Exosome-delivered circRPS5 inhibits the progression of melanoma via regulating the miR-151a/NPTX1 axis.

BACKGROUND: Circular RNAs (circRNAs) have been reported to exert critical functions in tumorigenesis and development. However, the underlying mechanism by which circRNAs regulate melanoma progression remain to be elucidated. METHODS: The differentially expressed circRNAs were first identified by circRNA-seq, and circRNAs were validated via qRT-PCR and Sanger sequencing. Then, the impact of circRPS5, miR-151a and NPTX1 expression on the progression of melanoma cell were determined by gain- and loss-of-function assays. The relationship between circRPS5, miR-151a, and NPTX1 was predicted by StarBase website and authenticated by luciferase reporter assay. The melanoma cells-derived exosomes were characterized using nanoparticle tracking analysis (NTA) and western blot. RESULTS: CircRPS5 was significantly downregulated in melanoma tissues and cell lines. Functionally, circRPS5 suppressed the proliferation, migration, and invasion of melanoma cells, and induced cell cycle arrest and apoptosis in vitro. Mechanistically, circRPS5 harbor miR-151a, acting as miRNA sponge, and then miR-151a targeted the 3'-UTR of NPTX1. Finally, circRPS5 was mainly incorporated into exosomes to inhibit the progression of melanoma cells. CONCLUSIONS: This finding reveal circRPS5 suppressed the progression of melanoma through miR-151a/NPTX1 pathway, and may provide a promising therapeutic strategies for melanoma.

More flexible and more innovative: the impact of flexible work arrangements on the innovation behavior of knowledge employees.

Flexible work arrangements (FWA) are becoming increasingly widespread as an efficient means of coping with a dynamic and competitive business environment. Existing studies have primarily examined the impact of FWA as a management system; however, its impact on employee innovation behavior has not been fully explored. Based on the self-determination theory, this study constructed a moderated mediation model that empirically examined the influence of FWA on the innovation behavior of knowledge employees. Our findings are as follows: (1) FWA can activate innovation behavior among knowledge employees; (2) thriving at work plays a partial mediating role; (3) human resource policies that facilitate opportunities have a positive moderating effect. The findings fill a theoretical research gap and provide insights for managers on implementing FWA to promote the innovative behavior of knowledge employees.

Comparison between the indocyanine green fluorescence and blue dye methods for sentinel lymph node biopsy using novel fluorescence image-guided resection equipment in different types of hospitals.

Sentinel lymph node biopsy (SLNB) has become a standard of care to detect axillary lymph metastasis in early-stage breast cancer patients with clinically negative axillary lymph nodes. Current SLNB detection modalities comprising a blue dye, a radioactive tracer, or a combination of both have advantages as well as disadvantages. Thus, near-infrared fluorescence imaging using indocyanine green (ICG) has recently been regarded as a novel method that has generated interest for SLNB around the world. However, the lack of appropriate fluorescence imaging systems has hindered further research and wide application of this method. Therefore, we developed novel fluorescence image-guided resection equipment (FIRE) to detect sentinel lymph nodes (SLNs). Moreover, to compare the ICG fluorescence imaging method with the blue dye method and to explore the universal feasibility of the former, a different type of hospital study was conducted. Ninety-nine eligible patients participated in the study at 3 different types of hospitals. After subcutaneous ICG allergy testing, all the patients were subcutaneously injected with methylene blue and ICG into the subareolar area. Consequently, 276 SLNs (range 1-7) were identified in 98 subjects (detection rate: 99%) by using the ICG fluorescence imaging method. In contrast, the blue dye method only identified 202 SLNs (range 1-7) in 91 subjects (detection rate: 91.92%). Besides, the results of the fluorescence imaging method were similar in the 3 hospitals. Our findings indicate the universal feasibility of the ICG fluorescence imaging method for SLNB using the fluorescence image-guided resection equipment in early breast cancer detection.

Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has attracted more attention both clinically and experimentally because of its high-risk biological characteristics and lacking of effective treatment method. The purpose of this retrospective study was to find out the incidence of triple-negative breast cancer (TNBC) in all kinds of breast cancers and to compare and analyze the clinicopathological features, recurrence, metastasis and prognosis of patients with TNBC and non-triple negative breast cancer (non-TNBC). METHODS: A total of 1578 female patients with primary breast cancer were diagnosed and treated at the department of General Surgery, the Chinese PLA General Hospital, China, from Jan. 2004 to Jun. 2009. The 1578 breast cancer patients were divided into two groups: the TNBC group and the non-TNBC group. The clinical features and prognosis of the two groups were compared. RESULTS: The incidence of TNBC was 20.41%. Compared with the non-TNBC, the TNBC were characterized as younger age, higher histological grade, higher rate of positive lymph node, bigger tumor size, higher clinical stage at diagnosis, higher histological grade, quicker and easier recurrence and metastasis and lower 5-year DFS rate and 5-year OS rate. The metastasis of TNBC had obvious organic tendency. The lungs, liver and brain were the first three most common sites of metastases. The information of age, the tumor size, lymph node status, clinical stage, histological grade, pathological types and operation method, especially the age and lymph node status play the important roles in judging the prognosis of TNBC. CONCLUSIONS: According to this study we found that TNBC was a distinct subgroup of breast cancer with particular clinicopathologic behavior. Compared with the non-TNBC, TNBC was characterized by more aggressive behavior, and lower DFS and OS rate. The metastasis of TNBC had obvious organic tendency. The information of age, the maximum diameter of the tumor, lymph node status, clinical stage, histological grade, pathological types and operation method, especially the age and lymph node status played the important roles in judging the prognosis of TNBC patients.

Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes.

Advanced medical imaging technology has allowed the use of fluorescence molecular imaging-guided breast cancer surgery (FMI-guided BCS) to specifically label tumour cells and to precisely distinguish tumour margins from normal tissues intra-operatively, a major challenge in the medical field. Here, we developed a surgical navigation system for real-time FMI-guided BCS. Tumours derived from highly metastatic 4T1-luc breast cancer cells, which exhibit high expression of matrix metalloproteinase (MMP) and human epidermal growth factor receptor 2 (HER2), were established in nude mice; these mice were injected with smart MMP-targeting and "always-on" HER2-targeting near-infrared (NIR) fluorescent probes. The fluorescence signal was imaged to assess in vivo binding of the probes to the tumour and metastatic sites. Then, orthotopic and metastatic breast tumours were precisely removed under the guidance of our system. The post-operative survival rate of mice was improved by 50% with the new method. Hematoxylin and eosin staining and immunohistochemical staining for MMP2 and CD11b further confirmed the precision of tumour dissection. Our method facilitated the accurate detection and complete removal of breast cancer tumours and provided a method for defining the molecular classification of breast cancer during surgery, thereby improving prognoses and survival rates.

Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology.

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.

[Effects of mammalian-target-of-rapamycin pathway on lapatinib resistance in breast cancer MDA-MB-231 cells].

OBJECTIVE: To establish a lapatinib resistance cell line for elucidating the mechanisms of drug resistance of lapatinib in human breast cancer cells. METHODS: The human breast cancer MDA-MB-231 cells were exposed in an incremental dose of lapatinib to establish a lapatinib resistance rMDA-MB-231 cell line. The assay of methyl thiazolyl tetrazolium (MTT) was used to detect the cytotoxic activity of lapatinib against MDA-MB-231 and rMDA-MB-231 cells. The protein expression was detected by Western blot. Small interfering RNA was used to specifically knock down mammalian-target-of-rapamycin (mTOR) in rMDA-MB-231 cells. Apoptosis was determined by fluorescein isothiocyanate (FITC)-annexin V/PI staining and flow cytometry. RESULTS: The human breast cancer lapatinib resistance cell line rMDA-MB-231 was induced by lapatinib. The half maximal inhibitory concentration (IC50) values of lapatinib against MDA-MB-231 and rMDA-MB-231 cells were (6.1 ± 0.6) and (34.9 ± 2.7) µmol/L respectively (P < 0.01). Compared with MDA-MB-231 cells, the protein expression of mTOR in rMDA-MB-231 cells was significantly up-regulated. The protein expression of mTOR was significantly down-regulated by specific siRNA duplexes in rMDA-MB-231 cells. After siRNA interference, 20 µmol/L lapatinib was added into control, negative siRNA control and mTOR-targeted siRNA groups respectively. The percents of cell apoptosis in control, negative control and targeted siRNA groups were 13.4% ± 2.5%, 14.2% ± 2.8% and 34.6% ± 5.8% respectively, there was no significance between the first two groups (P > 0.05) , and there was significant difference between the control and targeted siRNA group (P < 0.01) . CONCLUSIONS: The up-regulation of mTOR plays an important role in the lapatinib-resistant phenotype of human breast cancer rMDA-MB-231 cells. And the down-regulation of mTOR increases the apoptotic death of lapatinib against rMDA-MB-231 cells.