Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment.

Purpose. The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.

Cyclin D1 amplification in multiple myeloma is associated with multidrug resistance expression.

BACKGROUND: Cyclin D1 is involved in normal regulation of the cell cycle and in neoplasia. Inhibition of cyclin D1 function markedly attenuates the proliferation of fibroblasts of colon, esophageal, lung, and pancreatic cancer. However, the prognostic value of overexpression of cyclin D1 in multiple myeloma is still a point of debate. This study aimed at evaluating the effect of cyclin D1 gene amplification in multiple myeloma on overall survival and response to therapy. PATIENTS AND METHODS: Fifty patients with multiple myeloma were retrospectively studied. Cyclin D1 gene amplification was studied in bone marrow biopsies of these patients using FISH. An immunohistochemical study of the bone marrow biopsies was done to detect MDR1 protein expression. The correlations between the cyclin D1 gene amplification and overall survival and MDR1 expression were studied and analyzed statistically. RESULTS: Cyclin D1 gene amplification was found in 20% of myeloma patients and was associated with higher percentage of plasma cell infiltration of the bone marrow and increased liability for multiple osteolytic lesions. Cyclin D1-positive patients had a significantly lower progression-free and overall survival and higher levels of MDR1 compared with cyclin D1-negative patients. Cyclin D1 levels showed a highly statistically significant positive correlation with MDR1 levels (R, 0.8 and P < .0001). CONCLUSION: We suggest that there is an association between cyclin D1 gene amplification and disease severity, unfavorable prognosis, and increased expression of MDR1 in multiple myeloma patients.