Tumor suppression in human skin carcinoma cells by chromosome 15 transfer or thrombospondin-1 overexpression through halted tumor vascularization

The development of skin carcinomas presently is believed to be correlated with mutations in the p53 tumor suppressor and ras gene as well as with the loss of chromosome 9. We now demonstrate that, in addition, loss of chromosome 15 may be a relevant genetic defect. Reintroduction of an extra copy of chromosome 15, but not chromosome 4, into the human skin carcinoma SCL-I cells, lacking one copy of each chromosome, resulted in tumor suppression after s.c. injection in mice. Transfection with thrombospondin-1 (TSP-1), mapped to 15q15, induced the same tumor suppression without affecting cell proliferation in vitro or in vivo. Halted tumors remained as small cysts encapsulated by surrounding stroma and blood vessels. These cysts were characterized by increased TSP-1 matrix deposition at the tumor/stroma border and a complete lack of tumor vascularization. Coinjection of TSP-1 antisense oligonucleotides drastically reduced TSP-1 expression and almost completely abolished matrix deposition at the tumor/stroma border. As a consequence, the tumor phenotype reverted to a well vascularized, progressively expanding, solid carcinoma indistinguishable from that induced by the untransfected SCL-I cells. Thus, these data strongly suggest TSP-1 as a potential tumor suppressor on chromosome 15. The data further propose an unexpected mechanism of TSP-1-mediated tumor suppression. Instead of interfering with angiogenesis in general, in this system TSP-1 acts as a matrix barrier at the tumor/stroma border, which, by halting tumor vascularization, prevents tumor cell invasion and, thus, tumor expansion.

Letter from William Croswell to Charles Stimpson, 1820 January 15

Draft of a one-page letter regarding Croswell's Mercator map.

[Certificate of admission of Charles Ammi Cutter], 1851 July 15

Photocopy of an abstract of laws and regulations, and the certificate of admission of undergraduate Charles Ammi Cutter signed by President Jared Sparks on July 15, 1851.

Response to remarks by Charles Mordaunt on United States trade with England,

"Lines occasioned by the assertion of Sir Charles Mordaunt in debate, that the Americans could not catch a mouse or shave themselves without having recourse to Birmingham." Undated, unsigned poem, likely by Tudor, in response to remarks made by Mordaunt during a debate on the Orders in Council in the English Parliament.

The invention of letters annotated by Charles Pinckney Sumner, ca. 1795-1796

Interleaved second-edition copy of Robert Treat Paine's poem "The Invention of Letters" with handwritten excerpts of 18th century poetry copied by Charles Pinckney Sumner. The excerpts appear to be verses alluded to, or emulated, by Paine in the poem. For example, Paine's verse includes "Beneath the shade, which Freedom's oak displays" and Sumner on the opposite page quoted Alexander Pope's poetry, "Beneath the shade a spreading beech displays." The excerpts include poetry by Alexander Pope, James Thompson, Robert Dodsley, William Falconer, William Hayley, Samuel Rogers, Richard Brinsley Sheridan, Thomas Gray, and John Denham.

Rhine River Region, ca. 1680 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Neueste Beschreibung des gantzen Rhein-Stroms. It was published by Johann Christoph Lochner, Buchhandler, ca. 1680. Scale [ca. 1:930,000]. Covers the Rhine River region. Map in German.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, roads, cities and other human settlements, fortifications, territorial boundaries, and more. Relief shown pictorially. Includes also 15 city views: Bonn, Brysach, Bingen, Rheinfelden, Speyer, Maintz, Bacharach, Trarbach, Basel, Strasburg, Andernach, Wormbs, Cobolentz, Cöllen, Heydelberg.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.