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The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan–Meier method and log-rank test. Toxicities and response rates were compared using Fisher’s exact test. Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64–1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68–1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59–1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52–1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3–4 toxicities in the CCRT/AC arm. The most common grade 3–4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC.

To investigate the correlation of CD4Fifty-nine patients with NSCLC treated with radical surgery were followed up for 5 years. Blood Treg cells were examined during the follow-up using flow cytometry (FCM). The sensitivity and specificity of Treg cells to predict recurrence of NSCLC were analyzed using receiver-operating characteristic (ROC) curve and compared with those of carcinoembryonic antigen (CEA) and cytokeratin21-1 (Cyfra21-1). The influences of gender, age, occupation and radiotherapy on survival time of the patients were analyzed with Kaplan-Meier method.Among the 59 patients, the shortest survival time was 23 months while the longest time was over 67 months. Nineteen patients had NSCLC recurrence, and 17 (28.81%) of them died of metastasis during the follow-up. The frequencies of blood Treg cells in patients who did not receive radiotherapy and in patients with tumor recurrence were significantly higher than those in patients receiving radiotherapy and in patients free of recurrence (P=0.000). ROC curves showed that the area under curve (AUC) lowered in the order of Treg cells, Cyfra21-1, CEA (P=0.002, 0.006 and 0.013, respectively) with 95% confidence interval (CI) of 0.649-0.981, 0.621-0.936 and 0.584-0.944, respectively. At the cut-off value of 7.53%, the sensitivity and specificity of Treg cells to predict NSCLC recurrence was 91.42% and 87.59%, respectively. The five-year survival rate of the 59 patients was 71.18% (42/59), and Kaplan-Meier analysis revealed a longer survival time in female patients (P=0.038), in patients below 50 years of age (P=0.013), in patients not engaging in mental work (P=0.029), and in patients receiving radiotherapy (P=0.003).Treg cells has a better efficiency than Cyfra21-1 and CEA to predict tumor recurrence in patients with NSCLC following radical surgery. The male gender, an age beyond 50 years, an occupation of mental work, and failure to receive radiotherapy are all risk factors for recurrence of NSCLC.

The purpose of this prospective study is to investigate the predictive and prognostic significance of the Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC). Immunohistochemical assays were performed to detect the RKIP protein expression of samples from 212 patients with locoregionally advanced NPC. All patients were assigned randomly into the inductive chemotherapy plus radiation therapy (IC + RT) group, the concurrent chemoradiotherapy (CCRT) group, the inductive chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) group, and the radiation therapy alone (RT) group. The patients in the IC + RT group were treated with IC using 2-3 cycles of cisplatin (80 mg/m(2)) and fluorouracil (500 mg/m(2)), repeated every 3 weeks, followed by radiotherapy. Those in the CCRT group were treated with weekly cisplatin (40 mg/m(2)) for 6-7 cycles during radiotherapy. In the IC + CCRT group, the chemotherapy prior to radiation was similar to the cisplatin-fluorouracil regimen in the IC + RT group, whereas it cisplatin regimen was identical to that in the CCRT group. The results show that RKIP is an independent prognostic factor for 5-year distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). Patients with high RKIP expression benefited more from reduced metastasis in the IC + RT and the IC + CCRT group, with improved OS and PFS in each treatment group compared with that among patients with low RKIP expression. In the high RKIP expression subgroup, chemotherapy combined with radiotherapy improved the DMFS when compared with the RT group, but this effect was not observed in the low RKIP expression subgroup. RKIP was predictive of distant metastasis with good sensitivity and specificity. Clinically, high RKIP expression inhibited distant metastasis in advanced NPC, and its detection might be used to predict distant metastasis with good sensitivity and specificity. The effect of chemotherapy on distant metastasis in combined chemoradiotherapy might be related to the RKIP expression level. Patients with high RKIP expression showed more improved OS and PFS than their low RKIP expression counterparts. Higher RKIP expression improves the DMFS of patients who receive inductive high-dose cisplatin-based chemoradiotherapy, with or without concurrent cisplatin. Low RKIP expression is also a predictive marker for cancer progression and metastasis, which could be used to stratify patients with high risk of metastasis and death.

Insulin receptor substrate-2(IRS-2) belongs to a family of cytoplasmic adaptor proteins, which link insulin, insulin-like growth factor-1(IGF-1), and cytokine receptor tyrosine kinases to signaling pathways regulating metabolism, growth, differentiation, reproduction, and homestasis. Deficiency of IRS-2 in mice causes type 2 diabetes mellitus (T2DM), suggesting that abnormal structure and dysfunction of the IRS-2 gene may contribute to the pathogenesis of T2DM. Variations in the open reading frame (ORF) and promoter region of IRS-2 gene in patients with T2DM have been reported over the past few years. These genetic variations are from ethnically different patients, confounding any analysis of the contribution of IRS-2 gene variations to the development of T2DM. The 3'-untranslated region(3'-UTR) of IRS-2 gene variation may be contribute to the T2DM. So far, the relationship between 3'-UTR of IRS-2 gene variations and T2DM have not been investigated. Based on the 3'-UTR of eukaryotic gene plays an important role in the eukaryotic gene regulation, we investigated abnormalities of IRS-2 gene 3'-UTR and their relation with T2DM in the Chinese population. Genomic DNA was extracted from leukocyte of 128 patients with T2DM and 125 control subjects in Hunan, China. A segment of IRS-2 gene 3'-UTR was scanned by polymerase chain reaction (PCR)-denaturing high-performance liquid chromatography (DHPLC). All PCR products with abnormal DHPLC pattern were submitted to DNA sequence analysis. A T--C mutation at 4064 bp of IRS-2 gene 3'-UTR was found in 18 patients with T2DM, while it was only found in 5 control subjects. The incidence of the mutation in patients with T2DM were much higher than that in contol subjects (14.1% vs 4.0%, x2 = 7.748, P = 0.005). These results indicate that the T4064--C in IRS-2 gene 3'-UTR may be related to Chinese patients with T2DM.

To study the genetic variation in 5'-regulatory region of aldose reductase (AR) gene that might influence expression and the relationship between variations and diabetic complication (DC), PCR-single stranded conformational polymorphism (SSCP) was used to screen the 5'-regulatory region of AR gene in Chinese patients with type 2 diabetes mellitus. A novel mutation, C(-167) --A substitution which created a new CCAAT box was found only in two diabetic patients. These two patients have no retinopathy, and the AR activity of their erythrocytes was within low range in patients without DC. The DNA segments of AR wild type and mutant were subcloned into pCAT reporter vector, and CAT assays were performed to assess promoter activity. The interaction between the DNA segments and nuclear proteins was determined by using competitive gel electrophoretic mobility shift assay (EMSA). The transcriptional activity of mutant (5.7% +/-2.9%) was lower than that of wild type (15.7% +/- 4.1%) (P0.01), and the mobility shift of mutant was also slower than that of wild type. The results indicated the mutation C(-167) --A in AR gene might prevent or delay the development of DC by repressing the expression of AR gene.

1. Many clinical studies have suggested a relationship between oestrogen and insulin sensitivity. In the present study, HepG2 cells were divided into four groups: (i) control, incubated with 1 nmol/L insulin; (ii) the HI group, which was incubated with 100 nmol/L insulin to induce insulin resistance; (iii) the E2 group, in which control cells were incubated with 1 nmol/L insulin plus 1 nmol/L oestradiol; and (iv) the HI + E2 group, in which insulin-resistant cells were incubated with 100 nmol/L insulin + 1 nmol/L oestradiol. 2. A high concentration of insulin decreased the activity of phosphofructo-1-kinase (PFK), pyruvate dehydrogenase (PDH) and glycogen synthase (GS), as well as decreasing the expression of insulin receptor (IR) and insulin receptor substrate-2 (IRS-2). High insulin had no effect on glucose transport or the expression of insulin receptor-1 (IRS-1). 3. The addition of oestradiol to control cells increased glucose transport, the activity of PFK, PDH and GS and the expression of IRS-1 and IRS-2, but had no effect on the expression of IR. 4. Treatment of insulin-resistant HepG2 cells with oestradiol attenuated HI-induced decreases, except for IR, and the expression of IRS-1 was significantly higher than control, attaining levels seen in group 3. The expression of IRS-2 was significant higher than in insulin-resistant cells, but did not reach control levels. Changes in the activity of PFK, PDH and GS were the same as the changes seen in the expression of IRS-2. 5. These results suggest that high concentrations of insulin induce insulin resistance in HepG2 cells, whereas oestradiol improves glucose metabolism and insulin signal transduction of cells by enhancing the activity of key enzymes involved in glucose metabolism and the expression of IRS-1 and IRS-2.