Circular RNA 0007255 regulates the progression of breast cancer through miR-335-5p/SIX2 axis.

BACKGROUND: Breast cancer (BC) is a common cancer in women worldwide. Emerging evidence has indicated that circular RNA hsa-circ_0007255 (circ_0007255) is a prognostic mediator in BC progression. However, the functional role of circ_0007255 needs to be determined. METHODS: The expression of circ_0007255, microRNA (miR)-335-5p, and SIX Homeobox 2 (SIX2) was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Actinomycin D and RNase R treatment was performed to analyze the stability of circ_0007255. Additionally, Seahorse extracellular flux, colony formation and transwell analyses were carried out to detect oxygen consumption ratio (OCR), colony formation and cell mobility, respectively. The interaction between miR-335-5p and circ_0007255 or SIX2 was confirmed via dual-luciferase reporter assay. A xenograft tumor model was established to explore the role of circ_0007255 in vivo. RESULTS: Circ_0007255 and SIX2 were overexpressed, but miR-335-5p was diminished in BC tissues and cells. Circ_0007255 absence inhibited oxygen consumption, colony formation, cell migration and invasion, and these effects were particularly abrogated via miR-335-5p upregulation in BC cells. Moreover, SIX2 deficiency eliminated the promotion effects of miR-335-5p inhibitor on oxygen consumption, colony formation, and cell mobility in BC cells. Importantly, circ_0007255 inhibited tumor growth in vivo. Mechanically, circ_0007255 was a sponge of miR-335-5p to regulate SIX2 expression in BC progression. CONCLUSION: Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR-335-5p/SIX2 axis, and might be a promising biomarker for BC treatment. KEY POINTS: Significant findings of the study: Levels of circ_0007255 and SIX2 were upregulated, but miR-335-5p was diminished in BC tissues and cells. Circ_0007255 was an oncogene in BC development and exerted its function via miR-335-5p/SIX2 axis in BC. Tumor growth was reduced by circ_0007255 absence. WHAT THIS STUDY ADDS: Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR-335-5p/SIX2 axis, and might be a promising biomarker for BC treatment.

A randomized Phase III trial of neoadjuvant recombinant human endostatin, docetaxel and epirubicin as first-line therapy for patients with breast cancer (CBCRT01).

To further assess the efficacy and safety of recombinant human endostatin (rh-endostatin), a Phase III, multicenter, prospective, randomized, controlled clinical trial was conducted. Patients to be treated with neoadjuvant docetaxel and epirubicin (DE) or DE plus rh-endostatin (DEE) were eligible for this trial. The primary endpoint was clinical/pathological response. Secondary endpoints included adverse events and quality of life (QOL). Finally, 803 patients were enrolled and randomly assigned to receive DE (n = 402) or DEE (n = 401) regimen. After three cycles of neoadjuvant therapy, "complete response" achieved in 14.2% of patients in DEE group versus 6.7% in DE group, "partial response" achieved in 76.8% versus 71.1%, while "stable disease" in 6.0% versus 18.9%, "progressive disease" in 3.0% versus 3.2% of patients. The rate of objective response in DEE and DE group was 91.0% and 77.9%, respectively (p < 0.001). In spite of a relatively higher pathological complete response achieved following the combination therapy, no significant difference was found between two arms. Adverse events were mostly of Grades 1-2. No significant difference in adverse event and QOL was found between the two arms. In conclusion, the combination of chemotherapy and rh-endostatin achieved better outcomes than chemotherapy alone, and thus can be considered as a promising therapeutic strategy for breast cancer.

A Special Tear Pattern of Anterior Horn of the Lateral Meniscus: Macerated Tear.

BACKGROUND: We describe a special, interesting phenomenon found in the anterior horn of the lateral meniscus (AHLM): most tear patterns in the AHLM are distinctive, with loose fibers in injured region and circumferential fiber bundles were separated. We name it as macerated tear. The goal of this study was to bring forward a new type of meniscal tear in the AHLM and investigate its clinical value. MATERIALS AND METHODS: AHLM tears underwent arthroscopic surgery from January 2012 to December 2014 were included. Data regarding the integrity of AHLM were prospectively recorded in a data registry. Tear morphology and treatment received were subsequently extracted by 2 independent reviewers from operative notes and arthroscopic surgical photos. RESULTS: A total of 60 AHLM tears in 60 patients (mean age 27.1 years) were grouped into horizontal tears (n = 15, 25%), vertical tears (n = 14, 23%), complex tears (n = 6, 10%), and macerated tears (n = 25, 42%). There were 6 patients with AHLM cysts in macerated tear group and one patient in vertical tear group. 60 patients were performed arthroscopic meniscus repairs and were followed-up with averaged 18.7 months. Each group had significant postoperative improvement in Lysholm and IKDC scores (p < 0.05). However, the macerated tear group showed least functional recovery of Lysholm and IKDC scores compared to other groups (p < 0.05). In addition, there were no differences in postoperative range of motion, return to work, or return to sport/other baseline activities between the four groups (p > 0.05). CONCLUSIONS: This study demonstrated that the macerated tear is common in the tear pattern of AHLM. However, feasibility of the treatment of this type of meniscal tear, especially the meniscus repairs still requires further study.

Magnetic resonance imaging: a valuable method for diagnosing chronic lumbago caused by lumbar muscle strain and monitoring healing process.

BACKGROUND: Magnetic resonance imaging (MRI) is the most sensitive technique for evaluating the healing process and should be performed before the patients return to their exercise routines. The aim of this research was to diagnose chronic lumbago associated with lumbar muscle strain and to monitor healing process by MRI. METHODS: Sixty-fve symptomatic cases of chronic lumbago caused by lumbar muscle strain were collected from March 2009 to October 2011. MRI was used to examine, diagnose and monitor the healing process. The control group included 65 random cases of asymptomatic volunteers. MRI methods included routine sequences of GRE T1WI, TSE T2WI and special sequences of T2-STIR-FS, combined with DWI. We compared the MRI characteristics of symptomatic cases before and after healing and with asymptomatic controls. RESULTS: The important MRI characteristics of chronic lumbago with lumbar muscle strain included: (1) The low back muscle showed edema. (2) The low back intermuscular spaces showed edema and/or fluid. (3) The low back spaces beside the spinous process showed edema and/or fluid. (4) The low back vertebral articular process fossae or transverse process fossae showed fluid. Of these image characteristics, the intermuscular space edema provided the best diagnostic sensitivity, Se = 83%, with YI = 0.63, p = 74%. The low back muscle edema provided the best diagnostic specificity, Sp = 100%, with YI = 0.66, Π = 83%. And the spaces edema beside the spinous process provided the best diangnostic accuracy, Π = 86%, with YI = 0.71, Se = 80%, Sp = 91%. The diagnosis accurate could be improved by combining multiple MRI characteristics. The diagnostic accuracy could achieve Π = 93%, with YI = 0.86, Se = 100% and Sp = 86% when two characteristics were combined. After rehabilitation care, the edema disappeared on the repeated MRI. CONCLUSIONS: MRI may well be a useful diagnostic method for lumbago with lumbar muscle strain. Combining routine sequences with T2-STIR-FS and DWI sequences could demonstrate the pathological changes of lumbar muscle strain and monitor the healing.

Dynamic contrast-enhanced MR imaging in a phase â ¡ study on neoadjuvant chemotherapy combining Rh-endostatin with docetaxel and epirubicin for locally advanced breast cancer.

BACKGROUND: Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients. METHODS: The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group) or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group). The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery. RESULTS: The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021) and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000), Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000), tumor signal enhanced ratio (64% vs. 48%, P = 0.018), and K(trans) (67% vs. 39%, P = 0.026) in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000). Moreover, the microvessel density value was significantly correlated with K(trans) after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00). CONCLUSIONS: The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and K(trans), could provide non-invasive evaluation for chemotherapeutic efficacy and, consequently, optimization of individual chemotherapy for locally advanced breast cancer patients.

S100B promotes the proliferation, migration and invasion of specific brain metastatic lung adenocarcinoma cell line.

Brain metastasis frequently occurs in cancer patients and is associated with a poor prognosis. We previously reported that S100B was highly expressed in PC14/B, a specific brain metastatic lung adenocarcinoma cell line, which suggests that it is associated with brain metastasis of lung cancer. However, the role of S100B in brain metastasis remains to be elucidated. In this study, using PC14/B cell line, we found that siRNA mediated depletion of S100B in PC14/B cells led to notable differences in cell proliferation, apoptosis, cell cycle progression, colony formation ability, cell migratory and invasive activity compared with the mock-transfected cells. Therefore, our data suggest that S100B promotes the brain metastasis of lung adenocarcinoma by promoting cell proliferation, preventing apoptosis and increasing cell migration and invasion.