Solution–Air Interface Synthesis and Growth Mechanism of Tooth Enamel-like Hydroxyapatite/Chondroitin Sulfate Films

Hierarchically self-assembled hydroxyapatite (HAP) and organic composite resembling tooth enamel has potential biological and surgery applications. Controlled fabrication remains a great challenge. In this work, large-scale translucent hydroxyapatite (HAP) and chondroitin sulfate (ChS) composite films are fabricated by a unique solution–air interface method. The products excellently represent the characteristic hierarchical “prism” structure of tooth enamel. We demonstrate that the films are formed by evaporation-induced nucleation at the interface and subsequent self-confined spherulitic growth. The supersaturation at the interface increases upon solution evaporation, and the local high supersaturation triggers preferred nucleation there. The spherulitic growth is regulated by ChS and limited by the interfaces between the spherulites as well as the solution and air. Consequently, HAP/ChS films with the hierarchically self-assembled prism structure are produced. We emphasize that the mechanism can excellently explain the unique prism structure formation in tooth enamel and in self-assembled nanorod arrays. The findings provide insight into the fundamentals of hierarchical assembly in nature (e.g., assembly of tooth enamel). Moreover, the approach could be expanded to design and grow other sophisticated functional structures

Acute toxicities during the treatment of 181 patients with nasopharyngeal carcinoma.

<p>RTOG, Radiation Therapy Oncology Group.</p><p>Kruskal-Wallis analysis.</p><p>Acute toxicities during the treatment of 181 patients with nasopharyngeal carcinoma.</p

Survival curves for Han and Uyghur patients who received intensity-modulated radiation therapy for nasopharyngeal carcinoma.

<p>Survival curves for Han and Uyghur patients who received intensity-modulated radiation therapy for nasopharyngeal carcinoma.</p

Comparisons of 3-year and 5-year survival rates for Han and Uyghur patients.

<p>OS, overall survival; DFS, disease-free survival; LC, local control; RC, regional control; DMFS, distant metastasis-free survival.</p><p>Comparisons of 3-year and 5-year survival rates for Han and Uyghur patients.</p

Patient characteristics.

a<p>t-test.</p><p>WHO, World Health Organization.</p><p>Patient characteristics.</p

Univariate analysis of OS and DFS for Han and Uyghur patient.

<p>OS, overall survival; DFS, disease-free survival.</p><p>Univariate analysis of OS and DFS for Han and Uyghur patient.</p

Additional file 1: of Activated innate lymphoid cell populations accumulate in human tumour tissues

Figure S1. Representative staining of ILC populations. ILC were gated on lineage negative, CD45+, CD127+ cells and based on the expression of CRTH2 and c-Kit divided into ILC1 (CRTH2-, c-Kit-), ILC2 (CRTH2+, c-Kit +/−) and ILC3 (CRTH2-, c-Kit+). Figure S2 Representative example of ILC1, ILC2, ILC3 phenotypic analysis from benign breast tissue. Figure S3 Representative example of ILC1, ILC2, ILC3 phenotypic analysis from malignant breast tissue. Figure S4 Representative example of ILC1, ILC2, ILC3 phenotypic analysis from malignant GI tumour tissue. Figure S5 Representative example of ILC1, ILC2, ILC3 phenotypic analysis from paralesional GI tumour tissue. Table S1 Patient characteristics. (PDF 5287 kb

Concomitant Targeting of Multiple Key Transcription Factors Effectively Disrupts Cancer Stem Cells Enriched in Side Population of Human Pancreatic Cancer Cells

<div><p>Background</p><p>A major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs).</p> <p>Objective</p><p>To identify side population (SP) cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs) and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.</p> <p>Methods</p><p>Flow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP) cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO) designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.</p> <p>Results</p><p>CSCs were enriched in the side proportion (SP) cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN–SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.</p> <p>Conclusion</p><p>The findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a potential anti-pancreatic cancer agent worthy of further studies in preclinical settings.</p> </div

Enhanced drug resistance of SP cells and suppression by cdODN-SOC.

<p>(<b>A</b>) Percent cell survival measured by MTT assay in PANC-1 CSCs. All cells were all treated with varying concentrations of gemcitabine and with lipofectamine 2000. Symbols are experimental data and the lines represent best fits to Hill equation. ***p<0.001 vs SP alone for comparison of IC50 values; n=4. (B) Percent apoptotic cells measured by ELISA to quantify DNA fragmentation in PANC-1 CSCs. All cells were all treated with varying concentrations of gemcitabine and with lipofectamine 2000. Symbols are experimental data and the lines represent best fits to Hill equation. ***p<0.001 vs SP alone for comparison of IC50 values; n=4. Quantitatively the same results were obtained from SW1990 and BxPc-3 CSCs (data not shown).</p

Analysis of the side population (SP) in three human pancreatic cancer cell lines PANC-1, SW1990, and BxPc-3, using flow cytometry and Hoechst33342 dye.

<p>(<b>A</b>) Examples of floe cytometry analysis of SP cells in the presence or absence of 30 µM verapamil, cdODN-SOC (a complex decoy oligodeoxynucleotide carrying <i>cis</i>-elements for Sox2, Oct4 and c-Myc), or NC–ODN (negative control cdODN). (<b>B</b>) The SP proportions as percentage of total population. ***<i>p</i><0.001 <i>vs</i> Control; n=4.</p