Other highlights in the March 1 JNCI

February 28, 2006

Study Details New Model for Angiogenesis Switch in Tumors

A recent study has described a new method to examine the process by which tumor cells develop an angiogenic phenotype, a phenotype in which they recruit new blood vessels, thus enabling them to grow rapidly. The new model may ultimately help scientists monitor when tumors become angiogenic, and how the switch to this more dangerous phenotype occurs.

The timing of when the switch from nonangiogenic to angiogenic phenotype occurs in tumors is not well understood. Judah Folkman, M.D., and George Naumov, Ph.D., of the Children's Hospital Boston and Harvard Medical School in Boston, and colleagues were able to separate populations of nonangiogenic and angiogenic tumor cells from human tumors.

Folkman and colleagues observed that angiogenic tumor cells, when injected into mice, induced angiogenesis and underwent rapid tumor growth. Nonangiogenic tumor cells grew equally well in laboratory dishes. However, most nonangiogenic tumor cells when injected into mice were unable to recruit new blood vessels and formed only tiny "pinhead" sized tumors that did not expand further and were harmless to the mice. Some of these nonangiogenic tumors switched on angiogenesis after several months, or up to a year (half the lifetime of a mouse). After the angiogenic switch, these tumors grew as rapidly in the mice as the tumors that were originally angiogenic.

The authors write, "These models can permit further studies of the angiogenic switch, especially the different stages and timing of the process. Also, this approach may be suitable for the study of sensitive angiogenesis-based biomarker assays and novel treatment strategies."

In an accompanying editorial, Giovanna Tosato, M.D., and Masashi Narazaki, M.D., Ph.D., of the National Cancer Institute in Bethesda, note the importance of the angiogenic phenotype for growth and metastasis in many tumors, and discuss other ways in which benign tumors may progress and angiogenic therapies could be used. They write, "Based on the observations made by Naumov et al. in this issue and by many others, particularly interesting approaches would be to prevent the angiogenic switch or to turn it off before tumors acquire a large blood supply. Understanding the molecular basis for the angiogenic switch and how to regulate it seems like a very good start."


Article: Bess Andrews, Director of Public Affairs, Children's Hospital Boston,
617-355-6420, elizabeth.andrews@childrens.harvard.edu
Editorial: Tracy Thompson, 301-451-4347, thompstr@mail.nih.gov

Meat Intake Associated with Noncardia Gastric Cancer Risk

According to a new study, having a high consumption of total meat, red meat, and processed meat is associated with increased risk of a type of gastric cancer called noncardia gastric cancer, gastric cancer beyond the part of the stomach directly below the esophagus, known as the cardia.

Carlos A. Gonzalez, M.D., Ph.D., at the Catalan Institute of Oncology in Barcelona, and colleagues studied 521,457 men and women age 35-70 from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort for an average of 6.5 years and determined their rate of gastric cancers and of a type of esophageal cancer called esophageal adenocarcinoma. Using information on diet, the researchers could determine associations between meat intake and risk of gastric cancer.

Increased risk of noncardia gastric cancer was associated with total meat intake, red meat intake, and processed meat intake, but not with white meat intake. The association seems to be restricted to those subjects with a concurrent infection with Helicobacter pylori, intestinal bacteria that causes gastric cancer. Meat intake was not associated with risk of cardia gastric cancer.

Contact: Georgina Llongueras, Catalan Institute of Oncology, 34-932607316 x7316, pla.comunicacio@ico.scs.es.

Study Finds BAY 43-9006 May Have Anti-Cancer Activity in Thyroid Cancer

A compound called BAY 43-9006 known to inhibit proteins often involved in cancer, called tyrosine kinases, may have anticancer activity in thyroid cells, according to a new study.

The RET tyrosine kinase has been associated with thyroid cancer. Previous studies showed that a compound known as BAY 43-9006 inhibited other tyrosine kinases. Massimo Santoro, M.D., Ph.D., at the Universia di Napoli, and colleagues tested the effects of BAY 43-9006 on thyroid cancer cells. They found that BAY 43-9006 inhibits the function of the RET tyrosine kinase, including forms that are resistant to other inhibitors, and suggest it may have anti-oncogenic activity in thyroid cancer cells carrying the RET tyrosine kinase.

Contact: Massimo Santoro, 39-081-7463056, masantor@unina.it

Macromolecular Drug Carriers Weighted to Target Tumors

A new study has identified the molecular weight of a macromolecular drug carrier that best penetrates a tumor and its vasculature and remains stable once inside. The information may be useful for targeting tumors with anti-cancer drugs.

Ashutosh Chilkoti, Ph.D., of Duke University in Durham, and colleagues investigated how molecular weight influences the accumulation of a model macromolecular drug carrier, called dextrans, in mice carrying a squamous cell carcinoma tumor. They tested a range of fluorescent-labeled dextrans, with molecular weights from 3.3kDa to 2 MDa, which were intravenously administered and visualized with intravital microscopy.

The authors found that the largest molecules did not penetrate far into the tumor, but accumulated to the highest extent. Smaller molecules penetrated farther into the tumor, but did not accumulate to the same level as their larger counterparts. Dextrans accumulated optimally in tumors at weights of 40-70 kDa. This information may be used for finding appropriate macromolecular carriers to target tumors in the future.

The authors write, "The findings of this study are important because they can be used to optimize delivery of all macromolecular therapeutic agents, including cytokines, antibodies, and antiangiogenic drugs that are gaining importance as therapeutic agents."

Contact: Becky Levine, 919-660-1308, Levin005@mc.duke.edu

Study Characterizes PMS2 Gene Mutation Phenotype

A new study provides a description of the phenotype associated with homozygotic deficiency or mutation in a DNA repair gene called PMS2, which can place a person at high risk for cancer. Mutant PMS2 shows low heterozygote penetrance, meaning that the phenotype associated with mutant PMS2 doesn't often affect people heterozygous for the mutant gene. Eamonn Sheridan, M.D., at St. James's University Hospital in Leeds, and colleagues examined the phenotype, or physical traits, associated with homozygous PMS2 deficiency in 13 Pakistani children in the United Kingdom. The authors found that the syndrome is characterized by patches of "café-au-lait" skin pigmentation and an onset of a number of characteristic tumors.

The syndrome can easily be mistaken for a genetic disorder called neurofibromatosis type 1. The authors suggest that understanding the phenotype of the homozygous PMS2 mutation can help distinguish between the two disorders, and that making an accurate early diagnosis is essential for optimal treatment.

Contact: Hannah Love, 113-343-4100, pressoffice@leeds.ac.uk

Also in the March 1 JNCI:
  • Delayed Intervention May Combat Overtreatment of Prostate Cancer, Study Suggests: http://www.eurekalert.org/emb_releases/2006-02/jotn-dim022306.php
  • HPV Infection a Top Risk Factor for Cervical Adenocarcinoma Worldwide, Study Says: http://www.eurekalert.org/emb_releases/2006-02/jotn-hia022306.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/a.

    Journal of the National Cancer Institute

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