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Researchers at Duke University report that they have found - on the surface of cells inside blood vessels - a type of enzyme, called ATP synthase.
The enzyme apparently provides the energy for the growth of blood vessels, said Salvatore Pizzo, a member of the Duke team and co-author of a study appearing today in the Proceedings of the National Academy of Sciences.
Without such energy, he said, tumors can never grow beyond the size of a pin head.
Researchers in many labs have recently been studying the growth of blood vessels that supply cancer tumors with oxygen and nutrients - searching for possibles to shut off that blood vessel growth.
The research intensified after Judah Folkman of Children's Hospital in Boston showed that a compound he calls angiostatin could stop tumor growth in mice by blocking the formation of blood vessels.
In all, a number of compounds that can block blood vessel formation have been discovered. In fact, a separate paper in Proceedings today reports on isolating such a substance from cartilage. Researchers have been able to isolate angiostatin, which also occurs naturally in the body, and synthesize it in laboratories.
But exactly how angiostatin and similar compounds work has not been known. The Duke discovery may be the answer.
"Until now, people knew that angiostatin blocked blood vessel growth, but there was no obvious mechanism," Pizzo said. "Now we know why it works."
The study "is a big jump ahead," Folkman said, "... because it identifies a protein that binds (attaches to) angiostatin" and suggests how angiostatin prevents blood vessel growth. The discovery puts researchers on track to isolate a compound from angiostatin that could work more directly to block blood vessel formation, he said.
The discovery of ATP on the surface of endothelial cells, the lining of blood vessels, came as a surprise, Pizzo said. The enzyme was previously found only inside cells.
"ATP is what the cells use as a fuel, as an energy source," Pizzo said. "It is present inside the cell, in the mitochondria, and is the little energy factory for the cell."
The enzyme apparently is activated when the blood's oxygen content is lowered. Nature may have designed ATP as a healing mechanism, to build new vessels so the body can repair tissue damaged by injury or disease, Pizzo said.
"Tumors are that way," he said. "Tumors tend to take advantage of a normal mechanism in the body and then exaggerate it to their own growth advantage."
When tumors do form, cells in the center of the growth are deprived of oxygen. That may trigger the formation and action of ATP, Pizzo said.
With a better understanding of how ATP causes blood vessels to grow, researchers also might be able to use the enzyme to promote beneficial blood vessel growth, such as in heart disease or diabetes, Pizzo said.
Starting today, in the military equivalent of a grand jury proceeding, Army prosecutors will lay out a damning case against Hale. It includes allegations that he carried on sexual affairs with wives of officers under his command, then lied to Pentagon officials and threatened some of the women to cover up his alleged misdeeds.
Hale has adamantly denied the charges, so the courtroom showdown at this Army base 50 miles south of Seattle could be long and bitter. And there is more at stake than Hale's fate. The case also could establish a precedent for how the armed services deal with violations of military law, in particular sexual misconduct, in their top ranks.
"This is a very unusual and important case," said Andy Bacevich, a former Army officer who teaches at Boston University and writes frequently on military matters. "In the past, allegations of this kind of misconduct by senior officers were handled very quietly. But now that doesn't wash anymore."
The case is the latest in a series of high-profile incidents in the military involving alleged sexual misconduct, lies and abuse of power.
Late last year, Pentagon investigators charged Navy Rear Adm. John Scudi with steering military contracts to a woman with whom he had an adulterous affair. To avoid the spectacle of a trial, he was forced to retire at a reduced rank and lost a substantial amount of his retirement benefits. Former Sgt. Major Gene McKinney, the Army's senior enlisted member, was tried last year on charges that he sexually harassed six women, but was convicted only on one count of obstruction of justice.
Hale's hearing is also being closely watched throughout the military because it will follow so soon after the Senate's decision not to remove President Clinton from office even though the House impeached him on charges of perjury and obstructing justice to hide his affair with Monica S. Lewinsky.
The new "interior enforcement strategy,'' outlined in an internal INS document, affords a measure of relief to the estimated 5.5 million illegal immigrants living in the United States and the thousands of businesses that employ them.
But it is generating intense criticism within the INS and among advocates of a tougher stand on illegal immigration. They say
the new policy undermines the INS's commitment to removing illegal aliens, essentially ignoring them as long as they do not
commit a crime that brings them to the agency's attention.
``There is resistance ... because, basically, if you get through the border, you're home free,'' a senior INS field manager said.
``Everybody recognizes that, and the aliens know that by now.'' He added, ``We basically have ceased work-site enforcement. ...
We're extremely frustrated. Morale is low.''
The strategy shift underscores the nation's ambivalence about illegal immigration. While most Americans oppose the idea of
sneaking across the border or overstaying a visa, there also is widespread recognition that illegal immigrants typically work
hard, often at jobs Americans shun.
The change also reflects the political reality that has doomed previous crackdowns on illegal employment. According to INS
insiders, neither the Democrats nor the Republicans have demonstrated the political will to seriously reduce the illegal work
force, in large part because key constituencies oppose such efforts. On the Democratic side, interior enforcement directed
against undocumented workers tends to alienate lawyers, ethnic lobbies, civil rights groups and, increasingly, unions trying to
organize the newcomers. For the Republicans, work-site raids often pose problems because they arouse bitter complaints from
business and agricultural interests.
The strategy document, which has been distributed to INS field offices but has not been publicly released, says the agency's
goal in interior enforcement is to ``reduce the size and annual growth of the illegal resident population.'' The INS has used new
powers under a 1996 immigration law to step up deportations in recent years, removing a record 169,000-plus people in fiscal
1998. But the increased expulsions are not keeping pace with the estimated 275,000 illegal immigrants who permanently
settle in the United States every year, much less putting a dent in the core illegal population.
The top priority, the document says, is to identify and remove ``criminal aliens,'' many of whom ``are released before their legal
status is ascertained or before the INS can be called'' to pick them up. The agency estimates some 221,000 foreign-born
criminals are in federal, state or local jails _ two-thirds of them illegal immigrants. As many as 142,000 others are on parole or
probation but are subject to removal under the immigration law. An additional 161,000 are ``abscondees'' who disappeared after
receiving deportation orders.
The next interior enforcement priority is dismantling networks that smuggle illegal aliens, an underground industry that makes
as much as $8 billion a year worldwide. These networks have grown increasingly sophisticated, often recruiting and
transporting illegal workers to job sites with employers' knowledge and participation, the document says.
The strategy also calls for action against fraud that enables illegal aliens to obtain legal documents and other benefits, often
through high-quality counterfeiting and false claims to U.S. citizenship.
The last priority is to change ``hiring practices'' by building ``relationships'' with employers, openly conducting ``audits and
surveys'' and inviting ``employer cooperation'' in identifying illegal workers. The document says work-site enforcement has
failed to deter illegal immigration, ``yielding uneven results in communities and across industries'' and prompting numerous
complaints.
The strategy was drafted by Joseph R. Greene, the INS district director in Denver, at the direction of Robert L. Bach, executive
associate commissioner for policy and planning. The INS still could use work-site raids and arrests, Greene said, ``but the goal
is not simply to remove a bunch of people from the work site and leave it at that. The goal is changing the way employers do
business.''
Critics within the INS and the Border Patrol support going after alien smugglers and document counterfeiters but say work-site
enforcement is vital to the fight against illegal immigration. INS field offices already have sharply curtailed raids because of
new restrictions from headquarters and budget cuts, officials said.
``We're out of that business,'' one INS district director said. He said employers ``are not going to comply (with immigration
laws) if there's no reason to comply, no social outrage, no law that's being enforced.'' The idea that employers can be persuaded
not to hire illegal workers, who will then go home, ``is a fairy tale,'' he said.
The INS actions are ``telling would-be illegal aliens that if you don't get caught entering the United States, we'll look the other
way so you can stay,'' said Rep. Lamar S. Smith, R-Texas, chairman of the House Judiciary immigration subcommittee.
Rep. Nathan Deal, R-Ga., whose north Georgia district has large numbers of illegal workers from Mexico, said the new strategy
also signals employers that ``they don't have to worry about the sanctions'' enacted in 1986 as part of an immigration reform
package that offered legal status to about 2.7 million illegal aliens. The sanctions were supposed to stop further illegal
immigration, but the undocumented population has doubled since then.
Dan Stein, director of the Federation for American Immigration Reform, which advocates reducing immigration levels, called
the strategy a ``capitulation'' to pressure from the ``alien rights lobby'' and ``cheap-labor interests.''
``Never before has the INS explicitly abandoned the goal of apprehending large numbers of illegal immigrants who are residing
in the U.S. interior,'' he said. ``It's a complete surrender. ... Criminal aliens should be an enforcement priority, but not political
cover for ignoring the rest of the job.''
An INS official, speaking on condition of anonymity, said the strategy ``signals an inability within current resources to deal
with the undocumented population in the United States.''
While the INS budget has risen to almost $4 billion and the Border Patrol has nearly doubled in size in the past five years,
relatively little has been spent to enforce immigration laws inside the country, even though more than 40 percent of the illegal
population originally came in legally and overstayed their visas. Of 2,000 INS special agents, about 1,750 conduct
investigations of alien smuggling; illegal employment; various types of fraud, including fake marriages; and immigrants'
involvement in drug trafficking and violent gangs.
``That's half the size of the (D.C.) police force to cover not only the entire nation but the entire world,'' the official said. ``If
Congress and the administration were serious, how'd we end up with 1,750 agents to do all this work?
``No one has stepped up to the plate when it comes to interior enforcement,'' he said. ``The border is easy money politically.
But the interior is a political minefield.''
LA TIMES-WASHINGTON POST-03-15-99 1410EST
03-16-99
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