Phase II study of mitoxantrone and ketoconazole for hormone‐refractory prostate cancer

Abstract

The motion of DNA chain under electric field when it is in transient contact with the solid surfaces in aqueous solution was studied by single molecule fluorescence microscopy at the total internal reflection geometry (TIRFM). In situ observation discovered that single λ‐DNA chains driven by electric field made transient contact with the solid surface and made hitting–sliding–leaving‐like motion along the surface. By varying the surface chemistry, from the negative‐charged silanol group‐rich surface to positive‐charged amino group‐rich surface, as well as hydrophobic surfaces, the dependence of DNA mobility on the surface–DNA interaction was studied. The results show that a dependence of the mobility of DNA on the surface polarity with respect to DNA itself. The study on different surfaces rich of silanol, amide, amino, and methyl groups show a sequence of DNA mobility of silanol > amide > amino. The mobility of DNA on methyl terminated surface was found to be similar to that on amino surface. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2541–2546, 2009

Evidence for Mitoxantrone-induced Block of Inwardly Rectifying K+Channels Expressed in the Osteoclast Precursor RAW 264.7 Cells Differentiated with Lipopolysaccharide

“…It can intercalate into DNA, thereby inhibiting the topoisomerase II enzyme and preventing the ligation of DNA strands and delaying cell-cycle progression. Its therapeutic ef�icacy has been reported in numerous malignancies, including advanced prostate or breast cancers with osseous metastasis [5][6][7]. Despite its ability to disrupt DNA synthesis and repair, this drug was demonstrated to exert some effects on ion currents and membrane potential in heart cells [8].…”

Inhibition of proliferation and migration of melanoma cells by ketoconazole and Ganoderma immunomodulatory proteins

“…Co-administration of CYP3A inhibitor and ketoconazole with the proteasome inhibitor bortezomib has been reported to increase the blood proteasome inhibitory effect in patients with advanced solid tumors by 35% (18). Ketoconazole also enhances the effect of chemotherapeutic agents, including doxorubicin (19), mitoxantrone (20) and docetaxel (3). Oral delivery of pacitaxel with a dual CYP3A4 inhibitor has been demonstrated to effectively inhibit tumor growth in B16 F10 melanoma tumor-bearing mice (21).…”

A Phase I Clinical Study of High Dose Ketoconazole Plus Weekly Docetaxel for Metastatic Castration Resistant Prostate Cancer

“…At the standard single-agent dose of 1200 mg/day, 30% to 80% of patients have a PSA decline of ≥ 50% (22, 26–29). Ketoconazole also appears to enhance the antitumor activity of chemotherapeutic agents, including doxorubicin (11) and mitoxantrone (30). Improved response rates have been observed with an adriamycin-ketoconazole regimen (55%) compared to adriamycin alone (33%).…”