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Magnesium and its alloys are currently in the spotlight of global research because of the need to limit energy consumption and reduce the environmental impact. In particular, their low densities compared to other structural metals make them a very attractive alternative in the automobile and aerospace industries. However, their low strength compared to other structural materials (e.g. Al and steels) has limited their widespread application. This dissertation presents the results of developing and investigation of a high strength nanostructured magnesium-aluminum alloy and composite. The nanostructured magnesium alloy is prepared by cryomilling and consolidated by spark-plasma-sintering. Focused ion beam is used to prepare micropillars with different diameters ranging from 1.5 to 8 µm and micro-compression test is conducted by nanoindenter in order to evaluate the mechanical properties. The yield strength obtained in the present study is around three times higher than conventional magnesium alloys (120 MPa vs. 370 MPa). The yield strength of the nanostructured magnesium alloy is further improved through hot extrusion, resulting in a yield strength of 550 MPa and an ultimate strength of 580 MPa. The nanostructured magnesium alloy exhibits a strong size-dependence, and a significant improvement in strength is observed when the pillar diameter is reduced to below 3.5 µm. The deformation mechanisms of the compressed pillars were characterized using transmission electron microscopy. The size-induced strengthening is attributed to a less number of dislocation sources along with a higher activity of non-basal deformation mechanisms. We have also developed a high strength and thermally stable nanostructured magnesium composite by adding diamantane. A yield strength of 500 MPa is achieved, moreover, excellent thermal stability is demonstrated in the magnesium alloy containing diamantanes. The strength and grain size are thermally stable after annealing at 400°C for 100 hours. In contrast, the yield strength of the alloy without diamantanes decreases significantly after annealing due to severe grain growth. These results suggest that diamantanes are pinning the grain boundaries and inhibiting grain growth at elevated temperatures. Finally, molecular dynamics simulations and finite element analysis are used to explore the deformation mechanisms of magnesium with different grain sizes at atomic resolutions and correct tapering effect on micro-compression test, respectively. The results in the dissertation show that nanostructured Mg-Al alloy and Mg-Al-Diamantane composite are promising materials for aerospace and automobile industries.

Augmenting the biological function of adipose-derived stromal cells (ASCs) is a promising approach to promoting tissue remodeling in regenerative medicine. Here, we examined the effect of ginsenoside Rg1 on the paracrine activity and adipogenic differentiation capacity of human breast ASCs (hbASCs) in vitro. hbASCs were isolated and characterized in terms of stromal cell surface markers and multipotency. Third-passage hbASCs were cultured in basic media only or basic media containing different concentrations of G-Rg1 (0.1–100 μM). Cell proliferation was assessed by CCK-8 assay. Paracrine activity was assessed using ELISA. Gene expression was measured by qRT-PCR. Adipogenic differentiation capacity was evaluated by Oil red O staining. We found that hbASCs differentiated into adipocytes, osteoblasts, and chondrocytes in appropriate induction culture medium. hbASCs showed expression of CD29, CD44, CD49d, CD73, CD90, CD105, and CD133 but not CD31 and CD45 surface markers. G-Rg1 increased hbASC proliferation and adipogenic differentiation capacity at lower concentrations (0.1–1 μM) and had the opposite effects at higher concentrations (10–100 μM), while enhanced paracrine activity was observed in all experimental groups compared with control group, and the activation effect of lower concentration G-Rg1 was greater than at higher concentration. These results indicate that G-Rg1 can enhance the proliferation, paracrine activity, and adipogenic differentiation capacity of hbASCs within a certain concentration range. Therefore, the use of G-Rg1 may be beneficial to ASC-assisted fat graft regeneration and soft tissue engineering.

Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified via cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study’s findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.

Purpose The aim of this study was to evaluate the role of mesh technique in the reconstruction of the extensor mechanism after resection of proximal tibial tumors. Methods We retrospectively analyzed the cases of 14 patients who were diagnosed with proximal tibial tumors at our center and reconstructed with tumor prosthesis, gastrocnemius muscle, and mesh between 2012 and 2017. The treatment strategies for patellar tendon reconstruction primarily involve gastrocnemius reconstruction to cover the tumor prosthesis and mesh reconstruction for the patellar ligament. Results Among the 14 patients, the mean was 1.57° (range 0–12°) for active extension versus 105.00° (range 80–120°) for active flexion. The mean for passive extension was 0°. The passive flexion mean was 115.00° (range 90–120°). The extensor lag averaged 1.57° (range 0–12°), and the mean Musculoskeletal Tumor Society score (MSTS) was 23.57 (range 19–27). The average follow-up for all patients was 23.50 months (range 14–37). During the recent follow-up, all patients were able to walk without crutches. Two patients underwent above-the-knee amputation for local recurrence of the tumor, and lung metastasis occurred in three patients after operation. There were no postoperative complications. Conclusions Extensor lag was remarkably reduced in the surgery group in comparison to previous study reports. Surgical resection is a simple, reliable, and effective method to remove and control the tumor. Mesh reconstruction of patellar ligament is effective to reconstruct the extensor mechanism of the knee after excision of tumor.

This work aimed to observe the effects of short hairpin RNA (shRNA)-silenced FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231. qRT-PCR and Western blot analysis were applied to detect the mRNA and/or protein expression of FBI-1, Bcl-2, Bax, cleaved-Caspase 3 and Survivin. RNA interference method was used to silence FBI-1 expression in MDA-MB-231 cells. CCK-8 and colony formation assay were employed to detect the cell proliferation. Flow cytometry was employed for examining cell apoptosis. In vivo tumorigenicity of MDA-MB-231 cells was detected by tumor transplantation in nude mice. The results showed that the mRNA and protein expressions of FBI-1 were higher in MDA-MB-231 cells compared with those in normal human mammary epithelial cells MCF-10A. FBI-1 gene silencing inhibited proliferation and induced apoptosis of MDA-MB-231 cells in vitro, together with decreased Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Moreover, FBI-1 gene silencing inhibited the tumorigenesis of MDA-MB-231 cells in vivo. These results suggest that silencing of FBI-1 gene inhibits proliferation, induces apoptosis and suppresses the tumorigenesis of MDA-MB-231 cells.

Bin Liu,1,* Zhenchao Yuan,1,* Chang yuan Wei2 1Department of Bone and Soft Tissue Neurosurgery, 2Department of Breast Tumor Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China *These authors contributed equally to this work Objective: The incidence rate of thoracic metastasis from breast cancer is increasing. Microwave ablation is one type of clinical therapy used to treat metastatic spine disease, although it can cause protein denaturation and immediate cell death, and coagulative necrosis can occur. Minimally invasive open decompression is associated with lower rates of surgical complications in comparison to traditional open surgery. Therefore, it is an alternative therapeutic option for spinal metastases. This study aimed to assess the efficacy of microwave ablation with minimally invasive open decompression in the management of breast cancer patients with thoracic metastasis.Methods: This single-institution retrospective study investigated 23 cases of thoracic metastasis from breast cancer treated with combined microwave ablation and minimally invasive open decompression. Patients that presented with indications for surgery underwent surgical treatment. Data were collected for pain scores, the Frankel Grade classification system for acute spinal injury, the Karnofsky performance status (KPS) scale and complications due to treatment.Results: Of the 23 patients included in this study, all were successfully treated with microwave ablation and minimal invasive open decompression using our metrics. Of those, 18 patients (78.3%) showed improvement in their KPS results while 5 (21.7%) had alleviation of KPS. All 23 patients showed improvement in their Frankel Grade, suggesting improved neurological function following surgery. Most of the patients reported pain relief. Postoperative complications occurred in 4 patients.Conclusion: Microwave ablation combined with minimally invasive open decompression therapy for breast cancer patients with thoracic metastatic tumors is an alternative treatment that maintains or improves functional outcome in comparison to open surgery. Keywords: breast cancer, thoracic metastatic tumors, microwave ablation, minimally invasive open decompression

Triple-negative breast cancer (TNBC) tumors do not express estrogen, progesterone or HER2/neu-receptors. There are no specific treatment guidelines for TNBC patients, however, it has been postulated that their phenotypic and molecular similarity to BRCA1-associated cancers would confer sensitivity to certain cytotoxic agents, including platinum. The aim of this meta-analysis was to evaluate the clinical outcome of breast cancer patients treated with platinum-based chemotherapy who had TNBC compared with those with non-TNBC. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout December 2011 to identify trials evaluating the use of platinum-based chemotherapy for patients with breast cancer. The methodological quality was assessed in accordance with the QUOROM statement. Seven studies met the eligibility criteria, with a total of 717 patients. Of these patients, 225 were TNBC patients (31%), 492 were non-TNBC patients (69%), 275 received platinum-based neo-adjuvant chemotherapy and 442 had advanced/metastatic breast cancers. The results showed that during neo-adjuvant chemotherapy, the clinical complete response (cCR) rate and the pathological complete response (pCR) rates were significantly higher for the TNBC group compared with the non-TNBC group (OR, 2.68; 95% CI, 1.69-6.57; P=0.03 and OR, 2.89; 95% CI, 1.28, 6.53; P= 0.01, respectively). However, in advanced/metastatic breast cancers, the cCR, partial response (PR) and the disease control rates for the TNBC group were not significantly different compared with the non-TNBC group. The 6-month progression-free survival (PFS) rate for the TNBC group was higher than that of the non-TNBC group in all patients (OR, 1.81; 95% CI, 1.11-2.96; P= 0.02). However, the 1- and 2-year PFS rates were not significantly different (OR, 1.42; 95% CI, 0.69-2.92; P=0.35 and OR, 1.11; 95% CI, 0.35-3.52; P= 0.85, respectively). Furthermore, the PFS rates were not significantly different between the groups in patients with advanced/metastatic breast cancer. In conclusion, platinum-based chemotherapy in the breast cancer patients with TNBC showed an improved short-term efficacy compared with the non-TNBC group during neo-adjuvant chemotherapy, but has not yet been demonstrated to have an improved effect in advanced breast cancer.

Qin-Guo Mo*,De-Quan Li*, Jian-Hong Zhong, Chang-Yuan Wei Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this workIn the recent issue of Breast Cancer: Targets and Therapy, some questions about adjuvant systemic therapy1 and bone loss and skeletal-related events in postmenopausal women with hormone receptor-positive breast cancer2 were discussed by two reviews.View original paper byLeone and colleagues.

Background: Iodine 125 (125I) seed irradiation is an effective non-surgical treatment for unresectable hepatocellular carcinoma (HCC) patients. However, the safety and tolerability of 125I seed sequential irradiation therapy remain unclear, there is no unified standard of brachytherapy radiation dose, and further study on the basic radiobiology of continuous rate irradiation is necessary. Methods: Forty Kunming-mice (KM-mice, China) were injected with suspensions of human hepatocellular carcinoma cells (H22) to create an animal model and mimic 125I seed implantation. The survival rates of mice, curative effect, pathological impairments including apoptosis and necrosis were investigated. The mice were randomly divided into four groups, A, B, C and D. In group A, 0.78 mCi 125I seeds were implanted into the tumor focus. In groups B and C, 0.58 mCi and 0.38 mCi 125I seeds were inserted at the same location, respectively. Group D was a control group, without any treatment. After 28 days of therapy, the survival rates and the tumor size were measured, and pathological impairments was measured by light or electron microscopy. Results: The tumor volume inhibition rate was 68.21% ± 3.21%, 51.38% ± 4.96%, and 35.71% ± 2.79% after 0.78 mCi, 0.58 mCi, and 0.38 mCi 125I seeds irradiation, respectively. However, radiation-related side effects were also observed in the high-dose group. Pathological results showed that radiation effect was closely associated with radiation dose, as the increase of radiation dose, an increase in apoptosis and necrosis was detected. Significant cellular impairments were noted by pathological analysis under electron microscopy. Conclusions: Our results demonstrate that the Kunming-mouse is an ideal animal to study 125I brachytherapy, and the curative effect was closely associated with radiation dose. High-dose of brachytherapy may effectively increase apoptosis and necrosis in liver cells in KM-mice. A dose of 0.58 mCi 125I radioactive particles may be a safe, effective and minimally invasive therapeutic option for liver cancer.

Background: To investigate the prognostic value of hormone receptor (HR) status conversion after neoadjuvant chemotherapy (NAC) in patients with primary breast cancer. Methods: 267 stage II-III breast cancer patients treated with NAC who had residual disease in the breast after NAC were retrospectively studied. The patients were divided into four groups based on the HR status: Group A, patients with HR-positive both before and after NAC; Group B, patients with HR status positive-to-negative change; Group C, patients with HR status negative-to-positive change; Group D, patients with HR-negative both before and after NAC. Patients with positive HR status (regardless of before or after NAC) were treated with adjuvant endocrine therapy, and a survival analysis was performed. Results: In total, 15.7% of patients had HR status change after NAC. progression-free survival (PFS) in Group A was similar to that in Group C (hazard ratio, 1.16; P = 0.652), but that in Group B was significantly lesser than that in Group A (hazard ratio, 6.88; P = 0.001), and that in Group C was significantly longer than that in Group D (hazard ratio, 6.88; P = 0.001). A similar pattern of results was obtained for overall survival (OS). Conclusions: The switch of HR status after NAC is remarkable for breast cancer. An HR switch may identify patients who would benefit from adjuvant endocrine therapy and impact the long-term outcome.

A standard systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) is yet to be identified. Sorafenib has been developed for the treatment of solid tumors, including breast cancer, as an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. The aim of the present study was to assess the efficacy and safety of sorafenib in patients with HER2-negative ABC by performing a meta-analysis. A literature search was applied to databases, including PubMed, EMBASE, the Cochrane Library Databases, American Society of Clinical Oncology and the European Society for Medical Oncology, with the search terms ‘advanced breast cancer’ and ‘sorafenib’ and relevant studies were selected for analysis. The data extracted from the selected studies included progression-free survival (PFS), time to progression (TTP), overall survival (OS) and overall response rate (ORR). Major adverse events (AEs) were also analyzed. A total of four randomized controlled trials containing 844 cases were identified. Combined results revealed that when compared with chemotherapy (or with anti-hormone receptor therapy) alone, sorafenib-based therapy significantly increased the PFS [hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.54–1.02] and TTP (HR, 0.74; 95% CI, 0.50–0.97), but not the OS (HR, 0.95; 95% CI, 0.75–1.15) and ORR (relative risk, 1.19; 95% CI, 1.01–1.39). In addition, the incidence of grade 3/4 AEs, including hand-foot skin syndrome, anemia, fatigue, rash and stomatitis, were significantly increased in patients that received sorafenib-based therapy. Therefore, the results from the current meta-analysis indicated that sorafenib-based therapy improved the PFS and TTP in patients with HER2-negative ABC, but not the OS and ORR. In addition, combination treatment was associated with increased toxicities and frequently required dose reductions.