BackgroundStomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome.ResultsWe analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis.ConclusionsWe report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors.

(J Korean Assoc Oral Maxillofac Surg 2012;38:2-8)Introduction: Auto-tooth bone graft material consists of 55% inorganic hydroxyapatite (HA) and 45% organic substances. Inorganic HA possesses properties of bone in terms of the combining and dissociating of calcium and phosphate. The organic substances include bone morphogenetic protein and proteins which have osteoinduction capacity, as well as the type I collagen identical to that found in alveolar bone. Auto-tooth bone graft material is useful as it supports excellent bone regeneration capacity and minimizes the possibility of foreign body reaction,genetic diseases and disease transmission. Materials and Methods: Implant placement combined with osteoinductive regeneration,preservation of extraction socket, maxillary sinus augmentation, and ridge augmentation using block type,powder type, and block+powder type autobone graft materialwere performed for 250 patients with alveolar bone defect and who visited the Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University from September 2009 to August 2011. Results: Clinical assessment: Among the 250 patients of auto-tooth bone graft, clinical assessment was performed for 133 cases of implant placement. The average initial stabilization of placed implants was 74 implant stability quotient (ISQ). Radiological assessment: The average loss of crestal bone in the mandible as measured 6 months on the average after the application of prosthesis load was 0.29 mm, ranging from 0 mm to 3.0 mm. Histological assessment: In the histological assessment, formation of new bone, densified lamellated bone, trabecular bones, osteoblast, and planting fixtures were investigated. Conclusion: Based on these results, we concluded that auto-tooth bone graft material should be researched further as a good bone graft material with osteoconduction and osteoinduction capacities to replace autogenous bone, which has many limitations.

Purpose: Extensive research is actively ongoing for development of an ideal bone substitute that meets the gold standard. Tooth was selected as a donor site for evaluation of potentials in bone substitutes based on its similar chemical compositions to alveolar bone. Previous studies have evaluated inorganic components of autogenous tooth bone graft material (AutoBT) and osteoconductivity. In continuation from the previous studies, the current study was conducted for analysis of organic components and evaluation of osteoinductivity of AutoBT. Methods: Forty-six extracted teeth were collected from actual patients (Korea Tooth Bank, R&D Institute). Extracted teeth were processed into AutoBT and implanted in dorsal subcutaneous muscular tissues of 15 athymic mice. Biopsy samples were harvested at two, five, and eight weeks. The Bradford assay, sodium dodecyl sulphate polyacrylamide gradient gel, and western blotting were performed for investigation of organic contents of AutoBT. Results: Histology analyses showed signs of new bone formation as early as two weeks. Results of the Bradford assay indicated the existence of noncollagenous proteins (NCP). 0.29% (2.89 mg/g) of proteins were extracted by weight in the root portion of AutoBT; 0.02% (0.029 mg/g) and 1.79% (17.93 mg/g) of proteins were measured by weight in crown and block-form of AutoBT, respectively. However, recombinant human bone morphogenetic protein-2 was not observed in AutoBT. Conclusion: Within the limitation of the current study, AutoBT induced new bone formation by NCP embedded in dentin.

BackgroundThis study examined the osteoinductive activity of demineralized dentin matrix (DDM) from human and polydeoxyribonucleotide (PDRN) for nude mice.MethodsTwenty healthy nude mice, weighing about 15~20 g, were used for the study. DDM from human and PDRN were prepared and implanted subcutaneously into the dorsal portion of the nude mice. The nude mice were sacrificed at 1, 2, and 4 weeks after grafting and evaluated histologically by hematoxylin-eosin and Masson’s trichrome staining. The specimens were also evaluated via a histomorphometric study.ResultsThe DDM and PDRN induced new bone, osteoblasts, and fibroblasts in soft tissues. The histological findings showed bone-forming cells like osteoblasts and fibroblasts at 1, 2, and 4 weeks. New bone formation was observed in the histomorphometric study. In particular, the ratio of new bone formation was the highest at 2 weeks compared with the first week and fourth week.ConclusionsIn this study, we showed that the PDRN used in this experimental model was able to induce bone regeneration when combined to the DDM.

BackgroundPentoxifylline is a methylxanthine derivative with significant anti-inflammatory, anti-fibrotic, and anti-proliferative properties. Studies have shown that pentoxifylline may have renoprotective effects in patients with diabetic nephropathy. However, most of these studies were limited by small sample sizes. Therefore, we investigated whether pentoxifylline could reduce proteinuria in patients with diabetic nephropathy and residual proteinuria who received an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB). We also studied the effects of pentoxifylline on glycemic control, insulin resistance, and inflammatory parameters.MethodsThis was a prospective, randomized double-blind, placebo-controlled, multi-center study. A total of 174 patients with type 2 diabetes and albuminuria (>30 mg/g of creatinine) who were taking the recommended dosage of ACEI or ARB for > 6 months and receiving conventional therapy for diabetes were randomly assigned to receive pentoxifylline (1200 mg, daily; n = 87) or a placebo (n = 87) for 6 months. The endpoints were the effects of pentoxifylline on proteinuria, renal function, glucose control, and inflammatory parameters.ResultsThe percentage changes in proteinuria from baseline in the pentoxifylline and placebo groups were a decrease of 23 % and 4 %, respectively (p = 0.012). In addition, significant reductions in fasting plasma glucose, glycated hemoglobin, and insulin resistance according to the homeostasis model assessment were observed in the pentoxifylline group compared to those in the placebo group. However there was no significant difference in serum tumor necrosis factor (TNF)-α between the groups.ConclusionsPentoxifylline therapy reduced proteinuria and improved glucose control and insulin resistance without significant change of serum TNF-α in patients with type 2 diabetic nephropathy. Therefore, pentoxifylline is a potential therapeutic alternative for treating diabetes and diabetic nephropathy.Trial registrationNCT01382303

Apo epsilon2 allele and epsilon2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that epsilon2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.

In this study, we investigated the hepatoprotective and anti-fibrotic effects of zingerone, one of the active components of ginger, against carbon tetrachloride (CCl4)- and dimethylnitrosamine (DMN)-induced liver injuries in rats, respectively. Oral administration of zingerone (10 mg/kg) reduced CCl4-induced abnormalities in liver histology, serum alanine aminotransferase and aspartate aminotransferase levels, and liver malondialdehyde levels. Zingerone treatment attenuated CCl4-induced increases in inflammatory mediators, including tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase mRNA levels. Western blot analysis showed that zingerone suppressed activation of nuclear factor-kappa B (NF-κB) p65 and phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinases (MAPKs). Liver fibrosis induced by DMN (10 mg/kg, intraperitoneally) was ameliorated by administration of zingerone (10 and 20 mg/kg, orally). Zingerone treatment reduced DMN-induced elevation of hydroxyproline content and hepatic stellate cell activation. In conclusion, zingerone showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream MAPKs. Moreover, zingerone had hepatoprotective and anti-fibrotic effects against DMN-induced liver injury suggesting its usefulness in the prevention of liver inflammation and the development of hepatic fibrosis.

Purpose:This study examined the osteoinductive activity of demineralized human dentin matrix for nude mice.Methods:Twenty healthy nude mice weighing about 15 to 20 g were used for study. Demineralized human dentin matrix was prepared and implanted into the dorsal portion of nude mice (subcutaneous), which were sacrificed at two, four, and eight weeks after demineralized dentin matrix grafting and evaluated histologically by H&E and Masson trichrome staining. The specimens were also evaluated histomorphometrically.Results:The demineralized dentin matrix induced bone and cartilage formation independently in soft tissues. Histological examination showed bone-forming cells such as osteoblasts and fibroblasts at two, four, and eight weeks.Conclusion:These results suggest that demineralized human dentin matrix has osteoinductive ability, and is a good alternative to autogenous bone graft materials.