Synthesis of spiro[4.4]thiadiazole derivatives via double 1,3-dipolar cycloaddition of hydrazonyl chlorides with carbon disulfide.

An operationally simple and convenient synthesis method toward a series of diverse spiro[4.4]thiadiazole derivatives via double [3 + 2] 1,3-dipolar cycloaddition of nitrilimines generated in situ from hydrazonyl chlorides with carbon disulfide has been achieved under mild reaction conditions.

WITHDRAWN: Dual display bacteriophage as a platform for high sensitive detection of serum p53 antibodies in breast cancer patients.

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Clinical significance of preoperative detection of serum p53 antibodies and BRAF(V600E) mutation in patients with papillary thyroid carcinoma.

The goal of the present study was to evaluate the clinical and diagnostic value of both serum p53-antibodies (Abs) and preoperative fine needle aspiration cytology (FNAC) for BRAF mutation in patients with papillary thyroid carcinoma (PTC). A total of 312 patients, including thyroid adenoma (85) and PTC (227) were enrolled in this study. Two types of enzyme-linked immunosorbent assays (ELISA), phage-ELISA and p53-ELISA, were used to measure serum p53-Ab levels. Sanger sequencing was used to determine BRAF gene mutation in FNA samples. Phage-ELISA was more efficient than conventional p53-ELISA in measuring serum p53-Abs in PTC patients. BRAF mutation analysis with FNAC significantly improved PTC diagnostic sensitivity from 80.18% to 93.83% (P=0.001) and accuracy from 82.31% to 92.37% (P=0.005). Bothp53-Abs and BRAF mutation were positively associated with lymphatic metastasis and advanced TNM stages. Particularly, serum p53-Abs positively associated with multifocality (P=0.02), while BRAF mutation associated with extrathyoidal extension (P=0.01). Furthermore, PTC patients with both elevated serum p53-Abs and BRAF mutation had a higher prevalence of extrathyoidal extension (P=0.003), lymphnode metastasis (P=0.00), multifocality (P=0.04), and advanced TNM stages (P=0.004). Our results indicate that serum p53-Abs alone might not be a reliable biomarker for PTC diagnosis, but the combined analysis of serum p53-Abs and BRAF mutation in FNAC may be useful for optimizing surgical treatment and prognostic prediction of unfavorable clinicopathologic outcomes.

Serum anti-p53 antibody detection in carcinomas and the predictive values of serum p53 antibodies, carcino-embryonic antigen and carbohydrate antigen 12-5 in the neoadjuvant chemotherapy treatment for III stage non-small cell lung cancer patients.

BACKGROUND: The serum p53 antibody (s-p53 Ab) is a valuable prognostic factor for carcinomas, but its common detection method, based on enzyme linked immunosorbent assay (ELISA), needs to be improved due to low sensitivity. Although neoadjuvant chemotherapy (NACT) is widely used in the treatment of non-small cell lung cancer (NSCLC) in China, forecasting chemoresistance is still a pressing problem. METHODS: Hybrid phage and wild-type p53 protein (wt p53 protein) were produced before the establishment of phage-ELISA and p53-ELISA. S-p53 Abs of 829 patients with various types of cancer was detected by a double ELISA system. 47 ΙΙΙ stage NSCLC patients treated with mitomycin, vindesine and cisplatin (MCV)-based NACT were chosen for s-p53 Abs, carcino-embryonic antigen (CEA) and carbohydrate antigen (CA) 12-5 predictive value analysis. RESULTS: Through the combination of p53-ELISA and phage-ELISA (p53-phage ELISA), the sensitivity of s-p53 Abs in lung, breast, colorectal, gastric, esophageal, liver and ovarian cancer increased to 39.0%, 33.3%, 41.7%, 32.1%, 30.9%, 23.1% and 43.2% respectively. S-p53 Abs proved to correlate with nodal involvement, TNM stage, histological type (in lung cancer) or tumor size (in gastric cancer). As for the 47 ΙΙΙ stage NSCLC treated with NACT, s-p53 Abs and CA12-5 remarkably decreased after NACT treatment (P=0.034 and P=0.007) and pre-NACT low s-p53 Abs correlated with high objective chemoresponse rate (P=0.016). CONCLUSIONS: p53-phage ELISA system has an edge over single p53-ELISA. S-p53 Abs level correlates with cancer patients' clinicalpathological parameters and can predict the chemoresponse of ΙΙΙ stage NSCLC patients during MCV-based NACT treatment.

Neamine inhibits cell proliferation, migration, and invasion in H7402 human hepatoma cells.

OBJECTIVE: To explore the effect of neamine on cell proliferation, migration, and invasion in H7402 human hepatoma cells. METHODS: This study was conducted at the Institute of Genetics and Cytology, School of Life Science, Northeast Normal University, Changchun, China between October 2008 and February 2010. First, we employed the MTT (thiazol blue tetrazolium bromide) and soft agar assay to detect the effect of neamine on cell proliferation, and investigated the migration and invasion by using a transwell assay in H7402 cells. We, then, investigated nuclear translocation of angiogenin by immunofluorescence staining. Finally, we stable transfected H7402 cells with the plasmids pCI-Ang (+) and pCI-Ang (-), which contain the entire coding region of human angiogenin in the sense and antisense orientations, to obtain angiogenin under-expressing/over-expressing transfectants, and investigated the effect of neamine on angiogenin induced cell proliferation. RESULTS: The results showed that neamine positively inhibited the proliferation, migration, and invasion of H7402 cells. Nuclear translocation of angiogenin was blocked by neamine, and angiogenin-induced cell proliferation was inhibited by neamine. CONCLUSION: Neamine positively inhibited H7402 cells. Since the toxicity of neamine is much less than neomycin, and is close to that of streptomycin and kanamycin, it may serve as a lead agent for the development of hepatocellular carcinoma therapeutics.