OBJECTIVE: Malignant gliomas are the most common primary tumors of the central nervous system and the prognosis of patients with gliomas is poor. The combination of interferon-bata (IFN-beta) and temozolomide (TMZ) has shown significant additive antitumor effects in human glioma xenograft models. Considering that the poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor, the tropism of human bone marrow-derived mesenchymal stem cells (MSC) for malignant gliomas can be exploited to therapeutic advantages. We investigated the combination effects of TMZ and MSCs that secrete IFN-beta on gliomas. METHODS: We engineered human MSCs to secret mouse IFN-beta (MSC-IFN-beta) via adenoviral transduction and confirmed their secretory capacity using enzyme-linked immunosorbent assays. In vitro and in vivo experiments were performed to determine the effects of the combined TMZ and MSC-IFN-beta treatment. RESULTS: In vitro, the combination of MSC-IFN-beta and TMZ showed significantly enhanced antitumor effects in GL26 mouse glioma cells. In vivo, the combined MSC-IFN-beta and TMZ therapy significantly reduced the tumor size and improved the survival rates compared to each treatment alone. CONCLUSION: These results suggest that MSCs can be used as an effective delivery vehicle so that the combination of MSC-IFN-beta and TMZ could be considered as a new option for the treatment of malignant gliomas.
Animals ; Bone Marrow* ; Central Nervous System ; Enzyme-Linked Immunosorbent Assay ; Glioma* ; Heterografts ; Humans ; Interferon-beta* ; Mesenchymal Stromal Cells* ; Mice ; Prognosis ; Survival Rate ; Tropism

OBJECTIVES: A keratocystic odontogenic tumor (KOT) is a type of odontogenic tumor that mainly occurs in the posterior mandible. Most KOTs appear as solitary lesions; however, they sometimes occur as multiple cysts. This study analyzed the clinical features of multiple KOTs. MATERIALS AND METHODS: The participants were diagnosed with KOT by biopsy with multiple surgical sites, and were patients at the Pusan National University Hospital and the Pusan National University Dental Hospital from January 1, 2005 to March 31, 2016. Charts, records, images and other findings were reviewed. RESULTS: A total of 31 operations were conducted in 17 patients. The mean patient age was 28.4±20.1 years. Multiple KOTs were found to occur at a young age (P<0.01). The predominant sites were in the posterior mandible (28.6%). Most cases of multiple lesions appeared in both the upper and lower jaw, and 40.3% of lesions were associated with unerupted and impacted teeth. The overall recurrence rate measured by operation site was 10.4% (8/77 sites). No patients were associated with nevoid basal cell carcinoma syndrome. CONCLUSION: The pure recurrence rate was lower than estimated, but there was a higher possibility of secondary lesions regardless of the previous operation site; therefore, long-term follow-up is necessary.
Basal Cell Nevus Syndrome ; Biopsy ; Busan ; Clinical Study* ; Follow-Up Studies ; Humans ; Jaw ; Mandible ; Odontogenic Cysts* ; Odontogenic Tumors* ; Recurrence ; Retrospective Studies* ; Tooth, Impacted

Neuromedin B (NMB) acts as a growth factor or a morphogen and plays a role in cancer progression. Indeed, the NMB receptor (NMB-R) is overexpressed in different types of tumors. In our current study, we investigated the involvement of NMB-R in the proliferation of oral cancer cells. Human oral squamous cell carcinoma (SCC) and human oral cancer cells, SCC-25 cells were found to be NMB-R-positive. The NMB-R antagonist PD168368 inhibited the proliferation of SCC-25 cells and reduced their colony formation capacity. We also found that PD168368 induced the cell cycle arrest and apoptosis of SCC-25 cells in a dose-/time-dependent manner. Overall, this antitumor activity of PD168368 in human oral cancer cells suggests that NMB-R is a potential target for the future prevention and treatment of human cancers.
Apoptosis ; Carcinoma, Squamous Cell ; Cell Cycle Checkpoints ; Humans ; Mouth Neoplasms* ; Receptors, Bombesin*

BACKGROUND: Teeth requiring extraction before radiotherapy in head & neck cancer patients should be removed as long as possible before the initiation of radiation therapy. Conventionally, a minimum 2-week waiting primary healing period is recommended. Although the above 2-week period is ideal, it was not uncommon for the radiotherapist and cancer patient to feel an urgent need to process with radiotherapy despite the need for dental care. Therefore, alternative approaches for early radiotherapy, including conservative endodontic treatment and a 1-week waiting primary healing period after dental extraction at the time of radiotherapy, were considered and applied based on the experimental study. MATERIALS AND METHODS: Eighteen dogs were processed for histopathologic wound healing. The effect of the primary endodontic treatment and extraction before early radiotherapy was examined. RESULTS: No specific complication, such as, post-extraction wound infection, radiation osteitis and osteoradionecrosis, were encountered despite the early radiotherapy. CONCLUSION: Based on the experimental study, a minimum 1-week waiting primary healing period for oral care before radiotherapy is suitable for the early radiotherapy in head and neck cancer patients.
Animals ; Dental Care ; Dogs ; Head ; Head and Neck Neoplasms ; Humans ; Osteitis ; Osteoradionecrosis ; Tooth ; Tooth Extraction ; Wound Healing ; Wound Infection

PURPOSE: The study for bronchiectasis in children is rare in Korea. The aim of this study was investigate the clinical characteristic and associated etiology in pediatric patients with bronchiectasis. METHODS: We studied 29 pediatirc patients with bronchiectasis from January 2008 to December 2012 at Pusan National University Hospital. The age, sex, clinical symptoms, signs, radiologic findings, associated etiologic factors, and clinical course were investigated retrospectively. RESULTS: The median age at the time of diagnosis of bronchiectasis was 8.7 years. Chronic coughing was the most common symptom. The associated etiologies were immunodeficiency (31.0%), respiratory infection (27.6%), bronchiolitis obliterans (13.8%), interstitial lung disease (10.3%). The median age at the time of diagnosis of bronchiectasis in immunodeficient patients was 8.3 years. Post infectious bronchiectasis and severe respiratory symptom tend to occur in younger children. CONCLUSION: The risk factors of bronchiectasis in children are immunodeficiency and respiratory infection. Physicians should evaluate bronchiectasis in children with chronic cough.
Bronchiectasis* ; Bronchiolitis Obliterans ; Busan ; Child* ; Cough ; Diagnosis ; Humans ; Korea ; Lung Diseases, Interstitial ; Retrospective Studies ; Risk Factors

There are five principal causes for excessive bleeding in the immediate postextraction phase ; (1) Vascular wall alteration (wound infection, scurvy, chemicals, allergy) (2) Disorders of platelet function (genetic defect, drug-aspirin, autoimmune disease) (3) Thrombocytopenic purpuras (radiation, leukemia), (4) Inherited disorders of coagulation (hemophilia, Christmas disease, vitamin deficiency, anticoagulation drug-heparin, coumarin). If the hemorrhage from postextraction wound is unusually aggressive, and then dehydration and airway problem are occurred, the socket must be packed with gelatine sponge(Gelfoam) that was moistened with thrombin and wound closure & pressure dressing are applied. The thrombin clots fibrinogen to produce rapid hemostasis. Gelatine sponges moistened with thrombin provide effective coagulation of hemorrhage from small veins and capillaries. But, in dental alveoli, gelatine sponges may absorb oral microorganisms and cause alveolar osteitis (infection). This is a case report of bleeding control by continuous rubber strip & iodoform gauze drainage (without gelfoam packing) of active bleeding infection sites of three teeth extraction wounds in a 46-years-old female patient with advanced liver cirrhosis.
Avitaminosis ; Bandages ; Blood Platelets ; Capillaries ; Dehydration ; Drainage ; Dry Socket ; Female ; Fibrinogen ; Gelatin ; Gelatin Sponge, Absorbable ; Hemophilia B ; Hemorrhage ; Hemostasis ; Humans ; Hydrocarbons, Iodinated ; Liver ; Liver Cirrhosis ; Porifera ; Purpura, Thrombocytopenic ; Rubber ; Scurvy ; Thrombin ; Tooth ; Veins

The juxtaoral organ of Chievitz is an intramuscular embryonic structure of neuroepithelial origin, and is found near the insertion of the pterygomandibular raphae. The juxtaoral organ of Chievitz has no known function, however, its clinical implication and differential diagnosis should be considered. Here, we report a fibrous cord like mass in a 34-year-old woman that was incidentally found while her lower right third molar was extracted. Histologically, it showed epithelial cell nests with glandular or squamous differentiation, simulating odontogenic tumors or perineural invasion of carcinoma. However, they were positive for the S-100 protein, neuron specific enolase, the neural cell adhesion molecule, and nerve growth factor receptors by immunohistochemistry, supporting the theory that these cells are of neural origin. Awareness of the juxtaoral organ of Chievitz should be emphasized for the epithelial islands in this organ not to be misinterpreted as an invasive carcinoma, an odontogenic tumor, or perineural invasion by carcinoma.
Adult ; Diagnosis, Differential ; Embryonic Structures ; Epithelial Cells ; Female ; Humans ; Immunohistochemistry ; Islands ; Molar, Third ; Neural Cell Adhesion Molecules ; Odontogenic Tumors ; Phosphopyruvate Hydratase ; Receptors, Nerve Growth Factor ; S100 Proteins

BACKGROUND: Squamous cell carcinoma (SCC) is the most commonly occurring malignant tumor in the oral cavity. In South Korea, it occurs most frequently in the mandible, tongue, maxilla, buccal mucosa, other areas of the oral cavity, and lips. Radial forearm free flap (RFFF) is the most widely used reconstruction method for the buccal mucosal defect. The scar of the forearm donor, however, is highly visible and unsightly, and a secondary surgical site is needed when such technique is applied. For these reasons, buccal fat pad (BFP) flap has been commonly used for closing post-surgical excision sites since the recent decades because of its reliability, ease of harvest, and low complication rate. CASE PRESENTATION: In the case reported herein, BFP flap was used to reconstruct a cheek mucosal defect after excision. The defect was completely covered by the BFP flap, without any complications. CONCLUSION: Discussed herein is the usefulness of BFP flap for the repair of the cheek mucosal defect. Also, further studies are needed to determine the possibility of using BFP flap when the defect is deep, and the maximum volume that can be harvested considering the changes in volume with age.
Adipose Tissue ; Carcinoma, Squamous Cell ; Cheek ; Cicatrix ; Epithelial Cells ; Forearm ; Free Tissue Flaps ; Humans ; Korea ; Lip ; Mandible ; Maxilla ; Methods ; Mouth ; Mouth Mucosa ; Tissue Donors ; Tongue

PURPOSE: Adenoid cystic carcinoma (ACC) is a high-grade malignant tumor of the salivary glands, clinically characterized by multiple recurrences and late distant metastasis. Biological markers for assessing the prognosis of ACC have remained elusive. The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC. MATERIALS AND METHODS: In this study, 48 surgical samples were used to assess the expressions of ATM and its downstream target p53. Fisher's exact test and Kaplan-Meier analysis were conducted to evaluate the role of ATM, p53, and phospho-p53 (S15) protein expressions in predicting patient survival and distant metastasis. RESULTS: Myb expression was positive in 85.4% of ACCs, but did not reflect patient survival rate. In contrast, low expression of ATM in cancer cells was significantly correlated with poor survival rate (p=0.037). Moreover, under positive p53 expression, low expression of ATM was highly predictive of poor survival in ACC (p=0.017). CONCLUSION: These data indicate that combined assessment of ATM and p53 expression can serve as a useful prognostic marker for assessing survival rate in patients with ACC of the salivary glands.
Adenoids* ; Ataxia Telangiectasia ; Biomarkers ; Carcinoma, Adenoid Cystic* ; Humans ; Kaplan-Meier Estimate ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Salivary Glands* ; Survival Rate

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although advances have been made in the treatment of MS, such as the use of IFN-β, glucocorticoids and stem cells, the therapeutic effects of these treatments are not sufficient. In the present study, we evaluated whether the combination of methylprednisolone (MP) and human bone marrow-derived mesenchymal stem cells (BM-MSCs) could enhance the therapeutic effectiveness in experimental autoimmune encephalomyelitis (EAE), a model for MS. EAE was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55). The immunized mice received an intraperitoneal injection of MP (20 mg/kg), an intravenous injection of BM-MSCs (1 × 10⁶ cells) or both on day 14 after immunization. Combination treatment significantly ameliorated the clinical symptoms, along with attenuating inflammatory infiltration and demyelination, compared to either treatment alone. Secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17) was significantly reduced, and anti-inflammatory cytokines (IL-4, IL-10) was significantly increased by the combination treatment as compared to either treatment alone. Flow cytometry analysis of MOG-reactivated T cells in spleen showed that combination treatment reduced the number of CD4⁺CD45⁺ and CD8⁺ T cells, and increased the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells. Furthermore, combination treatment enhanced apoptosis in MOG-reactivated CD4⁺ T cells, a key cellular subset in MS pathogenesis. Combination treatment with MP and BM-MSCs provides a novel treatment protocol for enhancing therapeutic effects in MS.
Animals ; Apoptosis ; Central Nervous System ; Clinical Protocols ; Cytokines ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Flow Cytometry ; Glucocorticoids ; Humans* ; Immunization ; Injections, Intraperitoneal ; Injections, Intravenous ; Mesenchymal Stromal Cells* ; Methylprednisolone* ; Mice ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; Stem Cells ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Therapeutic Uses