KS NEWS AND CONFUSION

Several different news reports on Kaposi's sarcoma (KS) may have much long-term importance. Unfortunately they have little immediate relevance to treatment -- and they have caused some confusion.

New Treatment in Japan?

On February 22 Robert Gallo, M. D., of the U. S. National Cancer Institute, presented an overview on AIDS to an academic meeting at Fordham University. A short section of the talk implied that a much better potential treatment for KS has been developed in Japan -- but did not say whether there had been any human test:

"We have compounds from a company in Japan that wipe out the Kaposi's sarcoma in a way I have never seen before. That is, no toxicity, and the tumor's gone, and never reappears.

"So now comes the politics of forming the collaboration, getting the compound, and all these things that are the most confusing things about recent science, I would say."

Such a statement might normally have been ignored by the academic audience. But the New York Native published a transcript of the talk in its March 12 issue, with part of the above quote on page one. A number of people have called the National Cancer Institute, but little additional information has been released.

In response to an inquiry of Congressman Sidney R. Yates (D- Chicago), the National Cancer Institute released the following statement:

"The compounds to which Dr. Gallo referred are under preclinical development. Any activity seen to date is based on laboratory observations and should not be construed as implying that these compounds are cures for Kaposi's sarcoma. Further testing will be required before it may be determined whether these compounds would be effective or safe for use in patients. Dr. Gallo has indicated that his laboratory will pursue establishing collaboration with this company to further investigate these compounds."

Even a successful animal test would be important, however, because there is a good "mouse model" for KS. In the same talk, Dr. Gallo summarized some of the most important animal work, which has been published. When certain cells which cause human KS are injected into immune-deficient mice, they caused a KS lesion to form within 10 days. But the cells in the lesion turned out to be mouse KS cells. Apparently certain abnormal cells cause KS by secreting a chemical, apparently a kind of growth factor, which causes abnormal growth of blood vessels, resulting in KS lesions. The fact that the same chemical causes human KS in humans and mouse KS in mice suggests that the mice with KS could be used to screen various substances (some of which might already be available in familiar drugs or even in foods) to find ways to destroy the unwanted growth factor or block or reduce its effects. Dr. Gallo's remark quoted above suggests that a good candidate has already been found. (For background on the KS tests in mice, see Nakamara and others, 1988, and Salahuddin and others, 1988.)

We do not have any more information at this time. We are checking a rumor of a successful human test in Japan, but have not been able to substantiate it.

One AIDS research physician guessed that the compound might possibly be beta-cyclodextrin tetradecasulfate or a chemical relative, used in combination with certain steroids. This antiangiogenic substance (one which prevents unwanted growth of blood vessels) is being tested as a possible cancer treatment, because solid tumors must stimulate growth of blood vessels in order nourish themselves if they grow beyond a certain size.

For more information on this chemical, which U. S. researchers obtain from Japan, see Folkman and others, 1989, and Folkman, 1989. The latter, an editorial in The New England Journal of Medicine, is especially important because it mentions a number of approaches to control of abnormal blood-vessel growth, approaches which may not yet have been investigated for KS. (However, the unprecedented single case of successful treatment of pulmonarycapillary hemangiomatosis, described by White and others and discussed in Folkman's editorial, used alpha interferon, which is already used for KS. We do not know of any human use of beta-cyclodextrins.)

Scientists often discuss the appropriate time to release their findings, and they usually conclude that the right time is after the work is "finished," i.e. well-packaged for publication or presentation to a scientific meeting. Sometimes this approach works badly. U. S. institutional leadership has been slow to mobilize to treat AIDS seriously as an emergency, and therefore the pace of progress is unduly influenced by "the politics of forming the collaboration, getting the compound, and all these things." The public cannot trust that major opportunities will automatically be followed up vigorously. But when even a member of Congress gets the brush-off (the reply to Congressman Yates above could loosely be translated as "get lost," as it leaves no role for his further involvement), the public and its representatives are denied the opportunity to bring attention and resources to bear to overcome the mindless delays which usually set the real pace of research, in AIDS and other diseases as well.

Among many ways to seek one's place in the world, public service usually works better than possession and control of secrets. But too often, career structures encourage the latter.

KS Is Not Cancer; Is It Also Not AIDS?

While KS is often called a cancer in the general press (and sometimes even in technical papers), experts have long realized that it is not really a cancer (as first suggested by Costa and Rabson, 1983). Biologically, the cells in KS lesions do not behave as cancer cells. Clinically, there are many differences also; San Francisco physician Marcus Conant summarized some of them in a recent public meetings on AIDS. It is generally believed that KS is caused by one or more growth factors. If so, it should potentially be easier than cancer to treat.

Is KS really AIDS? Researchers have long noted that it has a very unusual epidemiology, very different from AIDS itself. For example, it is about 20 times as common in gay or bisexual men with AIDS as in hemophiliac men with AIDS. Women infected with AIDS through heterosexual contact are more likely to have KS if their partners are bisexual than if they are IV drug users. KS is 300 times more common in people with AIDS than in people with other immune deficiencies; by contrast, the incidence of non-hodgkins lymphoma is about the same. Children are unlikely to have KS -- but all 12 children younger than 5 years who have KS are from Florida, and 11 of the 12 have Haitian mothers. This epidemiology has led researchers to suggest that KS may be caused by a yet-unknown infectious disease, usually transmitted sexually (Beral and others, 1990).

Many minor epidemics are always occurring, in the modern, cosmopolitan world at least, and usually they pass without being noticed. Some experts believe that KS might have been another hardly-noticed disease, except that many people also had immune deficiencies due to HIV, and as a result the KS was much worse than it otherwise would have been.

This theory suggests that some persons who were HIV negative would also have been likely to get KS, although probably a mild form. Such cases have now been found (Friedman-Kien and others, 1990). Unfortunately, only a small percentage of persons with KS were HIV negative; the researchers had to test 349 people with KS to find the six. These six had a very mild disease, with complete or almost complete recovery, after a median time of five years since diagnosis.

Since KS has by definition been classified as AIDS, due to decisions made early in the history of the epidemic when much less was known, many people diagnosed with KS never took the HIV antibody test; they were assumed to be positive since they had AIDS by definition. Now it appears that a few patients with KS may be HIV negative and not really have AIDS at all (except by the old definition, which is still in force). These people may be able to live for a normal lifespan, with little or no treatment.

Researchers would like to get in touch with anyone who is HIV negative but has or has had KS.

References

Beral V and others. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection? The Lancet, volume 335, page 123-128, January 20, 1990.

Costa J and Rabson AS. Generalized Kaposi's sarcoma is not a neoplasm. The Lancet, page 58, January 1/8, 1983.

Folkman J. Successful treatment of an angiogenic disease. The New England Journal of Medicine, volume 320 number 18, pages 1211-1212, May 4, 1989.

Folkman J and others. Control of angiogenesis with synthetic heparin substitutes. Science, volume 243, pages 1490-1493, March 17, 1989.

Friedman-Kien AE and others. Kaposi's sarcoma in HIV-negative homosexual men. The Lancet, volume 335, pages 168-169, January 20, 1990.

Nakamura S and others. Kaposi's sarcoma cells: Long-term culture with growth factor from retrovirus-infected CD4+ T cells. Science, volume 242, pages 426-430, October 21, 1988.

Salahuddin SZ and others. Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro. Science, volume 242, pages 430-433, October 22, 1988.

White CW and others. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. The New England Journal of Medicine, vol. 320 number 18, pages 1197- 1200, May 4, 1989.