Cell Physiological Phenomena ; Electromagnetic Fields

Objective To investigate the biodistribution,excretion and other pharmacokinetics,of 188Re-1-hydroxy-1,1-ethylidene disodium phosphonate (HEDP) in cancer patients with osseous metastases who were suffering form bone pain. Methods A single dose (20,30,40,and 50 MBq/kg,10 patients in every group) of 188Re-HEDP was administered as a bolus injection,meanwhile dynamic images on patient's chest were collected for 30 min. Anterior and posterior whole-body images were obtained at 1,2,4,5,12,24,36,48,60 and 72 h after injection of 188Re-HEDP. By region of interest (ROI) technology,the curve of time-background corrected counts of left cardiac ventricle could be generated,and the background-corrected counts of various organs and total whole body could be calculated as a geometric mean using the anterior and posterior scans,and transformed to the percentage injected dose ( % ID). Urine was collected after injection of 188Re-HEDP. Counts of urine were measured by γ counter. Analysis of variance and t-test were used. Results Linear relationship of metabolism of 188Re-HEDP was observed in the doses from 20 to 50 MBq/kg,with correlation coefficient r2 = 0. 9376. A two-compartment model was the best fit for metabolism of 188Re-HEDP with the parameters median area under curve (AUC) 3.32 × 105,3.97 × 105,7.83 × 105,8.58 ×105,respectively; median α 0.06,0.05,0.04,0.06 respectively; median β 1.16 ×10-3,1.16 × 10-3,1.03 × 10-3,1.15 × 10 -3 respectively; median A 3591.21,4858.23,5642. 48,4167.05 respectively; median B 293.97,352.95,614.41,1063.82 respectively; median T1/2(α) 12.51,12.83,15.41,12.02 min respectively; median T1/2(β) 595.47,596.50,673.09,600.93 min respectively in the doses of 20,30,40and 50 MBq/kg. 188Re-HEDP was taken up mainly by bone up to 40% ID at 4 h. Urine profile showed that 66.79 % ID was eliminated within 24 h,being its 74% collected along the first 5 h after-administration.Conclusions In the doses of 20,30,40 and 50 MBq/kg,metabolism of 188Re-HEDP presented linear model. Pharmacokinetics of 188 Re-HEDP followed a two-compartment model administrated by blood vessel.Following injection,188 Re-HEDP was taken up mainly by bone and excreted by uropoietic system.

Objective To investigate the role of RANKL/RANK/OPG system in bone metabolism of ankylosing spondylitis (AS) by detecting bone mineral density, bone metabolism factors such as osteoprotegerin (OPG), soluble receptor activator of nuclear factors-κB ligand (sRANKL) and the expression of membrane-bound (mb) RANKL in the peripheral blood T lymphocytes. Methods Bone mineral density of AS patients were measured by dual-energy X-ray absorptiometry (DEXA) and serum levels of OPG, sRANKL,tartrate resistant acid phosphatase 5b (TRACP-5b) and bone alkaline phosphatase (BALP) were determined by enzyme-linked immunosorbent assay (ELISA). The percentages of CD4+/RANKL+ and CD8+/RANKL+ in the peripheral blood were detected with flow cytometry. T-test, x2-test were used for statisical analysis. Results ① The incidence of osteopenia and osteoporosis in AS was 47% and 37% respectively. ② Serum RANKL,TRACP-5b levels and RANKL/OPG ratio were higher in AS patients than those in normal controls (P<0.05).But there was no significant difference in OPG and BALP between AS patients and normal controls. ③There were positive linear correlation between serum levels of RANKL and OPG, sRANKL and TRACP-5b, OPG and TRACP-5b in AS (P<0.01). ④ The prevalence of CD4+/RANKL+ cells in the peripheral blood of AS patients was significantly higher than that in the normal controls (P<0.05). Conclusion There is a high incidence of bone loss in AS patients. Increased bone resorbtion is the feature of bone metabolism in AS.RANKL/RANK/OPG system may play an important role. The imbalance of RANKL/RANK/OPG system may be one of the bone loss mechanisms of AS. CD4 + T lymphocyte may play an important role in osteoclasts differentiation and bone resorption in AS by up-regulating the expression of RANKL.

Clinical Medicine ; methods ; Drug Therapy, Combination ; Holistic Health ; Humans ; Integrative Medicine ; methods ; Medicine, Chinese Traditional ; methods

Apoptosis ; radiation effects ; Cell Cycle ; radiation effects ; Cells, Cultured ; Electromagnetic Fields ; Gene Expression ; radiation effects ; Mutation ; radiation effects ; Recombination, Genetic ; radiation effects ; Yeasts ; cytology ; genetics ; radiation effects

Antimicrobial peptides are a class of small peptides with anti-extrogenous pathogen activities.They are derived from organism and possess antibacterial,antifungus,antiviruses and anticancer cell actions.In recent years,it’s found that some microbial pathogens are able to resist antimicrobial peptides.The constitutive and inducible mechanism of a pathogen resists a given peptide were reviewed in this paper.

ObjectiveTo study the effect of low-intensity millimeter wave(MMW)irradiation on the immune adhesion function of erythrocytes in mice with tumor.Methods60 healthy male mice were randomized into two groups:irradiation group(n=30) and control group(n=30).All mice were injected into abdominal cavity with A's abdominal juice cancer-cell(1×106/ml,0.2ml).MMW(36GHz,0.73-1.46mw/cm2)was used to irradiate the back of mice in irradiation group,once a day for 8 days.Control group received false irradiation using the same method.At 0d,3d,6d after irradiation, the erythrocytes were extracted from vein blood in the mice,and the RBC-C3b receptor rosettes rate(RCR),tumour-RBC rosette rate(TRR),RBC-SOD and RBC-LPO were determined.ResultsAt 3d after radiation,the RBC-C3b and TRR of irradiation group were higher than that of control group (P<0.01) and RBC-LPO was lower (P<0.05),while there was no significant difference on activity of RBC-SOD(P>0.05). there were no significant difference on all index between two groups at 0d and 6d(P>0.05).ConclusionsLow-intensity millimeter wave irradiation can improve the immune adhesion function of erythrocytes in mice with tumor.

The nuclear factor kappa B(NF-kappaB) plays a crucial role in inflammatory, immune response, embryo development, cell proliferation and apoptosis, cell cycle control as well as tumorgenesis. In recent years, a variety of investigations have demonstrated that NF-kappaB was closely associated with the pathogenesis of hematological malignancies such as leukemia, lymphoma and multiple myeloma. Nowadays, increasingly attention has been paid to the studies on the activation and its mechanism of NF-kappaB in the hematogenic malignancies. So that, in this article, progress on these aspects is reviewed.
Hematologic Neoplasms ; metabolism ; pathology ; Humans ; NF-kappa B ; metabolism

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

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