Dae-Ho Leem

Sulforaphane enhances caspase-dependent apoptosis through inhibition of cyclooxygenase-2 expression in human oral squamous carcinoma cells and nude mouse xenograft model

In this study, we found that oral squamous cell carcinomas (OSCCs) in Korean patients have a high level of COX-2 expression when compared with normal mucosa. Sulforaphane (SFN), rich in cruciferous vegetables, has been reported to display anti-cancer activity against many cancers. However, the effect and molecular mechanism of SFN in the proliferation of OSCC still remains unclear. To elucidate this mechanism, we investigated the anti-proliferative effect of SFN on KB and YD-10B cells and demonstrated that SFN significantly induced caspase-dependent apoptosis. Also, we observed that SFN inhibited COX-2 but not COX-1. In addition, bcl-2 protein, one of downstream targets of COX-2, was down-regulated by SFN. Furthermore, SFN also inhibited tumor growth in KB cell xenografts. These results show that SFN can act as a potent anti-oral cancer compound by inhibiting COX-2 activity.

Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit cancer growth by inhibiting the activity of cyclooxygenase (COX). However, there is increasing evidence that the COX-independent pathway may be also involved in the inhibitory effect of NSAIDs against tumor progression. Tolfenamic acid is a NSAID that exhibits anticancer activity in pancreatic and colorectal cancer models. In the present study, the anti-tumor effect of tolfenamic acid in KB human oral cancer cells is investigated. The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G1 population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase. In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells. These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway. These results suggest that tolfenamic acid-induced apoptotic cell death inhibits cancer growth by activating the p38 MAPK pathway for cancer prevention.

Sulforaphane Increases Cyclin-Dependent Kinase Inhibitor, p21 Protein in Human Oral Carcinoma Cells and Nude Mouse Animal Model to Induce G2/M Cell Cycle Arrest

Previously, our group reported that sulforaphane (SFN), a naturally occurring chemopreventive agent from cruciferous vegetables, effectively inhibits the proliferation of KB and YD-10B human oral squamous carcinoma cells by causing apoptosis. In this study, treatment of 20 and 40 µM of SFN for 12 h caused a cell cycle arrest in the G2/M phase. Cell cycle arrest induced by SFN was associated with a significant increase in the p21 protein level and a decrease in cyclin B expression, but there was no change in the cyclin A protein level. In addition, SFN increased the p21 promoter activity significantly. Furthermore, SFN induced p21 protein expression in a nude mouse xenograft model suggesting that SFN is a potent inducer of the p21 protein in human oral squamous carcinoma cells. These findings show that SFN is a promising candidate for molecular-targeting chemotherapy against human oral squamous cell carcinoma.

Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells.

Diindolylmethane (DIM), an isothiocyanate found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC6H5, which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC6H5 decreased the number of viable KB cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of death receptor 5 and the cleavage of Bid and caspase 8. Studies on the mechanism of action showed that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC6H5 was mediated by endoplasmic reticulum stress. In addition, C-DIMs inhibited cell proliferation and induced PARP cleavage through death receptor 5 and CHOP in HEp-2 and HN22 cells. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in human oral cancer cells through the endoplasmic reticulum stress pathway.

Long‐term follow‐up of autogenous tooth bone graft blocks with dental implants

Demineralized dentin matrix block (ABTB: Autogenous Tooth Bone Graft Block) is 3‐D scaffold with same components and geometry with alveolar bone. ABTB is well incorporated and remodelled into cortico‐cancellous bone with dental implant. The shape and volume were maintained with little marginal bone loss after average 44 months of follow‐up.

KO-202125, a sauristolactam derivate, induces apoptosis to prevent KB human oral squamous carcinoma cells through inhibition of cyclooxygenase-2 expression.

In a previous study, we demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in Korean patients having oral cancer. The goal of this study was to study whether KO-202125 (KO), a sauristolactam derivative in KB human oral squamous carcinoma cells, inhibits the activity of COX-2 enzyme and induces apoptotic cell death. In this study, it was shown that KO inhibited COX-2 mRNA and protein and its catalytic activity (prostaglandin E2), but not COX-1. The antiproliferative effect of KO on KB cells was also examined. The results showed that KO significantly decreased the number of viable cells and showed morphological changes in a concentration-dependent manner. The decrease in cell number was associated with apoptotic cell death evidenced by cleaved poly ADP ribose polymerase (PARP), nuclear fragmentation, sub-G1 population and annexin V positivity. Interestingly, KO is more potent than celecoxib, which is a well-known selective COX-2 inhibitor, although more studies are needed to prove it. Altogether, these results show that KO can act as a potent antioral cancer drug candidate by regulating COX-2 activity.

Immediate placement and functional loading of implants on canine with fixed partial denture for a patient having canine protected occlusion: a case report

Conventional implant protocols required a load-free healing period of three to six months between placement and functional loading of the implants. Many efforts have been made to minimize the duration of treatment time. Several literatures have documented immediate function with provisional or definitive prosthesis within a week of the placement in response to these demands. In addition, immediate implant placement has advantages such as shortened treatment time and preservation of soft tissue architectures. This article presents immediate implant placement into fresh extraction sockets followed by functional immediate loading with provisional prosthesis on canine and premolars for a patient having canine protected occlusion.

Utility of sodium tetradecyl sulfate sclerotherapy from benign oral vascular lesion.

BackgroundHemangioma and vascular malformation are benign vascular lesions that often occur in cephalic and cervical region. Currently, surgical resection, laser therapy, angiographic embolization, use of steroids, and sclerotherapy are used as treatments.Case presentationThis study reports three cases of benign vascular lesions that are remarkably treated by sodium tetradecyl sulfate (STS) injection, of which occurred in oral cavity and around the mouth. Three percent of STS was diluted with 0.9 % of normal saline, and it was injected to the lesion site at least once. The result of treatment was evaluated based on clinical findings.ConclusionSurgical treatment of hemangioma and vascular malformation occurred in oral cavity is not normally used because of esthetic issues and potential hemorrhage. On the other hand, sclerotherapy using STS is an effective therapy compare to surgical treatment. Despite the number of STS injection was different for each patient, all three patients had reached satisfactory level through the treatment with gradual diminution of lesions.

Decompression Device Using a Stainless Steel Tube and Wire for Treatment of Odontogenic Cystic Lesions: A Technical Report.

Decompression is considered an effective treatment for odontogenic cystic lesions in the jaw. A variety of decompression devices are successfully used for the treatment of keratocystic odontogenic tumors, radicular cysts, dentigerous cysts, and ameloblastoma. The purpose of these devices is to keep an opening between the cystic lesion and the oral environment during treatment. The aim of this report is to describe an effective decompression tube using a stainless steel tube and wire for treatment of jaw cystic lesions.