Atypical Peripheral Retinal Necrosis Without Ocular Inflammation and Retinal Whitening in a Patient With Acute Myelogenous Leukemia: A Case Report.

Retinal necrosis is a severe condition that threatens visual function. It is caused by viruses that are known to cause acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN), which are called necrotizing herpetic retinopathies (NHR). ARN causes severe intraocular inflammation, including anterior chamber intravitreal cells, keratic precipitate, vitreous opacity, and retinal vasculitis, whereas intraocular inflammation in PORN is considered mild or virtually absent. In addition, PORN is a disease that manifests in immunosuppressive patients, such as those with acquired immunodeficiency syndrome. Here, we present a case of unilateral retinal necrosis after chemotherapy, allogeneic peripheral blood stem cell transplantation, and cord blood transplantation for acute myelogenous leukemia (AML) in a 31-year-old male patient. AML treatment resulted in metabolic remission, and oral steroids and tacrolimus were continued. After two days, the patient visited an ophthalmologist because he noticed a sudden onset of floaters and visual field disturbance in the left eye. The peripheral retina was already necrotic in all layers, causing total retinal detachment. Intraocular inflammation, retinal opacity, or hemorrhagic spots in the fundus were not observed. His previous CD4 count was 43 cells/µL. A polymerase chain reaction test of the anterior chamber fluid revealed varicella-zoster virus (VZV), and vitrectomy was performed four days after disease onset. The excised vitreous demonstrated minimal opacity. The peripheral necrotic retina was excised, photocoagulation was performed on the residual retinal limbus, and silicone oil was injected to maintain retinal attachment. The retinal restoration was maintained under silicone oil tamponade, and corrected visual acuity improved to 20/32 without strong inflammation after vitrectomy. However, two months postoperatively, he contracted coronavirus disease 2019 (COVID-19), his general condition rapidly deteriorated, and he died. This case of retinal necrosis without inflammatory results in an immunocompromised patient and VZV detection in an intraocular sample led us to suspect PORN. However, the patchy or spread retinal whitening characteristic of PORN was completely absent, whereas the well-defined, peripheral, full-layer retinal necrosis characteristic of ARN was present. Thus, this is a rare case of VZV-induced NHR with partial features of PORN and ARN that progressed very silently.

Surgically-Induced Necrotizing Scleritis After Scleral Buckling With Stenotrophomonas maltophilia Infection.

Surgically induced necrotizing scleritis (SINS) is a rare inflammatory disease of the sclera that occurs following ocular surgery, specifically pterygium surgery and scleral buckling. Here, we report a case of SINS in a 78-year-old female patient after segmental scleral buckling for rhegmatogenous retinal detachment. The retina was restored after scleral buckling, and the postoperative course was uneventful. However, the patient developed ocular discharge and conjunctival hyperemia, indicating infection, after two months. The sclera became thinner and intraocular inflammation developed after buckle removal. Stenotrophomonas maltophilia was isolated from the ocular discharge, and the patient was treated with antibacterial agents susceptible to the bacteria. However, her symptoms persisted, and corrected visual acuity decreased from 20/25 to 20/1000. Oral steroid treatment was initiated because of the suspicion of SINS. Intraocular inflammation gradually subsided, the thin sclera was covered by conjunctival tissue, and the patient's corrected visual acuity improved to 20/32, which stabilized her condition. Infection with Stenotrophomonas maltophilia after scleral buckling is extremely rare, and SINS development in such cases is unprecedented.

A Case of Post-cataract Surgery Endophthalmitis Successfully Treated with Conservative Therapy.

BACKGROUND: Postoperative endophthalmitis after cataract surgery often requires emergency surgery if caused by an infection. However, early reoperation after the surgery put a heavy mental burden on the patient. Here we report a relatively mild case of postoperative endophthalmitis in which emergency surgery was avoided through careful observation including gram stain and culture test. CASE: 87-year-old male. The patient had a sudden decrease in visual acuity on the 4th day after cataract surgery of the left eye performed at another hospital and visited his previous doctor on the following day. Postoperative endophthalmitis was suspected, so he was referred to our department on the same day. The inflammation was observed in the anterior segment of the left eye. The gram staining results for collected anterior aqueous humor were negative. The patient was followed up with continued medication and careful observation without undergoing emergency surgery. The inflammation of the anterior segment subsequently improved. The patient underwent a left vitrectomy three months later to remove residual vitreous opacity. CONCLUSION: Postoperative endophthalmitis after cataract surgery is often indicated for emergency surgery, but there can be cases in which conservative therapy with thorough observation succeeds in retaining visual function.

Drinking Molecular Hydrogen Water Is Beneficial to Cardiovascular Function in Diet-Induced Obesity Mice.

Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases as a suppressor of free radical chain reactions. Here, the cardiovascular protective effects of the intake of molecular hydrogen water (MHW) were investigated using high-fat diet-induced obesity (DIO) mice. MHW was prepared using supplier sticks and degassed water as control. MHW intake for 2 weeks did not improve blood sugar or body weight but decreased heart weight in DIO mice. Moreover, MHW intake improved cardiac hypertrophy, shortened the width of cardiomyocytes, dilated the capillaries and arterioles, activated myocardial eNOS-Ser-1177 phosphorylation, and restored left ventricular function in DIO mice. MHW intake promoted the histological conversion of hypertrophy to hyperplasia in white and brown adipose tissues (WAT and BAT) with the upregulation of thermogenic and cardiovascular protective genes in BAT (i.e., Ucp-1, Vegf-a, and eNos). Furthermore, the results of a colony formation assay of bone-marrow-derived endothelial progenitor cells (EPCs) indicated that MHW activated the expansion, differentiation, and mobilization of EPCs to maintain vascular homeostasis. These findings indicate that the intake of MHW exerts cardiovascular protective effects in DIO mice. Hence, drinking MHW is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome.

Anti-VEGF Therapy and Retinal Photocoagulation to Prevent Recurrence of Central Retinal Vein Occlusion: Two Case Reports of Young Patients.

Case 1: An 18-year-old man. On initial examination, he was diagnosed with central retinal vein occlusion (CRVO) due to optic papillitis. He had no previous systemic and ocular medical history. His best corrected visual acuity was 20/20 for the right eye, but macular edema accompanied by serous retinal detachment was observed about 2 months after the initial examination. Intravitreal anti-VEGF injection was performed, and the symptoms improved. Then, additional photocoagulation was applied to the retinal nonperfusion area, to maintain its normal state. Case 2: A 36-year-old man. He was diagnosed with neovascular glaucoma associated with CRVO in the right eye by his previous physician. Panretinal photocoagulation and intravitreal anti-VEGF injection were performed under maximum-tolerated medical therapy for the right eye. He had diabetes. On initial examination, his visual acuity was 20/100 and his intraocular pressure was 19mmHg. Macular edema and iris neovascularization recurred half a year later, so intravitreal anti-VEGF injection and additional photocoagulation were applied to nonperfusion area. After that, both macular edema and iris neovascularization have settled down. Conclusions: Intravitreal anti-VEGF injection is effective in young patients with CRVO. Also, photocoagulation to nonperfusion area in addition to the continuous treatment with intravitreal anti-VEGF injection seems effective for preventing recurrence.

[Efficacy of Primary Prophylaxis with Pegfilgrastim after Docetaxel for Castration-Resistant Prostate Cancer].

Febrile neutropenia(FN)occurs in 3-25% of patients with castration-resistant prostate cancer(CRPC)receiving docetaxel( DTX). Therefore, the need for granulocyte colony-stimulating factor with DTX as prophylaxis has not been established. Herein, we report the efficacy of primary prophylaxis with pegfilgrastim after DTX in patients with CRPC. The subjects were 30 CRPC patients who received DTX at our hospital between January 2013 and October 2017. Twelve patients underwent primary prophylaxis with pegfilgrastim(Peg-G group), whereas the other 18 did not(control group). FN developed in 1(8.3%) and 8(44.4%)patients in the Peg-G and control groups, respectively(p=0.049). No significant differences were observed in RDI between the 2 groups. The average medical cost per course of DTX was lower in the Peg-G group than in the control group. These results demonstrate that primary prophylaxis with pegfilgrastim is useful because DTX induces FN at a high frequency in patients with CRPC, and pegfilgrastim significantly reduces its incidence without increasing the medical cost.

[A case of myasthenia-like symptoms induced by cibenzoline overdosage].

The present patient was an 87-year-old man who had been taking cibenzoline for tachyarrhythmia. Five years after initiation of administration, he was referred to our hospital for ptosis that worsened from midday, as well as weakness of the facial and limb muscles. He tested negative for anti-acetylcholine receptor antibody but positive in the edrophonium test, suggesting that he had myasthenia gravis. He was admitted to our hospital 3 years later due to worsening symptoms of ptosis and muscle weakness. He had hypoglycemia, cardiac conduction defect, and renal dysfunction. In addition, blood concentration of cibenzoline was markedly high (1,850 ng/ml). We terminated the administration of cibenzoline, after which the patient's neurologic symptoms improved. Our findings suggest that cibenzoline toxicity must be considered in differentiating myasthenia gravis when a patient also presents with renal dysfunction.

Sentinel lymph node biopsy reduces the incidence of secondary neck metastasis in patients with oral squamous cell carcinoma.

It has recently been established that sentinel node biopsy (SNB) is an applicable and feasible procedure for the prediction of neck lymph node status in patients with early oral squamous cell carcinoma (OSCC) who are clinically negative for neck metastasis (cN0). The aim of this study was to retrospectively compare excision followed by watchful waiting with excision and SNB, in order to determine the effectiveness of SNB. A total of 125 patients with cN0 early OSCC were divided into two groups, namely the excision alone (n=78) and excision with SNB (n=47) groups. The clinical data of these two groups between 2006 and 2013 were analyzed. In the excision with SNB group, the negative predictive value and false-negative rate of SNB were 94% (30/32) and 18% (2/11), respectively. Secondary neck metastasis, also known as delayed neck metastasis, occurred in 24.2% of the patients in the excision alone group and 4.9% of the patients in the excision with SNB group. The 5-year overall survival (OS) rates were 84.0 and 97.5% in the excision alone and excision with SNB groups, respectively. Significant differences were found in the rate of secondary neck metastasis and OS between the two groups. SNB may be effective in the detection of occult neck lymph node metastasis, with a reduction in the incidence of secondary neck metastasis and improvements in the 5-year OS in patients with early-stage (stage I/II) oral cancer.

Relationship of Prescribed Drugs with the Risk of Fall in Inpatients.

Falls are common in elderly patients and are often serious. Several drugs have been associated with an increased risk of fall. Older adults often take multiple drugs for chronic diseases, and thus may be at increased risk from drugs associated with fall. We investigated the association between drug use and falling in hospitalized older people, with the goal of identifying medications that may increase the risk of a fall. A retrospective case control study was performed at the National Hospital Organization Kumamoto Saishunso Hospital in Japan. Medications taken by patients who fell (n=57) were compared with those taken by patients who did not fall (n=63). The median age (interquartile range; IQR) of the fall and non-fall groups were 75.0 (67.0-83.0) and 80.0 (70.3-84.5) years, respectively. The characteristics of the two groups were similar, with no significant differences in age, sex, or body weight. The probability of falling increased when the patients used zolpidem [odds ratio (OR)=2.47; 95%CI: 1.09-5.63; p<0.05] and calcium channel antagonists (OR=0.299; 95%CI: 0.13-0.68; p<0.01), and was also related to physical factors (OR=2.27; 95%CI: 1.01-5.09; p<0.05). Elderly patients taking zolpidem may fall due to sleepiness, and blood pressure control may be important to prevent orthostatic high blood pressure. In the treatment of elderly people, medical staff should try to choose drugs that prevent fall or are not associated with falling.

The tumour stromal features are associated with resistance to 5-FU-based chemoradiotherapy and a poor prognosis in patients with oral squamous cell carcinoma.

It has been increasingly recognized that the tumour microenvironment is a critical factor involved in cancer progression. However, little is known about the clinical value of the stromal features in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the clinical significance of cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) in OSCC. OSCC specimens were obtained from 60 patients who underwent surgery following 5-fluorouracil-based chemoradiotherapy. Paraffin-embedded sections obtained from biopsy specimens were immunohistochemically analysed. The associations among CAFs, TAMs and various clinicopathological features were examined, and the effects of CAFs and TAMs on the prognosis were evaluated. In the group with a high level of CAFs, the incidence of advanced pT- and pN-stage cases was significantly higher than that in the group with the low level. A high TAMs tumour expression was significantly correlated with a poor response to preoperative chemoradiotherapy. A Kaplan-Meier analysis revealed that higher numbers of CAFs and TAMs were significantly correlated with a poor prognosis. These findings suggest that TAMs are a potential biomarker for predicting the clinical response to 5-FU-based chemoradiotherapy, and the expression status of the CAFs and TAMs may be useful for making treatment decisions to improve the survival of OSCC patients.

Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS.

PURPOSE: The peptides derived from ideal cancer-testis antigens, including LY6K, CDCA1, and IMP3 (identified using genome-wide cDNA microarray analyses), were used in immunotherapy for head and neck squamous cell cancer (HNSCC). In this trial, we analyzed the immune response to and safety and efficacy of vaccine therapy. EXPERIMENTAL DESIGN: A total of 37 patients with advanced HNSCC were enrolled in this trial of peptide vaccine therapy, and the OS, PFS, and immunologic response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and pentamer assays. The peptides were subcutaneously administered weekly with IFA. The primary endpoints were evaluated on the basis of differences between HLA-A*2402-positive [A24(+)] patients treated with peptide vaccine therapy and -negative [A24(-)] patients treated without peptide vaccine therapy among those with advanced HNSCC. RESULTS: Our cancer vaccine therapy was well tolerated. The OS of the A24(+) vaccinated group (n = 37) was statistically significantly longer than that of the A24(-) group (n = 18) and median survival time (MST) was 4.9 versus 3.5 months, respectively; P < 0.05. One of the patients exhibited a complete response. In the A24(+) vaccinated group, the ELISPOT assay identified LY6K-, CDCA1-, and IMP3-specific CTL responses in 85.7%, 64.3%, and 42.9% of the patients, respectively. The patients showing LY6K- and CDCA1-specific CTL responses demonstrated a longer OS than those without CTL induction. Moreover, the patients exhibiting CTL induction for multiple peptides demonstrated better clinical responses. CONCLUSIONS: The immune response induced by this vaccine may improve the prognosis of patients with advanced HNSCC.

Osteopontin-integrin α(v)ß(3) axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma.

Clinical applications of a chemotherapeutic agent, 5-fluorouracil (5-FU) in oral squamous cell carcinoma (OSCC) have been limited because of drug resistance. This study aimed to identify novel mechanisms of 5-FU resistance. Here we found increased osteopontin (OPN) gene expression in OSCC tissues with resistance to 5-FU-based chemoradiotherapy. OPN overexpression in OSCC cells led to 5-FU resistance and abrogated the prosurvival effect of the drug in a mouse xenograft model. OPN-induced 5-FU resistance required integrin αvß3. Targeting integrin αvß3 reversed the resistance in a 5-FU-resistant clone highly expressing OPN. Our data suggest that the OPN-integrin αvß3 axis is crucial for 5-FU resistance in OSCC.

Post-vitrectomy observation of Coat's disease associated with exudative retinal detachment, successfully treated with long-term silicone oil tamponade.

BACKGROUND: Treating Coat's disease with exudative retinal detachment remains a challenge, since vitreous surgery is frequently accompanied by serious complications such as secondary glaucoma. CASE: A 25-year-old woman with Coat's disease of the right eye had cystic exudative retinal detachment along the naso-inferior vessels at the peripheral retina, due to 5-o'clock telangiectasia. Right visual acuity was finger counting. This patient underwent vitrectomy simultaneously with cataract surgery, completed with silicone oil replacement, with thorough drainage of subretinal exudates through the artificial break. Although the complication of secondary glaucoma developed as a result of using silicone oil, approximately three years after the operation, this condition was ameliorated by removing the silicone oil. Thus, blindness was prevented in this patient. CONCLUSION: Long-term tamponade with silicone oil facilitates performing vitreous surgery in this patient suffering from Coat's disease associated from exudative retinal detachment.

Overexpression of fibronectin confers cell adhesion-mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells.

The tumor-associated microenvironment has been shown to protect tumor cells from treatment, and the extracellular matrix (ECM) is known to affect drug resistance as a key regulator of the tumor microenvironment. However, little is known about cell adhesion-mediated drug resistance (CAM-DR) due to cell-ECM contact in patients with oral squamous cell carcinoma (OSCC). In the present study, we evaluated the ECM molecule fibronectin (FN) using DNA microarray data obtained from parental and 5-FU-resistant OSCC cell lines. We investigated the effects of cell adhesion to FN on 5-FU resistance in OSCC cells and examined the activation of FN receptor ß1 integrin-mediated survival regulators such as ILK, Akt and NF-κB. In addition, we investigated whether FNIII14, a 22-mer peptide derived from FN that potently prevents ß1 integrin-mediated adhesion to FN, could overcome CAM-DR against 5-FU in OSCC cells and examined the activation of survival regulators and apoptosis-related molecules. Consequently, we obtained the following results. FN was extracellularly overexpressed in the 5-FU-resistant cells compared with that observed in the 5-FU-sensitive cells. Cell adhesion to FN enhanced 5-FU resistance and activated integrin-mediated ILK/Akt/NF-κB survival signaling in the 5-FU-resistant OSCC cells. Furthermore, the inhibition of cell adhesion to FN by FNIII14 enhanced chemosensitivity to 5-FU and apoptosis by suppressing ILK/Akt/NF-κB signaling in the 5-FU-resistant cells. These novel findings demonstrate that FN is a potentially useful biomarker and therapeutic target for improving the treatment of OSCC, particularly in the setting of 5-FU resistance.

A low Dicer expression is associated with resistance to 5-FU-based chemoradiotherapy and a shorter overall survival in patients with oral squamous cell carcinoma.

BACKGROUND: The deregulation of microRNA (miRNA) is associated with multiple processes involved in cancer progression. RNase III endonucleases, Dicer and Drosha, are key enzymes for miRNA biogenesis, and it has been reported that altered expressions of these molecules affect the clinical outcomes of patients with various cancers. However, the clinical value of measuring the levels of Dicer and Drosha in oral squamous cell carcinoma (OSCC) patients is unclear. The purpose of this study was to determine the clinical significance of the expressions of Dicer and Drosha in patients with OSCC. METHODS: Oral squamous cell carcinoma specimens were obtained from 61 patients who underwent surgery following 5-fluorouracil-based chemoradiotherapy at Kumamoto University Hospital between October 2003 and January 2009. Paraffin-embedded sections obtained from biopsy specimens were immunohistochemically analyzed. The associations between Dicer, Drosha, and various clinicopathological features were examined, and the effects of Dicer and Drosha on the prognosis were evaluated. RESULTS: A low Dicer tumor expression was significantly correlated with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis based on the overall survival revealed the Dicer expression status (hazard ratio, 0.34; P = 0.048) and pathological response to chemoradiotherapy (hazard ratio, 0.21; P = 0.014) to be significant prognostic factors in OSCC patients. On the other hand, the Drosha expression was not associated with any clinicopathological features or the prognosis. CONCLUSION: These results suggest that Dicer is a potential biomarker for predicting the clinical response to 5-FU-based chemoradiotherapy and the overall survival in patients with OSCC.

Topical dorzolamide for macular edema in the early phase after vitrectomy and epiretinal membrane removal.

BACKGROUND: The purpose of this study was to evaluate prospectively the efficacy of a topical carbonic anhydrase inhibitor in macular edema after vitrectomy. METHODS: Forty patients were included, all of whom had undergone vitrectomy combined with phacoemulsification and intraocular lens implantation for epiretinal membrane. Twenty eyes from 40 patients received topical 2% dorzolamide three times a day. The patients were followed up for at least 3 months. In this study, we evaluated the effect of dorzolamide on visual acuity, intraocular pressure, central macular thickness, and aqueous flare. RESULTS: Mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity preoperatively and 2 weeks, 1 month, and 3 months after surgery was 0.48 ± 0.23, 0.60 ± 0.16, 0.40 ± 0.29, and 0.24 ± 0.32, respectively, in the treatment group, and 0.40 ± 0.09, 0.44 ± 0.12, 0.32 ± 0.10, and 0.16 ± 0.09, respectively, in the control group. No statistically significant difference was observed between the two groups. Mean central macular thickness preoperatively and at 2 weeks and 3 months after surgery was 572.6, 427.2, and 333.4 µm, respectively, in the treatment group, and 571.4, 485.2, and 388.4 µm, respectively, in the control group. Mean aqueous flare preoperatively, and 1 month and 3 months after surgery was 8.6, 34.2, and 23.5 photon counts per millisecond (pc/ms), respectively, in the treatment group, and 9.7, 24.7, and 23.4 pc/ms, respectively, in the control group. No statistically significant differences were observed between data from the two groups. However, statistically significant (P < 0.05) differences in mean central macular thickness at 1 month and mean aqueous flare at 2 weeks after surgery were found between the treatment group (358.8 µm, 36.8 pc/ms) and the control group (467.8 µm, 64.0 pc/ms). Differences in mean intraocular pressure preoperatively and at 2 weeks, 1 month, and 3 months after surgery were not statistically significant between the two groups. Intraocular pressure never exceeded 21 mmHg. CONCLUSION: Topical dorzolamide significantly reduced mean central macular thickness at 1 month and mean aqueous flare at 2 weeks after surgery for epiretinal membrane compared with controls. Although further investigation of more cases and longer follow-up are needed, this study suggests that topical dorzolamide can be efficacious in reducing macular edema in the early phase after vitrectomy via its anti-inflammatory effect.

[Endothelial progenitor cell biology in retinopathy of prematurity].

Endothelial progenitor cells (EPC) play an important function in vasculogenesis and acquire a capability for vascular repair and formation as they differentiate. We examined the kinetics of EPCs from the viewpoint of EPC biology by creating oxygen-induced retinopathy (OIR) in a mouse model imitating retinopathy of prematurity (ROP), which causes pathological retinal neovascularization. Delayed differentiation, mobilization, and tissue recruitment of EPCs were obvious in the vaso-oblitelative phase, but they were promoted in the vascular proliferative state. Moreover, pathological retinal vasculature in OIR was repaired by the intravitreally transplanted definitive EPCs. These results suggest that delay of bone marrow derived EPC differentiation is a factor of morbid retinal blood vessels' formation in OIR. Aberrant kinetics of bone marrow derived EPC contribute to the formation of the retinal blood vessels, and it was proved that understanding and improving EPC differentiation can constitute a diagnostic and remedial base concept in the diagnosis of ROP.

Expression of PCNA, ICAM-1, and vimentin in lens epithelial cells of cataract patients with and without type 2 diabetes.

OBJECTIVE: In order to explore the pathological feature in the progression of cataract with type 2 diabetes, we compared the expression of proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule-1 (ICAM-1), and vimentin in lens epithelial cells (LECs) of cataract patients with and without type 2 diabetes. METHODS: The indirect immunoperoxidase technique was performed on anterior capsules obtained from 25 patients with type 2 diabetes (DM group) and 25 patients without diabetes (control group). Immunohistochemical difference in the expression of PCNA, ICAM-1, and vimentin in LECs between the 2 groups was investigated. RESULTS: PCNA expression was decreased (P=0.036) but ICAM-1 expression was significantly increased (P<0.0001) in the DM group as compared with that in the control group. No difference was noted in the expression of vimentin between the 2 groups (P=0.264). CONCLUSIONS: Decreased proliferation of LECs and increased expression of ICAM-1 in LECs might play an important role in the progression of cataract with type 2 diabetes.

Selective inhibition of nuclear factor-κB by nuclear factor-κB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma.

Nuclear factor-κB (NF-κB) activation contributes to the development of metastasis, thus leading to a poor prognosis in many cancers, including OSCC. However, little in vivo experimental data are available about the effects of NF-κB inhibition on OSCC metastasis. OSCC sublines were established from a GFP-expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to the in vivo passage number after cervical lymph node metastasis by a serial orthotopic transplantation model. In vitro migration and invasion were assessed in these cells, and the NF-κB activities and expression of NF-κB-regulated metastasis-related molecules were also examined. In in vivo experiments, the metastasis and survival of tumor-engrafted mice were monitored. Furthermore, the effects of a selective NF-κB inhibitor, NEMO-binding domain (NBD) peptide, on metastasis in GSAS/N5-engrafted mice were assessed, and engrafted tongue tumors were immunohistochemically examined. Highly metastatic GSAS/N3 and N5 cells showed an enhanced NF-κB activity, thus contributing to increased migration, invasion, and a poor prognosis compared with the parent cells. Furthermore, the expression levels of NF-κB-regulated metastasis-related molecules, such as fibronectin, ß1 integrin, MMP-1, -2, -9, and -14, and VEGF-C, were upregulated in the highly metastatic cells. The NBD peptide suppressed metastasis and tongue tumor growth in GSAS/N5-inoculated mice, and was accompanied by the downregulation of the NF-κB-regulated metastasis-related molecules in engrafted tongue tumors. Our results suggest that the selective inhibition of NF-κB activation by NBD peptide may provide an effective approach for the treatment of highly metastatic OSCC.