Breast cancer resistance protein (BCRP)/MXR/ABCG2 is a new member of the family of ATP-dependent drug efflux proteins. Whereas overexpression of another member of this family, P-glycoprotein, minimally affects the cytotoxicity of camptothecins (CPTs), overexpression of wildtype as well as certain mutant BCRPs confers resistance to CPT analogues that are used clinically, including topotecan and ...

PURPOSE 9-Nitrocamptothecin (9NC) is an oral camptothecin analogue currently administered at 1.5 mg/m(2)/day x 5 days/week in Phase III studies for pancreatic carcinoma. In an effort to increase the dose administered per day and determine whether the daily dose or number of days of treatment influence toxicity, we performed a Phase I study of 9NC using intermittent schedules of administration. ...

Ovarian cancer is the fifth leading cause of the cancer-related death among women. 9-nitrocamptothecin (9-NC) is a water-insoluble derivative of camptothecin used for the treatment of patients with advanced ovarian cancer. Previous studies showed that the encapsulation of 9-NC in poly (lactic-co-glycolic acid, PLGA) nanoparticles increased the cytotoxic effect of the drug on different cancer ce...

Camptothecin is a natural, water-insoluble alkaloid produced by two Asian trees, Camptotheca acuminata and Mappia foetida. In the 1970s, preliminary clinical trials with camptothecin demonstrated promising antitumor activity, for example, in gastric cancer. Unfortunately, there were also severe side effects, including poorly predictable hemorrhagic cystitis, gastrointestinal toxicities and myel...

As a first step towards improving the aqueous stability of 9-aminocamptothecin (9AC), a detailed kinetic and thermodynamic investigation of the hydrolysis reaction of 9AC was carried out, using a first derivative absorption spectrophotometry technique. It was found that 9AC-lactone decayed with a half-life of 25 min in PBS at pH 7.4 and 310.15K. The activation energy (Ea) associated with the hy...

Stimulation of CD95 leads to oligomerization of this receptor and the recruitment of the Fas-associated death domain (FADD) and procaspase-8 to form the death-inducing signaling complex (DISC). Subsequent proteolytic activation of caspase-8 at the DISC leads to the activation of downstream caspases and execution of apoptosis. The anticancer drug 9-nitrocamptothecin (9NC) inhibits the nuclear en...

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these p...

BACKGROUND Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC an...

9-nitrocamptothecin (9-nc) is a semisynthetic and a low soluble analogue of camptothecin alkaloids that target nuclear enzyme topoisomerase i. the unstable lactone form of 9-nc in biological fluids requires for its cytotoxic activity. to improve aqueous solubility and stability in biological media, 9-nc was loaded in polymeric nanoparticles. in this paper, we studied the effect of peg percent (...

We have previously shown that high levels of HER-2/neu protein were overexpressed in human Ewing's sarcoma cells (TC71, SK-ES1) relative to normal human osteoblasts. The purpose of this study was to determine whether herceptin alone or in combination with chemotherapeutic agents could inhibit the growth of Ewing's sarcoma in vitro and in vivo. Western blot analysis showed that the protein level...