Editor's note: Science Scan is a quick round-up of recently published,biotechnology-related research.
Aborting Angiogenesis Down-SizesEarly Stage Tumors 89 Percent
A growing solid tumor doesn't really get off the ground until it startsnetworking its own blood supply. In transgenic mice programmed toincur pancreatic islet cell carcinoma, this angiogenesis takes off atfive to seven weeks of life. It's preceded by the onset of malignancyat three to five weeks, and followed by progression to full-blowntumors at 10 to 14 weeks.
At the University of California, San Francisco, hormone researcherDouglas Hanahan and his co-workers undertook to nip this cancer notin the bud but just after angiogenesis kicks in. They report in thecurrent issue of the Proceedings of the National Academy of Sciences(PNAS), dated March 5, l996, that: "Antiangiogenic therapy oftransgenic mice impairs de novo tumor growth." Co-authors of theirpaper include surgeon Judah Folkman of Harvard Medical School.
This first test of anti-angiogenic agents in transgenic mice reducedtumor volume by 89 percent, and the network of blood-deliveringcapillaries shrank to 40 percent that of control animals.
The PNAS paper observed that although islet cell tumors are rare inpeople, "this transgenic model presents an important tool for studying. . . human epithelial cancers, such as breast, prostate and bladdercarcinoma."
To switch off proliferation of blood vessels, the team treated theirmice with a combination of three compounds known to inhibitangiogenesis: an alpha/beta interferon, minocycline, (an antibacterialdrug,) and a synthetic fungal derivative, AGM-1470.
"Angiogenesis inhibitors," the Californians proposed, "will prove tobe effective in combination with conventional cancer therapeuticstrategies that target tumor cells."
Mapping Gene-Controlling TissueGrowth Clarifies Puzzling Syndrome
Six fingers and/or toes, extra nipples (in males as well as females)plus stature in the 6.5-foot-tall range are only the mildest signs ofSimpson Dysmorphia Syndrome.
Better known to medical geneticists as Simpson-Golabi-Behmelsyndrome (SGBS), it reflects the congenital disruption of a gene thatcontrols tissue growth. SGBS's congenital malformations range fromheart defects, enlarged and misshapen kidneys and skeletalabnormalities to undescended testes and deformed sexual organs _but not mental retardation.
Babies born with the disease also have a predisposition forneuroblastoma and Wilm's tumor, the latter, a kidney cancer ofembryonic origin. Both malignancies occur in young children.
A visiting scientist at Washington University in St. Louis, discoveredthe broken X-linked gene that causes this inherited multi-havocaffliction. A paper in the March issue of Nature Genetics reports:"Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome."
How the authors found it on the X chromosome's long arm is a casehistory in gene mapping.
While on sabbatical at St. Louis, Italian physician and scientistGuiseppe Pilia, the article's first author, took an interest in two celllines maintained since 1974 at the National Institutes of Health. Bothfemale patients' symptoms suggested they might have had SGBS, aninherited disease unrecognized till a decade ago.
Pilia found faulty X chromosomes in both cell samples, one a DNAswap between the X and chromosome 1, the other, with chromosome16. This looked to him like two breaks in the same gene.
Pilia localized the normal gene to a site on X, based on a map of theregion he had developed with Washington University's Center forGenetics in Medicine, and confirmed its translocation tochromosomes 1 and 16.
The St. Louis Center is mapping human chromosome X as aparticipant in the international genome-mapping project.
The normal GPC3 gene's nucleotide sequence, Pilia found, closelyresembled a rat gene that codes for a cell-surface proteoglycan, ormucopolysaccharide, of unknown function, called glypican.
"The isolation of GPC3 will have immediate clinical applications,"observed molecular microbiologist David Schlessinger, the paper'ssenior author, "because it now will be possible to distinguish SGBSfrom Beckwith-Wiedeman Syndrome (BWS), which results from afaulty gene somewhere on chromosome 11." BWS has symptoms incommon with SGBS.
Eighth Herpesvirus Nominated AsKaposi's Sarcoma Co-Factor
In the 1800s, an Austrian dermatologist, Moritz Kaposi, describedthe skin cancer that bears his eponym as a sarcoma affecting elderlyJewish men.
A century later, along came HIV and AIDS. Now, life-threateningKaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, andHIV infection is a major KS risk factor. Besides skin lesions, thecancer attacks visceral organs inside the body.
Suspicion that a separate passenger pathogen rather than the AIDSvirus itself caused the once-rare malignancy found support inDecember 1994, with discovery by Columbia University researchersof the eighth human herpesvirus in the KS tissue of AIDS patients.
Yet homosexual men with AIDS are 20 times more likely to developKS than AIDS-afflicted children and hemophiliacs made HIV-positive by virus-contaminated donor blood. So it looked as if theeighth herpesvirus may be an agent of sexually transmitted disease, acofactor of homosexually transmitted HIV.
The new agent is now dubbed "KS-associated herpesvirus" (KSHV)or human herpesvirus 8 (HHV8).
The March 1996 Nature Medicine reports extensive DNA analysis, invitro culture and electron microscopy of HHV8 by a multi-disciplinary team at the University of California, San Francisco, ledby virologist Don Ganem. Its data, the article states, "represent thefirst demonstration of the latent and lytic [i.e., productive] cycles ofKSHV/HHV8, and have several implications."
Among the pay-offs it lists a ready source of virus for study of viraltransmission; structural studies of the virion; analysis of themolecular biology of viral replication and assembly; examining theeffects of candidate antiviral drugs; a source of antigens forserodiagnostic tests. n
(c) 1997 American Health Consultants. All rights reserved.