Magnetic Resonance Imaging as a Predictor of Pathologic Response in Patients Treated with Neoadjuvant Systemic Treatment for Operable Breast Cancer (TBCRC 017)

Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer has prompted interest in whether patients with pCR can be identified preoperatively and potentially spared the morbidity of surgery. This multicenter retrospective study was performed to estimate the accuracy of preoperative MRI in predicting pCR in the breast

K-Ras-Independent Effects of the Farnesyl Transferase Inhibitor L-744,832 on Cyclin B1/Cdc2 Kinase Activity, G2/M Cell Cycle Progression and Apoptosis in Human Pancreatic Ductal Adenocarcinoma Cells

Pancreatic ductal adenocarcinoma is a highly lethal malignancy that is resistant to traditional cytotoxic therapy. High rates of activating codon 12 K-Ras mutations in this disease have generated considerable interest in the therapeutic application of novel farnesyl transferase inhibitors (FTIs). However, a comprehensive analysis of the effects of FTI treatment on pancreatic cancer cells has not been performed. Treatment of five different human pancreatic cancer cell lines with FTI L-744,832 resulted in inhibition of anchorage-dependent growth, with wide variation in sensitivity among different lines. Effective growth inhibition by L-744,832 correlated with accumulation of cells with a tetraploid (4N) DNA content and high levels of cyclin B1/cdc2 kinase activity, implying cell cycle arrest downstream from the DNA damage-inducible G2/M cell cycle checkpoint. In addition, sensitive cell lines underwent apoptosis as evidenced by changes in nuclear morphology and internucleosomal DNA fragmentation. L-744,832 at a concentration of 1 µM additively enhanced the cytotoxic effect of ionizing radiation, apparently by overriding G2/M checkpoint activation. The effects of FTI treatment on cell growth and cell cycle regulation were associated with changes in posttranslational processing of H-Ras and N-Ras, but not K-Ras. The results confirm the potential therapeutic efficacy of FTI treatment in pancreatic cancer, and suggest that farnesylated proteins other than K-Ras may act as important regulators of G2/M cell cycle kinetics

Validation of an algorithm for the nonrigid registration of longitudinal breast MR images using realistic phantoms

Purpose: The authors present a method to validate coregistration of breast magnetic resonance images obtained at multiple time points during the course of treatment. In performing sequential registration of breast images, the effects of patient repositioning, as well as possible changes in tumor shape and volume, must be considered. The authors accomplish this by extending the adaptive bases algorithm (ABA) to include a tumor-volume preserving constraint in the cost function. In this study, the authors evaluate this approach using a novel validation method that simulates not only the bulk deformation associated with breast MR images obtained at different time points, but also the reduction in tumor volume typically observed as a response to neoadjuvant chemotherapy