Recently, we developed a new tensor for total knee arthroplasty (TKA) procedures enabling soft tissue balance assessment throughout the range of motion while reproducing post-operative joint alignment with the patello-femoral (PF) joint reduced and the tibiofemoral joint aligned. Using the tensor with a computer-assisted navigation system, we investigated the relationship between various intra-operative joint gap values and their post-operative flexion angles. An increased value during the extension to flexion gap and a decreased value during the flexion to deep flexion gap with PF joint reduced, not everted, showed an inverse correlation with post-operative knee flexion angle, not pre-operative flexion angle. In conclusion, understanding the characteristics of joint gap kinematics in posterior-stabilized TKA under physiological and reproducible joint conditions may enable the prediction of the post-operative flexion angle and help to determine the appropriate intra-operative joint gap.

This study is the largest LMSoB case series ever reported. Surgical treatment with wide margins was the only treatment that proved to be effective, whereas adjuvant chemotherapy in the present setting did not improve the overall survival. J. Surg. Oncol. 2016;114:495-500. © 2016 Wiley Periodicals, Inc.

Mitochondria play an essential role in cellular energy metabolism and apoptosis. Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression. In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation. Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH) cells in vitro. We also demonstrated that transcutaneous application of carbon dioxide (CO2) to rat skeletal muscle induces PGC-1α expression and causes an increase in mitochondrial proliferation. In this study, we utilized a murine model of human MFH to determine the effect of transcutaneous CO2 exposure on PGC-1α expression, mitochondrial proliferation and cellular apoptosis. PGC-1α expression was evaluated by quantitative real-time PCR, while mitochondrial proliferation was assessed by immunofluorescence staining and the relative copy number of mitochondrial DNA (mtDNA) was assessed by real-time PCR. Immunofluorescence staining and DNA fragmentation assays were used to examine mitochondrial apoptosis. We also evaluated the expression of mitochondrial apoptosis related proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We show that transcutaneous application of CO2 induces PGC-1α expression, and increases mitochondrial proliferation and apoptosis of tumor cells, significantly reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade, including caspase 3 and caspase 9, were elevated in CO2 treated tumors compared to control. We also observed an enrichment of cytochrome c in the cytoplasmic fraction and Bax protein in the mitochondrial fraction of CO2 treated tumors, highlighting the involvement of mitochondria in apoptosis. These data indicate that transcutaneous application of CO2 may represent a novel therapeutic tool in the treatment of human MFH.

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Background: Tumor hypoxia is a common feature of various human malignancies. Hypoxia contributes to tumor progression, and is a major cause of tumor resistance to chemotherapy. Hypoxia-inducible factor (HIF)-1 is a key transcription factor in hypoxic responses, and regulates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, and invasion. We previously demonstrated that transcutaneous application of carbon dioxide (CO 2 ) induced oxygenation in the treated tissue in vivo, therefore, we hypothesized that transcutaneous CO 2 exposure could enhance the chemosensitivity by reducing hypoxia in a tumor tissue. The aim of this study was to examine the effect of oxygenation by transcutaneous application of CO 2 on the therapeutic efficacy of doxorubicin (DOX) to treat human malignant fibrous histiocytoma (MFH) in vivo. Methods:In this study, we utilized a murine model of human MFH, and mice were randomly divided into four groups: control, CO 2 , DOX and combination (CO 2 + DOX) treatment groups to examine the effect of transcutaneous application of CO 2 on the hypoxic condition, and to assess the therapeutic effect of combination therapy using transcutaneous CO 2 and DOX treatment in vivo.Results: Transcutaneous application of CO 2 treatment decreased HIF-1α expression in human MFH tumor tissues, suggesting that our transcutaneous CO 2 treatment reduced the hypoxic conditions. Furthermore, transcutaneous CO 2 treatment alone had an antitumoral effect, and increased the chemotherapeutic effect of DOX on MFH tumor growth in vivo, with no observable effects on body weight. Conclusions:Our findings in this study strongly indicate that our transcutaneous CO 2 system has antitumor effects and can enhance the chemosensitivity of tumor cells by reducing the local hypoxic conditions.