Loss of DCC expression in neuroblastoma is associated with disease dissemination.

DCC, a candidate tumor suppressor gene from chromosome 18q21, is most highly expressed in the developing nervous system. In vitro studies suggest a role for DCC in neuronal differentiation, and 18q allelic loss occurs in a subset of neuroblastomas. To address the hypothesis that loss of DCC function may contribute to tumorigenesis in cells of neural origin, we utilized a combination of RNase protection, immunoblotting, and immunohistochemical approaches to characterize DCC expression in 62 primary neuroblastomas and 16 neuroblastoma cell lines. The DCC protein was undetectable in 38% of the primary tumors and 56% of the cell lines. Of note, primary tumors lacking DCC expression were more likely to have been obtained from patients with disseminated or stage D disease (P = 0.01). In addition, loss of DCC expression was observed in three of six primary tumors from stage DS patients. No consistent relationship between the loss of DCC expression and N-myc amplification was observed in our studies. Our findings suggest that loss of DCC expression may contribute to the dissemination of neuroblastoma cells, perhaps through alterations in growth and differentiation pathways distinct from those regulated by N-myc.

Pouchitis: pathogenesis, diagnosis, and management.

The current treatment of choice for patients requiring colectomy for ulcerative colitis or familial adenomatous polyposis (FAP) is ileoanal anastomosis with pouch creation. Symptomatic inflammation of this pouch, a condition known as pouchitis, will develop in up to 40% of patients who undergo this surgery. Patients will present with crampy abdominal pain, fever, rectal bleeding, and diarrhea, and they may have either acute intermittent attacks or a chronic pouchitis syndrome. Most reported cases of pouchitis have occurred in patients with a previous history of ulcerative colitis, whereas complications develop in only a handful of patients with FAP. The etiology of pouchitis is probably a multifactorial event involving genetic, immune, microbial, and toxic mediators. The initial medical management of pouchitis usually relies on metronidazole; however, other drugs that are useful for ulcerative colitis have been found to be beneficial for pouchitis. Studying the etiology and management of pouchitis may help elucidate the pathogenesis of inflammatory bowel disease.

New therapies for idiopathic ulcerative colitis.

Medical and surgical management of ulcerative colitis has advanced far in the last decade. New time-released ASA compounds and enemas have decreased the side effects of sulfasalazine and allowed delivery of higher doses of the active compound to the site of action. New steroid compounds have reduced the potential for systemic adrenal glucocorticoid suppression. However, therapy is still directed only against secondary immune and inflammatory responses. Until the cause of UC is discovered, well-designed and well-performed clinical trials must continue to try to identify agents that combine low toxicity with high therapeutic potential.