Antigens, CD ; metabolism ; Antigens, CD20 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Axilla ; Histiocytic Sarcoma ; drug therapy ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, IgE ; metabolism

Diagnosis, Differential ; Histiocytoma, Benign Fibrous ; metabolism ; pathology ; Histiocytosis, Langerhans-Cell ; metabolism ; pathology ; Histiocytosis, Sinus ; metabolism ; pathology ; surgery ; Humans ; Infant ; Male ; S100 Proteins ; metabolism ; Xanthogranuloma, Juvenile ; metabolism ; pathology

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Humans ; Metals ; Microwaves ; adverse effects ; Occupational Exposure ; adverse effects ; analysis ; Workplace

PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

Objective To construct transgenic mice tissue-specifically co-expressing human DAF/CD59 in the vascular endothelia and to investigate the ability to protect against human comple- ment-mediated attack.Methods Transgenic mice were generated by co-microinjection of hDAF/CD59 expression constructs driven by the human intercellular adhesion molecule-2(ICAM-2)promoter.PCR and Southern blot of genomic DNA were used to assess the presence of hDAF/CD59 in the genome of the founders,and the expression at protein level was measured by flow cytometry.Immunohistochemis- try was used to detect the distribution of hDAF/CD59.An ex vivo perfusion model was used to com- pare hearts from these hDAF/CD59 transgenic mice with hDAF hearts.Results After microinjection of genes,11 of 135 mice born were shown to be double-transgenic,and human DAF/CD59 were ex- pressed on the surface of leucocytes in 6 of the 11 DAF/CD59-integrated mice.Expression levels of 6 founders ranged from 80% to 95% of that in human leucocytes.Human DAF/CD59 were strongly expressed in the vascular endothelia of heart,kidney,with little or no positive staining observed in non- endothelial cells.Compared to hDAF hearts that maintained approximately 20% maximum work during perfusion with 20% human plasma,these endothelial-specific hDAF/CD59 hearts were further protected with work maintained at 40% of the maximum level during 60 min.Conclusion The intro- duced hDAF/CD59 genes have been integrated and specifically expressed in the vascular endothelia. The endothelial co-expression of hDAF/CD59 can provide greater protection against human complement-mediated attack than the expression of hDAF alone.

Objective To evaluate the association between interleukin-I(IL-1)loci polymorphisms and increased risk of gastric carcinoma in samples from northern Chinese population.Methods Blood sam- ples from 126 patients with gastric cancer and 125 controls with chronic gastritis were collected.Genomic DNA was extracted and polymorphisms at -31(C to T),-511(C to T)and at intron 2(86-bp VNTR)of IL-I RN were genotyped by PCR-CTPP,PCR-RFLP and PCR.For detection of Hp infection fast urenase test,~(14)C breath test and serum anti-Hp IgG antibody assay were used.Results Five kinds of polymorphism of IL-IRN were found as 1/1,1/3,1/4,1/2 and 2/2,and the frequencies in patients were 76.19%、4.76%、6.35%、11.90% and 0.79%,respectively.However,the frequencies in controls were 76.00%、4.00%、4.80%、13.60% and 1.60%.No significant differences were observed between cases and controls in each genotype.The polymorphism of IL-IB-31 allele was C/C,C/T and T/T.The frequencies in patients were 12.70% ,47.62% and 39.68%,and in controls 28.00%,48.80% and 23.20% respectively.IL-1B- 31 T/T carriers were at an increase risk of gastric cancer with an odds ratio of 3.772(95% CI,1.786- 7.966).IL-IB-511 alleles were C/C,C/T and T/T.The frequencies in patients were 19.20%,56.80% and 24.00% and in controls,23.38%,49.19% and 27.42% respectively.No significant differences were observed between cases and controls in each genotype.Conclusion In Chinese population,the polymor- phism of IL-1B-31 alleles may be associated with the susceptibility of gastric cancer.However,no evidence was found to support that the polymorphisms of IL-1RN and IL-I B-511 alleles had relationship with gastric cancer.

Objective To study the relationship of urine RBC morphology between UF-100 urine sediment analytic instrument andphase contrast microscope.Methods The UF-100 urine sediment analytic instrument to analyze 500 urine specimens and study the relation-ship of urine RBC morphology between urine sediment analytic instrument and phase contrast microscope.Results The according perceptionof Normocytic,Microcytic and Non-classified RBC between phase contrast microscope and UF-100 urine sediment analytic instrument RBC-info are 91.4%,94.4%,83.3% respectively,the according perception between phase contrast microscope and RBC-P70Fsc are 94.9%,95.7%,94.7% respectively,and the according perception between phase contrast microscope and RBC Fsc-DW are 84.4%,86.8%,90.5% respectively,the specificity of UF-100 and phase contrast microscope in glomerular hematuria and non-glomerular hematuria are84.3%,88.1% and 83.3%,87.9% respectively.Conclusion The results show that the UF-100 urine sediment analytic instrument issimply operating,fast and high accurate,and which can instruct clinical dignose,therapy and prognosis judgement.

Objective:To analyze the activities of human NKG2D ligand MICA/B promoter induced by 5-Fu.Methods:The 5'-end flanking regions of MICA /B promoter and their different truncated fragments were amplified from A549 genome by PCR. The resulting amplicons were cloned into pGL3-Basic vector to generate the MICA/B luciferase reporter plasmids. All the constructs were transiently transfected A549 cells. The promoter region activities were determined by dual-luciferase reporter assays. The effect of 5-Fu on the promoter activities of MICA/B was also tested.Results and Conclusion:The 5'-end flanking regions of MICA /B promoter and five of their different truncated fragments were successfully obtained. The normalized luciferase reporter gene activities driven by the above promoters and fragments were 3.61,2.26,1.63,0.313,0.711 and 0.663 for MICA and 17.49,10.11,7.398,0.822,0.997 and 0.49 for MICB,respectively. Promoter activities in transiently transfected A549 cells treated by 20,40,80,160 and 320 μg/m of 5-Fu increased 1.69,1.48,1.62,1.55 and 1.78 fold for MICA and 1.44,1.87,1.38,1.19 and 1.25 fold for MICB. Our results suggest that 5-FU can significantly up-regulate the promoter activity of both MICA and MICB.

ObjectiveTo investigate the effect of out-patient training combined with family training under doctor's instructions on children with cerebral palsy (CP).Methods80 CP children were selected as treatment group and trained one to three months by therapists at out-patient department, then continually trained at family by parents who received doctor's instructions 30 min once every two or three months. 60 CP children in hospital were selected as control group. Rehabilitative effects of two groups were compared.ResultsIn the first and third month after training completed, movement growth of treatment group was not different from that of control group (P>0.05), but in the sixth month, was significant different from that of control group (P<0.05). The effect of treatment group was better than that of control group.ConclusionOut-patient training combined with family training under doctor's instructions can decrease treatment expenses, and is convenient and effective for CP children.