OBJECTIVETo prepare arsenic trioxide (As2O3)-loaded biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles (NPS) and evaluate the glomeration ability, appearance, structure, surface and release characteristics of the NPs.

METHODSWith PLGA as the carrier material, As2O3 NPs (As2O3-NPS) were prepared with the method of matrix and ultrasound emulsification. According to the criteria of the diameter of the NPs, drug loading (DL) and embedding ratio (ER), the process of NP preparation was optimized by scanning electron microscopy (SEM), ultraviolet spectroscopy (UV), and XPS.

RESULTSThe As2O3-NPS prepared were uniformly spherical with an average diameter of 210-/+23 nm, DL of 29.6% and ER of 82.1%. The drug release assay in vitro showed a sustained drug-release capacity of the preparation.

CONCLUSIONAs2O3-NPS may serve as a carrier of As2O3 to change the pharmacokinetics of As2O3 in vivo, allow slow drug release, and prolong the drug circulation time after intravenous injection, thereby producing better antitumor effects.

Arsenicals ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Drug Carriers ; Nanoparticles ; Oxides ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Particle Size ; Polyglycolic Acid

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; Cisplatin ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Middle Aged ; Oxides ; administration & dosage

OBJECTIVETo assess the efficiency of eluting stent coated with arsenic trioxide (As(2)O(3)) suspended in poly-L-lactic acid (PLLA) to prevent in-stent restenosis in rabbits.

METHODSForty-five male New Zealand white rabbits were assigned to three groups (n = 15 for each group) at random: uncoated stents, stents coated with PLLA or stents coated with As(2)O(3) in PLLA. Animals were euthanized 28 days after stent implantation into the iliac arteries of rabbits. Neointimal thicknesses and apoptosis of vascular smooth muscle cell (VSMC) were measured. Stents coated with As(2)O(3) in PLLA were implanted in another 48 male New Zealand white rabbits, As(2)O(3) concentrations in serum and arterial tissue at implantation site were measured at 2 h and 1, 3, 7, 14, 28 days after As(2)O(3) eluting stent implantation (n = 8 for each time point).

RESULTSNeointimal hyperplasia was significantly reduced 51% and 31% and apoptosis significantly increased (21.0 +/- 3.3; 6.2 +/- 1.9(*); 5.3 +/- 2.1(*), (*)P < 0.01 vs. As(2)O(3) eluting stent) with As(2)O(3) eluting stent, versus PLLA-coated stents and uncoated stents. As(2)O(3) concentrations in arterial tissue at implantation site were 18.6 +/- 9.1 (ng/mg) at 1 day and 0.3 +/- 0.1 (ng/mg) at 28 days after stent implantation.

CONCLUSIONSAs(2)O(3) coated stents released As(2)O(3) to local tissue for at least 28 days, suppressed neointimal hyperplasia in rabbit iliac arteries and increased local VSMC apoptosis might be one of the mechanisms for inhibiting restenosis by As(2)O(3) coated stents.

Animals ; Apoptosis ; drug effects ; Arsenicals ; administration & dosage ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Iliac Artery ; Male ; Muscle, Smooth, Vascular ; cytology ; Oxides ; administration & dosage ; Rabbits ; Random Allocation

OBJECTIVETo observe the safety and efficacy of early or non-early controlled-release arsenic-trioxide (As(2)O(3))-eluting stents on reducing in-stent neointimal hyperplasia.

METHODSBare stents, stents coated with polybutyl methacrylate/Nano silica (containing 200 microg of As(2)O(3) per stent or not), stents coated with polybutyl methacrylate/Nano silica inside (containing 200 microg of As(2)O(3) per stent or not) and poly-lactide-co-glycolide (PLGA) outside were deployed with mild oversizing in left anterior descending (LAD) and circumflex coronary arteries (LCX)of 30 canines (n = 6, 12 stents for each group).

RESULTSThe mean injury scores were similar in all groups at 4 weeks post stents implantation while the mean neointimal thickness, neointimal area and degree of stenosis were significantly reduced and the lumen area significantly increased in canines receiving single coating stents containing As(2)O(3) compared with single or double coating stents and bare stents groups (all P < 0.01). These effects were further enhanced in canines implanted with double coating stents containing As(2)O(3) (all P < 0.01 vs. single coating stents containing As(2)O(3)). No intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis, inflammatory cells infiltration were observed in all stenting groups.

CONCLUSIONSControlled-release As(2)O(3)-eluting stents resulted in a significant inhibition of neointimal hyperplasia in the canine coronary arteries 4 weeks after stents implantation and the effects is more significant with controlled-release of As(2)O(3) at non-early stage than that at early stage.

Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Animals ; Arsenicals ; administration & dosage ; pharmacology ; Coronary Restenosis ; etiology ; prevention & control ; Disease Models, Animal ; Dogs ; Drug-Eluting Stents ; Oxides ; administration & dosage ; pharmacology

To clarify the source of deviations of drug combination effects evaluated with different drug interaction mathematical models, the cytotoxicity of SAHA and arsenic trioxide and their combinations were observed in a series of human cancer cell lines and a normal cell line. The combined effects were evaluated with three drug interaction models: Loewe Additivity (LA), Bliss Independence (BI) and Chou's Median Effect Model. The evaluations with three different models were further compared with each other. We demonstrated that when dose-response curves were fitted with the same method, similar evaluated results for drug combinations would be derived with different models. The deviations of evaluated effects of drug combinations were attributed to different curve fitting methods used rather than the models themselves. The effects of drug combinations showed discrepancies on different cell lines, and at different combined drug concentrations on same cell line.
Antineoplastic Agents ; administration & dosage ; pharmacology ; Arsenicals ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Interactions ; Humans ; Hydroxamic Acids ; administration & dosage ; pharmacology ; Models, Chemical ; Oxides ; administration & dosage ; pharmacology

Antineoplastic Combined Chemotherapy Protocols ; Arsenicals ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; secondary ; Chemoembolization, Therapeutic ; methods ; Humans ; Liver Neoplasms ; Lung Neoplasms ; drug therapy ; secondary ; Niacinamide ; administration & dosage ; analogs & derivatives ; Oxides ; administration & dosage ; Phenylurea Compounds ; administration & dosage

OBJECTIVETo retrospectively analyze the treatment outcomes and side effects of childhood acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) or ATRA + arsenic trioxide (As2O3).

METHODSFrom 1992 to 2006, 45 patients with newly diagnosed APL were enrolled. All of them were PML-RAR alpha positive. 24 patients were induced with ATRA (group A) and 21 with ATRA + As2O3 (group B). The remission rate and side effects were observed.

RESULTS1) 19 (79.2%) patients in group A achieved CR, while 21(100%) patients in group B achieved CR. The CR rate in group A was lower than that in group B (P=0.027). 2) The recovery time of coagulation parameters and PLT count in group B was shorter than that in group A. 3) The overall survival (OS) and event-free survival(EFS) in group A were 77.8% and 66.9% at 41 months of follow-up, and in group B were 100% and 100% respectively at 34 months of followup. Group A had a significant lower EFS (P=0.0357)than group B. 4) The time of PML-RAR alpha fusion gene converting to negative in group A was longer (P=0.026) than that in group B.

CONCLUSIONSATRA + As2O3 for patients with newly diagnosed childhood APL is a feasible treatment with higher CR rate, less side effects and longer long-term survival.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Oxides ; administration & dosage ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; administration & dosage

Adult ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Apoptosis ; drug effects ; Arsenicals ; administration & dosage ; therapeutic use ; Chromosome Aberrations ; Humans ; Infusions, Intravenous ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; pathology ; Male ; Oxides ; administration & dosage ; therapeutic use ; Remission Induction

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Oxides ; administration & dosage ; therapeutic use ; Tretinoin ; administration & dosage

OBJECTIVETo explore the significance of combined therapy of arsenic trioxide (As2O3) and all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL).

METHODSRetrospective study of 80 APL patients was performed and the complete remission (CR), the recovery time of peripheral hemoglobin and platelet, the early mortality, and the adverse reaction rates were analyzed between the ATRA group and the ATRA combined As2O3 group (combined group).

RESULTSCR rate of the combined group and the ATRA group was 91.7% and 87.5% respectively, which showed no significant difference; time of reaching CR, hemoglobin recovery, and platelet recovery for the combined group were 28.0 +/- 7.8 days, 22.36 +/- 8.72 days and 19.38 +/- 9.52 days respectively, while those were 47.7 +/- 10.9 days, 28.40 +/- 8.95 days and 28.03 +/- 7.29 days for the ATRA group, which suggested a significantly shorter period of the combined group of achieving recovery. With 7.1% compared to 13.2%, the early mortality of the combined group seemed lower than that of the ATRA group but with no significance observed (P>0.05). The adverse reaction rates of the two groups also lacked any significant difference (P>0.05).

CONCLUSIONCompared with using ATRA alone, the combined therapy of AS2O3 and ATRA was dominant in achieving CR and recovery for APL. Besides, the combined therapy carries the promise of reducing the early mortality with no aggravation of the adverse reaction.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; administration & dosage ; Remission Induction ; Retrospective Studies ; Tretinoin ; administration & dosage ; Young Adult