Parasitic leiomyoma in the trocar site after laparoscopic myomectomy: A case report.

BACKGROUND: Laparoscopic myomectomy is increasingly used for resecting gynecological tumors. Leiomyomas require morcellation for retrieval from the peritoneal cavity. However, morcellated fragments may implant on the peritoneal cavity during retrieval. These fragments may receive a new blood supply from an adjacent structure and develop into parasitic leiomyomas. Parasitic leiomyomas can occur spontaneously or iatrogenically; however, trocar-site implantation is an iatrogenic complication of laparoscopic uterine surgery. We describe a parasitic leiomyoma in the trocar-site after laparoscopic myomectomy with power morcellation. CASE SUMMARY: A 50-year-old woman presented with a palpable abdominal mass without significant medical history. The patient had no related symptoms, such as abdominal pain. Computed tomography findings revealed a well-defined contrast-enhancing mass measuring 2.2 cm, and located on the trocar site of the left abdominal wall. She had undergone laparoscopic removal of uterine fibroids with power morcellation six years ago. The differential diagnosis included endometriosis and neurogenic tumors, such as neurofibroma. The radiologic diagnosis was a desmoid tumor, and surgical excision of the mass on the abdominal wall was successfully performed. The patient recovered from the surgery without complications. Histopathological examination revealed that the specimen resected from the trocar site was a uterine leiomyoma. CONCLUSION: Clinicians should consider the risks and benefits of laparoscopic vs laparotomic myomectomy for gynecological tumors. Considerable caution must be exercised for morcellation to avoid excessive tissue fragmentation.

Laparoscopic Gastrectomy Using Instruments with a Minimal Diameter for Early Gastric Cancer: A Feasible Alternative to Conventional Laparoscopic Gastrectomy for Experienced Surgeons.

Background: The application of laparoscopic surgery using instruments that are 3 mm or less in diameter for patients with early gastric cancer (EGC) has not yet been established. We aimed to evaluate the feasibility and safety of laparoscopic gastrectomy using instruments with minimal diameter. Methods: We retrospectively analyzed 41 patients who underwent laparoscopic subtotal gastrectomy with D1-positive lymph node dissection for EGC. Among them, 17 patients underwent laparoscopic gastrectomy using instruments with a minimal diameter (experimental group), while 24 patients underwent conventional laparoscopic gastrectomy (control group). In the experimental group, we used two 3-mm trocars, one 5-mm trocar, and the GelPOINT® Advanced Access Platform. We compared operative outcomes between the two groups and assessed the learning curve of laparoscopic gastrectomy using instruments with minimal diameter. Results: The operative outcomes were similar between the two groups. The preoperative-to-postoperative day 2 ratio of neutrophil count in the experimental group was significantly lower than in the control group (2.07 versus 2.65; P = .038). Morbidity was not observed in the experimental group and 3 patients experienced complications in the control group, although it was not significantly different (P = .252). The operation time according to the accumulation of cases was stable without any significant change in the experimental group. Conclusions: Laparoscopic gastrectomy using instruments with minimal diameter is technically feasible and safe for EGC and could also be a good alternative to conventional laparoscopic gastrectomy to minimize the impact of surgical invasiveness when performed by experienced surgeons.

A Rare Nasopharyngeal Teratoma Arising From the Vomer.

Teratomas are rare germ cell neoplasms derived from the 3 germinal layers (ectoderm, mesoderm, and endoderm). Nasopharyngeal teratoma is a very rare teratoma arising anywhere from the oronasal cavity, regarded as an expanding, avity filling lesion, with a high mortality rate because of severe airway obstruction, especially in the neonatal period and make up only 2% of all teratomas. The authors present a case of an infant girl with a single, finger-like, hairy teratoma arising from the vomer and protruding from the mouth with bilateral complete cleft palate, cleft lip, and cleft alveolus. Complete intraoral resection of the teratoma and cleft lip repair was conducted simultaneously. Reconstruction of the cleft palate was performed at a later stage. Recurrence occurred 9 months after surgery and extended complete surgical excision was performed after recurrence, with no recurrence observed again to date. Histopathologic examination confirmed the diagnosis of congenital mature teratoma.

Osteogenic potency of nacre on human mesenchymal stem cells.

Nacre seashell is a natural osteoinductive biomaterial with strong effects on osteoprogenitors, osteoblasts, and osteoclasts during bone tissue formation and morphogenesis. Although nacre has shown, in one study, to induce bridging of new bone across large non-union bone defects in 8 individual human patients, there have been no succeeding human surgical studies to confirm this outstanding potency. But the molecular mechanisms associated with nacre osteoinduction and the influence on bone marrow-derived mesenchymal stem cells (BMSC's), skeletal stem cells or bone marrow stromal cells remain elusive. In this study we highlight the phenotypic and biochemical effects of Pinctada maxima nacre chips and the global nacre soluble protein matrix (SPM) on primary human bone marrow-derived stromal cells (hBMSCs) in vitro. In static co-culture with nacre chips, the hBMSCs secreted Alkaline phosphatase (ALP) at levels that exceeded bone morphogenetic protein (rhBMP-2) treatment. Concentrated preparation of SPM applied to Stro-1 selected hBMSC's led to rapid ALP secretions, at concentrations exceeding the untreated controls even in osteogenic conditions. Within 21 days the same population of Stro-1 selected hBMSCs proliferated and secreted collagens I-IV, indicating the premature onset of an osteoblast phenotype. The same SPM was found to promote unselected hBMSC differentiation with osteocalcin detected at 7 days, and proliferation increased at 7 days in a dose-dependent manner. In conclusion, nacre particles and nacre SPM induced the early stages of human bone cell differentiation, indicating that they may be promising soluble factors with osteoinductive capacity in primary human bone cell progenitors such as, hBMSC's.

Influence of different palate repair protocols on facial growth in unilateral complete cleft lip and palate.

OBJECTIVE: To address the question of whether one- or two-stage palatal treatment protocol has fewer detrimental effects on craniofacial growth in patients aged 5 years with unilateral complete cleft lip and palate. MATERIALS AND METHODS: Forty patients with non-syndromic unilateral complete cleft lip and palate (UCCLPs) who had received primary cleft lip repair at age 6-12 months and cleft palate repair at age 18-30 months were selected in this study. Eighteen UCCLP patients who received two-stage palate repair were selected as group 1, and 22 UCCLP patients who received one-stage palate repair were selected as group 2. The control group consisted of 20 patients with unilateral incomplete cleft lip (UICL patients) whose age and gender matched with UCCLP patients. A one-sample Kolmogorov-Smirnov test was used to analyze the nature of data distribution. Bonferroni test and Kruskal-Wallis H tests were used for multiple comparisons. RESULTS: Both case groups showed reduced maxillary sagittal length (ANS-PMP, A-PM, p < 0.05) and retrusion of the maxilla (S-Ptm, p < 0.05), A point and ANS point (Ba-N-A, Ba-N-ANS, p < 0.05). Patients treated with two-stage palate repair had a reduced posterior maxillary vertical height (R-PMP, p < 0.05). CONCLUSIONS: Our results indicated that maxillary sagittal length and position could be perturbed by both one- and two-stage palate repair. Vomer flap repair inhibited maxilla vertical growth. Delayed hard palate repair showed less detrimental effects on maxillary growth compared to early hard palate repair in UCCLP patients aged 5 years.

Requirement of Runx3 in pulmonary vasculogenesis.

Runx3 is essential for normal vertebrate lung development and Runx3 knockout (KO) mice die within 24 h after birth because of various organ defects including defects in alveolar expansion. For proper early lung development, vasculogenesis and angiogenesis are necessary in humans. Previous studies have reported that various signaling molecules, such as CD31, VEGF and vWF, are closely related to lung vasculogenesis and angiogenesis. To confirm the relationship between Runx3-related lung defects and vasculogenesis, the localization of various blood vessel markers is examined in WT and Runx3 KO mouse lungs at PN1. Our results indicate that CD31, VEGF and vWF were dramatically up-regulated by a loss of Runx3 during lung development. Moreover, U0126, a MEK inhibitor, rescued the lung phenotype and vascularization by regulation of ERK signaling. Therefore, it was concluded that lung vasculogenesis and angiogenesis were induced in the Runx3 KO mouse, which shows lung defects, by increased CD31, VEGF and vWF.

The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model.

BACKGROUND: The exact mechanism of the inflammatory changes occurring during the development of Behçet's disease (BD) remains unclear. OBJECTIVE: We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model. METHODS: The classical vs. alternative activated macrophage ratio (M1/M2 ratio) was calculated by analyzing the surface markers CD16/32 and CD23 as M1 and M2 markers, respectively, by flow cytometry. mRNA expression of interferon (IFN)-γ and interleukin (IL)-6 as M1 and arginase-1, FIZZ-1, and MHC-II as M2 markers were analyzed by reverse transcription-polymerase chain reaction. Cytokine levels were assessed by enzyme-linked immunosorbent assay. RESULTS: The M1 phenotype was upregulated in BD mice, and an increased M1/M2 ratio was observed compared to that in asymptomatic BD normal and normal healthy mice. Recombinant (r)IFN-γ significantly increased the M1/M2 ratio (1.74±0.42) compared with that of rIL-4 (0.83±0.20). BD mice treated with rIL-4 showed a decreased M1/M2 ratio (1.2±0.3) compared to that of the rIFN-γ- (2.1±2.3) treated group and also showed ameliorated BD symptoms accompanied by downregulation of IL-17 and IL-6 and up-regulation of IL-4. CONCLUSION: Therefore, modulation of macrophage phenotypes could be an effective therapeutic approach for treating BD in the future.

Tocotrienols enhance melanosome degradation through endosome docking/fusion proteins in B16F10 melanoma cells.

Vitamin E inhibits tyrosinase activity and acts as a melanogenesis inhibitor in epidermal melanocytes in vitro. However, there is no direct evidence indicating that melanosomes are degraded in lysosomes in the presence of vitamin E. To determine whether vitamin E-induced melanosome disintegration is related to the expression of endosome docking/fusion proteins in B16F10 melanoma cells, electron microscopy, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR were used to observe the effects of tocomin (α-tocopherols and α,γ,δ-tocotrienols in palm oil) on B16F10 melanoma cells. Melanosomal integrity was lost in lysosomes of B16F10 melanoma cells when treated with tocomin, indicating that tocomin caused the degradation of melanosomes in the lysosomal compartment. RT-PCR and real-time PCR analysis demonstrated mRNA expression of tyrosinase and the endosome docking/fusion proteins (syntaxin7, Rab7, Vps11, Vps16, Vps33, Vps39, and Vps41). Expression of syntaxin7, Vps16, Vps33, and Vps41 mRNA increased significantly in cells treated with tocomin compared with that in controls. These results indicate that the tocomin-induced degradation of melanosomes in the lysosomal compartment occurs with an increase in endosome docking/fusion proteins (syntaxin7, Vps16, Vps33, and Vps41) in cultured B16F10 melanoma cells.

Expression patterns of ABCG2, Bmi-1, Oct-3/4, and Yap in the developing mouse incisor.

Recent studies have demonstrated the existence of dental stem cells in the continuously growing tooth. However, much remains to be learned about the complex mechanism involving stem cells during tooth development. We determined the expression patterns of four stem cell markers ABCG2, Bmi-1, Oct-3/4, and Yap in the developing mouse incisors between embryonic day (E) 11 and postnatal day (PN) 20. ABCG2 was localized strongly in the perivascular region of the incisor mesenchyme from E11 to PN20, and in the odontoblasts from E18 to PN20. Bmi-1 was expressed in both the dental epithelium and mesenchyme from E11 to E14. The expression of Bmi-1 was noticeably reduced at E16, and was restricted to the apical bud from E16 to PN20. Oct-3/4 was localized in the nucleus of the cells in the superficial layer and stellate reticulum within the dental epithelium from E11 to E14 and in the apical bud from E16 to PN20. Meanwhile, once the ameloblasts and odontoblasts began to appear at E16, they expressed Oct-3/4 in the cytoplasm. Yap was expressed in most of the basal cells of the incisor dental epithelium from E11 to E14, but was expressed mainly in the transit-amplifying (TA) cells within the basal cell layer from E16 to PN20. The unique and overlapping expression patterns of ABCG2, Bmi-1, Oct-3/4, and Yap suggest the independent and interactive functions of the four stem cell markers in the developing mouse incisor.

Lung tissue regeneration after induced injury in Runx3 KO mice.

Runx3 is essential for normal murine lung development, and Runx3 knockout (KO) mice, which die soon after birth, exhibit alveolar hyperplasia. Wound healing, tissue repair, and regeneration mechanisms are necessary in humans for proper early lung development. Previous studies have reported that various signaling molecules, such as pErk, Tgf-beta1, CCSP, pJnk, Smad3, and HSP70 are closely related to wound healing. In order to confirm the relationship between lung defects caused by the loss of function of Runx3 and wound healing, we have localized various wound-healing markers after laser irradiation in wild-type and in Runx3 KO mouse lungs at post-natal day 1. Our results indicate that pERK, Tgf-beta1, CCSP, pJnk, and HSP70 are dramatically down-regulated by loss of Runx3 during lung wound healing. However, Smad3 is up-regulated in the Runx3 KO laser-irradiated lung region. Therefore, the lung wound-healing mechanism is inhibited in the Runx3 KO mouse, which shows abnormal lung architecture, by reduced pErk, Tgf-beta1, CCSP, pJnk, and HSP70 and by induced Smad3.

Tumor necrosis factor alpha small interfering RNA decreases herpes simplex virus-induced inflammation in a mouse model.

BACKGROUND: Anti-TNFalpha antibodies have been used for treating inflammation in patients. But, more effective and safer drugs need to be developed for improved future therapeutic use. OBJECTIVES: To inhibit the expression of TNFalpha, we used small interfering RNAs (siRNAs) to reduce over expression of TNFalpha in vitro in cell cultures and in an in vivo Behcet's disease-like (BD) mouse model for amelioration of chronic inflammation. METHODS: TNFalpha siRNA was injected intraperitoneally twice with a 1-week interval. To compare the efficacy of TNFalpha siRNA versus an anti-TNFalpha antibody, Infliximab and Etanercept were administered to symptomatic mice with inflamed tissue. RESULTS: Intraperitoneal delivery of TNFalpha siRNA effectively decreased BD symptoms in 18 of 32 cases (56.3%). Scrambled siRNA treatment decreased BD symptoms in 2 of 19 cases (10.5%). Infliximab was effective in 11 of 27 cases (40.7%) and Etanercept was also effective in 9 of 25 cases (36.0%) at the end of the second week after treatment. TNFalpha siRNA reduced serum levels of TNFalpha (1.57 +/- 0.43pg/ml), compared to levels in mice not injected (84.02 +/- 24.59pg/ml) (p<0.01) or scramble injected (118.89 +/- 20.08pg/ml) (p<0.01). After single injection of TNFalpha siRNA, improvement of BD symptoms showed at 9 +/- 7th day on an average, contrary, in Infliximab injected group, improvement was apparent at 15 +/- 4th day after injection (p<0.05). CONCLUSION: We show that siRNAs can be employed to inhibit cytokine gene expression in an in vivo disease mouse model. This inhibition may, therefore, be attributed to the improvement of inflammatory symptoms.

Implications for tooth development on ENU-induced ectodermal dysplasia mice.

BACKGROUND: In this study, the mutated phenotypes were produced by treatment of chemical mutagen, N-ethyl-N-nitrosourea (ENU). We analyzed the mutated mice showing the specific phenotype of ectodermal dysplasia (ED) and examined the affected gene. METHODS: Phenotypes, including size, bone formation, and craniofacial morphology of ENU-induced ED mice, were focused. Tooth development and expression of several molecules were analyzed by histologic observations and immunohistochemistry. We carried out genome-wide screening and quantitative real-time PCR to define the affected and related genes. RESULTS: As examined previously in human ectodermal dysplasia, ENU-induced ED mice showed the specific morphologic deformities in tooth, hair, and craniofacial growth. Tooth development in the ENU-induced ED mice ceased at early cap stage. In addition, skeletal staining showed retardation in craniofacial development. Finally, the affected gene, which would be involved in the mechanism of ED, was located between the marker D3Mit14 and D3Mit319 on chromosome 3. CONCLUSIONS: The affected gene in ENU-induced ED mice showed several defects in ectodermal organogenesis and these results indicate that this gene plays an important role in mouse embryogenesis.

Branching patterns and intraosseous course of the mental nerve.

PURPOSE: The purpose of this study was to clarify the branching patterns of the mental nerve (MN) and intraosseous courses of the MN branches, and to determine the clinical relevance of the various courses of the MN branches. MATERIALS AND METHODS: We investigated the topography of the MN by dissecting 31 hemifaces of Korean cadavers. Based on the distribution area of the MN, it was divided into angular (A), medial inferior labial (ILm), lateral inferior labial (ILl), and mental (M) branches. We classified the branching patterns of the 4 branches of the MN into 5 types. RESULTS: Type II, in which the MN divided into 3 branches (A, ILm, and M), with the ILl branch separating from the A branch, was the most common (35.4%). The MN was classified based on the shape of the anterior loop into loop, straight, and vertical patterns, which constituted 61.5%, 23.1%, and 15.4%, respectively. In the mandibular canal, the inferior alveolar nerve completely divided into the MN and the dental nerve, which supplies the teeth. In 17 cases (81%), the nerve bundles constituting the A branch were located at the superior aspect, whereas the nerve bundles of the inferior labial and mental branches were in the middle and inferior aspects within the mandibular canal, respectively, at the mental foramen region. CONCLUSION: These observations can help clinicians to predict the location or extent of paresthesia in the facial region according to the location and extent of nerve damage during dental implant surgery or genioplasty.

Sodium selenite induces superoxide-mediated mitochondrial damage and subsequent autophagic cell death in malignant glioma cells.

Malignant gliomas are resistant to various proapoptotic therapies, such as radiotherapy and conventional chemotherapy. In this study, we show that selenite is preferentially cytotoxic to various human glioma cells over normal astrocytes via autophagic cell death. Overexpression of Akt, survivin, XIAP, Bcl-2, or Bcl-xL failed to block selenite-induced cell death, suggesting that selenite treatment may offer a potential therapeutic strategy against malignant gliomas with apoptotic defects. Before selenite-induced cell death in glioma cells, disruption of the mitochondrial cristae, loss of mitochondrial membrane potential, and subsequent entrapment of disorganized mitochondria within autophagosomes or autophagolysosomes along with degradation of mitochondrial proteins were noted, showing that selenite induces autophagy in which mitochondria serve as the main target. At the early phase of selenite treatment, high levels of superoxide anion were generated and overexpression of copper/zinc superoxide dismutase or manganese superoxide dismutase, but not catalase, significantly blocked selenite-induced mitochondrial damage and subsequent autophagic cell death. Furthermore, treatment with diquat, a superoxide generator, induced autophagic cell death in glioma cells. Taken together, our study clearly shows that superoxide anion generated by selenite triggers mitochondrial damage and subsequent mitophagy, leading to irreversible cell death in glioma cells.

Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype.

Chronic exposure of many human hepatoma cell lines to a low dose (LD) of doxorubicin induced a senescence-like phenotype (SLP) accompanied by enlargement of cells and increased senescence-associated beta-galactosidase activity. LD doxorubicin-induced SLP was preceded by multinucleation and downregulation of multiple proteins with mitotic checkpoint function, including CENP-A, Mad2, BubR1, and Chk1. LD doxorubicin-treated cells eventually underwent cell death through mitotic catastrophe. When we investigated whether LD doxorubicin-induced cell death shares biochemical characteristics with high dose (HD) doxorubicin-induced apoptosis in Huh-7 cells, we observed that externalization of phosphatidyl serine and release of mitochondrial cytochrome c into the cytosol was associated with both types of cell death. However, propidium iodide exclusion assays showed that membrane integrity was lost in the initial phase of LD doxorubicin-induced cell death through mitotic catastrophe, whereas it was lost during the late phase of HD doxorubicin-induced apoptosis. Furthermore, HD doxorubicin-induced apoptosis but not LD doxorubicin-induced mitotic catastrophe led to transient activation of NF-kappaB and strong, sustained activations of p38, c-Jun N-terminal kinase, and caspases. Collectively, these results indicate that different doses of doxorubicin activate different regulatory mechanisms to induce either apoptosis or cell death through mitotic catastrophe.

Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades-Behçet's disease-like mouse model.

The aim of this work was to study the effects and side effects of gemcitabine (2',2'-difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin lesions of a herpes simplex virus (HSV)-induced Adamantiades-Behçet's disease (ABD)-like mouse model. For the dose-escalation study, ICR mice were treated intraperitoneally with dFdC over 5 days. For the efficacy study, ICR mice were inoculated with HSV and classified as having ABD according to a revised Japanese classification, and then 18 ABD mice were randomly assigned to placebo, 0.06 or 0.12 microg of dFdC/day over 5 days. Serum levels of interleukin-4 (IL-4), IL-6, IL-10, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were determined using enzyme-linked immunosorbent assay. After application of 3 microg of dFdC over 5 days, alanine aminotransferase increased (P = 0.032), but all other kidney and liver parameters were unchanged. In ABD mice, 5 days of dFdC treatment with 0.06 or 0.12 microg of dFdC/day resulted in a dose-dependent improvement of cutaneous manifestations by more than 60% (P = 0.017). There was no significant change in cytokine levels, and none of the cytokine levels correlated with response to treatment. Moreover, dFdC shows promising effects to improve cutaneous lesions in the HSV-induced ABD-like mouse model. In this animal model, effects of dFdC on the cytokine profile remained inconclusive.

Thalidomide upregulates macrophage inflammatory protein-1alpha in a herpes simplex virus-induced Behçet's disease-like animal model.

The mechanism of action of thalidomide in the treatment of patients with Behçet's disease (BD) is poorly understood. There is some evidence to suggest that certain immunological abnormalities are associated with the pathogenesis of BD. A BD-like mouse model induced by herpes simplex virus (HSV) inoculation shows similar immunological abnormalities. In this study, thalidomide was administered in order to understand the mechanism for the improvement in symptoms in BD-like mice. Eight out of ten thalidomide-treated mice showed improvement but none of ten placebo-treated mice (P < 0.005). The improvements were seen in mucocutaneous symptoms. The mice were sacrificed on the 6th day, and the spleens subjected to RT-PCR, FACS, Western blot and immunohistochemical analysis. IL-2, IL-4, IL-6, IL-10, IFN-gamma, TNFalpha, TGFbeta, MCP-1, RANTES, perforin, IP-10, FasL, FasR and MIP-lalpha were determined. Among these, TNFalpha, MIP-1alpha, perforin and Fas were influenced by thalidomide treatment. These results suggest that thalidomide can attenuate HSV-induced BD-like symptoms in mice through the downregulation of TNFalpha (P < 0.005) and the upregulation of MIP-1alpha (P < 0.005), perforin (P < 0.05) and FasR (P < 0.1).

In vitro evidence of the role of COX-2 in attenuating gastric inflammation and promoting gastric carcinogenesis.

Although gastric adenocarcinoma is one of the most common malignancies in the world, little is known about its exact molecular processes in development and progression. Recent studies suggest that COX-2 is important in carcinogenesis of gastrointestinal cancers, and is especially involved in carcinogenesis in a mouse model of familial adenomatosis polyposis. To understand the role of COX-2 in gastric carcinogenesis and Helicobacter pylori-associated gastritis, we measured COX-2 expression in 170 human gastric carcinoma tissues byimmunohistochemical analysis and compared the expression of COX-2 in paired tissues obtained from normal-looking and cancer-bearing mucosa. Further evidence of the involvement of COX-2 in gastritis and gastric carcinogenesis was obtained by establishing stable cell lines overexpressing COX-2. After subcloning of COX-2 into pCB7 mammalian expression vector, two stable cell lines named MKN-28-COX-2 and MKN-45-COX-2 were generated by transfection of COX-2 cDNA. To understand the effect of COX-2 on gastritis, we performed an electrophoretic mobility shift assay of NF-kappaB (inflammation-associated transcription factor), and measured malondialdehyde levels and chemiluminescence activities in both mock-transfected MKN and MKN-COX-2 cells after stimulation of H. pylori (1 x 10(6) CFU/mL) and neutrophils (10(2) cells/mL). A marked attenuation of NF-kappaB bindings and generation of free radicals was observed in COX-2 overexpressed cells. Another set of experiments, including the growth inhibition by TGF-beta treatment, Matrigel invasion assay, and apoptosis assay, was done. COX-2 showed the advantage of the escape from the growth inhibition by TGF-beta through decreasing TGF-beta RII expression and increased cell invasiveness. In conclusion, COX-2 expression seems to be induced to attenuate the degree of atrophic gastritis, the initial event in gastric carcinogenesis, and promote gastric carcinogenesis.