Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment.Breast cancer is one of the most common and feared cancers faced by women worldwide. According to the latest statistics on cancer, breast cancer has already been the second leading cause of death for women in the United States. 1 However, the treatment of patients who are diagnosed at an advanced stage and curative surgical treatments are sometimes difficult due to the presence of recurrence and metastases. Furthermore, the long-term prognosis of curatively resected advanced breast cancer remains unsatisfactory because of its high recurrence rate after surgery. Currently, the available chemotherapeutic reagents have only limited efficacy against these recurrent diseases. In particular, the prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. 1-7 Multimodal therapy with more specific and effective strategy is urgently needed.So far, the increasing evidence from preclinical and clinical data suggests that the oncolytic viral therapy could be an effective therapeutic modality in the treatment of advanced cancer. Various strains of viruses, such as adenovirus, herpes simplex virus, Newcastle disease virus, measles virus, vesicular stomatitis virus and vaccinia virus are being evaluated for their oncolytic capability and many of them have already progressed to the clinical trial phase. Among them, the oncolytic herpes simplex virus (HSV) is an ideal candidate because of its broad host range, tumor selective viral distribution and the characteristic of being controlled by antiviral drugs. 6-9 HF10 is a highly attenuated, replication-competent mutant strain of HSV-1 and displays strong tumor killing activity in vivo and in vitro. [10][11][12] We previously performed a phase I dose-escalation clinical trial using HF10 for the patients with recurrent breast cancer or unresectable pancreatic cancer and demonstrated its safety and efficacy. 13,14 However, studies with the oncol...

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Eicosapentanoic acid (EPA) is an antioxidant and omega‐3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel can be used as a carrier of a physiologically active substance that release it gradually for an average of ~3 weeks. Therefore, this study aimed to clarify the effect of EPA‐incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo. Ten‐week‐old male C57BL/6J mice were randomly divided into six groups (n = 6): Sham, destabilization of the medial meniscus (DMM), Corn: DMM + 2 µL corn oil, EPA injection alone (EPA‐I): DMM + 2 µL corn oil + 125 μg/μL EPA, Gel: DMM + gelatin hydrogels, and EPA‐G: DMM + 125 μg/μL EPA‐incorporating gelatin hydrogels. The mice were euthanized at 8 weeks after DMM or Sham surgery, and subjected to histological evaluation. Matrix‐metalloproteinases‐3 (MMP‐3), MMP‐13, interleukin‐1β (IL‐1β), p‐IKK α/β, CD86, and CD163 protein expression in the synovial cartilage was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of macrophage. Histological score was significantly lower in EPA‐G than in EPA‐I. MMP‐3‐, MMP‐13‐, IL‐1β‐, and p‐IKK α/β‐positive cell ratio was significantly lower in EPA‐G than in EPA‐I. However, CD86‐ and CD163‐positive cell ratio was not significantly different between EPA‐I and EPA‐G. The average‐sum F4/80 score of macrophage in EPA‐G was significantly lower than that in EPA‐I. EPA‐incorporating gelatin hydrogels were shown to prevent OA progression in vivo more effectively than EPA injection alone. Our results suggested that intra‐articular administration of controlled‐release EPA can be a new therapeutic approach for treating OA.

Duchenne muscular dystrophy (DMD) is an intractable genetic muscular disorder characterized by the loss of DYSTROPHIN. The restoration of DYSTROPHIN is expected to be a curative therapy for DMD. Because muscle stem cells (MuSCs) can regenerate damaged myofibers with full-length DYSTROPHIN in vivo, their transplantation is being explored as such a therapy. As for the transplanted cells, primary satellite cells have been considered, but donor shortage limits their clinical application. We previously developed a protocol that differentiates induced pluripotent stem cells (iPSCs) to MuSCs (iMuSCs). To ameliorate the respiratory function of DMD patients, cell transplantation to the diaphragm is necessary but difficult, because the diaphragm is thin and rapidly moves. In the present study, we explored the transplantation of iMuSCs into the diaphragm. First, we show direct cell injection into the diaphragm of mouse was feasible. Then, to enhance the engraftment of the transplanted cells in a rapidly moving diaphragm, we mixed polymer solutions of hyaluronic acid, alginate and gelatin to the cell suspension, finding a solution of 20% dissolved hyaluronic acid and 80% dissolved gelatin improved the engraftment. Thus, we established a method for cell transplantation into mouse diaphragm and show that an injectable hyaluronic acid-gelatin solution enables the engraftment of iMuSCs in the diaphragm.

Introduction The objective of this study is to investigate the effect of gelatin microspheres incorporating growth factors on the therapeutic efficacy in cell transplantation. The strength of this study is to combine gelatin hydrogel microspheres incorporating basic fibroblast growth factor and platelet growth factor mixture (GM/GF) with bioabsorbable injectable hydrogels (iGel) for transplantation of adipose-derived stem cells (ASCs). Methods The rats ASCs suspended in various solutions were transplanted in masseter muscle. Rats were euthanized 2, 7, 14 days after injection for measurement of the number of ASCs retention in the muscle and morphological evaluation of muscle fibers and the inflammation of the injected tissue by histologic and immunofluorescent stain. Results Following the injection into the skeletal muscle, the GM/GF allowed the growth factors to release at the injection site over one week. When ASCs were transplanted into skeletal muscle using iGel incorporating GM/GF (iGel+GM/GF), the number of cells grafted was significantly high compared with other control groups. Moreover, for the groups to which GM/GF was added, the cells transplanted survived, and the Myo-D expression of a myoblast marker was observed at the region of cells transplanted. Conclusions The growth factors released for a long time likely enhance the proliferative and differentiative capacity of cells. The simple combination with iGel and GM/GF allowed ASCs to enhance their survival at the injected site and consequently achieve improved therapeutic efficacy in cell transplantation.