Other highlights in the February 1 JNCI

A new study suggests that the protein STAT1, which negatively regulates cell growth and survival, can suppress tumor growth in squamous cell carcinoma of the head and neck (SCCHN) tumors. When the promoter region of the STAT1 gene is chemically modified by a process called promoter hypermethylation, thereby inhibiting STAT1 expression, the result can increase SCCHN tumor growth.

Researchers have suggested that dysregulation of STAT proteins could play a role in tumor formation and growth. The exact mechanism by which STAT1 gene methylation is altered in SCCHN tumors had not been determined.

Jennifer Rubin Grandis, M.D., at the University of Pittsburgh, and colleagues compared expression of STAT1 in SCCHN tumors and in tissue samples from patients without cancer. They found that STAT1 expression was lower in tumors than in normal tissue. In separate laboratory experiments, they found that SCCHN cells ceased growing and died when STAT1 expression was increased above normal levels. They also found that STAT1 expression was reduced in many of the SCCHN tumors by a process called promoter hypermethylation. When they treated cells with a drug called azacytidine, which reverses hypermethylation, STAT1 expression increased and those tumor cells became more responsive to treatment with the cancer drug cisplatin. The authors suggest that STAT1 works as a tumor suppressor for SCCHN cells, but when expression is lowered, SCCHN tumors grow.

In an accompanying editorial, Heehyoung Lee, Ph.D., and Hua Yu, Ph.D., of the Beckman Research Institute in Duarte, Calif., write, "The present study … reveals a novel regulatory mechanism for STAT1 in cancer. Their data show that the STAT1 promoter is hypermethylated in SCCHN tissues and cell lines and that demethylation of the STAT1 promoter can sensitize tumor cells to chemotherapeutic agent-induced apoptosis."

Contacts:

Article: Clare Collins, 412-624-2607, collcx@upmc.edu
Editorial: Roya Navqi, 213-241-7163, maqvi@coh.org

Study Examines How IL-12 May Work in Neuroblastoma

Interleukin 12 (IL-12), a molecule that helps mediate the immune response, may induce tumor regression in neuroblastomas, according to a new study.

Neuroblastoma is the most common extracranial solid tumor in children. Patients with neuroblastoma have a poor prognosis, and doctors continue to research novel therapies and strategies for treatment.

Jon M. Wigginton, M.D., and Tahira Khan, Ph.D., of the National Cancer Institute, and colleagues studied the effects of the immune response regulator IL-12 on neuroblastoma tumors in mice. Eight (80%) of 10 mice treated with IL-12 experienced complete tumor regression compared with 10% of mice treated with a control substance. Based on this and other key findings of their study, they suggest that IL-12 acts on neuroblastoma by inhibiting the activity of a protein that prevents apoptosis called Akt.

Contact: NCI Press Officers, National Cancer Institute, 301 496-6641, ncipressofficers@mail.nih.gov

Labeling System May Help Track Virus-Based Cancer Therapy

A new study suggests that a unique labeling system could be used to monitor the effects of oncolytic adenoviruses, viruses that are engineered to target cancer cells, replicate within them, and cause cancer cells to die.

Although many studies have investigated the use of oncolytic adenoviruses for cancer therapy, very few approaches have been successful. Part of the problem with further developing this treatment approach is that it is very difficult to determine whether the virus has reached the target tumor cells.

David T. Curiel, M.D., Ph.D., and Masato Yamamoto, M.D., Ph.D., of the University of Alabama in Birmingham, and colleagues designed a genetic labeling system with fluorescent labels to tag and detect adenovirus particles in mice carrying tumors derived from cancer cells containing the adenovirus. Detection of the labeled virus corresponded with oncolytic adenovirus replication, and labeling did not affect the labeled virus negatively.

The authors suggest this type of labeling may be used in the future to assess oncolytic adenovirus function in animals.

Contact: David T. Curiel, 205-934-8627, david.curiel@ccc.uab.edu, Masato Yamamoto, 205-975-0172, masato.yamamoto@ccc.uab.edu

Large Population-based Study Examines Risk for AML Following Hodgkin Lymphoma

Many people with Hodgkin lymphoma survive their disease; however, these patients are at an increased risk for acute myeloid leukemia (AML) in the years following treatment. Lois B. Travis, M.D., Sc.D., of the National Cancer Institute, and colleagues identified 35,511 1-year Hodgkin lymphoma survivors in Nordic countries and North America between 1970 and 2001 and calculated the excess absolute risk of developing AML. They examined the effect of age at Hodgkin lymphoma diagnosis, whether risk declines after a certain time period, and if there is a lesser risk for patients treated in later calendar years when newer chemotherapy regimens were introduced.

The authors found that the excess absolute risk of AML was highest during the first 10 years after diagnosis with Hodgkin lymphoma, although risk remained elevated after that time period. They observed a greater excess of AML in patients treated at age 35 or older compared with those treated at younger ages. The excess for AML declined substantially after 1984. The authors suggest that modifications in chemotherapy treatment may account for the decreased risk found.

Contact: NCI Press Officers, National Cancer Institute, 301-496-6641, ncipressofficers@mail.nih.gov

Also in the February 1 JNCI:

Studies Examine Associations Between Surgery Volume, Surgeon Specialty, and Mortality Rates in Ovarian Cancer: http://www.eurekalert.org/emb_releases/2006-01/jotn-sea012606.php

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.