Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Annually, 35,000 to 40,000 American men die of prostate cancer (PC). Another 200,000 are diagnosed with the malignancy, which is the second leading cause of neoplastic deaths among U.S. males. PC is a slow-growing disease, which strikes its victims relatively late in life. In fact, many, if not most, of them are less likely to succumb to PC than to other casualties of aging.

Early diagnosis and close monitoring are the best defenses against PC. In recent decades, urologists have welcomed discovery of PSA - prostate-specific antigen - a tumor marker of the disease. It proved to be clinically useful in diagnosing PC, but turned out to be of limited specificity to prostate cancer.

Men who have noncancerous benign prostatic hyperplasia, which mimics PC, can also show elevated PSA. Besides limited diagnosis, PSA offered weak prognosis - predicting the course a patient's PC was likely to take. (See BioWorld Today, Oct. 10, 2002, p. 1.)

Now a team of prostate-oriented oncologists at M.D. Anderson Cancer Center in Houston reports, "Fingerprinting the circulating repertoire of antibodies from cancer patients." Their article appears in the January 2003 issue of Nature Biotechnology.

The paper's co-senior authors are researchers at Anderson's department of genitourinary medical oncology. The department's chairman is Christopher Logothetis, who said, "This study validates the hypothesis that humoral response can serve as a labeling system' of human cancer."

"By looking at the patterns of antibodies from cancer patients," added co-author Renata Pasqualini, "we found that immunological reactivity against a protein present at high levels in prostate tumors correlated with poor prognosis and advanced disease. We searched for peptides that are recognized by antibodies in the serum of prostate cancer patients. They turned out to be part of a tumor antigen called GRP78."

The team used this antigen to screen the blood of 108 patients with advanced PC, and 71 healthy, matched controls. Their combinatorial phage-display scheme involved four main steps:

• First, getting rid of ubiquitous antibodies found in all serum samples;

• Second, incubating to purification of cancer-specific serum antibodies;

• Third, identifying synthetic antigens that bind these cancer-specific antibodies;

• Fourth, isolating the natural antigens that elicited the cancer-specific antibodies in the first place.

"These antibodies," Pasqualini noted, "can be used to discover what protein fragments they are recognizing, and correlate their presence with patterns and speed of disease progression. We have demonstrated that phage-display technology is effective in identifying such antibodies."

The long-term purpose of their project is to identify circulating antibodies that can serve as an early warning system based on the antitumor immune responses of individual patients

"GRP78 is a heat shock protein [HSP]," Pasqualini explained, "that becomes expressed at high stress levels when cells are exposed to low levels of glucose or oxygen. HSPs seem to play a role in signaling the body's immune system into action. We do not yet know, and are currently investigating," she observed, "whether or not GRP78 contributes directly to progression of prostate cancer.

"Our results may be clinically meaningful because the presence of antibodies against this particular antigen correlated with disease progression and patient survival. We showed that positive serum reactivity to the peptide was specifically linked to disease progression, with metastatic development and overall shorter survival averaging 32.7 months in 43 individuals of our large PC patient population."

Logothetis made the point, "If the disease is detected at early states, prostate cancer can be managed by local treatments into specific target tissues such as the bones of the skeleton. When this happens, therapeutic options are more limited. Novel tools for biochemically staging disease would help physicians and patients evaluate and select the most appropriate clinical approach."

Co-author Wadih Arap cautioned, "Before this novel blood test can be used clinically, it needs extensive validation. The information based on this retrospective preliminary analysis may, in the future, be useful for physicians to decide among the many therapeutic options available for prostate cancer patients. As of today," he concluded, "these options are largely dependent on the stage of the disease."

Gene For Antiscorbutic Vitamin C, Deficient In Scurvy, Finally Found In Fresh Strawberries

In the remote past of the hunter-gatherer lifestyle, vitamin C deficiency must have been a rarity. It's found in fresh fruits and vegetables, which were probably consumed by Homo sapiens 10,000 years ago. But with the advent of civilization, scurvy ravaged the crews on long sea voyages.

In 1697, the British Navy's Lord Anson set sail to circumnavigate the globe. Of his original crew of 1,955 men, 997 had died of scurvy by the time his ship returned to England in 1744. Ten years later, in 1754, a controlled clinical trial on another British vessel, fed 12 scurvy patients a variety of foods. The two sick crew members who got oranges and lemons were fit for duty in less than a week. But it took till 1795 before the British fleet formally ordered citrus fruits for all hands.

Spanish plant scientists have just discovered in fresh strawberries the gene for vitamin C. Their paper in Nature Biotechnology, published online Jan. 13, 2003, bears the title: "Engineering increased vitamin C levels in plants by overexpression of a D-galacturonic acid reductase." Its co-authors are molecular biologists at the University of Malaga in Spain.

The juiciest, sweetest and ripest strawberries have the highest levels of vitamin C - and now scientists know why. The gene in question is specifically switched on in ripening strawberries. There it encodes an enzyme that helps to synthesize ascorbic acid - the vitamin's other name. The article's senior author noted, "We have shown that by putting this gene into a different plant, Arabadopsis thaliana, we can double or triple the amount of vitamin C it contains. We are now trying to increase the ascorbic acid in commercially important plants, such as tomatoes and potatoes."