Pulmonary metastases frequently develop in patients with aggressive bladder cancer, yet investigation of this process at the molecular level suffers from the poor availability of human metastatic tumor tissue and the absence of suitable animal models. To address this, we developed progressively more metastatic human bladder cancer cell lines and an in vivo bladder-cancer lung-metastasis model, and we successfully used these to identify genes of which the expression levels change according to the degree of pulmonary metastatic potential. By initially intravenously injecting the poorly metastatic T24T human urothelial cancer cells into nude mice, and then serially reintroducing and reisolating the human tumor cells from the resultant mouse lung tumors, three derivative human lines with increasingly metastatic phenotypes, designated FL1, FL2, and FL3, were sequentially isolated. To identify the genes associated with the most lung-metastatic phenotype, the RNA complement from the parental and derivative cells was evaluated with oligonucleotide microarrays. In doing so, we found 121 genes to be progressively up-regulated during the transition from T24T to FL3, whereas 43 genes were progressively downregulated. As expected, many of the genes identified in these groups could, according to the ascribed functions of their protein product, theoretically participate in tissue invasion and metastasis. In addition, the magnitude of gene expression changes observed during the metastatic transition correlated with the in vivo propensity for earlier lung colonization and decreased host survival. To additionally define which genes found in the experimental system were of relevance to human bladder cancer lung metastasis, we evaluated gene expression profiles of 23 primary human bladder tumors of various stages and grades, and then we compared these gene expression profiles to the altered profiles in our model cell lines. Here we found that the expression of epiregulin, urokinase-type plasminogen activator (uPA), matrix metalloproteinase (MMP)14, and tissue inhibitor of metalloproteinase (TIMP-2) were consistently and progressively upregulated when viewed as a function of tumor stage in tissues of patients versus the metastatic potential seen in the mouse lung model. The strong correlation of these four markers between the experimental and clinical situations helps validate this system as a useful tool for the study of lung metastasis and defines targets of therapy that may reduce the incidence of this process in patients.

The initiation of new blood vessels through angiogenesis is critical to tumor growth. Tumor cells release soluble angiogenic factors that induce neovascularization, without which nutrients and oxygen would not be available to allow tumors to grow more than 2-3 mm in diameter. This "angiogenic switch" or angiogenic phenotype requires an imbalance between proangiogenic and antiangiogenic factors since the formation of new blood vessels is highly regulated. This review discusses angiogenesis mediators, and the potential for manipulation of angiogenic factors as a practical cancer therapy, particularly in prostate cancer.

Digital breast tomosynthesis (DBT) is an emerging technology used in diagnostic breast imaging to evaluate potential abnormalities. In DBT, the compressed breast tissue is imaged in a quasi-three-dimensional manner by performing a series of low-dose radiographic exposures and using the resultant projection image dataset to reconstruct cross-sectional in-plane images in standard mammographic views. Improved visualization of breast detail at diagnostic DBT allows improved characterization of findings, including normal structures and breast cancer. This technology reduces the summation of overlapping breast tissue, which can mimic breast cancer, and provides improved detail of noncalcified mammographic findings seen in breast cancer. It also assists in lesion localization and determining mammographic extent of disease in women with known or suspected breast cancer. The authors review the potential uses, benefits, and limitations of DBT in the diagnostic setting and discuss how radiologists can best use DBT to characterize lesions, localize potential abnormalities, and evaluate the extent of known or suspected breast cancer. The authors' experience shows that DBT can be implemented effectively in the diagnostic workflow to evaluate and localize potential lesions more efficiently. DBT may potentially replace conventional supplemental mammography at diagnostic workup and obviate ultrasonography in select cases.

The nipple-areolar complex may be affected by many normal variations in embryologic development and breast maturation as well as by abnormal processes of a benign or malignant nature. Benign processes that may affect the nipple-areolar complex include eczema, duct ectasia, periductal mastitis, adenomas, papillomas, leiomyomas, and abscesses; malignant processes include Paget disease, lymphoma, and invasive and noninvasive breast cancers. Radiologists should be aware of the best methods for evaluating each of these entities: Many disorders of the nipple-areolar complex are unique or differ in important ways from those that occur elsewhere in the breast, and they require a diagnostically specific imaging evaluation. Patients may present with benign developmental variations; inversion, retraction, or enlargement of the nipple, which may have either a benign or a malignant cause; a palpable mass; nipple discharge; skin changes in and around the nipple; infection with resultant nipple changes or a subareolar mass; or abnormal findings at routine mammographic screening. Further diagnostic imaging may include repeat mammography, breast ultrasonography, galactography, and magnetic resonance imaging. When skin changes are present, a clinical evaluation by the patient's primary care physician, dermatologist, or surgeon should be part of the diagnostic work-up.

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