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Other highlights in the November 3 JNCI

Journal of the National Cancer Institute

Method Could Improve Irinotecan Chemotherapy Effectiveness

Assessing how quickly the body metabolizes the drug midazolam combined with genotyping could help to optimize irinotecan chemotherapy, according to a new study.

Irinotecan has been approved for use as part of first- and second-line chemotherapy for colorectal cancer and also has moderate activity against breast cancer, relapsed or refractory non-Hodgkin lymphoma, and lung cancer. Response to the drug varies in different people because of variations in the enzymes that metabolize the drug, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1).

Alex Sparreboom, Ph.D., of the National Cancer Institute, and colleagues demonstrated in 30 cancer patients that the speed at which the body metabolizes the drug midazolam was associated with CYP3A4 phenotype and is closely related to how quickly the body metabolizes irinotecan. They also found that a specific UGT1A1 mutation was associated with increased amounts of the active inrinotecan metabolite. They conclude that combining CYP3A4 phenotyping with UGT1A1 genotyping could assist with the optimization of irinotecan chemotherapy. The method is currently undergoing validation in a prospective study.

Contact: National Cancer Institute Press Office, 301-496-6641,

Height, Obesity, and Activity Level Associated With Endometrial Cancer Risk

Greater height and obesity and lower levels of physical activity are all associated with an increased risk of endometrial cancer, according to a new study.

Obesity is an established risk factor for endometrial cancer, and there has been some evidence that body mass at younger ages, weight change, height, and physical activity may also be associated with a woman's risk of this cancer. To investigate these possible associations, Leo J. Schouten, M.D., Ph.D., of Maastricht University in the Netherlands, and colleagues conducted a case-cohort study using data from more than 62,000 women in The Netherlands Cohort Study on Diet and Cancer.

The researchers found that women 175 cm (5 feet 9 inches) or taller had an increased risk of endometrial cancer compared with women less than 160 cm (5 feet 3 inches) in height. Women with a body mass index (BMI) of 30 or greater had a higher risk compared with women with a BMI between 20 and 22.9. BMI at age 20 and BMI gain since age 20 were also associated with endometrial cancer risk. In addition, women who spent 90 minutes or more each day doing physical activities had a lower risk of the cancer than women who spent less than 30 minutes each day doing physical activities.

Contact: Caroline Roulaux, Communications Office, Maastricht University, 31-43-388-3084,

MYH Gene Mutations May Account for Many Hereditary Colorectal Cancers

As many as 20% of colorectal cancer patients have a family history of the disease, but familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer account for less than 3% of all colorectal cancer cases. Researchers have suggested that it is likely that many cases of familial colorectal cancer are associated with mutations in as-yet unidentified genes.

In a new study, Steven Gallinger, M.D., of the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto, and colleagues used a population-based series of more than 1,200 colorectal cancer patients and more than 1,200 healthy control subjects from Ontario, Canada to investigate associations between colorectal cancer risk and two mutations in the MYH gene, which is involved in repairing damage to DNA. They found that people who carried one or two copies of the mutated MYH gene had an increased risk of colorectal cancer and were more likely to have first- or second-degree relatives with colorectal cancer. The authors suggest that the two MYH gene mutations may account for a substantial fraction of hereditary colorectal cancers.

Contact: Kathy Pyatt, Public Relations, Mt. Sinai Hospital, 416-586-5311,

Mesenchymal Stem Cells Could Deliver Therapeutic Proteins to Cancers, Mouse Study Shows

Many biologic agents, such as interferon beta, have limited utility because of excessive toxicity when delivered systemically. In a new study, Michael Andreeff, M.D., Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues demonstrated in a mouse model that mesenchymal stem cells, which are derived from bone marrow cells, could be used to deliver interferon beta to tumors. They suggest that mesenchymal stem cells could be an effective platform for delivering therapeutic proteins to specific cancer sites.

Contact: Laura Sussman, M. D. Anderson Cancer Center, 713-745-2457,

Adding Histamine to Melphalan in Isolated Limb Perfusion Improves Tumor Response in Animal Model

Isolated limb perfusion (ILP) is a treatment method in which high concentrations of drugs are administered to a limb containing an unresectable tumor that is temporarily isolated from the rest of the body's circulatory system. In a new study, Timo L. M. ten Hagen, Ph.D., of the Daniel den Hoed Cancer Center in Rotterdam, Netherlands, and colleagues found that, in an animal model, adding histamine to melphalan in ILP improved tumor response compared with melphalan alone. They state that these results warrant further evaluation in a clinical setting.

Contact: Timo L. M. ten Hagen, Daniel den Hoed Cancer Center,

Also in the November 3 JNCI:

  • Impaired Antigen Presentation and Effectiveness of Combined Active/Passive Immunotherapy for Epithelial Tumors
  • Transferrin-conjugated Liposome Targeting of The Photosensitizer A1PcS4 to Rat Bladder Carcinoma Cells
  • Eating Fruits and Vegetables Associated With Reduction in Cardiovascular Disease, But Not Cancer:


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