By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.
A lottery lurks in breast cancer. The odds are two in three that a mammary carcinoma tumor will harbor estrogen receptors (ERs) in its cells. Patients with ER-positive tumors have a slightly better prognosis that those with ER-negative cancer. Postmenopausal women enjoy a small added edge. Clinicians who treat the disease must bet on their patients¿ ER profile to benefit from estrogen hormone therapy.
A paper in the Proceedings of the National Academy of Sciences (PNAS), dated Aug. 28, 2001, is titled: ¿The nuclear factor kappa B (NF-kB): A potential therapeutic target for estrogen receptor negative breast cancer.¿ Its senior author is molecular biologist Arthur Pardee, at the Harvard-affiliated Dana-Farber Cancer Institute in Boston. The first author is molecular biologist D. K. Biswas, a research scientist in Pardee¿s lab.
¿There is no therapy for estrogen receptor negatives,¿ Biswas told BioWorld Today. ¿Breast cancers are normally treated with antihormones, but the class of mammary carcinomas that do not have the receptors cannot be treated with antihormones.
¿We have been looking for a drug target against this class of breast cancers,¿ Biswas went on, ¿and how such a target works in tumor-cell proliferation and apoptosis ¿ programmed cell death. As reported in this PNAS,¿ he continued, ¿we have found the target ¿ nuclear factor kappa B, a protein kinase transcription factor linked with cytokine production ¿ and we have found a chemical compound against it.
¿The main point I would emphasize,¿ Biswas observed, ¿is not the compound alone, because there may be several other chemicals that will affect this target. We still have to find chemical compounds that can affect the functions of those targets. We have tested one compound in cultured tumor cells and now preclinically in animals, where it inhibited the growth of tumors. A significant aspect of this result is that this drug did not cause any damage to other vital organs, such as liver and lungs ¿ a very important issue in chemotherapy. That was the main point of our paper. It shows for the first time that such a compound can be used as an anticancer drug.¿
The team¿s in vivo experiment implanted ER-negative mouse mammary epithelial tumor cells into mice, then treated these animals with their experimental inhibitor of protein kinase, designated Go6976. It arrested growth of tumors, in which it caused extensive necrotic degeneration. They report rapid regression of the full-grown tumors, without toxic side effects. Moreover, Go6976 blocked the anti-apoptotic action of NF-kB, specific to tumor cells.
Subbing For Fraught Embryonic Stem Cells, Adult Brain Cells Show Multiple Versatility
As the bio-politico-ethical furor over embryonic stem cells hots up around the world, voices persist, proposing an acceptable alternative ¿ adult stem cells. These offer hope for tissue replacement in brain injury and neurodegenerative diseases, such as Parkinson¿s and Alzheimer¿s. But adult brain cells are vanishingly rare and hard to find, amounting to a scant 5 percent of cerebral stem cells.
That trace number rises to a robust 80 percent in a recent issue of Nature, dated Aug. 16, 2001. Its title: ¿Purification of a pluripotent neural stem cell from the adult mouse brain.¿ Its authors are at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia. Transplanted into developing mouse brains, the purified cells generated neuronal and glial support cells. A further step will be to develop drugs that can push the brain stem cells to generate the new neurons.
Hence, they may have properties previously thought to exist only in the controversial embryonic stem cells. Inside the brain, the bashful adult stem cells hunker down at two hard-to-spot sites in the walls of ventricles ¿ the cavities filled with cerebrospinal fluid. In this remote region, only one cell in 300 is a bona fide stem cell.
Besides turning into new nerve cells, these stem cells have the potential of creating a large variety of non-neural tissue types. The co-authors found that more than half of their winkled-out adult brain stem cells were capable of transforming into muscle cells.
Interferon Shows Foot Over Current Antiviral Drugs As Effective Therapy For Hepatitis C Virus Infection
Infection with hepatitis C virus (HCV) is a leading worldwide cause of chronic liver disease ¿ cirrhosis and hepatocellular carcinoma. Prospects for a vaccine seem remote, given HCV¿s propensity for changing its genomic spots, and the human immune system¿s failure to generate neutralizing antibodies against the virus. Another strike is the ineffectiveness of antiviral drugs, notably ribavirin and interferon-alpha. Development of newer treatments is crippled by the lack of tissue-permissive culture systems for studying HCV replication.
Interferon directly blocks the replication of many viruses, but its effect on HCV is based largely on hunches. A system able to recapitulate the early steps of the HCV life cycle is reported in the Proceedings of the National Academy of Sciences (PNAS), dated Aug. 14, 2001. Its title: ¿Hepatitis C viral replication is directly inhibited by IFN-a in a full-length binary expression system.¿ Its authors are at the Harvard-affiliated Massachusetts General Hospital. They demonstrate that the lead therapeutic drugs, ribavirin and amantadine, have no direct antiviral effects; interferon does.
Two Experimental Drugs For Huntington¿s Disease Compared; One Excelled ¿ Slightly
Scientists at 23 U.S. and Canadian sites have released results from a 30-month randomized, double-blind, placebo-controlled trial of 347 patients with early stage Huntington¿s disease (HD). It compared two experimental drugs for therapy of HD ¿ Vitaline¿s CoQ10 and AstraZeneca¿s Remacemide. The report appears in the August 2001 issue of the journal Neurology. Its title: ¿Huntington¿s Disease Study Group: A randomized, placebo-controlled trial of coenzyme Q10 and Remacemide in Huntington¿s disease.¿
Participants who took the product of Vitaline Corp., of Ashland, Ore., experienced 15 percent less decline in total functioning capacity. Those given Remacemide showed no noticeable improvement. Vitaline¿s CoQ10 has obtained orphan drug status from the FDA for treatment of HD. AstraZeneca¿s drug has not yet received FDA approval.