ABSTRACT
Rectal cancer is a common type of malignant tumor, with increasing incidence over the previous years. Total mesorec-tal excision is the most important treatment for rectal cancer. Advanced rectal cancer presents high local recurrence rate and low sphinc-ter preservation rate. For locally advanced rectal cancer, neoadjuvant chemoradiotherapy is the optimal management strategy. In this re-gard, clinicians have focused on investigating the clinical effects of rectal cancer after neoadjuvant chemoradiotherapy. Prediction and evaluation of rectal cancer after neoadjuvant therapy can be used to determine further necessary treatments, effect on quality of life, and survival time of patients.
ABSTRACT
Through phage display, we tried to find out whether the N-terminal fragment of glucogan-like peptide 1 receptor (nGLP-1R) still had binding activity to Exendin-4 after missing one or two gene segments. By error-prone PCR, We constructed a randomly mutated phage display peptide library with different length of the N-terminal (21-145 residues) extracellular domain of glucogan-like peptide 1 receptor (GLP-1R) from rat lung. A mutant named EP16 without binding activity was found by ELISA. Through sequence alignment we found that EP16 missed the first 20 and last 10 amino acids and the 52nd tryptophan was mutated to arginine. In order to determine why Ep16 did not show its binding ability to Exendin-4, a wild type EP16 without the first 20 and last 10 amino acids and nGLP-1R(W52R) was constructed in which the 52nd tryptophan was mutated to arginine. The contrastive analysis showed that the substitution of W52R led to a markedly reduced binding ability of EP16. The mutation of the conserved W52 could change the biologic activity of the protein. The lack of the first 20 and last 10 amino acids had no effect on its biologic activity. Therefore, the mutation of a single amino acid residue of the key sequence could change the biologic activity of the nGLP-1R.
Subject(s)
Animals , Rats , Amino Acid Sequence , Amino Acid Substitution , Binding Sites , Glucagon-Like Peptide-1 Receptor , Molecular Sequence Data , Mutagenesis, Site-Directed , Mutation , Peptide Fragments , Chemistry , Genetics , Metabolism , Peptides , Metabolism , Protein Binding , Receptors, Glucagon , Chemistry , Genetics , Metabolism , Venoms , MetabolismABSTRACT
Intraperitoneal chemotherapy is a useful treatment of advanced gastric cancer.Following intraperitoneal chemotherapy, the concentration of drugs in the peritoneum and in the portal vein was high, lasting and sustained.Early post-operation chemotherapy showed better results.This article will summarize the newest research progress of intraperitoneal chemotherapy in the treatment of advanced gastric cancer.
ABSTRACT
Objective To explore the mechanism of the cell-cycle arrest induced by human melanoma differentiation associated gene-7 (mda-7/IL-24) in chronic myelocytic leukemia cell line K562. Methods Microarray analysis was performed to determine the genes that were differentially regulated by mda-7/IL-24 in K562 cells, and was validated by realtime PCR. The phosphorylated pRb were detected by Western blotting analysis. Results A microarray analysis showed that G_0/G_1 phase-associated genes p21~(WAF-1) and BCCIP were up-egulated, while cdk6 and Smurf2 were down-regulated. The directional change in the expression of the four genes was successfully validated with real-time quantitative RT-PCR. pRb Set~(795) phosphorylation was observed with no modification of the pRb protein level. Conclusion These results suggest that IL-24/mda-7 may inhibit K562 proliferation and induce G_0/G_1 cell cycle angst by up-regulating p21~(WAF-1) and BCCIP, down-regulating cdk6 and Smurf2.