BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells.

Treatment of colorectal cancer (CRC) remains a challenge because of the lack of effective early treatment strategies and high incidence of relapse. 5-Fluorouracil (5-FU) is a typical CRC treatment. Bromosporine is an innovative bromodomain and extraterminal domain (BET) inhibitor. We investigated if CRC could be targeted by the combination of 5-FU and bromosporine in a synergistic manner in vivo and in vitro. Our findings shown that the combination treatment inhibits cell viability, formation of colonies, increased apoptosis and cell cycle arrest at G0-G1. In addition, the expression level of BRD4 was high in HCT116 cells exposed to 5-FU that showed lower apoptosis against the parental cells. Moreover, the 5-FU-resistance was reversed significantly by BRD4 knockdown or inhibition. The drug combination showed increased activity against tumor than individual drug exposure in the xenograft model. In conclusion, this work serves as a basic clinical evaluation of 5-FU and bromosporine as an effective therapeutic approach for CRC.

ORLNC1 Suppresses Cell Growth in HER2-Positive Breast Cancer via miRNA-296 Sponging.

BACKGROUND: Accumulating research has demonstrated that aberrant levels of long noncoding RNAs (LncRNAs) are related to cancer progression. The effects of ORLNC1 in HER2+ breast cancer have yet to be explored. METHODS: Real-time PCR was used to examine the expression of LncRNA ORLNC1 in HER+ breast cancer. CCK-8, wound healing and cell invasion assays were used to examine the effect of LncRNA ORLNC1 on HER+ breast cancer cells. Luciferase reporter assay was utilized to determine the regulatory relationship between LncRNA ORLNC1 and miR-296. Western blotting was used to measure the expression of PTEN. Xenograft mouse model was used to examine the effect of LncRNA ORLNC1 on tumor progression in vivo. RESULTS: In this study, our findings revealed downregulation of ORLNC1 in HER2+ breast cancer specimens and cell lines. Low levels of ORLNC1 were related to poor prognosis and advanced cancer stage. Using gain- and loss-of-function assays, the ability of these tumor cells to proliferate was found to be inhibited by ORLNC1 in vitro and in vivo. Further analyses revealed that miR-296/PTEN axis is directly targeted by ORLNC1. Consequently, over-expression of miR-296 efficiently abrogated the upregulation of PTEN induced by ORLNC1, suggesting that ORLNC1 positively regulates PTEN expression by competitively binding to miR-296. CONCLUSION: Our results indicate that lncRNA ORLNC1 acts as a tumor suppressor by regulating the miR-296/PTEN axis in HER2+ breast cancer.

Classification of premolars sagittal root position and angulation for immediate implant placement: a cone beam computed tomography study.

OBJECTIVES: Sagittal root position (SRP) and buccal plate thickness are important considerations in implant treatment planning. The objective of this study was to classify the relationship of the SRP and angulation to the osseous housing to assist treatment plan making for immediate implant placement in the premolar region. STUDY DESIGN: We classified the SRP and angulations of the maxillary and mandibular premolars and measured the buccal plate thickness of 150 patients using cone beam computed tomography to support clinical decision making. RESULTS: Regarding SRP types, 41.67%, 51.83%, 3.67%, and 2.83% of maxillary premolars and 84.33%, 15%, 0%, and 0.67% of mandibular premolars were classified as types B, M, L, and N, respectively. In terms of angulation, 20.83%, 46%, 32.17%, and 1% of maxillary premolars and 2%, 5.33%, 36.67%, and 56% of mandibular premolars were grouped into classes 1, 2, 3, and 4, respectively. The buccal bone thickness at most locations in premolar regions was <1 mm. CONCLUSIONS: The classification of SRP and angulation will assist in treatment plan making for immediate implant placement in the premolar region.

Depletion of Fibroblast Growth Factor 12 Restrains the Viability, Stemness, and Motility of Colorectal Cancer.

Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. CRC patients have a poor prognosis due to tumor metastasis and recurrence. Fibroblast growth factor 12 (FGF12), a member of the FGF family, is highly expressed in several cancers. However, little is known about the roles of FGF12 in CRC progression. Methods: The overall survival (OS) of CRC patients was detected via Kaplan-Meier analysis. The FGF12 expression in both CRC tissues and cells was analyzed by qRT-PCR, immunohistochemistry (IHC), and western blotting (WB). LoVo and SW480 cells were transfected with shFGF12 lentivirus to silence FGF12. In vivo and in vitro experiments were performed to explore the FGF12 functions in CRC, including CCK-8, Edu, flow cytometry, Transwell, EMT, cancer stemness, and tumor xenograft experiments. Results: FGF12 was upregulated in both CRC cells and tissues. High expression of FGF12 indicated a shorter OS in CRC patients. FGF12 knockdown inhibited the proliferation, invasion, stemness, and EMT of CRC cells. FGF12 knockdown promoted CRC cell apoptosis in vitro. 740 Y-P (a PI3K/AKT pathway activator) restored the proliferation, stemness, invasion, and EMT in FGF12-deficient cells and reversed LoVo cell apoptosis induced by FGF12 depletion. Depletion of FGF12 inhibited tumor growth, EMT, cancer stemness, and PI3K/AKT pathway in a xenograft mouse model. Conclusions: FGF12 predicts bad clinical outcome and modulates the viability, stemness, and motility of CRC cells. Our study may provide a new insight for the diagnosis and treatment of CRC.

Evaluation of a dynamic navigation system for training students in dental implant placement.

OBJECTIVE: Computer-guided simulation systems may offer a novel training approach in many surgical fields. This study aimed to compare dental students' learning progress in dental implants placement between a dynamic navigation system and a traditional training method using a simulation model. METHODS: Senior dental students with no implant placement experience were randomly assigned to implant placement training using a dynamic navigation system or a traditional freehand protocol. After training, 3-dimensional (3D) deviation at implant platform, 3D deviation at implant apex, and deviation of implant axis between the planned and placed implant positions were measured using superimposed cone beam computed tomography scans. RESULTS: Six students were trained in this study. Students showed significantly greater improvement in implant placement after training using the dynamic navigation system than after using the traditional freehand protocol. Overall deviation of implant axis (P < 0.001) and 3D apex deviation (P = 0.014) improved with training using the dynamic navigation system, but differences in 3D platform deviation (P = 0.513) were not statistically significant. CONCLUSIONS: A dynamic navigation system may be a useful teaching tool in the early development of clinical skills in implant placement for the novice practitioners. Novice practitioners exhibited significant improvement in angulation deviation across implant placement attempts with dynamic navigation system training.

miR-372 promotes breast cancer cell proliferation by directly targeting LATS2.

MicroRNAs (miRs) have previously been demonstrated to be important in the tumorigenesis and progression of breast cancer. miR-372 was previously revealed to be involved in various types of human cancer, however its function in breast cancer remains largely unknown. The present study demonstrated that miR-372 is frequently overexpressed in breast cancer cell lines and tissues. The downregulation of miR-372 markedly inhibited cell proliferation, arrested the cell cycle in the G1/S phase, and increased the apoptosis of breast cancer cells. Consistently, an in vivo xenograft study also demonstrated the suppressive effects of miR-372 knockdown on tumor growth. Further studies revealed that miR-372 modulated the expression of large tumor suppressor kinase 2 (LATS2) by directly targeting its 3'-untranslated region in breast cancer cells. Furthermore, silencing of LATS2 was able to rescue the effect of the miR-372 inhibitor. Overall, the results suggest that miR-372 functions as an oncogenic miRNA in breast cancer by targeting LATS2.

Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load.

This study was a meta-analysis of the literature on the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Four observational studies and one randomized controlled trial involving 585 pregnant women and 595 newborns were included in the meta-analysis. TDF was more effective than the placebo in reducing vertical transmission in HBeAg-positive chronic hepatitis B (CHB) pregnancies with high serum HBV-DNA levels (OR = 0.21, 95% CI = 0.07-0.61) at 4-12 months, infant HBV DNA seropositivity at delivery (OR = 0.16, 95% CI = 0.07-0.37), and a severe flair in maternal alanine aminotransferase (ALT) levels (OR = 0.43, 95% CI = 0.19-0.95) during pregnancy. In addition, TDF showed more improvement in HBV DNA suppression at delivery (OR = 254.46, 95% CI = 28.39-2280.79). No significant differences were found in HBeAg seroconversion or ALT normalization; or in rates of cesarean section, emergent cesarean section, postpartum hemorrhage, prematurity, congenital malformations, or infant death. However, TDF induced more drug-related adverse events (OR = 2.33, 95% CI = 1.39-3.89) and elevated creatine kinase (CK) (OR = 9.56, 95% CI = 1.17-78.09) than in controls. The available evidence suggests that TDF is effective and safe in preventing vertical transmission of hepatitis B in pregnancies exhibiting a high viral load.