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• W2582265804 abstract "1369 Objectives The American Cancer Society projected nearly 221,000 men would be diagnosed with prostate cancer and that over 27,000 would succumb to the disease in 2015. Despite significant advances in development of new treatments, prostate cancer remains a deadly disease upon progression to the castration resistant state. The current study tests the hypothesis that combining micro-tubule inhibiting taxane chemotherapy with BB2 receptor targeted radiotherapy will be synergistic and lead to increased prostate cancer cell kill resulting in enhancement of overall treatment efficacy. Methods Peptide (DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) was commercially synthesized and radiolabeled with lutetium chloride (Lu-177) using an Eckert & Ziegler Modular-Lab PharmTracer cassette based radiosynthesizer. Lu-177 labeled peptide (TRT) radiochemical purity was determined by HPLC. Cultured human prostate cancer cell lines (PC-3, LNCAP, and LNCAP C42) were plated at appropriate concentrations and allowed to adhere overnight prior to treatment with vehicle or docetaxel at 1.25, 2.5, and 5.0nM. After 24hrs, the media was removed from all wells and fresh growth media was added. Cells were treated with TRT at 5, 10, 20, 40, and 60uCi/well with combination treatments conducted at 10, 20, and 40uCi/well. Media was refreshed at 72hrs post TRT addition. MTT reagent was added to each well at 72, 96, and 120hrs post TRT addition. The plates were then incubated for 4 hrs prior to removal of all media. Plates were read at 540nm and absorbance was normalized to non-treated controls. Synergy was evaluated using Biosoft® Calcusyn software. Cell cycle analysis was performed in all three cell lines at 24, 48, and 72hrs after treatment with docetaxel at 1.25, 2.5, and 5.0nM. Results PC-3 cells exposed to the combination treatment (docetaxel + TRT) exhibited synergy with 1.25nM + 40uCi, 2.5nM + both 20uCi and 40uCi/well at 72 hrs post TRT addition. Slight synergy was achieved at 5nM + 40uCi and moderate synergy with 1.25nM + 20uCi at 72hrs post TRT addition. The LNCAP cell line exhibited synergy with treatment at 1.25nM + both 20uCi and 40uCi/well and moderate synergy with 2.5nM + both 20uCi and 40uCi/well at 96hrs post TRT treatment. The LNCAP C42 cell line showed slight synergy with treatment of 1.25nM + 40uCi/well at 72hrs and 2.5nM + 20uCi/well at 96hrs post TRT addition. Conclusions Combination treatment using the radiosensitizer, docetaxel, and TRT exhibited varying levels of synergy across the 3 cell panel including androgen independent and androgen dependent human prostate cancer cell lines. Synergy between TRT and chemotherapy was demonstrated at concentrations of chemotherapy previously shown to be effective for control of prostate cancer in preclinical xenograft models. Further preclinical prostate cancer xenograft studies are underway to optimize synergy for therapeutic effectiveness." @default.
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• W2582265804 date "2016-05-01" @default.
• W2582265804 modified "2023-09-25" @default.
• W2582265804 title "Assessing Synergy of Chemotherapy and Targeted Radiotherapy in Prostate Cancer: A Preclinical In-vitro Evaluation" @default.
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