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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.
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CONTEXT: Hyperthermia has now been used to treat many kinds of solid malignancies. However, the applied thermal parameters about heat temperature and time varied all over the world, and no consensus about the optimal formula had been reached. Microwave ablation, as one of thermal ablation methods, is usually applied based on the fixed parameters of power and duration. As a result, too high temperature or overheating might not be avoided and excessive heating might cause some additional side effects to normal tissues. AIMS: To explore the optimal parameters of power and duration for the HELA and MG-63 cells in vitro. SETTINGS AND DESIGN: With a temperature-controlled microwave workstation, a microwave thermal ablation experiment was performed in vitro. SUBJECTS AND METHODS: The HELA and MG-63 cells were heated with 40°C, 45°C, 50°C, 55°C, and 60°C lasting for 5-30 min, respectively. Then, the cell viability was detected using four methods: Flow cytometer assay, nicotinamide adenine dinucleotide-diaphorase staining, Calcein-acetoxymethyl ester staining immediately after treatment, and CCK-8 assay 24 h later. RESULTS: The temperature-controlled microwave has an excellent ablation effect on both cell lines. Furthermore, when the thermal stimulation reached 55°C 25 min and 55°C 20 min for the HELA and MG-63 cells, respectively, or 60°C 5 min for both, all the viability indexes indicated immediately devitalization. CONCLUSION: It presented a preliminary minimum lethal dose of heat was validated on the cellular level in vitro, which should be verified and corrected further in vivo.
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Microondas , Temperatura , Biomarcadores , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Dihidrolipoamida Deshidrogenasa/metabolismo , Citometría de Flujo , Fluoresceínas , Células HeLa , Humanos , Hipertermia Inducida/métodosRESUMEN
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.
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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.
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Proteína Proapoptótica que Interacciona Mediante Dominios BH3/farmacología , Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Osteosarcoma/patología , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/química , Sitios de Unión , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Furina/metabolismo , Células HeLa , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacología , Osteosarcoma/genética , Osteosarcoma/metabolismo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/farmacología , Estructura Terciaria de Proteína/fisiología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/farmacología , Transfección , Células Tumorales CultivadasRESUMEN
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.