ABSTRACT
PURPOSE: To determine whether exercise training would increase lymphocyte activation in patients with breast cancer following chemotherapy. Activation was determined by the presence of CD4(+)CD69(+) T-helper lymphocytes, mitogen-induced proliferation, and levels of cytokines produced by mitogen-stimulated lymphocytes and in the patients' plasma. METHODS: Patients with breast cancer (N = 28) who participated in a 6-month exercise program were compared with patients (N = 21) who did not exercise. Following chemotherapy, and 3 and 6 months later, patients underwent fitness evaluations and had blood drawn. The exercise program consisted of resistance training and aerobic activity at 60-75% functional capacity three times a week with a personal trainer. Immunochemistry and flow cytometry were used to measure the number of CD4(+)CD69(+) blood lymphocytes. Whole blood was stimulated with concanavalin A (ConA), phytohemagglutin (PHA), or pokeweed mitogen (PWM) to determine proliferation potential. Enzyme-linked immunosorbent assays (ELISA) were used to determine the concentration of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) in the culture medium of mitogen-stimulated lymphocytes as well as the plasma concentrations of IL-6, soluble IL-6 receptor, soluble gp130, and IFN-gamma. Analysis of groups across time was done using the Wilcoxon signed rank test, and comparisons of groups were done using the Mann-Whitney U test. RESULTS: The exercising patients showed increases in maximal oxygen uptake and upper body strength. This group also showed a greater percentage of CD4(+)CD69(+) cells and a greater level of tritiated thymidine incorporation (DNA synthesis) when stimulated with ConA, PHA, and PWM at the end of the intervention. Plasma and mitogen-stimulated IL-6 and IFN-gamma production were similar in both groups. CONCLUSION: Exercise may improve immune function by increasing lymphocyte activation in patients with breast cancer following treatment.
Subject(s)
Breast Neoplasms/immunology , Exercise Therapy , Lymphocyte Activation , Adult , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , CD4-Positive T-Lymphocytes , Cell Proliferation , Cytokines/analysis , Female , Flow Cytometry , Humans , Immunohistochemistry , Lectins, C-Type , Middle Aged , Physical FitnessABSTRACT
Dermatofibrosarcoma protuberans (DFSP) is a rare superficial sarcoma usually affecting the trunk, with significant risk of local recurrence. It is characterized by the presence of ring chromosomes or chromosomal translocations fusing the promoter of the collagen gene COL1A1 to the platelet-derived growth factor beta-chain gene PDGFB, increasing the production of PDGF locally and promoting autocrine or paracrine tumor growth. Fewer than 5% of patients with DFSP develop metastatic sarcoma, with a poor subsequent prognosis. Imatinib (STI-571) was developed as an inhibitor of the PDGF receptor tyrosine kinase and has proven clinical activity against chronic myelogenous leukemia (expressing bcr-abl) and gastrointestinal stromal tumors (expressing c-kit). We describe 2 patients with metastatic and unresectable metastases from DFSP treated with imatinib. After confirmation of negative CD117 status of 2 sarcomas arising from DFSP, patients were given imatinib 400 mg po qd and assessed at regular intervals for their tolerance and response to therapy. One patient had a transient response, then progressed rapidly and died of disease. Another patient showed a partial response to therapy after 2 months, with resolution of superior vena cava syndrome and shrinking of metastatic lung lesions. His response is ongoing after 6 months of therapy. These clinical data confirm findings from models of DFSP and support the use of imatinib in the rare setting of metastatic DFSP. Imatinib may be useful for patients with locally advanced DFSP, when other options for local therapy are limited.
