BACKGROUND/ PURPOSE: Local and systemic control of soft tissue sarcoma (STS) remains a clinical challenge, particularly for retroperitoneal, deep truncal, or advanced extremity disease. 2',2'-Difluoro-2'-deoxycytidine (gemcitabine) is a potent radiosensitizer in many tumor types, but it has not been studied in human STS. The purpose of this study was to determine the radiosensitizing potential of gemcitabine in preclinical models of human STS. MATERIALS AND METHODS: The in vitro radiosensitizing activity of gemcitabine was assessed with clonogenic survival assay on three human STS cell lines: SK-LMS-1 (leiomyosarcoma), SW-872 (liposarcoma), and HT-1080 (fibrosarcoma). Cell cycle distribution was determined using dual-channel flow cytometry. The in vivo radiosensitizing activity of gemcitabine was assessed with subcutaneous SK-LMS-1 nude mice xenografts. Tumor-bearing mice were treated with concurrent weekly gemcitabine and fractionated daily radiotherapy (RT) (2 Gy daily) for 3 weeks (a total dose of 30 Gy). RESULTS: The 50% inhibitory concentration (IC(50)) of gemcitabine for the human STS cell lines ranged from 10 to 1000 nM. Significant in vitro radiosensitization was demonstrated in all three human STS cell lines using gemcitabine concentrations at and below the IC(50). Maximal radiosensitization was associated with accumulation of cells in early S-phase. SK-LMS-1 xenografts displayed significant tumor growth delay with combined gemcitabine and RT compared to either treatment alone. Treatment related toxicity was greatest in the gemcitabine plus RT arm, but remained at an acceptable level. CONCLUSIONS: Gemcitabine is a potent radiosensitizer in preclinical models of human STS. Clinical trials combining gemcitabine and RT in human STS are warranted.
BACKGROUND/ PURPOSE: Local and systemic control of soft tissue sarcoma (STS) remains a clinical challenge, particularly for retroperitoneal, deep truncal, or advanced extremity disease. 2',2'-Difluoro-2'-deoxycytidine (gemcitabine) is a potent radiosensitizer in many tumor types, but it has not been studied in human STS. The purpose of this study was to determine the radiosensitizing potential of gemcitabine in preclinical models of human STS. MATERIALS AND METHODS: The in vitro radiosensitizing activity of gemcitabine was assessed with clonogenic survival assay on three human STS cell lines: SK-LMS-1 (leiomyosarcoma), SW-872 (liposarcoma), and HT-1080 (fibrosarcoma). Cell cycle distribution was determined using dual-channel flow cytometry. The in vivo radiosensitizing activity of gemcitabine was assessed with subcutaneous SK-LMS-1 nude mice xenografts. Tumor-bearing mice were treated with concurrent weekly gemcitabine and fractionated daily radiotherapy (RT) (2 Gy daily) for 3 weeks (a total dose of 30 Gy). RESULTS: The 50% inhibitory concentration (IC(50)) of gemcitabine for the human STS cell lines ranged from 10 to 1000 nM. Significant in vitro radiosensitization was demonstrated in all three human STS cell lines using gemcitabine concentrations at and below the IC(50). Maximal radiosensitization was associated with accumulation of cells in early S-phase. SK-LMS-1 xenografts displayed significant tumor growth delay with combined gemcitabine and RT compared to either treatment alone. Treatment related toxicity was greatest in the gemcitabine plus RT arm, but remained at an acceptable level. CONCLUSIONS:Gemcitabine is a potent radiosensitizer in preclinical models of human STS. Clinical trials combining gemcitabine and RT in human STS are warranted.
Authors: A Eisbruch; D S Shewach; C R Bradford; J F Littles; T N Teknos; D B Chepeha; L J Marentette; J E Terrell; N D Hogikyan; L A Dawson; S Urba; G T Wolf; T S Lawrence Journal: J Clin Oncol Date: 2001-02-01 Impact factor: 44.544
Authors: O Merimsky; I Meller; G Flusser; Y Kollender; J Issakov; M Weil-Ben-Arush; E Fenig; G Neuman; D Sapir; S Ariad; M Inbar Journal: Cancer Chemother Pharmacol Date: 2000 Impact factor: 3.333
Authors: S R Patel; V Gandhi; J Jenkins; N Papadopolous; M A Burgess; C Plager; W Plunkett; R S Benjamin Journal: J Clin Oncol Date: 2001-08-01 Impact factor: 44.544
Authors: C H Crane; R A Wolff; J L Abbruzzese; D B Evans; L Milas; K Mason; C Charnsangavej; P W Pisters; J E Lee; R Lenzi; S Lahoti; J N Vauthey; N A Janjan Journal: Semin Oncol Date: 2001-06 Impact factor: 4.929
Authors: C J McGinn; M M Zalupski; I Shureiqi; J M Robertson; F E Eckhauser; D C Smith; D Brown; G Hejna; M Strawderman; D Normolle; T S Lawrence Journal: J Clin Oncol Date: 2001-11-15 Impact factor: 44.544
Authors: Ahmedin Jemal; Rebecca Siegel; Elizabeth Ward; Taylor Murray; Jiaquan Xu; Carol Smigal; Michael J Thun Journal: CA Cancer J Clin Date: 2006 Mar-Apr Impact factor: 508.702
Authors: William W Tseng; Shouhao Zhou; Christina A To; Peter F Thall; Alexander J Lazar; Raphael E Pollock; Patrick P Lin; Janice N Cormier; Valerae O Lewis; Barry W Feig; Kelly K Hunt; Matthew T Ballo; Shreyaskumar Patel; Peter W T Pisters Journal: Cancer Date: 2015-07-15 Impact factor: 6.860
Authors: Sandhya Clement; Jared M Campbell; Wei Deng; Anna Guller; Saadia Nisar; Guozhen Liu; Brian C Wilson; Ewa M Goldys Journal: Adv Sci (Weinh) Date: 2020-10-28 Impact factor: 16.806
Authors: Mina S Makary; Stuart Ramsell; Eric Miller; Eliza W Beal; Joshua D Dowell Journal: World J Gastroenterol Date: 2021-11-21 Impact factor: 5.742