Anti-cancer drugs
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Overexpression of Skp2, the ubiquitin ligase subunit that targets p27 for degradation, is often observed in cancers, and is associated with aggressive tumor proliferation and poor prognosis. As there is no drug at present that specifically targets Skp2, studies were undertaken to examine the effects of commonly used drugs on Skp2 regulation. Doxorubicin is among the most effective antitumor agents used for the management of breast cancer, but its effect on Skp2 expression is unknown. ⋯ Doxorubicin arrested MCF-7 cells at G1/S and G2/M checkpoints, whereas MDA-MB-231 cells were arrested at G2/M only. The differential effects of doxorubicin on Skp2 expression in breast cancer cells depend upon the specific cell cycle checkpoints activated by the drug. These changes induced by doxorubicin, however, do not significantly affect p27 expression in these cell lines, suggesting that the potential of a given drug to alter p27 expression through Skp2 modulation might depend on its specific action on cell cycle arrest.
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Ductal carcinoma in situ (DCIS) is a preinvasive breast lesion accounting for approximately 30% of all newly detected breast cancers in the US. DCIS has been separated into two groups by architecture (comedo versus noncomedo) and nuclear grade. The expression of biological markers in DCIS, however, would reflect the true biologic potential of the lesion. ⋯ They are not candidates for tamoxifen; trastuzumab has an undetermined role in DCIS. In this report, we present a case of a 45-year-old woman diagnosed with invasive breast cancer and ER-negative/HER-2-positive DCIS who developed recurrence and progression of DCIS as manifested by a new palpable mass while receiving trastuzumab as part of adjuvant treatment for invasive breast cancer. The potential clinical implications are discussed.
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The objective was to evaluate the efficacy and toxicity of leucovorin plus 5-fluorouracil combined with oxaliplatin (modified FOLFOX regimen) every 2 weeks on previously untreated advanced colorectal cancer patients in the Chinese population. Fifty-one inpatients were enrolled to receive 85 mg/m oxaliplatin intravenously over a 2- h period on day 1, together with 400 mg/m2 leucovorin over 2- h, followed by a 46-h infusion of 5-fluorouracil at 2600 mg/m2 every 2 weeks. Treatment was given until progression or unmanageable toxicity ensued. ⋯ Median progression-free survival was 7.7 months (95% confidence interval 6.8-8.6) and median overall survival was 15.0 months (95% confidence interval 13.1-16.9). Toxicities were mild: five patients (9.8%) reported grade 3-4 neutropenia, 33 patients (64.8%) experienced grade 1-3 neurotoxicity and only six patients (11.8%) experienced grade 3 neurotoxicity. The leucovorin plus 5-fluorouracil combined with oxaliplatin (modified FOLFOX) regimen is active and well tolerated in patients with previously untreated advanced colorectal cancer in the Chinese population.
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Development of treatments to improve the outcomes achieved with single-agent gemcitabine therapy for metastatic pancreatic cancer remains a research priority. G-FLIP (gemcitabine, 5-fluorouracil, leucovorin and cisplatin) is a four-drug regimen designed to maximize sequence-dependent synergy, while attempting to minimize toxicity among the four drugs. The dose-limiting toxicities and maximum tolerated dose of irinotecan as part of the G-FLIP regimen have been published. ⋯ Common grade 1-2 toxicities per patient included nausea/vomiting (69%), diarrhea (45%), constipation (21%) and fatigue (39%). In conclusion, G-FLIP is a feasible outpatient regimen with acceptable toxicity for metastatic pancreatic cancer patients. Disease control rate (stable disease rate plus partial or complete responses) and 1-year survival outcomes are encouraging.
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Comparative Study
Antitumor activity of Titanocene Y against freshly explanted human breast tumor cells and in xenografted MCF-7 tumors in mice.
Bis-[(p-methoxybenzyl)cyclopentadienyl] titanium dichloride, better known as Titanocene Y, is a newly synthesized transition metal-based anticancer drug. We studied the antitumor activity of Titanocene Y with concentrations of 2.1, 21 and 210 micromol/l against a freshly explanted human breast cancer, using an in-vitro soft agar cloning system. ⋯ A further preclinical development of Titanocene Y was warranted and therefore an MCF-7 human breast cancer xenograft nonobese diabetic/severe combined immunodeficient mouse model was used. Titanocene Y was given for 21 days at 30 mg/kg/day (75% of the maximum tolerable dose of Titanocene Y), which resulted in the reduction of the tumor volume to around one-third, whereas no mouse was lost because of the surprisingly low toxicity of Titanocene Y.