ABSTRACT
AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.
Subject(s)
Abiraterone Acetate/adverse effects , Abiraterone Acetate/therapeutic use , Androgens/deficiency , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prednisolone/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Prednisolone/administration & dosage , Progression-Free Survival , Treatment OutcomeABSTRACT
There is increasing evidence that omega-3 polyunsaturated fatty acids (PUFAs) have therapeutic potential in various animal models of neuronal injury. However, very few studies have examined the effect of medium-chain fatty acids (MCFAs) on neuronal injury. So in the present study we synthesized various MCFAs and their derivatives, and found that exposure to trans-2-decenoic acid ethyl ester (DAEE) markedly activated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured cortical neurons. Therefore, we examined the effect of DAEE treatment on a rat model of spinal cord injury. DAEE (150 µg/kg body weight) administered after hemisection of the spinal cord resulted in improved functional recovery, decreased the lesion size, increased the activation of ERK1/2, and enhanced the expression of bcl-2 and brain-derived neurotrophic factor (BDNF) mRNA in the injury site of the spinal cord. Furthermore, it also increased neuronal survival after spinal cord injury. These results indicate that the possibility that DAEE will become a promising tool for reducing the secondary damage observed following primary physical injury to the spinal cord.
Subject(s)
Fatty Acids, Monounsaturated/therapeutic use , Fatty Acids, Unsaturated/therapeutic use , Motor Activity/drug effects , Recovery of Function/drug effects , Spinal Cord Injuries/drug therapy , Analysis of Variance , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cells, Cultured , Cerebral Cortex/cytology , Disease Models, Animal , Embryo, Mammalian , Female , Gene Expression Regulation, Enzymologic/drug effects , Glial Fibrillary Acidic Protein/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neurons/drug effects , Neurons/metabolism , Phosphopyruvate Hydratase/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Spinal Cord Injuries/physiopathologyABSTRACT
We performed an improved search for nu(mu) --> nu(e) oscillation with the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment, using the full data sample of 9.2 x 10(19) protons on target. No evidence for a nu(e) appearance signal was found, and we set bounds on the nu(mu) --> nu(e) oscillation parameters. At Deltam(2)=2.8 x 10(-3) eV(2), the best-fit value of the K2Knu(mu) disappearance analysis, we set an upper limit of sin(2)2theta(mue) < 0.13 at a 90% confidence level.
ABSTRACT
We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.
ABSTRACT
We have carried out the experiments for polarizing protons in single crystals of p-terphenyl doped with 0.1 mol% pentacene. The experiments have been performed in a magnetic field of 3 kG at room temperature or at 77 K. We obtained the polarization of 1.3% for protons in bulk at room temperature by using a pulsed dye-laser with the wavelength of 590 nm, the average power of 150 mW, and the repetition rate of 50 Hz. The polarization at 77 K reached 18% by irradiation with the dye-laser of 500 mW, 50 Hz and the same wavelength. The polarization of protons was measured by the neutron transmission method also. The result was consistent with that measured by the nuclear magnetic resonance.
ABSTRACT
alpha-Mangostin, isolated from the stem bark of Garcinia mangostana L., was found to be active against vancomycin resistant Enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA), with MIC values of 6.25 and 6.25 to 12.5 microg/ml, respectively. Our studies showed synergism between alpha-mangostin and gentamicin (GM) against VRE, and alpha-mangostin and vancomycin hydrochloride (VCM) against MRSA. Further studies showed partial synergism between alpha-mangostin and commercially available antibiotics such as ampicillin and minocycline. These findings suggested that alpha-mangostin alone or in combination with GM against VRE and in combination with VCM against MRSA might be useful in controlling VRE and MRSA infections.
Subject(s)
Anti-Bacterial Agents/pharmacology , Garcinia mangostana , Phytotherapy , Plant Extracts/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Drug Synergism , Enterococcus/drug effects , Humans , Methicillin Resistance , Microbial Sensitivity Tests , Plant Bark , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Staphylococcus aureus/drug effects , Vancomycin ResistanceABSTRACT
We present results for nu(mu) oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced nu(mu) beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy-dependent disappearance of nu(mu), which we presume have oscillated to nu(tau). The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).
Subject(s)
CD4 Antigens/blood , Kidney Transplantation/immunology , Receptors, Interleukin-2/blood , T-Lymphocytes/immunology , Adolescent , Adult , Child , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Male , Middle Aged , Monitoring, Immunologic , Postoperative Period , Transplantation, HomologousSubject(s)
Antigens, CD/blood , CD28 Antigens/analysis , CD4 Antigens/blood , CD4-Positive T-Lymphocytes/immunology , Graft Rejection/diagnosis , Kidney Transplantation/immunology , Receptors, Interleukin-2/blood , T-Lymphocytes/immunology , Adolescent , Adult , Child , Female , Graft Rejection/blood , Graft Rejection/immunology , Humans , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Postoperative Period , T-Lymphocyte Subsets/immunologyABSTRACT
Five new stilbene dimers were isolated from the lianas of Gnetum parvifolium in addition to known stilbenoids. The structures of the compounds were established on the basis of spectroscopic evidence, including long-range coupling and nuclear Overhauser effect experiments, in NMR spectrum. Among the isolates, 2b-hydroxyampelopsin F showed potent inhibitory activity in the Maillard reaction.
Subject(s)
Plants, Medicinal/chemistry , Stilbenes/isolation & purification , Acetylation , Brazil , Magnetic Resonance Spectroscopy , Maillard Reaction , Methylation , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, UltravioletABSTRACT
A new resveratrol dimer and a new C-glucosyl resveratrol were isolated from stem wood of Hopea utilis along with nine stilbenoid derivatives comprising bergenin and (+)-lyoniresinol. The structures have been elucidated on the basis of the spectroscopic evidence.
Subject(s)
Benzofurans , Plant Stems/chemistry , Rosales/chemistry , Stilbenes/isolation & purification , Molecular Structure , Resveratrol , Spectrum Analysis , Stilbenes/chemistry , WoodABSTRACT
Protons in naphthalene and p-terphenyl doped with pentacene have been polarized up to 32% and 18%, respectively, at liquid nitrogen temperature in a magnetic field of 0.3 T by means of microwave-induced optical nuclear polarization. The polarization was measured by nuclear magnetic resonance as well as by the neutron transmission method. The relaxation time of the proton polarization at 0.0007 T and 77 K was found to be almost 3 h and the polarization enhancement reached a record value of 8x10(4). The usefulness of the method in many areas of physics and chemistry is discussed.
ABSTRACT
Two new stilbene glucosides [(+)-alpha-viniferin 13b-O-beta-glucopyranoside and resveratrol 12-C-beta-glucopyranoside] and two new resveratrol oligomers, hemsleyanols A and B, were isolated from the bark of Shorea hemsleyana along with four known resveratrol oligomers. The structures of the isolates, including the relative configurations, were established by spectroscopic data involving long-range coupling and nuclear Overhauser effect experiments.
Subject(s)
Malvaceae/chemistry , Stilbenes/isolation & purification , Magnetic Resonance Spectroscopy , Plant Stems/chemistry , Resveratrol , Stilbenes/chemistryABSTRACT
Sophoraflavanone G (5,7,2',4'-tetrahydroxy-8-lavandulylflavanone) has been referred as a phytochemical with the intensive antibacterial activity. To elucidate the pharmacological mechanism underlying an antibacterial action, sophoraflavanone G was isolated from Sophora exigua, thereafter its effect on membrane fluidity was studied using model membranes and compared with less active naringenin lacking 8-lavandulyl and 2'-hydroxyl groups. Highly purified sophoraflavanone G of 0.05-5 microg/ml, corresponding to the minimum growth inhibitory concentrations against various bacteria, significantly increased fluorescence polarization of the liposomes prepared from 1,2-dipalmitoyl-L-alpha-phosphatidylcholine and 1-palmitoyl-2-oleoyl-L-alpha-phosphatidylcholine. Such increases were found in both liposomes measured with two fluorescent probes to indicate an alteration of membrane fluidity in hydrophilic and hydrophobic regions, suggesting that sophoraflavanone G reduces the fluidity of outer and inner layers of membranes. Although naringenin also showed the membrane effect, it needed concentrations over 2.5 microg/ml to induce a significant reduction of membrane fluidity. Sophoraflavanone G is considered to exert an antibacterial effect by reducing the fluidity of cellular membranes.
Subject(s)
Anti-Bacterial Agents/pharmacology , Fabaceae , Flavanones , Flavonoids/pharmacology , Membrane Fluidity/drug effects , Plants, Medicinal , 1,2-Dipalmitoylphosphatidylcholine , Chromatography, High Pressure Liquid , Flavonoids/chemistry , Flavonoids/isolation & purification , Liposomes , Phosphatidylcholines , ThailandABSTRACT
Three resveratrol oligomers, vaticanols. A, B and C, as well as three known stilbenoids, resveratrol, piceid and epsilon-viniferin were isolated from the stem bark of Vatica rassak (Dipterocarpaceae). Their structures were determined by the analysis of NMR spectral data including the application of 2D methods.
Subject(s)
Stilbenes/isolation & purification , Trees/chemistry , Benzofurans/chemistry , Benzofurans/isolation & purification , Glucosides/chemistry , Glucosides/isolation & purification , Plant Extracts/chemistry , Plant Stems/chemistry , Resveratrol , Stilbenes/chemistryABSTRACT
Three stilbene oligomers, davidiols A-C were isolated from the roots of Sophora davidii in addition to the seven known phenols, leachianone A, sophoraflavanones G, H and I, miyabenol C, alpha-viniferin and epsilon-viniferin. Their structures and relative configurations were established by means of 2D-NMR spectroscopy including COLOC and PSNOESY.
Subject(s)
Plants/chemistry , Stilbenes/isolation & purification , Magnetic Resonance Spectroscopy , Plant Roots/chemistry , Spectrometry, Mass, Fast Atom Bombardment , Stilbenes/chemistryABSTRACT
From the bark of Hopea parviflora, two stilbenoids, named (+)-parviflorol and (-)-ampelopsin A, were isolated in addition to three known compounds: (+)-balanocarpol, (-)-epsilon-viniferin and (-)-hopeaphenol. Their structures were determined by analysis of spectral data, including 2D NMR and NOE experiments, respectively.
Subject(s)
Malvaceae/chemistry , Stilbenes/isolation & purification , Magnetic Resonance Spectroscopy , Plant Stems/chemistry , Stilbenes/chemistryABSTRACT
Two new norditerpenoid acids of the labdane-type (norgrindelic acids), 4,5-dehydro-6-oxo-18-norgrindelic acid (1) and 4beta-hydroxy-6-oxo-19-norgrindelic acid (2), as well as a new grindelic acid derivative, 18-hydroxy-6-oxogrindelic acid (3), were isolated from the aerial parts of Grindelia nana. In addition, the known compounds, 6-oxogrindelic acid, grindelic acid, methyl grindeloate, 7alpha,8alpha-epoxygrindelic acid, and 4alpha-carboxygrindelic acid were also isolated. The structures of the new compounds were characterized on the basis of spectroscopic analysis.
Subject(s)
Asteraceae/chemistry , Diterpenes/isolation & purification , Diterpenes/chemistry , Molecular Structure , Spectrum AnalysisABSTRACT
Four new C-glucopyranosides of resveratrol oligomers, hemsleyanosides A-D, were isolated from the bark of Shorea hemsleyana. The structures were established on the basis of spectroscopic evidence, including 1H-1H and 1H-13C long-range couplings and nuclear Overhauser effect experiments in the NMR spectrum.
Subject(s)
Benzylidene Compounds/isolation & purification , Glucosides/isolation & purification , Malvaceae/chemistry , Benzylidene Compounds/chemistry , Glucosides/chemistry , Magnetic Resonance Spectroscopy , Plant Stems/chemistryABSTRACT
Five new abietane derivatives which have a commonly rearranged abietane skeleton contained a 17(15-->16),18(4-->3)-diabeo-abietane framework, mandarones D-H, were isolated from the stem of Clerodendrum nmantarinorum Diels (Verbenaceae). The structures were characterized as (16S)-12,16-epoxy-11-hydroxy-17(15-->16), 18(4-->3)-diabeo-abieta-3,5,8,11,13-pentaene-7-one (mandarone D, 1), 12,16-epoxy-11,14-dihydroxy-17(15-->16),18(4-->3)-diabeo-abieta-3,5,8,11, 13,15-hexaene-7-one (mandarone E, 2), 12,16-epoxy-6,11,14-trihydroxy-17(15-->16),18(4-->3)-diabeo-abieta-3,5,8,11,13,15-hexaene-7-one (mandarone F, 3),12,16-epoxy-11,14-dihydroxy-6-methoxy-17(15-->16),18(4-->3)-diabeo-abieta-3,5,8,11,13,15-hexaene-2,7-dione (mandarone G, 4) and 12,16-epoxy-11,14-dihydroxy-17(15-->16),18(4-->3)-diabeo-abieta-3,5,8,11,13,15-hexaene-1,7-dione (mandarone H, 5) respectively, mainly based on the spectral analysis and by comparison with those of closely related compounds.