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Although forkhead box protein M1 (FOXM1) is markedly upregulated in human premalignant and oral squamous cell carcinoma (OSCC) tissues and cultured cells, the association of FOXM1 expression with OSCC prognosis is not well understood. The present study investigated the possible association of FOXM1 expression in patients with OSCC with their clinicopathological characteristics and clinical outcomes. The expression of FOXM1 protein in OSCC tissues from 119 patients was evaluated by immunohistochemistry, and the results demonstrated that FOXM1 overexpression in patients with OSCC was associated with tumour recurrence and poor prognosis. To study the in vitro effects of FOXM1, its expression was decreased by small interfering RNA (siRNA) in OSCC cell lines, and FOXM1 knockdown decreased the proliferative, migratory and invasive capacities of cells. FOXM1 inhibition by siRNA gave rise to reduced expression of vimentin and increased expression of E-cadherin. The present study reported FOXM1 as a novel predictor of tumour recurrence in patients with OSCC and its potential involvement in epithelial-mesenchymal transition in OSCC cells. [ABSTRACT FROM AUTHOR]

Background: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. Aims: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. Methods: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. Results: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. Conclusions: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC), and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin β4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC. [ABSTRACT FROM AUTHOR]

Abstract: We studied the effect of stereotactic surgery in cases of alcohol dependence. Twelve patients with a psychological dependence on alcohol (treated systematically with medication for detoxification 3–8 times in various rehabilitation centers before, but had relapsed within 2 weeks after withdrawal) were treated by ablating the nucleus accumbens (NAC) bilaterally using stereotactic surgery. The therapeutic effect and safety evaluation index of the surgery were analyzed. The timing of the conducted evaluations was preoperatively and in the sixth postoperative month. Currently, relapse has not occurred in 9 cases. Relapse occurred in 3 cases after surgery. The prevalence of relapse was 16.7% within 6 months, and 25% within 12 months. Non-specific complications of this type of surgery (e.g., intracranial hematoma, infection) were not observed. One case in 12 patients suffered dysosmia, but he recovered completely 4 months later after surgery. The full-scale intelligence quotient (FSIQ) and memory quotient (MQ) of these patients were significantly improved 6 months postoperatively compared with preoperatively. The severity of alcohol dependence scale and a scale measuring alcohol craving in these patients were significantly decreased. There were also significant changes over time in the Minnesota multiphasic personality inventory (MMPI) profile, suggesting a decrease in depression, irritability, and psychopathy. Ablating specified targets (NAC) using stereotactic surgery is a safe method to alleviate alcohol craving, reduce relapse rates and improve quality-of-life in patients with psychological dependence on alcohol. [Copyright &y& Elsevier]

Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Although the neuroprotective effects of ghrelin have been demonstrated in several studies, whether ghrelin reduces EBI after SAH remains unknown. In this study, we hypothesized that treatment with ghrelin would attenuate EBI after SAH, and that this protection would be mediated, at least in part, by activation of the PI3K/Akt signaling pathway. Adult male Sprague-Dawley rats ( n =100) were randomly divided into the following groups: control group ( n =20), SAH group ( n =20), SAH+vehicle group ( n =20), SAH+ghrelin group ( n =20) and SAH+ghrelin+LY294002 group ( n =20). The rats were injected with autologous blood (0.3 mL) into the prechiasmatic cistern to induce SAH. Ghrelin (80 μg/kg, IP), or an equal volume of vehicle, was administered immediately after surgery. The PI3K inhibitor, LY294002, was applied to manipulate the proposed pathway. Mortality, neurological scores, brain edema, cell apoptosis, and the expression of p-Akt, and cleaved caspase-3 proteins were assayed after 24 h SAH. Ghrelin significantly improved neurological function and reduced neuronal apoptosis and brain edema at 24 h after SAH. The level of p-Akt, expressed mainly in neurons, was markedly up-regulated. Additionally, the level of cleaved caspase-3 was decreased by ghrelin treatment. The beneficial effects of ghrelin in SAH rats were partially suppressed by LY294002. These results demonstrate that ghrelin may reduce EBI after SAH, via a mechanism involving the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal transcription regulator that controls the expression of numerous antioxidant and cytoprotective genes, was recently defined as a proto-oncogene. However, the role and mechanism of Nrf2 in glioma pathoetiology remain unclear. In the present study, we first evaluated the expression patterns of Nrf2 in normal human astrocytes and 3 glioblastoma (GBM) cell lines (U251, U87 and A172) and found that all 3 GBM cell lines overexpressed Nrf2, with the highest level observed in the U251 cells. We further assessed the biological effects of Nrf2 in U251 cells by specific knockdown of Nrf2 using lentivirus‑mediated RNA interference. We discovered that Nrf2 deficiency led to a decrease in U251 cell proliferation and caused intracellular redox imbalance [diminished glutathione (GSH) levels and increased reactive oxygen species (ROS) levels]. Both N-acetylcysteine and glutathione monoethyl ester (GMEE) supplementation completely eliminated the increased levels of ROS that were present in the Nrf2‑deficient U251 cells. However, only GMEE supplementation both reversed Nrf2 deficiency-induced cell growth arrest and restored intracellular GSH levels. Moreover, AKT and ERK1/2 signaling were both impaired in the Nrf2-knockdown U251 cells, but GMEE supplementation restored AKT signaling but not ERK1/2 signaling, and blocking AKT signaling with an AKT-specific inhibitor greatly diminished the GMEE-induced Nrf2-deficient cell proliferation. In conclusion, our findings revealed novel functions for Nrf2 in the regulation of redox status and cell proliferation, and that intracellular GSH levels and AKT signaling are required for this process, a new viewpoint by which to comprehend the role and underlying mechanism of Nrf2 in tumorigenesis.

Background: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status., Aims: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively., Methods: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving., Results: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group., Conclusions: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively., (© 2016 S. Karger AG, Basel.)

Distant metastasis is a common cause of mortality in patients with salivary gland adenoid cystic carcinoma (SACC). However, presently, the development of distant metastasis is unable to be predicted in clinical practice. Recent studies have shown that overexpression of podoplanin is associated with metastasis and survival in patients with several cancer types. The purpose of the present study was to determine whether podoplanin is overexpressed in SACC and whether such overexpression is associated with distant metastasis and survival. Podoplanin expression was determined using immunohistochemistry (IHC) in tumors from 40 SACC patients. The expression status was analyzed in regards to patient clinicopathological parameters and survival rates. Overexpression of podoplanin was detected in 13 (32.5%) of the 40 tumors. Overexpression was significantly associated with disease-free survival (P=0.025) and distant metastasis (P=0.015), although it was not associated with recurrence and overall survival. In conclusion, podoplanin is overexpressed in a subset of SACCs and may be a biomarker predicting distant metastasis in patients with SACC.

The contactin 1 (CNTN1) gene exerts oncogene‑like activities and its expression has been linked to several human malignancies. In this study, a possible association between CNTN1 expression and clinicopathological parameters and clinical outcomes in patients with oral squamous cell carcinoma (OSCC) was examined. CNTN1 protein expression was evaluated by immunohistochemistry in OSCC tissues of 45 patients. For the immunohistochemical assessment of CNTN1 expression, the cytoplasmic staining labeling index was analyzed using a semiquantitative score. The association between CNTN1 protein levels and clinicopathological factors was analyzed using the Mann-Whitney U test for categorical variables and the Kruskal-Wallis test for continuous variables. The effects of CNTN1 expression on overall and disease-free survival were assessed by using univariate survival analysis. The transcript levels of CNTN1 were detected in OSCC cell lines. In addition, specific siRNA against CNTN1 was applied to investigate the effect exerted by CNTN1 ablation on OSCC cell lines by proliferation and invasion assays in vitro. During follow-up, 16 patients (35.56%) had succumbed to OSCC; the median follow-up of patients was 5.0 years (range, 0.2-8.3). A high expression of CNTN1 was markedly associated with the regional lymph node metastasis of patients with OSCC (P=0.006). CNTN1 expression was significantly associated with overall survival of patients with OSCC (P=0.032; log-rank test) and disease-free survival of patients with OSCC (P=0.038; log-rank test). In addition, CNTN1 ablation notably suppressed the invasion potential of OSCC cell lines, but there was no significant change in the proliferation of OSCC cell lines by CNTN1 knockdown in vitro. The study supports CNTN1 as a novel predictor of regional lymph node metastasis in patients with OSCC and a prognostic marker for OSCC in patients.

Objective: To describe the application of lateral arm free flap (LAFF) in reconstruction of defects in the oral and maxillofacial regions following ablative oncological surgery., Subjects and Methods: The study included 16 patients (13 male, 3 female, mean age 56, range 35-69 years). Sixteen LAFF were harvested to reconstruct defects caused by the dissection of malignant tumors of the oral and maxillofacial regions. The tumor was squamous cell carcinoma of the tongue (6 cases), floor of the mouth (4), retromolar area (3), inner cheek (2), and lower gingival (1). Flap sizes ranging from 5 x 7 to 6 x 9 cm were harvested using a sterile tourniquet for bloodless technique. The anastomoses were carried out using a magnifier or microscope. All donor defects were closed primarily., Results: Fourteen flaps healed without venous insufficiency. One flap, in a female patient, survived with mild local microcirculatory obstruction but that of another female patient developed necrosis. There was no significant complication at the donor sites. The advantages of this flap include anatomically reliable vascular supply, accessible donor site, and the aesthetic quality of donor tissue is good. Compared with the radial artery, the posterior radial collateral artery is a nonessential vessel of the arm. The disadvantages are the relatively smaller vessel size for anastomosis and thicker subcutaneous tissue., Conclusions: For the repair of moderate-sized defects of the maxillofacial area, especially in male patients, the LAFF can be recommended., (2007 S. Karger AG, Basel)