PubMed | the Third Hospital of Nanchang City and Sun Yat Sen University
Type: | Journal: EBioMedicine | Year: 2016
Breast cancer patients with high proportion of cancer stem cells (BCSCs) have unfavorable clinical outcomes. MicroRNAs (miRNAs) regulate key features of BCSCs. We hypothesized that a biology-driven model based on BCSC-associated miRNAs could predict prognosis for the most common subtype, hormone receptor (HR)-positive, HER2-negative breast cancer patients.After screening candidate miRNAs based on literature review and a pilot study, we built a miRNA-based classifier using LASSO Cox regression method in the training group (n=202) and validated its prognostic accuracy in an internal (n=101) and two external validation groups (n=308).In this multicenter study, a 10-miRNA classifier incorporating miR-21, miR-30c, miR-181a, miR-181c, miR-125b, miR-7, miR-200a, miR-135b, miR-22 and miR-200c was developed to predict distant relapse free survival (DRFS). With this classifier, HR+HER2- patients were scored and classified into high-risk and low-risk disease recurrence, which was significantly associated with 5-year DRFS of the patients. Moreover, this classifier outperformed traditional clinicopathological risk factors, IHC4 scoring and 21-gene Recurrence Score (RS). The patients with high-risk recurrence determined by this classifier benefit more from chemotherapy.Our 10-miRNA-based classifier provides a reliable prognostic model for disease recurrence in HR+HER2- breast cancer patients. This model may facilitate personalized therapy-decision making for HR+HER2- individuals.
Xiong L.,Peoples Hospital of Gansu Province |
Zeng J.,Peoples Hospital of Gansu Province |
Yao A.,Tongji University |
Tu Q.,Peoples Hospital Of Jiujiang County |
And 3 more authors.
International Journal of Nanomedicine | Year: 2015
The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 µm) with a core (60±18 µm) and a mesoporous shell (180±42 m2/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 µg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration. © 2015 Xiong et al.
Liu K.,Guangxi Medical University |
Liu K.,The Third Hospital of Nanchang City |
Zhang Y.,Guangxi Medical University |
Zhang C.,Guangxi Medical University |
And 17 more authors.
Oncotarget | Year: 2016
The abnormality of DNA methylation is one of the major epigenetic alterations in the human hepatocellular carcinoma (HCC). We have assessed the global genomic DNA methylation profiles in human HCC patients by using the Infinium Human Methylation27 BeadChip. A CpG loci of S100A8 was found to be significantly hypomethylated in HCC. Pooled meta-analysis of five validation public datasets demonstrated its methylation level was significantly lower for HCC compared to paired adjacent normal tissues. Quantitative pyrosequencing analysis also showed that the S100A8 methylation level was decreased in cancer tissues (31.90%±13.31%) than that in the paired adjacent normal tissues (65.33%±3.64%, p<0.01). The area under the ROC curve (AUC) value was 0.950 (p<0.01). Kaplan-Meier survival curves revealed that hypomethylation of S100A8 was associated with shortened overall survival (OS) and progression-free survival (PFS) (log rank p<0.05). Multivariate Cox proportional hazards model also indicated significantly shorter OS (HR, 1.709; 95 % CI, 1.127-2.591) and PFS (HR, 1.767; 95 % CI, 1.168-2.974) were observed in the low-methylation-level group compared to the high-methylation-level group. Furthermore, S100A8 overexpression in Huh7 and MHCC-97H hepatoma cell lines led to increased cell proliferation, migration, invasion, and tumor growth. These findings suggested S100A8 methylation to be served as potential diagnosis and prognosis marker for HCC. S100A8 also may play as a tumor promoter in HCC.
Zhang C.-D.,Guangxi Medical University |
Zhang C.-D.,Affiliated Hospital of Youjiang Medical College for Nationalities |
Li H.-T.,Guangxi Medical University |
Liu K.,The Third Hospital of Nanchang City |
And 8 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014
Background: Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphisms in prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore, a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302H polymorphisms with PCa susceptibility. Materials and Methods: A comprehensive literature search was conducted to identify all case-control studies of CASP8 D302H and -652 6N del polymorphisms and PCa risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and the precision of the estimate, respectively. Results: Nine -625 6N del studies and 4 D302H studies were included. CASP8 -652 6N del and D302H polymorphisms were not significantly associated with PCa risk in the overall analyses. However, in the subgroup analysis stratified by ethnicity, -625 6N del was significantly associated with PCa risk in the East Asian and Indian populations under the recessive model. Furthermore, the subgroup analysis strongly suggested that D302H was associated with lower PCa risk in the Non-Indian population under the dominant model. Conclusions: In our meta-analysis, ethnic-specific differences were evident in the association of CASP8 -625 6N del and D302H polymorphisms with PCa risk.
PubMed | Jiangxi Science & Technology Research Center for Safety, The Third Hospital of Nanchang City, Southern Medical University and 6th Peoples Hospital of Shanghai
Type: | Journal: Toxicology in vitro : an international journal published in association with BIBRA | Year: 2016
Berberine, an isoquinoline plant alkaloid, exhibits a wide range of biochemical and pharmacological effects. However, the precise mechanism of these bioactivities remains poorly understood. In this study, we found significant similarity between berberine and two epigenetic modulators (CG-1521 and TSA). Reverse-docking using berberine as a ligand identified lysine-N-methyltransferase as a putative target of berberine. These findings suggested the potential role of berberine in epigenetic modulation. The results of PCR array analysis of epigenetic chromatin modification enzymes supported our hypothesis. Furthermore, the analysis showed that enzymes involved in histone acetylation and methylation were predominantly affected by treatment with berberine. Up-regulation of histone acetyltransferase CREBBP and EP300, histone deacetylase SIRT3, histone demethylase KDM6A as well as histone methyltransferase SETD7, and down-regulation of histone acetyltransferase HDAC8, histone methyltransferase WHSC1I, WHSC1II and SMYD3, in addition to 38 genes from histone clusters 1-3 were observed in berberine-treated cells using real-time PCR. In parallel, western blotting analyses revealed that the expression of H3K4me3, H3K27me3 and H3K36me3 proteins decreased with berberine treatment. These results were further confirmed in acute myelocytic leukemia (AML) cell lines HL-60/ADR and KG1-. Taken together, this study suggests that berberine might modulate the expression of epigenetic regulators important for many downstream pathways, resulting in the variation of its bioactivities.
PubMed | Jiangxi University of Traditional Chinese Medicine and The Third Hospital of Nanchang City
Type: Journal Article | Journal: Oncotarget | Year: 2016
In recent years, most studies on breast cancer relapse and metastasis have focused on non-luminal breast cancers (including the basal-like and HER-2 subtypes) because of their poor prognosis. However, the luminal B subtype is more common, but this type has not been investigated as thoroughly. In the current study, we collected data on 258 patients with luminal-B breast cancer patients with recurrence and metastasis served as the observation group, and 189 patients with non-luminal breast cancer during the same period served as the control group. This study aimed to investigate the pattern of recurrence and clinical outcome after follow-up treatment for luminal B breast cancer. We found a higher proportion of local recurrence and single bone metastasis in patients with luminal B breast cancer than in patients in the non-luminal groups. The risk of recurrence and metastasis in patients with luminal B breast cancer during a 2- to 5-year period and after 5 years was still present, but the risk in patients with non-luminal breast cancers had obviously decreased during the same period. Patients with luminal B breast cancer with recurrence or/and metastasis had a better prognosis after reasonable treatment. The recurrence patterns and clinical outcomes of patients with luminal B breast cancer according to HER2 status were also different, to some degree. These results are of potential clinical relevance especially for the monitoring of clinical prognosis and targeted therapy intervention for luminal B breast cancer.