Restoration of Proresolution Pathway with Exogenous Resolvin D1 Prevents Sevoflurane-Induced Cognitive Decline by Attenuating Neuroinflammation in the Hippocampus in Rats with Type 2 Diabetes Mellitus.

Sevoflurane (SEV), a commonly used volatile anesthetic, has been shown to cause cognitive decline in diabetic rats by aggregating neuroinflammation in the hippocampus, but the underlying mechanisms are unknown. Recent evidence suggests that neuroinflammation could be a consequence of failure to resolve inflammation by specialized pro-resolving lipid mediators including resolvin D1 (RvD1). Here we first examined whether type 2 diabetes mellitus (DM) alters RvD1 proresolution pathway. Diabetic Goto-Kakizaki (GK) rats and non-diabetic Wistar rats received control or 2.6% SEV exposure for 4 h. Seven days after exposure, GK control rats, compared with Wistar control rats, had significantly lower RvD1 levels in plasma and CSF and decreased RvD1 receptor FPR2 expression in the hippocampus. SEV increased RvD1 levels in plasma and CSF and FPR2 expression in the hippocampus in Wistar rats but not in GK rats. We next examined whether RvD1 treatment of GK rats can prevent SEV-induced neuroinflammation and cognitive decline. GK rats received control, SEV or SEV and once-daily treatment with exogenous RvD1 (0.2 ug/kg, ip) for 7 days. RvD1 administration markedly increased RvD1 levels in plasma and CSF and FPR2 expression in the hippocampus in GK rats received SEV. Compared with GK control rats, GK rats received SEV exhibited shorter freezing times in trace fear conditioning task, which was accompanied by increased microglia activity and pro-inflammatory cytokine expression in the hippocampus. RvD1 administration attenuated SEV-induced increases in microglia activity and pro-inflammatory cytokine expression in the hippocampus, preventing cognitive decline in GK rats. Notably, neither SEV nor RvD1 altered metabolic parameters in GK rats. The results suggest that RvD1 proresolution pathway is impaired in the brain of diabetic GK rats. which may enhance the susceptibility to SEV, contributing to neuroinflammation and cognitive decline. Restoration of RvD1 proresolution pathway in diabetic GK rats with exogenous RvD1 can prevent SEV-induced cognitive decline by attenuating neuroinflammation in the hippocampus.

Radiation-induced sarcoma of head and neck: 50 years of experience at a single institution in an endemic area of nasopharyngeal carcinoma in China.

Radiation-induced sarcoma in the head and neck (RISHN) is a rare condition whose clinical presentation and management remain difficult because of its low incidence. In this retrospective study, we analyzed the symptoms, diagnosis, and the treatment of 16,634 patients with head and neck disease, who received radiotherapy between 1960 and 2010 at the Affiliated Tumor Hospital and its predecessor, Guangxi Medical University, China. Among these patients, 16 with a first tumor of nasopharyngeal carcinoma (NPC) and 1 with squamous carcinoma of the tongue met the criteria of RISHN in the head and neck. Our epidemiological data showed that the incidence of RISHN rose from 0.06 to 0.17% from 1960 to 2010; the 3-year overall survival rate was 19.1%, and 3-year disease-free survival rate was 11.1%. The mean latency (SD) period was 93.2 (33) months. Based on the experiences at our institution, we suggest that RISHN is a rare complication after radiotherapy for head and neck tumors, especially NPC. Owing to its low incidence, it should not be a major factor affecting decisions about radiotherapy. Nevertheless, there may be a possibility of increasing incidence of RISHN after radiotherapy of NPC, as shown in our epidemiological results. Given the poor prognosis of RISHN, this possibility should be taken into serious consideration before determination of high-dose radiotherapy for patients with NPC and other head and neck tumors.

Eight-signature classifier for prediction of nasopharyngeal [corrected] carcinoma survival.

PURPOSE: Currently, nasopharyngeal carcinoma (NPC) prognosis evaluation is based primarily on the TNM staging system. This study aims to identify prognostic markers for NPC. PATIENTS AND METHODS: We detected expression of 18 biomarkers by immunohistochemistry in NPC tumors from 209 patients and evaluated the association between gene expression level and disease-specific survival (DSS). We used support vector machine (SVM)--based methods to develop a prognostic classifier for NPC (NPC-SVM classifier). Further validation of the NPC-SVM classifier was performed in an independent cohort of 1,059 patients. RESULTS: The NPC-SVM classifier integrated patient sex and the protein expression level of seven genes, including Epstein-Barr virus latency membrane protein 1, CD147, caveolin-1, phospho-P70S6 kinase, matrix metalloproteinase 11, survivin, and secreted protein acidic and rich in cysteine. The NPC-SVM classifier distinguished patients with NPC into low- and high-risk groups with significant differences in 5-year DSS in the evaluated patients (87% v 37.7%; P < .001) in the validation cohort. In multivariate analysis adjusted for age, TNM stage, and histologic subtype, the NPC-SVM classifier was an independent predictor of 5-year DSS in the evaluated patients (hazard ratio, 4.9; 95% CI, 3.0 to 7.9) in the validation cohort. CONCLUSION: As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.

Radiation-induced sarcoma in the head and neck region: a clinicopathologic and immunohistochemical study of 13 cases.

OBJECTIVES: To study the clinical and histological features of radiation-induced sarcoma in the head and neck (RISHN). METHODS: Medical records of 13 patients with RISHN treated at our institution between 1990 and 2011 were studied, and paraffin-embedded samples were analyzed by haematoxylin and eosin staining and immunohistochemistry to determine mitosis counts and assess expression of Ki-67, bcl-2, and survivin. RESULTS: Positive bcl-2 was observed in 12 (100%) and survivin in 10 (76.9%) patients. The Ki-67 labeling index ranged from 1% to 90%, and it showed significant positive correlation with mitosis count in RISHN tissues, based on Spearman analysis. Percentage of distal metastasis with T2b was significantly higher than T1b stage (P=0.035). CONCLUSIONS: Stage T2b may be a useful indicator for predicting distant metastasis of RISHN. The MIB-1 score may be used as a histological grading system for RISHN. In addition, bcl-2 and survivin protein may play an important role in pathogenesis and progression of RISHN.

[Relationship between combined multigene detection and response to adjuvant chemotherapy in early-stage non-small cell lung cancer].

OBJECTIVE: To evaluate the relationship between combined multigene detection and response to adjuvant chemotherapy and prognosis in early-stage non-small cell lung cancer (NSCLC). METHODS: Tissue microarray was prepared from samples of 86 cases of early-stage NSCLC who received adjuvant chemotherapy after radical surgery. The expressions of caspase-3, Fas, bax, bcl-2, survivin, PCNA, Ki67, MGMT, p53, p63, p73, p16, p27, VEGF, nm23, P-gp, MRP, LRP, GST-pi, Topo II, c-myc, cyclin-D1, Her-2, Cox-2, Ku70, Ku80, DNA-PKcs, ERCC1, MSH2, BCRP proteins were detected using immunohistochemical two-step method. RESULTS: The positive rate of the 30 genes in lung cancer tissue were 27.9% - 91.9%, respectively. By univariate analysis, the expression of 8 genes was shown to be related with SCLC adjuvant chemotherapy. The cases with higher expression of survivin, P-gp, LRP, Ki67, p53, ERCC1 and lower expression of bax,VEGF had worse prognosis. By logistic regression analysis, the ERCC1, survivin, bax and VEGF were a marker group. Multivariate analysis showed the predict value of the response to adjuvant chemotherapy in early-stage NSCLC was 96.5%. CONCLUSION: Survivin, ERCC1, bax and VEGF are an ideal marker group to predict the effect of adjuvant chemotherapy in early-stage NSCLC.

[Relationship between combined multigene detection and response to chemotherapy and prognosis in epithelial ovarian carcinomas].

OBJECTIVE: To evaluate the relationship between combined multigene detection and response to chemotherapy and prognosis in epithelial ovarian carcinomas (EOCS). METHODS: A total of 80 ovarian tissue samples taken from the surgical specimens of patients with EOCS of our hospital in the last two decades who had received chemotherapy after surgery were paraffin-embedded. The samples were divided into 2 groups, good prognosis group (patients who survived more than 2 years, n = 46) and poor prognosis group (patients who survived less than 2 years, n = 34). The expression levels of ToPo-II, Ki-67, MGMT, PCNA, p27, p53, p16, P-gp, LRP, GST-pi, bcl-2, C-myc, Fas, bax, MSH2, MRP and BCRP were investigated by the combination of tissue arrays and immunohistochemical streptavidin-biotin peroxidase (SP) method in all samples. Data were analysed with SPSS 12.0 for windows. RESULTS: There were statistically significant differences in the positive expression levels of P-gp, BCRP, MGMT, MSH2, p27 and p16 (62%, 50% and 50% in poor prognosis group vs 33%, 28% and 28% respectively, P < 0.05) in the good prognosis group, suggesting that the positive expression levels of P-gp, BCRP, MGMT, MSH2, p27 and p16 were related to the response to chemotherapy and prognosis in EOCS. And the positive expression of P-gp, BCRP and MSH2 (43%, 54% and 43%) indicated poor prognosis, while the positive expression of MGMT, p27 and p16 (18%, 29% and 24%, P < 0.05) indicated good prognosis. Cox multigene expression analysis confirmed that the positive expression levels of MRP, C-myc, LRP, p16, p27, MGMT, ToPo-II, P-gp and GST-pi were related to the response to chemotherapy and prognosis in EOCS. And the positive expression of MRP, C-myc, LRP, ToPo-II, P-gp and GST-pi indicated poor prognosis, while the positive expression of MGMT, p27 and p16 indicated good prognosis. Combined multigene detections were conducted among P-gp, BCRP, MGMT, MSH2, p27 and p16, and there were statistically significant differences in the positive coexpression of P-gp plus MGMT in the two groups (P < 0.05); indicating that the combined multigene expression were related to the response to chemotherapy and prognosis in EOCS. The predictive value to response to chemotherapy and prognosis of the positive coexpression of P-gp plus MGMT was 70%. CONCLUSIONS: By univariate and multivariate analyses, the positive expression of P-gp, MGMT, p27 and p16 are related to the response to chemotherapy and prognosis in EOCS. The combined multigene expression of P-gp plus MGMT are related to the response to chemotherapy and prognosis and could predict prognosis more effectively.