alpha-Interferon down-regulates epidermal growth factor receptors on renal carcinoma cells: relation to cellular responsiveness to the antiproliferative action of alpha-interferon.

The CaKi-I line of renal carcinoma (RC) cells is highly sensitive to the antiproliferative effect of human leukocyte interferon (IFN-alpha). These RC cells express high numbers of cell surface receptors for epidermal growth factor (EGF), and EGF stimulates their proliferation. IFN-alpha blocks EGF-stimulated proliferation of these cells and down-regulates EGF receptors (EGFR) by inhibiting EGFR synthesis. Although EGF stimulates the proliferation of RC cells resistant to the antiproliferative action of IFN-alpha, IFN-alpha treatment does not block the EGF-stimulated proliferation of these cells and has no effect on EGFR expression. Thus, the down-regulation of EGFR is specific for RC cells sensitive to IFN-alpha. While IFN-alpha does not affect the level of total cellular message or total polyadenylated message for the EGFR, IFN-alpha treatment decreases the level of cytoplasmic EGFR message. Analysis of polysome distribution of cellular mRNAs indicates that IFN-alpha treatment results in an accumulation of EGFR mRNA in lighter polysome fractions, consistent with a partial block in translational elongation. Thus, IFN-alpha regulates the expression of EGFR and possibly other growth-related proteins by post-transcriptional mechanisms, which may play an important part in the complex inhibitory action of IFN-alpha on RC proliferation.

The spectrum of benign and malignant etiologies of cervical node calcification.

OBJECTIVE: The purpose of this study was to determine if the presence and pattern of lymph node calcification can be used to make a limited differential diagnosis and differentiate benign from malignant disease. MATERIALS AND METHODS: Two radiologists reviewed each of 2300 neck CT scans obtained at our institution between January 1996 and July 1998 for the presence of nodal calcifications. The scans were obtained as 3-mm contiguous axial sections, and most were obtained with IV contrast material. Twenty-six scans revealed nodal calcification, which was classified as being within the node itself or along the periphery of the node. The diagnosis was established from surgical specimens for 20 patients and from CT-guided thin-needle biopsy for four patients. For two patients, the diagnosis was inferred from a previously well-documented case of the disease. RESULTS: Of the 2300 scans, 26 (1%) showed nodal calcification. Of these 26, eight (31%) were from patients with benign disease; six (23%) from patients with treated diseases, including four lymphomas and one infection; and 12 (46%) from patients with malignancies, including nine cases of head and neck primary tumors and three cases of metastatic adenocarcinoma from breast and lung primary tumors. CONCLUSION: Cervical node calcification is rare. On the basis of our limited number of cases, nodal calcification, regardless of its location within the node, is not a reliable predictor of either benign or malignant disease. However, nodal calcification does suggest a limited differential diagnosis that most commonly includes tuberculosis, treated lymphoma, and metastatic thyroid carcinoma, adenocarcinoma, or squamous carcinoma.

Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells.

The early events that occur after treatment of the highly interferon alpha (IFN-alpha)-sensitive human lymphoblastoid Daudi cell line with human leukocyte IFN-alpha have been examined. IFN-alpha treatment of Daudi cells results in a rapid and transient increase in the cellular content of diacylglycerol, which occurs in the absence of inositol phospholipid turnover, or an increase in intracellular calcium concentration. Furthermore, IFN-alpha treatment results in a selective, time-dependent activation of the Ca(2+)-independent epsilon isoform of protein kinase C (PKC), while the alpha isoform is unaffected by IFN-alpha treatment. In contrast, IFN-alpha treatment of an IFN-resistant subclone of Daudi cells had no effect on the diacylglycerol content of cells and on the activation of PKC-epsilon. The selective PKC inhibitor staurosporine blocked the transcriptional activation of IFN-alpha-stimulated genes, the cytoplasmic accumulation of mRNAs for these genes, and the induction of antiviral activity by IFN-alpha against vesicular stomatitis virus in IFN-sensitive cells. These observations suggest that transmembrane signaling of IFN-alpha involves diacylglycerol production and activation of PKC-epsilon in Daudi cells.