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View the Table of Contents for the February 1 issue of Cancer Research.
Page 1371
Frieboes et al. Page 1597
Computer simulations of a reaction-diffusion mathematical model and in vitro experiments predict that tumor morphology is a function of marginally stable environmental conditions. The authors propose that tumor morphogenesis in vivo may be a function of marginally stable environmental conditions caused by spatial variations in cell nutrients, oxygen, and growth factors, and that controlling these conditions by decreasing spatial gradients could benefit treatment outcomes. In contrast, they suggest current treatment, and especially antiangiogenic therapy, may trigger spatial heterogeneity (e.g., local hypoxia) thus causing invasive instability.
Konecny et al. Page 1630
Lapatinib is a selective inhibitor of both the EGFR and HER2 tyrosine kinases. To explore its therapeutic potential for the treatment of breast cancer, Konecny et al. designed preclinical models which demonstrate that lapatinib has particular antitumor activity in HER2-overexpressing breast cancer cells. It retained its antitumor activity in cells resistant to trastuzumab, and synergistic drug interactions were observed when it was combined with a monoclonal antibody such as trastuzumab. These observations provide a biologic rational to test lapatinib as a single agent or in combination with trastuzumab in HER2-overexpressing breast cancer and in patients with clinical resistance to trastuzumab.
Combined hyperinsulinism and hyperglycemia induces hepatocarcinogenesis after intrahepatic low-number transplantation of pancreatic islets in streptozotocin-diabetic Lewis rats. However, streptozotocin is genotoxic and may have contributed to the carcinogenic process. Dombrowski et al. have shown that hepatocarcinogenesis can also be initiated in spontaneously auto-immune diabetic rats, unequivocally excluding streptozotocin as a significant contributor. They demonstrated that insulin-induced, long-term, adaptive metabolic alterations of hepatocytes, including altered enzyme activities in the carbohydrate metabolism and altered signaling via the Ras-Raf-MAPK pathway and the IGF-1 axis, can be the starting point of a hepatocarcinogenic process.
Ménard et al. Page 1844
Ménard et al. sought to discover clinical biomarkers of radiation exposure using proteomic profiling strategies. High-throughput SELDI-TOF mass spectrometry generated high-resolution proteomic profiles of unfractionated serum samples from 68 patients before and during a course of radiotherapy. Supervised classification techniques accurately distinguished unexposed from radiation-exposed samples, and high from low dose-volume levels of exposure. Mass spectrometry of pooled sera identified 23 protein fragments/peptides uniquely detected in the radiation exposure group. Proteomic analysis for the discovery of clinical biomarkers of radiation exposure warrants further study, and may have broad implication in cancer care and population exposures to radiation.