Tanshinone IIA improves contextual fear- and anxiety-like behaviors in mice via the CREB/BDNF/TrkB signaling pathway.

Posttraumatic stress disorder (PTSD) is one of the most common psychiatric diseases, which is characterized by the typical symptoms such as re-experience, avoidance, and hyperarousal. However, there are few drugs for PTSD treatment. In this study, conditioned fear and single-prolonged stress were employed to establish PTSD mouse model, and we investigated the effects of Tanshinone IIA (TanIIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza, as well as the underlying mechanisms in mice. The results showed that the double stress exposure induced obvious PTSD-like symptoms, and TanIIA administration significantly decreased freezing time in contextual fear test and relieved anxiety-like behavior in open field and elevated plus maze tests. Moreover, TanIIA increased the spine density and upregulated synaptic plasticity-related proteins as well as activated CREB/BDNF/TrkB signaling pathway in the hippocampus. Blockage of CREB remarkably abolished the effects of TanIIA in PTSD model mice and reversed the upregulations of p-CREB, BDNF, TrkB, and synaptic plasticity-related protein induced by TanIIA. The molecular docking simulation indicated that TanIIA could interact with the CREB-binding protein. These findings indicate that TanIIA ameliorates PTSD-like behaviors in mice by activating the CREB/BDNF/TrkB pathway, which provides a basis for PTSD treatment.

Microwave Ablation of Primary Malignant Pelvic Bone Tumors.

Background: En bloc tumor resection followed by reconstruction is a widely used surgical treatment for malignant pelvic bone tumors. High rates of complications and mechanical instability often contribute to poor postoperative results. We attempted en bloc microwave ablation (MWA) in situ to improve the outcome. Methods: From May 1995 to December 2015, 104 patients with primary pelvic malignancy received radical MWA in our department. After careful dissection of the tumor-bearing bone from surrounding normal tissues with safe margins, a microwave antenna array was inserted into the tumor mass to emit electromagnetic energy, inducing tumor cellular death via thermocoagulation. The loose, devitalized tumor tissues were removed by cutting or curettage, leaving a defective bone scaffold. Re-strengthening by autograft or allograft was needed in most patients. Results: The over 3 years survival rate was 51.5% for high-grade malignancies (among them, 26.9% were osteosarcoma) and 94.8% for low-grade malignancies (chondrosarcoma). In most of the living patients, cosmetic and useful limbs were preserved. The mean functional score (Musculoskeletal Tumor Society) was 27 or 90% (range: 25-30, 75-100%). Among the 56 patients who belonged to the excellent function group, 11 were followed up for more than 10 years. The local recurrence rate was 8.6%. Among the 9 patients with recurrence, 5 died from disease, 2 were treated by hemipelvic amputation, and 2 underwent revision surgery with MWA and gained local control. The deep infection rate was 5.6%. All six patients with infection were healed by irrigation, debridement, and systemic antibiotic administration. Conclusion: Local, microwave-induced hyperthermia for treating malignant pelvic bone tumors is an effective alternative method. The oncological and functional results are encouraging. The use of MWA should be continued to evaluate and improve this new therapeutic system.

Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model.

The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post-surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T-lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma.

A novel recombinant immuno-tBid with a furin site effectively suppresses the growth of HER2-positive osteosarcoma cells in vitro.

Immunotherapy is a promising strategy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive tumors. Previously, we constructed an immuno-carboxy terminal fragment of Bid (immuno-tBid) and reported its specific and effective destruction of HER2-positive tumor cells. In this study, in order to further reduce the immunogenicity of the previous immuno-proapoptotic protein, we constructed a novel immuno-tBid by replacing domain II of Pseudomonas exotoxin A with a short furin cleavage sequence from the diphtheria toxin. In order to explore the possible application of this novel immuno-tBid in the treatment of osteosarcoma, we first examined the expression of the HER2 protein in a subclone of a human osteosarcoma cell line with relatively high metastatic potential (SOSP-9607-E10), as well as in clinical specimens of osteosarcoma. Quantitative real-time PCR and Western blot analysis revealed that the expression of HER2 was up-regulated in the SOSP-9607-E10 cells, while immunohistochemical analysis revealed that HER2 was overexpressed in 37% of the tissue specimens examined. Both HER2-positive SOSP-9607-E10 and SKBR-3 cells, as well as HER2-negative HeLa cells were transiently transfected with the novel immuno-tBid in order to study its specific pro-apoptotic effect. We demonstrate here that this novel immuno-tBid induces the specific destruction of HER2-overexpressing SOSP-9607-E10 cells through the release of cytochrome C. These results suggest that the novel immuno-tBid with a minimized exogenous fragment could represent a competitive approach for the treatment of HER2-positive osteosarcoma.

Bone tumors of the extremities or pelvis treated by microwave-induced hyperthermia.

From July 1992 through March 1999, 213 patients with malignant bone tumors of the extremities (176 patients) and pelvis (37 patients) were treated by microwave-induced hyperthermia. Osteosarcoma and chondrosarcoma were the most common diagnoses. The limb-salvage procedure was done as follows: After separating the tumor-bearing bone and the extraosseous mass from surrounding normal tissues with a proper margin, microwave energy was delivered into the tumor while the healthy tissues were protected carefully from overheating. Restrengthening of the devitalized bone was necessary in many cases. The eschar resulting from the heat necrosis was curettaged. Most patients can walk early with a partial weightbearing brace for support. The survival rate was 73.9%. Fracture, local recurrence, and infection were the main complications although the majority of complications occurred early in the study. Thermotherapy is a novel and effective way to treat bone tumors in selected patients.