NF-κB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1α

Several angiogenic factors and extracellular matrix-degrading enzymes that promote invasion and metastasis of cancer are produced by stromal fibroblasts that surround cancer cells. The expression of genes that code for some of these proteins is regulated by the transcription factor NF-κB. In this report, we demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but not ER-positive breast cancer cells induces NF-κB in fibroblasts. In contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF-κB in macrophages and endothelial cells. NF-κB activation in fibroblasts was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen activator (uPA), both of which promote angiogenesis and metastasis. A survey of cytokines known for their ability to induce NF-κB identified IL-1α as the factor responsible for NF-κB activation in fibroblasts. Analysis of primary breast carcinomas revealed the presence of IL-1α transcripts in majority of lymph node-positive breast cancers. These results along with the known role of IL-1α and IL-6 in osteoclast formation provide insight into the mechanism of metastasis and hypercalcemia in advanced breast cancers.

Naturally variant autosomal and sex-linked loci determine the severity of iron overload in β2-microglobulin-deficient mice

Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class I heavy chain paralogue gene HFE has been found to be a primary cause of HH. However, many individuals homozygous for the defective allele of HFE do not develop iron overload, raising the possibility that genetic variation in modifier loci contributes to the HH phenotype. Mice deficient in the product of the β2-microglobulin (β2M) class I light chain fail to express HFE and other MHC class I family proteins, and they have been found to manifest many characteristics of the HH phenotype. To determine whether natural genetic variation plays a role in controlling iron overload, we performed classical genetic analysis of the iron-loading phenotype in β2M-deficient mice in the context of different genetic backgrounds. Strain background was found to be a major determinant in iron loading. Sex played a role that was less than that of strain background but still significant. Resistance and susceptibility to iron overload segregated as complex genetic traits in F1 and back-cross progeny. These results suggest the existence of naturally variant autosomal and Y chromosome-linked modifier loci that, in the context of mice genetically predisposed by virtue of a β2M deficiency, can profoundly influence the severity of iron loading. These results thus provide a genetic explanation for some of the variability of the HH phenotype.

The sponges / by Robert von Lendenfeld.

v.42 (1915) text

" Lines upon the late proceedings of the College Government" collection, 1787-1917

This collection contains various manifestations of a humorous poem, most often called "Lines upon the late proceedings of the College Government," written by classmates John Quincy Adams and John Murray Forbes in 1787. Both Adams and Forbes were members of the class of 1787, and the poem recounts events surrounding the pranks and ensuing punishment of two members of the class behind them, Robert Wier and James Prescott. Wier and Prescott had been caught drinking wine and making "riotous noise," and they were publicly reprimanded by Harvard President Joseph Willard and several professors and tutors, including Eliphalet Pearson, Eleazar James, Jonathan Burr, Nathan Read, and Timothy Lindall Jennison. The poem mocks these authority figures, but it spares Samuel Williams, whom it suggests was the only professor to find their antics humorous.

Effects of tire pressures on flexible pavements. Final report.

Mode of access: Internet.

Corporation procedure : law, finance, accounting /

"Fourth printing."

Bird/aircraft hazards /

Item 431-I-7.

The life and writings of Thomas Paine; containing a biography

"Of this special de luxe Independence edition of the centenary issue of the writings of Thomas Paine there have been printed five hundred numbered copies." This set not numbered.

James R. Mann. Memorial addresses delivered in the House of Representatives of the United States in memory of James R. Mann, late a representative from Illinois. Sixty-seventh Congress. January 14, 1923.

"Proceedings in the Senate": p. 109-[113]

The Corsican; a diary of Napoleon's life in his own words, comp. by R. M. Johnston.

Mode of access: Internet.