Faculty Bibliography

It has been proposed that an adenovirus with the E1b-55kD gene deleted has a selective advantage in replicating in cancer cells that have mutations in the p53 gene (Bischoff et al., 1996). We have explored this hypothesis in several lung cancer cell lines, and evaluated potential mechanisms that might regulate the replication of Ad338, an E1b-55kD-deleted virus, with the objective of developing a rational approach for targeting gene therapy to lung tumors. Our data show that Ad338 replicates poorly in three lung cancer cell lines with various p53 mutations (H441, H446, and Calu1), yet this virus replicates to a high level in a lung cancer cell line with wild-type p53 (A549) and in a normal lung fibroblast line (IMR90). Viral DNA replication, expression of viral proteins, and shutoff of host cell proteins were not important variables in limiting the replication of the E1b-55kD-deleted virus. However, the cell lines resistant to host cell protein shutoff were also the most resistant to the cytopathic effect induced by mutant and wild-type virus and the only cells to survive for 8 days following infection. The E1b-55kD protein clearly has an important role in viral replication beyond its interaction with p53. Thus, an E1b-55kD-deleted virus cannot be used to specifically target viral replication to p53-mutated lung cancer cells

BACKGROUND, Fine-needle aspiration biopsy (FNA) has been successful in diagnosing epithelial lesions of the breast. Its role in the evaluation of spindle cell and mesenchymal lesions of the breast, which include a variety of benign and malignant conditions, is less clear. This article discusses the cytologic features and differential diagnosis of these lesions, as well as the potential diagnostic pitfalls associated with them. METHODS, FNAs of the breast, in which a spindle cell or mesenchymal component was a key or dominant feature, were retrieved. Fibroadenomas without cellular stroma and typical lipomas were excluded. RESULTS. Forty-six aspirates (0<87%) in a series of 5306 breast FNAs contained a significant spindle cell or mesenchymal component. The aspirates were classified into 4 categories: 1) reactive conditions, including 2 diabetic mastopathies, 3 granulation tissue specimens, and 7 granulomatous lesions; 2) benign neoplastic conditions, including 1 mammary hamartoma, 1 dermatofibroma, 1 fibromatosis, 2 granular cell tumors, 2 angiolipomas, and 7 cellular fibroadenomas; 3) low grade malignant neoplastic lesions, including 10 low grade phyllodes tumors; and 4) high grade malignant neoplastic lesions, including 1 metaplastic carcinoma with chondroid stroma, 1 pleomorphic liposarcoma, 2 malignant fibrous histiocytomas, 2 osteosarcomas, and 4 metastatic melanomas. A specific diagnosis was rendered in 38 cases (82<6%). The mammary hamartoma was diagnosed as fibrocystic changes; the dermatofibroma as benign spindle cell lesion, not otherwise specified (NOS); and the primary osteosarcoma as an atypical spindle cell proliferation, NOS. The reactive ductal epithelial cells in one of the granulomatous mastitis specimens, as well as the hyperplastic ductal epithelial cells in one of the phyllodes tumors, were interpreted as atypical ductal proliferation. The marked cytologic atypia displayed by one granular cell tumor was interpreted as low grade adenocarcinoma and the primary liposarcoma as poorly differentiated carcinoma. CONCLUSIONS. Breast lesions with a significant spindle cell or mesenchymal component are rarely encountered in FNA and constitute a heterogeneous group that may pose a diagnostic dilemma FNA should be the initial diagnostic procedure for investigating these lesions, as a specific diagnosis was rendered in the majority of cases. Cancer (Cancer Cytopathol) 1999;87:359-71. (C) 1999 American Cancer Society

The cysteine protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (LLnL) inhibited the growth of the Calu-1 lung carcinoma cells and induced a prolonged cell cycle arrest in the S phase. c-Jun N-terminal kinases (JNKs) participate in cellular responses to mitogenic stimuli, environmental stresses, and apoptotic signals but its role in cell cycle checkpoint control has not been elucidated. In this report, we examined the role of JNK in LLnL-induced S phase checkpoint by overexpression of a dominant-negative mutant of JNK1 (JNK1-APF) in Calu-1 cells. Expression of high levels of JNK1-APF blocked the growth-inhibitory effects of LLnL and abrogated S phase arrest induced by LLnL. These results support the role of JNK in the activation of cell cycle checkpoint induced by LLnL