Leg contracture in mice: an assay of normal tissue response

Stone, Helen B.

doi:10.1016/0360-3016(84)90177-9

Cited by 59 publications

(34 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2. For this radiation dose, the contraction observed was consistent with our previous studies (15) and other published studies (17). Halofuginone treatment at 1 and 5 μg/mouse resulted in significant protection against radiation-induced leg contraction when evaluated at both 3 and 4 months post-radiation treatment.…”

Section: Resultssupporting

confidence: 92%

See 1 more Smart Citation

Halofuginone mediated protection against radiation-induced leg contracture

Ishii

Choudhuri²,

Mathias³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 92%

“…Control animals received vehicle solution only. Fibrosis as measured by leg contraction was assessed as previously described (15,17). Briefly, a Lucite jig was made such that the body of the animal could be easily positioned within it and extension of the leg could be measured by referring to an inlaid ruler within the base of the jig.…”

Section: Methodsmentioning

confidence: 99%

Halofuginone mediated protection against radiation-induced leg contracture

Ishii

Choudhuri²,

Mathias³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

“…To determine the effect of nab-paclitaxel on chronic radiation-induced damage to normal tissues of the leg, an assay quantifying leg contracture was applied using mice in the TCD 50 experiment (30). Radiation-induced leg contracture in mice free from tumor recurrence was determined 120 days after radiation.…”

Section: Effect Of Nab-paclitaxel On Normal Tissue Radioresponsementioning

confidence: 99%

130-nm Albumin–Bound Paclitaxel Enhances Tumor Radiocurability and Therapeutic Gain

Wiedenmann

Valdecanas²,

Hunter³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: 130-nm albumin^bound paclitaxel (nab-paclitaxel) is a novel solvent-free albuminbound paclitaxel, designed to avoid solvent-related toxicity. Nab-paclitaxel has been successfully introduced into the clinic but its radiation-enhancing potential has not yet been evaluated. We conducted a preclinical evaluation of the radiation-modulating effects of nab-paclitaxel in tumor and normal tissues. Experimental Design: Mice bearing syngeneic ovarian or mammary carcinomas were treated with nab-paclitaxel, radiation, or combination of both. Nab-paclitaxel was administered at 90 mg/kg, 1.5 times the maximum tolerated dose for solvent-based paclitaxel. End points were antitumor efficacy (growth delay, radiocurability, and cellular effects) and normal tissue toxicity (gut and skin). Results: Nab-paclitaxel showed single-agent antitumor efficacy against both tumor types and acted as a radiosensitizer. Combined with radiation, nab-paclitaxel produced supra-additive effects when given before radiation. Nab-paclitaxel significantly increased radiocurability by reducing the dose yielding 50% tumor cure (TCD 50 ) from 54.3 to 35.2 Gy. Tumor histology following nab-paclitaxel treatment was characterized by pronounced necrotic and apoptotic cell death and mitotic arrest. Nab-paclitaxel did not increase normal tissue radioresponse. Conclusions: Nab-paclitaxel exhibited strong antitumor efficacy against both tumors as a single agent and it improved radiotherapy in a supra-additive manner. These improved effects were achieved without increased normal tissue toxicity to either rapidly or slowly proliferating normal tissues although the drug dose was 1.5 times higher than the maximum tolerated dose of solventbased paclitaxel. These preclinical findings show that combining nab-paclitaxel with radiotherapy would improve the outcome of taxane-based chemoradiotherapy. This novel taxane is thus a good candidate for testing in clinical chemoradiotherapy trials.Besides being very efficient cytotoxic drugs on their own, taxanes are also potent enhancers of tumor radiation response. In the clinical setting, taxanes are being used as radiationenhancing drugs in a variety of disease sites including nonsmall-cell lung cancer, head and neck, esophageal, gastric, cervical, urothelial, and nasopharyngeal carcinoma (1 -7).Taxanes are complex diterpenoids characterized by an extremely hydrophobic structure with sparse aqueous solubility (8). To overcome solubility problems, chemical solvents such as ethanol, Tween 80, and castor oil (Cremophor EL) are used in currently approved solvent-based taxane formulations. These solvents are known to cause biological and pharmacologic side effects, including dose-limiting toxicity, acute hypersensitivity reactions, and altered pharmacokinetics (resulting in a nonlinear pharmacokinetic profile). As a result, intensive research is being aimed at developing alternative formulations (8 -12).One such alternative is nab-paclitaxel (Abraxane), a novel, solvent-free 130-nm nanoparticle albumin -bound formu...

show abstract

“…To test whether BBI -which we identified as normal-cell-specific radioprotector in vitro [7] -acts as an inhibitor of radiation-induced fibrosis in vivo, we chose the radiation-induced leg contracture assay as a model system. This assay was originally developed by Stone [28] and is based on the radiation-induced fibrotic reorganization of connective tissue of the leg. Fibrotic tissue remodeling results in reduced elastic properties of the skin and subcutaneous tissue and leads to a measurably reduced elongation when the leg is actively extended.…”

Section: Discussionmentioning

confidence: 99%

“…At day 0 the right legs of mice were irradiated with a single dose of 55 Gy using a linac (Mevatron 60 /Siemens, Erlangen, Germany) and a dose rate of 2 Gy/min. Radiation-induced leg contracture was measured at 20-to 30-day intervals, starting at day 100 and ending at day 200 after local leg irradiation using the method by Stone [28]. For measurements, mice received isoflurane anesthesia and were placed in a metal jig with tails between the vertical posts of the jig.…”

Section: Reduction In Leg Contracturementioning

confidence: 99%