Histopathological Change of Oral Malignant Tumour and Epithelial Dysplasia Subjected to Photodynamic Therapy

Objectives: The purpose of this study is to analyze the morphological change of cell nuclei and the change of proliferating activity of oral malignancy and epithelial dysplasia between before and after photodynamic therapy in order to predict recurrence.Material and Methods: We experienced 14 cases of oral squamous cell carcinoma, one case of verrucous carcinoma and seven cases of epithelial dysplasia treated by photodynamic therapy (PDT). The mean nuclear area (NA) and coefficient of variation of the nuclear area (NACV) of 100 nuclei per slide were calculated using computer-assisted image analysis in hematoxylin and eosin stained biopsy specimens before and after PDT. Additionally, proliferating cell nuclear antigen (PCNA) immunohistochemistry was carried out in each specimen.Results: The mean NA after PDT was significantly lower than that before PDT in the nonrecurrent group. However, there was no significant difference in mean NA before and after PDT in the recurrent group. There were no significance differences in NACV before and after PDT in either the nonrecurrent or recurrent group. Furthermore, the PCNA labelling indices of the specimens after PDT was significantly lower than that before PDT in both the nonrecurrent and the recurrent group.Conclusions: Mean nuclear area in the biopsy specimen after photodynamic therapy is likely to be a predictive marker for the recurrence of oral squamous cell carcinoma or epithelial dysplasia subjected to photodynamic therapy, while coefficient of variation of the nuclear area and proliferating cell nuclear antigen labelling indices are less helpful in predicting the recurrence of such lesions

Bone Morphogenetic Proteins: Their History and Characteristics

Bone tissue engineering is expected to be utilized clinically as a patient friendly strategy instead of autogenous bone grafts, and bone morphogenetic protein (BMP) is applying for bone regeneration. BMPs have been found in the 1960s and their gene cloning has been succeeded two decades later, which revealed that BMPs were members of TGF-β superfamily. BMPs have critical functions in embryonic development and tissue generation, and BMPs induce bone formation in mammals though its primary functions are different. Subcutaneous implantation of BMP in rodent reproduces endochondral bone formation occurred in embryogenesis. Recombinant human BMPs are applied for spinal fusion and non-union fracture repair and also utilized in the field of oral and maxillofacial surgery such as sinus floor augmentation. BMP regenerates mandible bone after its segmental resection in non-human primates as a preclinical trial. However, the results were not conclusive in clinical studies especially in elderly patients. A high dose of BMP is required to restore large bone defects, but it may also induce life threatening significant edema. The further studies are necessary for effective and safe application of BMPs to restore large bone defects

Growth inhibition of HeLa cell by internalization of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) Tokyo

<p>Abstract</p> <p>Background</p> <p>Intravesical BCG immunotherapy is effective for preventing recurrence and progression in none muscle-invasive bladder cancer but the dosing schedule and duration of treatment remain empirical. The mechanisms by which intravesical BCG treatment mediates antitumor activity are currently poorly understood.</p> <p>Results</p> <p>HeLa cell infected with <it>Mycobacterium bovis </it>Bacillus Calmette-Guérin(BCG) Tokyo which were different multiplicity of infection(MOI). Proliferation of HeLa cell reduced in a dose-dependent manner by live BCG. The cytoplasm of the HeLa cell showed variety lysosomal stages by internalized and interacted BCG.</p> <p>Conclusion</p> <p>Proliferated Live BCG secreted the protein and depressed the growth of tumor. The possibility for clinical introduction of BCG therapy for carcinoma reported with review of literature.</p

Effective-mononuclear cell (E-MNC) therapy alleviates salivary gland damage by suppressing lymphocyte infiltration in Sjögren-like disease

Introduction: Sjögren syndrome (SS) is an autoimmune disease characterized by salivary gland (SG) destruction leading to loss of secretory function. A hallmark of the disease is the presence of focal lymphocyte infiltration in SGs, which is predominantly composed of T cells. Currently, there are no effective therapies for SS. Recently, we demonstrated that a newly developed therapy using effective-mononuclear cells (E-MNCs) improved the function of radiation-injured SGs due to anti-inflammatory and regenerative effects. In this study, we investigated whether E-MNCs could ameliorate disease development in non-obese diabetic (NOD) mice as a model for primary SS.Methods: E-MNCs were obtained from peripheral blood mononuclear cells (PBMNCs) cultured for 7 days in serum-free medium supplemented with five specific recombinant proteins (5G culture). The anti-inflammatory characteristics of E-MNCs were then analyzed using a co-culture system with CD3/CD28-stimulated PBMNCs. To evaluate the therapeutic efficacy of E-MNCs against SS onset, E-MNCs were transplanted into SGs of NOD mice. Subsequently, saliva secretion, histological, and gene expression analyses of harvested SG were performed to investigate if E-MNCs therapy delays disease development.Results: First, we characterized that both human and mouse E-MNCs exhibited induction of CD11b/CD206-positive cells (M2 macrophages) and that human E-MNCs could inhibit inflammatory gene expressions in CD3/CD28- stimulated PBMNCs. Further analyses revealed that Msr1-and galectin3-positive macrophages (immunomodulatory M2c phenotype) were specifically induced in E-MNCs of both NOD and MHC class I-matched mice. Transplanted E-MNCs induced M2 macrophages and reduced the expression of T cell-derived chemokine-related and inflammatory genes in SG tissue of NOD mice at SS-onset. Then, E-MNCs suppressed the infiltration of CD4-positive T cells and facilitated the maintenance of saliva secretion for up to 12 weeks after E-MNC administration.Discussion: Thus, the immunomodulatory actions of E-MNCs could be part of a therapeutic strategy targeting the early stage of primary SS

Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis

ラット前帯状回侵害受容性ニューロンのストレスによる応答変化

In the limbic system, the anterior cingulate cortex (ACCX) is one of the key areas involved in the close association between pain and emotion. However, neuronal changes in ACCX nociceptive responses after stress conditioning have not yet been quantitatively investigated. We investigated the modulation of nociceptive responses in the ACCX neurons following restraint stress in rats. The present study demonstrated that stress-conditioning enhanced excitatory nociceptive responses in the ACCX following tail stimuli in the mid-term (7 days). Short-term (3 days) and long-term (21 days) of stress conditioning did not affect these responses significantly. Nociceptive responses evoked by other sites of the body (nose, back and four paws) stimulation were not changed by stress-conditioning, indicating that neural information from the tail is important for emotional system modulation. It is suggested that the emotional/affective part of the pain sensation is strongly modified by stress through neuroplasticity in the ACCX.長崎大学学位論文 学位記番号:博(医歯薬)甲第640号 学位授与年月日:平成25年12月4日Author: Hiromi Yamashita, Jorge L. Zeredo, Kei Kaida, Mari Kimoto, Izumi Asahina, Kazuo TodaCitation: Journal of Integrative Neuroscience, 12(2), pp.235-246; 2013Nagasaki University (長崎大学)課程博

Epithelium-poor Odontogenic Fibroma with an Unusual Progress

Odontogenic fibroma (OF) is a relatively rare benign tumor derived from odontogenic ectodermal mesenchymal tissue. It is divided into central (COF) or peripheral OF (POF) based on the affected area. Regarding its pathological features, OF can also be classified as epithelium-rich (WHO type) or epithelium-poor (simple type), depending on the amount of odontogenic epithelium in the tumor. There is limited information available about the latter type because of its low incidence. We report case of simple type COF apparently like POF. A 52- year-old Japanese male was suffering from tenderness at the right posterior maxilla during occlusion with his removable partial denture. The lesion was diagnosed as a simple type OF arising at the edentulous region around the right molar site of the maxilla. A tumor resection was performed, and there was no evidence of recurrence at his 18-month follow-up examination. In addition, we provide a review of the literature with the most up-to-date information about this lesion so that it can be diagnosed correctly

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at −20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size

Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors.

Vascular invasion and lymph node metastasis have been used as histopathological prognosticators of cancers including oral squamous cell carcinoma (OSCC). In addition to metastatic potential via blood vessels, tumor-induced angiogenesis might also be associated with prognosis. However, the efficacy of combined evaluation of vascular invasion and angiogenesis-associated molecules for the prognosis of OSCC remains obscure. This is also the case in lymph node metastasis and lymphovasculogenesis-associated molecules. The aim of this study was to examine factors related to prognosis to improve the accuracy of prognostic prediction of OSCC using vasculogenesis-associated markers. Ninety specimens of patients from 1991 to 2002 with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed using antibodies for vascular endothelial growth factor (VEGF)-A, VEGF-C, cyclooxygenase (COX)-2 and Midkine. The ninety cases were composed of 72 well-differentiated, 12 moderately differentiated and 6 poorly differentiated OSCC. Efficient models of prognostic prediction were evaluated by extensive statistical analyses. The presence of vascular invasion or lymph node metastasis was confirmed to be significantly associated with poor prognosis in the univariate analysis. Multivariate logic regression analysis suggested that patients with the strongly positive expression of either VEGF-A or VEGF-C had a significant association with poor prognosis even in patients without vascular invasion and in early-stage patients. Neither COX-2 nor Midkine contributed to predict the prognosis of the patients. The strongly positive expression of VEGF-A or VEGF-C was suggested to reinforce the histopathological diagnosis of vascular invasion and improve the accuracy and efficacy of prognostic prediction of OSCC