News From The Journal Of The National Cancer Institute, May 26, 2009

Main Category: Cancer / Oncology
Also Included In: GastroIntestinal / Gastroenterology;  Breast Cancer;  Colorectal Cancer
Article Date: 28 May 2009 - 0:00 PDT

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Effects of MYC Protein and CIP2A in Gastric Cancer

The presence of the protein CIP2A in tumors is associated with early mortality for gastric cancer patients, according to a new study by Ari Ristimaki, M.D., Ph.D., of the Genome-Scale Biology Research program at the University of Helsinki and colleagues.

CIP2A was previously reported to interact and promote the stability of the MYC oncoprotein and to be overexpressed in head and neck and colon cancers, but its role in gastric cancer was unclear.

The researchers discovered that expression of CIP2A was associated with reduced overall survival among gastric cancer patients with tumors smaller than 5 centimeters, and that its presence increased proliferation and anchorage-independent growth. In addition, MYC appeared to promote expression of the CIP2A messenger RNA and protein.

"MYC and CIP2A appear to reinforce each other's expression (or inhibition) in a positive feedback loop that would appear to be an attractive target for cancer therapeutics," the authors write.

Variability of Interpretive Accuracy of Diagnostic Mammograms among Mammography Facilities

A new study found that diagnostic interpretative performance varies across mammography facilities.

Prior work demonstrated that screening mammography interpretive accuracy varies substantially by facility, but performance of diagnostic interpretation (i.e., exams performed to evaluate a clinical breast lump) was unknown. To determine if such variability exits, Sara L. Jackson, M.D., of the University of Washington School of Medicine in Seattle, and colleagues surveyed 45 facilities in the Breast Cancer Surveillance Consortium to compare mammography facility structure, organization, and interpretive processes. Analyzing data from over 28,000 diagnostic mammograms read by 118 radiologists, they assessed whether facility characteristics were associated with facility interpretive performance of diagnostic mammograms.

After adjustment for patient and radiologist characteristics, researchers found statistically significant variability for false-positive rates between facilities. False positive rates were higher at facilities reporting increased concern about malpractice.

"Analyses comparing differences among mammography facilities that do not adjust for important patient characteristics may falsely conclude that there is more facility variation in overall accuracy than what actually exists," the authors write.

RasGAP-Derived Peptide Improves Response to Chemotherapy in Mouse Models of Colon Cancer

Tumor-bearing mice treated with a peptide derived from the RasGAP signaling protein and either cisplatin or doxorubicin had reduced tumor growth compared with mice treated with the chemotherapy agent alone.

Tumors that lack proper activation of their cell death pathway may be resistant to chemotherapy. Therefore, restoring cell death, or apoptosis, signaling may restore drug sensitivity. Christian Widmann, Ph.D., of Lausanne University in Switzerland, and colleagues had previously shown that a small portion of the RasGAP signaling protein could increase cell death in tumor cells treated with cisplatin in vitro.

In the current study, Widmann and colleagues modified the peptide to increase its stability in vivo. They tested the safety of the peptide and its ability to improve responses to genotoxic agents, including cisplatin and doxorubicin, in mice bearing tumors derived from human colon cancer cells.

Mice treated with the modified peptide, known as RI•TAT-RasGAP317-326, and cisplatin or doxorubicin daily for 7 days showed reduced tumor growth compared with mice treated with cisplatin or doxorubicin alone.

"To our knowledge, this peptide is the only compound that has been shown to improve the efficacy of genotoxins and that behaves strictly as a chemosensitizer, that is, it has no effect on tumors by itself," the authors write. "This compound would therefore have the potential to improve the efficacy of chemotherapeutic agents that are currently used in the clinic, particularly in situations in which doses of genotoxin have to be lowered to reduce side effects."

Source:
Steve Graff
Journal of the National Cancer Institute