 in mice, primary cerebellar culture and cell lines were measured using RT-qPCR. Subcellular fractionation was performed to determine the subcellular localization of Gm15577.

RESULTSGm15577 was specifically expressed in mice cerebellum in a developmentally regulated manner, which could be abolished upon Nbs1-deficiency. Gm15577 was located in the intronic region of Negr1 in a reversed orientation. Gm15577 modulated the RNA expression of Negr1, Shh and β-catenin. NEGR1 had a distinct expression pattern between normal and medulloblastoma patients.

CONCLUSIONGm15577 may modulate cerebellar granule cell proliferation and differentiation by targeting Negr1, and their dysfunctions or abnormal expression may be related to tumorigenesis of medulloblastoma.

Animals ; Cell Differentiation ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cerebellar Neoplasms ; pathology ; Cerebellum ; cytology ; physiology ; Disease Models, Animal ; Humans ; Introns ; Medulloblastoma ; pathology ; Mice ; Mice, Knockout ; Neurogenesis ; Neurons ; physiology ; RNA, Long Noncoding ; metabolism

Objective: To investigate the role of Mic60 in cardiac aging. Methods: Wild-type and Mic60^{+ /-} male mice at age of 4-6 months (young group, n=6) and 18-20 months (aged group, n=9) were used. H&E and Masson staining of frozen and paraffin sections were subjected to morphologic evaluation of the cardiac tissue samples. SA-β-Gal staining was utilized to detect the activity of senescence-associated β-galactosidase. Western blot was performed to detect the expression of Mic60 and p21 in cardiac tissues. Results: Expression of Mic60 in mouse cardiac tissue increased in an age-dependent manner. Haploid insufficiency of Mic60 resulted in an increased left ventricular wall thickness [(1.32±0.09) mm vs.(1.12±0.09) mm, P<0.05], cardiomyocyte hypertrophy[(474.9±27.6) μm² vs.(358.8±48.7) μm², P<0.05] and interstitial fibrosis [ (38.24±7.58) ×10³μm² vs.(25.81±4.12)×10³μm^2, P<0.05], increased activity of SA-β-Gal (2.26±0.24 vs.0.25±0.05, P<0.01) and higher expression of p21 (P<0.01) in aged mouse cardiac tissue, but not in young mice. Conclusion Haploid insufficiency of Mic60 leads to cardiac hypertrophy, interstitial fibrosis, increased activity of SA-β-Gal and higher expression of p21 in aged cardiac tissue in mice, suggesting that Mic60 may prevent cardiac aging.

Objective To identify novel lncRNAs involved in cerebellar neurogenesis using neuronal specific Nbs1-deficient (Nbs1CNS-del) mouse model.Methods Microarray analysis was performed to identify differentially expressed lncRNAs between Nbs 1CNS-ctr and Nbs1CNS-del mice.Expression profiles of lncRNA Gm15577 and coding gene Negr1 in mice, primary cerebellar culture and cell lines were measured using RT-qPCR.Subcellular fractionation was performed to determine the subcellular localization of Gm15577.Results Gm15577 was specifically expressed in mice cerebellum in a developmentally regulated manner, which could be abolished upon Nbs 1-deficiency.Gm15577 was located in the intronic region of Negr1 in a reversed orientation.Gm15577 modulated the RNA expression of Negr1, Shh and β-catenin.NEGR1 had a distinct expression pattern between normal and medulloblastoma patients.Conclusion Gm15577 may modulate cerebellar granule cell proliferation and differentiation by targeting Negr 1, and their dysfunctions or abnormal expression may be related to tumorigenesis of medulloblastoma.