Erratum to "Isocudraxanthone K Induces Growth Inhibition and Apoptosis in Oral Cancer Cells via Hypoxia Inducible Factor-1α".

[This corrects the article DOI: 10.1155/2014/934691.].

Hepatitis B Virus-X Downregulates Expression of Selenium Binding Protein 1.

Selenium binding protein 1 (SELENBP1) has been known to be reduced in various types cancer, and epigenetic change is shown to be likely to account for the reduction of SELNEBP1 expression. With cDNA microarray comparative analysis, we found that SELENBP1 is markedly decreased in hepatitis B virus-X (HBx)-expressing cells. To clarify the effect of HBx on SELENBP1 expression, we compared the expression levels of SELENBP1 mRNA and protein by semi-quantitative RT-PCR, Northern blot, and Western blot. As expected, SELENBP1 expression was shown to be reduced in cells expressing HBx, and reporter gene analysis showed that the SELENBP1 promoter is repressed by HBx. In addition, the stepwise deletion of 5' flanking promoter sequences resulted in a gradual decrease in basal promoter activity and inhibition of SELENBP1 expression by HBx. Moreover, immunohistochemistry on tissue microarrays containing 60 pairs of human liver tissue showed decreased intensity of SELENBP1 in tumor tissues as compared with their matched non-tumor liver tissues. Taken together, our findings suggest that inhibition of SELENBP1 expression by HBx might act as one of the causes in the development of hepatocellular carcinoma caused by HBV infection.

A better facial contour accomplished by parotid duct preserving superficial parotidectomy.

Depression of facial contour after parotidectomy is still challenging to many of surgeons. A 68-year-old man presented with a 4-month history of a painless swelling in both parotid area. The mass was multiple and fixed at the parotid region. We conducted a parotid duct preserving bilateral superficial parotidectomy by one-stage operation to remove the multiple tumors. A lazy S incision was made in both preauricular area and the peripheral branches of the facial nerve were identified using surgical landmark. After dissecting the branches of the facial nerve and parotid duct, main parotid duct was preserved but only small fine ductules from the superficial lobe were ligated. Parotid gland was excised from its anterior aspect with about 1 cm of normal parotid tissue margin. The patient was followed up for 6 years to evaluate postoperative parotid gland function and the computed tomography (CT) was taken. Patient was satisfied with no significant complication such as sunken changes in facial contour, facial nerve function. As far as we know, it is the first study to compare long-term soft tissue contours of soft tissue of duct preserving superficial parotidectomy with duct sacrificing superficial parotidectomy by means of CT findings.

Traumatic Epidermoid Inclusion Cyst on Cheek Area.

An epidermoid inclusion cyst is basically an epidermoid cyst resulting from the traumatic implantation of epidermal elements into the dermis with their subsequent cystic transformation. A case of an epidermal inclusion cyst of the cheek region is described in a 54-year-old man, whose feature was rather unusual, in that it presented as a fixed, indurated, inflamed, and sometimes, mimicking a parotid gland infection. The cyst was particularly persistent and recurred within a month of its medical treatment and had to be re-excised along with the adjacent parotid mass.

Pathologic Patency Analysis of the Descending Branch of the Lateral Femoral Circumflex Artery in Head and Neck Reconstruction.

The pathophysiology of atherosclerotic lesion progression shows that the composition of an atherosclerotic lesion is related to the clinical status of the patient. In humans, certain artery types, such as the coronary artery, renal artery, and internal carotid artery at the level of the carotid sinus and aorta, are prone to develop clinically manifested atherosclerosis, whereas other artery types remain free of atherosclerotic disease. In head and neck reconstruction, various flaps are used. Especially, anterolateral thigh free flap is a good option for reconstruction. The descending branch of the lateral femoral circumflex artery (DLFCA) is useful as an alternative arterial graft and pedicle for anterolateral thigh flaps. However, no pathophysiological study has determined whether the DLFCA is atherosclerosis resistant. The authors studied the morphological characteristics of the DLFCA and assessed the correlation with the degree of atherosclerotic change. Seventeen perforators originating from the DLFCA were selected. All sections were classified into 6 lesion types according to the American Heart Association. Seven sections contained a stenotic area of at least 25% and 1 section was > 50%. All sections were classified as type 1. In conclusion, the DLFCA only has physiological adaptation in the intimal layer and no relationship with atherosclerotic risk factors. Therefore, the DLFCA is atherosclerosis resistant and surgeons should not hesitate to use the DLFCA.

Papillary Carcinoma Within a Thyroglossal Duct Cyst in a 17-Year-Old Child.

Thyroglossal duct cyst is a frequent event; however, papillary carcinoma within a thyroglossal duct cyst is rare, particularly in children. A 17-year-old girl presented with an asymptomatic mid-submental mass for the last 2 months. The diagnosis of thyroglossal duct cyst was made based on physical examination and computed tomography finding. After performance of Sistrunk procedure, an incidental papillary carcinoma within the thyroglossal duct cyst was observed on pathology. We reviewed the pediatric cases of thyroglossal duct carcinoma, and then decided not to perform a concurrent thyroidectomy. We will continue close follow-up for future thyroid involvement.

Fingertip Replantation Using Y-Shaped Vein Graft to Pulp Artery.

Re-establishing adequate venous outflow is the most important factor for success of fingertip replantation. However, in zone I level, replantation is very difficult, especially in repairing venous circulation. The authors have made an attempt to replantation using Y-shaped vein (YSV) graft to identify and repair veins easily in fingertip replantation. From January 2007 to December 2012, a total of 46 fingertip replantations in 44 consecutive patients with amputations in the Tamai zone I level were performed by using YSV graft. In all patients, arterial anastomosis was performed using YSV graft, and interpositional vein grafts were used for venous repair. The overall success rate of the YSV-grafted replantations was 91.3% (42/46). Postoperative vascular complications occurred in 6 YSV-grafted replantations (13%), and pulp atrophy in the YSV-grafted digits was 9.5% (4/42). Fingertip replantation in zone I level is a difficult territory to a microsurgeon, especially anastomosing veins. However, our YSV grafting technique has shown value in this setting, enabling better esthetic and functional results.

Isocudraxanthone K induces growth inhibition and apoptosis in oral cancer cells via hypoxia inducible factor-1α.

Isocudraxanthone K (IK) is a novel, natural compound from a methanol extract of the root bark of Cudrania tricuspidata. It has not been shown previously that IK possessed antitumor activity. We investigated the antitumor effects and molecular mechanism of IK and related signal transduction pathway(s) in oral squamous cell carcinoma cells (OSCCCs). The MTT assay revealed that IK had an antiproliferative effect on OSCCCs, in a dose- and time-dependent manner. IK induced apoptosis in OSCCCs, as identified by a cell-cycle analysis, annexin V-FITC and propidium iodide staining, and the nuclear morphology in cell death. IK caused time-dependent phosphorylation of Akt, p38, and ERK (extracellular signal-regulated kinase). In addition, IK increased the cytosolic to nuclear translocation of nuclear factor-κB (NF-κB) p65 and the degradation and phosphorylation of IκB-α in HN4 and HN12 cells. Furthermore, IK treatment downregulated hypoxia-inducible factor 1α (HIF-1α) and its target gene, vascular endothelial growth factor (VEGF). Cobalt chloride (CoCl2), a HIF-1α activator, attenuated the IK-induced growth-inhibiting and apoptosis-inducing effects, and blocked IK-induced expression of apoptosis regulatory proteins, such as Bax, Bcl-2, caspase-3, caspase-8, and caspase-9, and cytochrome c. Collectively, these data provide the first evidence of antiproliferative and apoptosis-inducing effects of IK as a HIF-1α inhibitor and suggest it may be a drug candidate for chemotherapy against oral cancer.

The role of PIN1 on odontogenic and adipogenic differentiation in human dental pulp stem cells.

Recently, the involvement of PIN1, a peptidyl-prolyl cis/trans isomerase, has been reported in age-related bone homeostasis and adipogenesis. However, the role of PIN1 during odontogenic and adipogenic differentiation remains to be fully understood, particularly regarding human dental pulp stem cells (HDPSCs). Thus, in the present study, we have investigated the role of PIN1 in odontogenic and adipogenic differentiation of HDPSCs and signaling pathways possibly involved. PIN1 mRNA and protein level were upregulated in a time-dependent manner during adipogenic differentiation, increasing until 1 day of odontogenic induction and then steadily declined during odontogenic differentiation. Treatment of a known PIN1 inhibitor, juglone, significantly increased odontogenic differentiation as confirmed by alkaline phosphatase (ALP) activity, calcium deposition, and mRNAs induction of odontogenic markers [ALP, osteopontin (OPN), osteocalcin (OCN), dentin sialophosphoprotein (DSPP), and dentin matrix protein 1 (DMP-1)]. On the contrary, adipogenic differentiation was dramatically reduced upon juglone treatment, with concomitant downregulation of lipid droplet accumulation and adipogenic marker genes [peroxisome proliferation-activated receptor gamma (PPARγ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (AP2)]. In contrast to PIN1 inhibition, the overexpression of PIN1 via adenoviral infection (Ad-PIN1) in HDPSCs inhibited odontogenic differentiation but increased adipogenic differentiation, in which stem cell property markers such as stage-specific embryonic antigen-4 (SSEA-4) and STRO-1 were upregulated during odontogenic differentiation but downregulated in adiopogenic differentiation. Consistently, juglone-mediated inhibition of PIN1 augmented the osteogenic medium (OM)-induced activation of bone morphogenetic protein (BMP), Wnt/ß-catenin, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB) pathway, which response was reversed by Ad-PIN1. Moreover, juglone blocked the adipogenic induction medium-induced activation of PPARγ, C/EBPα, C/EBPß, ERK, and NF-κB pathways, which was rescued by Ad-PIN1 infection. In summary, the present study shows for the first time that PIN1 acts as an important modulator of odontogenic and adipogenic differentiation of HDPSCs and may have clinical implications for regenerative dentistry.

Clinical analysis of an ultrasound system in the evaluation of skin cancers: correlation with histology.

BACKGROUND: The assessment of skin cancers in the clinical setting is often difficult, with important features such as depth and width remaining unknown until the biopsy with pathology reports are received. When we remove skin cancers, with those especially involving the face, aesthetics and invasion to surrounding structures such as bone and cartilage are important features for deciding the optimal surgical procedure and future reconstructive options. The aim of the study was to compare the accuracy of the ultrasound system in vivo and to correlate the results with the histopathological tumor thickness measured in skin cancer patients. PATIENTS AND METHODS: From March 2010 to February 2012, we reviewed 40 patients who comprised a total of 49 skin lesions involving the face, neck, and scalp. Each skin lesions were classified by 9 facial aesthetic units. The patient's various skin lesions were scanned using an ultrasound system device (Philips iU22 xMatrix US), with a 5-17-MHz compact linear transducer. Using the ultrasound system, we analyzed the shape, depth, echogenicity, size, invasion skin level, and vascularity of the skin cancer lesions. The results were correlated with the histology, with special note to the depth of involvement. RESULTS: Of the 40 patients recruited, 15 were male and 25 were female, ranging in age from 53 to 92 years (mean ± SD 78.7 ± 13.7 years). Clinically, 49 lesions suspicious of skin cancer were identified and ultrasounds were performed preoperatively. Depth was measured by ultrasound and histology. Mean ultrasound depth of skin lesion was 3.97 ± 3.15 mm (range 0.80-14.00), and it was found to be 4.04 ± 2.92 mm (range 1.00-14.00) based off of histology. There was excellent correlation (interclass correlation coefficient, 0.953) between the depth of the skin lesions measured histologically and by using the ultrasound. CONCLUSION: The ultrasound is not meant to replace histologic evaluations, but it can be used as another diagnostic tool to provide improved preoperative planning. It can be used as a noninvasive, easy, and low-cost screening method for various skin cancers, and provides valuable information such as lesion margins, shape, layers of involvement, and vascularity patterns.

Cavernous hemangioma with large phlebolith of the parotid gland.

Hemangiomas are vascular anomalies characterized by increased proliferation and turnover of endothelial cells. Hemangiomas of the parotid region are relatively uncommon in adult population, and there are a few reports of hemangioma with large phlebolith within the parotid gland. We herein report a case of it. Sialography may be a useful investigation method in the evaluation of radiopaque lesions localized intraglandularly in the parotid area to rule out the sialolith. Cavernous hemangioma with phleboliths should be included in the differential diagnosis of a swelling in the mandibular area.

Pediatric lipoblastoma of the neck.

BACKGROUND: Lipoblastoma is a rare, benign, and encapsulated tumor arising from embryonic white fat. Most of the cases occur in the extremities and the trunk; only a few cases in the head and the neck are reported. Thus, we present a case of lipoblastoma of the neck with a review of the literature. PATIENT AND METHOD: A 1-year-old male infant presented to our hospital, with a history of painless swelling in the left side of the neck for 3 months that was rapidly enlarged. His birth history and medical history were unremarkable. A physical examination demonstrated a soft and compressible mass in the left side of the neck. The mass was nontender to palpation and mobile without cellulitic changes in the overlying skin. A computed tomographic scan showed that the mass is heterogenous, has low attenuation in nature, and is 3.8 × 2.8 × 9 cm in size. RESULT: Under general anesthesia, transverse cervical incision was made through the neck wrinkle, and there was no invasion of any of the neck structures. Complete surgical excision demonstrated yellowish-white, irregular lobules of immature fat cells separated by a loose and myxoid connective tissue. Grossly, the mass was a homogeneous tan-pink gelatinous mass. A microscopic examination demonstrated a small number of capillaries and mature fat cells, and differentiating immature lipoblastoma cells were detected in the myxoid stroma. A pathologic finding confirmed the diagnosis of lipoblastoma. The postoperative course was uneventful. The patient underwent follow-up for 1 year after the operation, and there was no evidence of recurrence. CONCLUSIONS: The most common presentation of lipoblastoma is a painless, rapidly enlarging neck mass. Published reports showed that most of them occur before the age of 3 years. Complete surgical excision is the treatment of choice. Although lipoblastoma is an extremely rare benign tumor, it should be considered in the diagnosis of neck mass in children younger than 3 years.

Growth inhibition and apoptosis-inducing effects of cudraflavone B in human oral cancer cells via MAPK, NF-κB, and SIRT1 signaling pathway.

The goal of this study was to investigate the effect and molecular mechanism of cudraflavone B, a prenylated flavonoid isolated from the root bark of Cudrania tricuspidata, against oral squamous cell carcinoma cells. We observed that cudraflavone B inhibited proliferation of these cells in a time- and dose-dependent manner. At 15 µM, cudraflavone B induced cell death via apoptosis (characterized by the appearance of nuclear morphology) and increased the accumulation of the sub-G1 peak (portion of apoptotic annexin V positive cells). Treatment with cudraflavone B triggered the mitochondrial apoptotic pathway (indicated by induction of the proapoptotic protein p53 and the p21 and p27 effector proteins), downregulation of cell cycle regulatory proteins (e.g., p-Rb, changing Bax/Bcl-2 ratios, cytochrome-c release), and caspase-3 activation. Cudraflavone B time-dependently activated NF-κB, the MAP kinases p38, and ERK, and induced the expression of SIRT1. SIRT1 activator, resveratrol, dose-dependently attenuated the growth-inhibitory and apoptosis-inducing effect of cudraflavone B and blocked cudraflavone B-induced regulatory protein expressions in the mitochondrial pathway such as p53, p21, p27, Bax, caspase-3, and cytochrome-c. Conversely, treatment with SIRT1 inhibitor sirtinol caused opposite effects. These results demonstrate for the first time that the molecular mechanism underlying the antitumor effect in oral squamous cell carcinoma cells is related to the activation of MAPK/and NF-κB as well as of the SIRT1 pathway. Therefore, cudraflavone B may be a lead for the development of a potential candidate for human oral squamous cell carcinoma cells.

Involvement of Nrf2-mediated upregulation of heme oxygenase-1 in mollugin-induced growth inhibition and apoptosis in human oral cancer cells.

Although previous studies have shown that mollugin, a bioactive phytochemical isolated from Rubia cordifolia L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G1 phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF- κ B and NF- κ B-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF- κ B.

Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells.

Although previous studies have demonstrated that hydrogen sulfide (H(2)S) stimulated or inhibited osteoclastic differentiation, little is known about the effects of H(2)S on the differentiation of osteoblasts and osteoclasts. To determine the possible bioactivities of H(2)S on bone metabolism, we investigated the in vitro effects of H(2)S on cytotoxicity, osteoblastic, and osteoclastic differentiation as well as the underlying mechanism in lipopolysaccharide (LPS) and nicotine-stimulated human periodontal ligament cells (hPDLCs). The H(2)S donor, NaHS, protected hPDLCs from nicotine and LPS-induced cytotoxicity and recovered nicotine- and LPS-downregulated osteoblastic differentiation, such as alkaline phosphatase (ALP) activity, mRNA expression of osteoblasts, including ALP, osteopontin (OPN), and osteocalcin (OCN), and mineralized nodule formation. Concomitantly, NaHS inhibited the differentiation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in mouse bone marrow cells and blocked nicotine- and LPS-induced osteoclastogenesis regulatory molecules, such as RANKL, OPG, M-CSF, MMP-9, TRAP, and cathepsin K mRNA. NaHS blocked nicotine and LPS-induced activation of p38, ERK, MKP-1, PI3K, PKC, and PKC isoenzymes, and NF-κB. The effects of H(2)S on nicotine- and LPS-induced osteoblastic and osteoclastic differentiation were remarkably reversed by MKP-1 enzyme inhibitor (vanadate) and expression inhibitor (triptolide). Taken together, we report for the first time that H(2)S inhibited cytotoxicity and osteoclastic differentiation and recovered osteoblastic differentiation in a nicotine- and periodontopathogen-stimulated hPDLCs model, which has potential therapeutic value for treatment of periodontal and inflammatory bone diseases.

Porphyromonas gingivalis lipopolysaccharide regulates interleukin (IL)-17 and IL-23 expression via SIRT1 modulation in human periodontal ligament cells.

Increased interleukin (IL)-17 and IL-23 levels exist in the gingival tissue of periodontitis patients, but the precise molecular mechanisms that regulate IL-17 and IL-23 production remain unknown. The aim of this study was to explore the role of SIRT1 signaling on Porphyromonas gingivalis lipopolysaccharide (LPS)-induced IL-17 and IL-23 production in human periodontal ligament cells (hPDLCs). IL-17 and IL-23 production was significantly increased in LPS-treated cells. LPS treatment also led to the upregulation of SIRT1 mRNA and protein expression. LPS-induced IL-17 and IL-23 upregulation was attenuated by pretreatment with inhibitors of phosphoinositide 3-kinase (PI3K), p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and NF-κB, as well as neutralizing antibodies against Toll-like receptors (TLRs) 2 and 4. Sirtinol treatment (a known SIRT1 inhibitor) or SIRT1 knockdown by small interfering RNA blocked LPS-stimulated IL-17 and IL-23 expression. Further investigation showed that LPS decreased osteoblast markers (i.e., ALP, OPN, and BSP) and concomitantly increased osteoclast markers (i.e., RANKL and M-CSF). This response was attenuated by inhibitors of the PI3K, p38, ERK, JNK, NF-κB, and SIRT1 pathways. These findings, for the first time, suggest that human periodontopathogen P. gingivalis LPS is implicated in periodontal disease bone destruction and may mediate IL-17 and IL-23 release from hPDLCs. This process is dependent, at least in part, on SIRT1-Akt/PI3K-MAPK-NF-κB signaling.

Herpes zoster developing within recent subciliary incision scar.

Herpes zoster is a common dermatologic disease characterized by unilateral pain and vesicular lesions over the unilateral sensory dermatomes being caused by the reactivation of varicella zoster virus, and its incidence seems to be increasing recently. In case of involving the ganglion of the fifth cranial nerve (trigeminal nerve), it can descend down the affected nerve into the skin, then producing an eruption in the dermatome. Among the patients with this disease, about 40% to 50% had associated conditions such as diabetes mellitus, hypertension, pulmonary tuberculosis, liver diseases, peptic ulcer, hypothyroidism, or pharyngitis but rarely facial trauma. Generally, herpes zoster was commonly associated with systemic disorders, and the treatment duration was prolonged in associated diseases. However, herpes zoster occurring specifically at the site of previously traumatized facial bone has not yet been reported. Retrospective study of 1 case of herpes zoster with blow-out fracture, which had been treated with acyclovir and steroid, was done. Follow-up length was about 3 months. After treatment, the patient became stable, and there was no complication. We treated herpes zoster developing within a recent operative subciliary scar, and the case is presented with the review of literature. Finally, facial trauma or reconstruction of the orbital floor with alloplastic implant might be a risk factor for herpes zoster in traumatized patient.

Parotid gland tumors in a Korean population.

Salivary gland tumors occur in about 3% of the head and neck tumors, and among the salivary gland tumors, parotid gland tumor occurs in about 80%. Because of its low frequency and small cases, it is hard to establish the epidemiologic characteristics of the tumors. This study was performed retrospectively from February 1987 to August 2010. There were 95 male, and 76 female patients. Most of the patients complained of the painless and progressively enlarged mass in the preauricular area. Peak incidence of benign parotid gland tumor was at the fifth decade of life. In the malignant tumors, peak age in males was the eighth decade, and peak age in females was from the third to the fifth decade of life, which was relatively younger and has a broad range of spectrum. Pleomorphic adenoma was the most common benign tumor of the 93 cases (61.6%) followed by Warthin tumor, occurring in 20 cases (13.2%). Squamous cell carcinoma, reported in 6 cases (30%), is the most frequent. Mucoepidermoid carcinoma was the second leading tumor. In conclusion, parotid gland tumor incidence was found to be higher in males. Pleomorphic adenoma was the most commonly encountered type of parotid gland neoplasms, which is in agreement with findings from all of the published literature from all over world. In contrast to most of the previous studies, squamous cell carcinoma was the most frequent malignant tumor found. Based on the data in this study, it has significant clinical respect and is helpful in the management of parotid gland tumors in Orientals.