Biological Reconstruction Using Liquid Nitrogen-Treated Tumor Bearing Bone

In general, a tumor prosthesis is used for reconstruction after removal of osteosarcoma. However, the durability of artificial materials becomes a problem in the long term, and many patients inevitably undergo revision due to loose or damaged prostheses. Moreover, preservation of articular surface is the key to maintain better limb function for long duration. Reconstruction of affected limbs using biological materials has been sought to overcome the aforementioned problems. In some countries, it is significantly difficult to obtain allograft as a biological reconstruction material because of socio-religious or cost problem. Thus, a biological reconstruction method has been developed in which the patient’s affected bone is treated and used for reconstruction. Especially in recycling treatment for affected autologous bone, liquid nitrogen treatment has several favorable characteristics. There is optimal morphological fit because the treated bone itself is one’s own, and bone strength is maintained after treatment. Satisfactory bone union and bone regeneration are expected to be achieved due to good osteoconduction and osteoinduction because proteins and enzymes are preserved in the bone

Clinical and Biological Implications of Cancer Stem Cells in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis, and is one of the leading causes of cancer-related deaths worldwide. Recently, the development of therapeutic drugs via novel mechanisms of action, involving molecular-targeted drugs and immune checkpoint inhibitors, has progressed in the field of HCC. However, the recurrence rate remains high, and further improvement of the prognosis of patients with HCC is urgently needed. Cancer stem cells (CSCs) are a promising target for further development of novel anti-cancer drugs because they are reportedly involved in tumor initiation, maintenance, recurrence, and resistance to conventional therapies. Although several studies have already been conducted, the functions and roles of CSCs in the development and progression of tumors remain to be elucidated. In this review article, we will clarify the fundamental knowledge of CSCs necessary for the understanding of CSCs and will outline so-far identified markers specific to liver CSCs and the pathological and therapeutic implications of CSCs in HCC

Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion

Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (HCC). All-trans-retinoic acid (ATRA) was used in the in vitro experiments. Cell invasiveness was measured using trans-well invasion assay. ATRA significantly increased TFPI2 expression through RARα in a human HCC cell line known as HuH7. TFPI2 was vital in the ATRA-mediated suppression of HuH7 cell invasion. The musculo-aponeurotic fibrosarcoma oncogene homolog B (MAFB) significantly enhanced the activation of the TFPI2 promoter via RARα while MAFF inhibited it. The knockdown of RARα or MAFB counteracted the ATRA-mediated suppression of HuH7 cell invasion while the knockdown of MAFF inhibited the invasion. TFPI2 expression in HCC tissues was significantly downregulated possibly due to the decreased expression of RARβ and MAFB. Patients with HCC expressing low MAFB and high MAFF levels showed the shortest disease-free survival time. These results suggest that MAFB and MAFF play critical roles in the antitumor effects of retinoids by regulating the expression of retinoid target genes such as TFPI2 and can be promising for developing therapies to combat HCC invasion

Basic science and clinical frontiers of sarcoma treatment

金沢大学医薬保健研究域医学

Applications of external fixation in long bone tumor

There has been a dramatic improvement in the survival rate of patients with sarcomas and in the successful salvage of limbs as a result of progress in chemotherapy, radiological evaluation, surgical technique, and the technology of materials and implants. Complications, however, such as deep infection, fracture, bone resorption, and breakages of prostheses still occur. The challenge to provide long-lasting survival and function of the limb after reconstruction is now being met with biological solutions using living bone. The ideal reconstruction should have biological affinity, resistance to infection, sufficient biomechanical strength, and durability. Vascularized bone transfer has limitations in terms of length and strength. Since 1990, distraction osteogenesis, which can regenerate bone of sufficient strength for reconstruction, has been adopted for tumor surgery. © Springer-Verlag Italia 2008, 2012.[Book Chapter

The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing ανβ3 integrin in chick embryo and nude mouse models.

Echistatin, a cyclic RGD peptide, which is an antagonist of αvβ3 integrin (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic model. A high-metastatic variant of human osteosarcoma, 143B-LM4, overexpressing αvβ3 integrin was used. Tumor angiogenesis by high-metastatic variant 143B-LM4 cells in the CAM was significantly inhibited by echistatin (P<0.05) as was overall growth. A doxorubicin (DOX)-echistatin combination inhibited orthotopic tumor growth compared to untreated control (P<0.01) or DOX alone (P<0.05) in nude mice. Tumor-bearing mice treated with the DOX-echistatin combination survived longer than those treated with DOX alone or control PBS (P<0.01 and P<0.01, respectively). Echistatin also inhibited experimental lung metastasis of 143B-LM4 cells in nude mice. These results suggest that DOX in combination with a disintegrin has potential to treat osteosarcoma and that αvβ3 integrin may be a target for osteosarcoma

Disintegrin targeting of an αvβ3 integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro.

The in vitro efficacy of the disintegrin echistatin was tested on a high-metastatic variant of 143B human osteosarcoma, 143B-LM4, which over-expresses αvβ3 integrin. Echistatin is an RGD cyclic peptide and an antagonist of αvβ3 integrin. In the present study, echistatin inhibited cell proliferation, migration, invasion, and adhesion of 143B-LM4 cells. 143B-LM4 cell proliferation decreased after treatment with echistatin in a time-dependent and dose-dependent manner (P <0.01). In vitro migration and invasion of 143B-LM4 cells were also inhibited by echistatin in a dose-dependent manner (P <0.01, respectively). Cell adhesion to vitronectin of 143B-LM4 cells was also inhibited by echistatin in a dose-dependent manner (P <0.01). These results suggest that αvβ3 integrin may be an effective target for osteosarcoma

Applications of external fixation in long bone tumor

There has been a dramatic improvement in the survival rate of patients with sarcomas and in the successful salvage of limbs as a result of progress in chemotherapy, radiological evaluation, surgical technique, and the technology of materials and implants. Complications, however, such as deep infection, fracture, bone resorption, and breakages of prostheses still occur. The challenge to provide long-lasting survival and function of the limb after reconstruction is now being met with biological solutions using living bone. The ideal reconstruction should have biological affinity, resistance to infection, sufficient biomechanical strength, and durability. Vascularized bone transfer has limitations in terms of length and strength. Since 1990, distraction osteogenesis, which can regenerate bone of sufficient strength for reconstruction, has been adopted for tumor surgery. © Springer-Verlag Italia 2008, 2012.[Book Chapter