Cryoimmunology for malignant bone and soft-tissue tumors

Several new methods have recently been developed for the treatment of malignant bone and soft-tissue tumors, and many of these targeted therapies have yielded promising initial results in clinical settings. As more sarcomas become amenable to effective molecular-targeting therapy, the need to evaluate the synergistic effects of combination therapies with anticancer drugs will grow. Other immunologic therapies have also been reported, such as exogenous cytokines, dendritic cell (DC) therapy and peptide vaccines. Cryoimmunology has shown promising results in some malignant tumors after cryosurgery and is expected to influence the next generation of tumor immunotherapy. In this report, we describe the induction of a systemic antitumor immune response following liquid nitrogen cryotreatment of a destructive murine osteosarcoma. Combining tumor cryotreatment with DCs to promote tumor-specific immune responses enhanced systemic immune responses and inhibited metastatic tumor growth. We also describe the induction of a systemic antitumor immune response following reconstruction for malignant bone tumors using frozen autografts treated with liquid nitrogen. © Japan Society of Clinical Oncology 2011

Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases

Background: Clear cell sarcoma is a rare malignant tumor of soft tissue which is most commonly encountered in the extremities, especially in the foot and ankle. This tumor is slow-growing and looks like a benign tumor; it is therefore often treated inadequately and its high rate of recurrence and metastases results in a poor prognosis. Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anti-cancer drugs. This study reports the effect of caffeine-potentiated chemotherapy for clear cell sarcoma in five patients. Methods: Caffeine-potentiated chemotherapy was administered to five patients with clear cell sarcoma. Three to five courses of intra-arterial chemotherapy using cisplatin, doxorubicin and caffeine were administered preoperatively, at 3-week intervals. Conservatively, wide margin surgery was performed following the preoperative chemotherapy. Intravenous cisplatin and doxorubicin with caffeine were administered three to six times to the patients who responded to the preoperative chemotherapy. This study evaluated the response to chemotherapy, recurrence, metastasis and the overall prognosis in these five patients. Results: Four of the eligible patients responded to preoperative chemotherapy. Local recurrence occurred in only one of the five patients. Distant metastasis newly developed in one patient. All five patients survive. Conclusion: Caffeine-potentiated chemotherapy can be effective treatment for clear cell sarcoma not only as initial therapy, but also as salvage therapy. © 2011 Japan Society of Clinical Oncology

Correction of a Severe Poliomyelitic Equinocavovarus Foot Using an Adjustable External Fixation Frame

One-stage surgical correction of severe equinocavovarus deformity can result in complications ranging from skin necrosis to tibial nerve palsy. Fewer complications have been reported when severe deformities were treated by gradual correction using external frames such as the Ilizarov external fixator or the Taylor Spatial FrameTM. We describe a case of a 64-year-old female patient with severe poliomyelitic equinocavovarus whose deformity required her to ambulate using the dorsum of her right foot as a weightbearing surface. We treated the deformity with gradual correction using a Taylor Spatial FrameTM, followed by ankle arthrodesis. At the most recent postoperative evaluation, 20 months after the initial surgery, the patient was pain free and ambulating on the sole of her right foot. © 2014 American College of Foot and Ankle Surgeons

High-grade undifferentiated pleomorphic sarcoma of pelvis treated with curettage and bone graft after complete remission following caffeine-potentiated chemotherapy

金沢大学医薬保健研究域医学

Innovative antimicrobial coating of titanium implants with iodine

Background: Postoperative infection associated with implants remains a serious complication in orthopedic surgery. Several biomaterial surface treatments have been proposed as a means of reducing the incidence of implantassociated infections. In this study, a clinical trial was performed using an iodine-supported titanium that suppresses the microbial activities. Methods: A total of 222 patients with postoperative infection or compromised status were treated using iodinesupported titanium implants. The mean age of the patients was 49.4 years (range 5-85 years). One hundred twentyseven patients were male and 95 were female. In 158 patients, iodine-supported implants were used to prevent infection, such as compromised hosts and conditions, and in 64 patients to treat active infection. White blood cell (WBCs) and C-reactive protein (CRP) levels were measured pre- and postoperatively in all patients. To confirm whether iodine from the implant affected physiological functions, thyroid hormone levels in the blood were examined. Both examinations were conducted sequentially for a year. Radiological evaluations were performed regularly after the operation. The chronological changes of the iodine amount were evaluated using half pins removed after completion of external fixation. Results: The mean follow-up period was 18.4 months (range 3-44 months). Acute infection developed in three tumor cases among the 158 patients on preventive therapy. All three recovered without removal of the implants. Infection was cured in all 64 patients with infection. Median WBC levels were in the normal range, and median CRP levels returned to <0.5 within 4 weeks after surgery. Abnormalities of thyroid gland function were not detected. None of the patients experienced loosening of the implants. There were two patients with mechanical implant failure, which was treated by re-implantation. Excellent bone ingrowth and ongrowth were found around all hip and tumor prostheses. One year later, the amount of iodine on external fixation pins remained about 20-30 %. Conclusions: Iodine-supported titanium implants can be very effective for preventing and treating infections after orthopedic surgery. Cytotoxicity and adverse effects were not detected

Current status of immunotherapy for sarcomas

金沢大学医薬保健研究域医学系Although the development of anticancer drugs has improved the outcomes of bone and soft tissue sarcomas, the clinical outcome of patients with relapsed sarcomas remains unsatisfactory due to therapeutic toxicities and resistance to anticancer drugs. Therefore, novel therapeutic modalities are needed to improve the outcome of patients with bone and soft tissue sarcomas. Dendritic cells present tumor antigens and stimulate immune responses, and immune cells, such as cytotoxic T lymphocytes, kill tumor cells by recognizing tumor antigens. However, immune-suppressive conditions by immune regulator PD-1, CTLA-4 and regulatory T cells help tumor growth and progression. In this report, current immunotherapies including cellular immunotherapy and checkpoint inhibitors are introduced, and the advantages and disadvantages of the treatments are discussed. © 2017 2017 Future Medicine Ltd.Embargo Period 12 month

Over 10-year follow-up of functional outcome in patients with bone tumors reconstructed using distraction osteogenesis

Background: The aim of this study was to investigate the long-term functional capabilities of patients who underwent bone distraction for the treatment of bone defects caused by bone tumor excision. Methods: Bone distraction was indicated for patients with stage IIB malignant bone tumors when chemotherapy was judged to be effective and an epiphysis could be preserved or for patients with low-grade or aggressive benign bone tumors. Twenty-two patients who underwent reconstruction with bone distraction and were followed up for at least 10 years were retrospectively investigated. Patients included 8 males and 14 females, with a mean age of 25.3 years. Tumor types included seven osteosarcomas, two osteofibrous dysplasias, one Ewing\u27s sarcoma, five low-grade osteosarcomas, two adamantinomas, and five giant cell tumors. Chemotherapy was performed during bone distraction in 8 cases. Bone transport was used in 17 cases, while shortening distraction was used in 5 cases. Results: The mean distraction length was 8.1 cm, and the mean external fixation period was 301 days. The average Musculoskeletal Tumor Society score (used to measure functional outcome) was 91.5 % at mean follow-up of 202 months. Fourteen patients were able to play sports without any difficulty. Conclusions: Epiphyseal preservation and reconstruction by bone distraction require both time and effort, but can provide excellent long-term outcomes, resulting in a stable reconstruction that functionally restores the natural limb. © 2012 The Japanese Orthopaedic Association

Caffeine activates tumor suppressor PTEN in sarcoma cells

金沢大学医薬保健研究域医学系The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Akt activation exerts a strong anti-apoptotic effect and inhibits key pro-apoptotic proteins. We investigated the effect of caffeine in the prevention of tumor cell proliferation and induction of cell death. We found that caffeine induced increased intracellular cAMP levels, PTEN activation and Akt inactivation, which together prevented proliferation of human osteosarcoma cells (MG63) and fibrosarcoma cells (HT1080). PTEN knockdown by siRNA reduced the effects of caffeine on Akt inactivation in osteosarcoma cells. These results indicate that the tumor suppressor PTEN signaling pathway contributes to the growth-inhibitory effect of caffeine on sarcoma cells. Our data suggest that caffeine and other drugs that act on this pathway could have promising therapeutic effects in the treatment of sarcoma patients

Инновационный потенциал и инновационная активность вузов УрФО

<p>Characteristics of the study patients.</p