NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
March 20, 2007 • Volume 4 / Number 12 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

New Molecular Imaging Compound Pinpoints Metastases in Mice

Researchers have created a new imaging compound that fluoresces only when processed by cancer cells. Use of this compound allowed scientists to visualize 92 percent of the very small tumors in the peritoneum - the tissue that lines the wall of the abdomen - in mice with ovarian cancer. The results were published in the March 15 Cancer Research.

The team led by Dr. Hisataka Kobayashi from the Molecular Imaging Program in NCI’s Center for Cancer Research (CCR) created a compound consisting of the protein avidin, which binds to a protein commonly found on cancer cells that have spread to the peritoneum, joined to three molecules of the fluorescent compound rhodamine X. This complex, called Av-3ROX, is taken up by a cancer cell after binding to its surface and is subsequently broken down in the lysosome. When enzymes in the lysosome break the molecule into smaller pieces, the fluorescence from rhodamine X is released, enabling the cancer cell to be detected using imaging techniques.

To verify that Av-3ROX was specifically internalized into tumor cells, the investigators used cells that carried the gene for red fluorescent protein (RFP) to induce tumors and peritoneal metastases in mice. The investigators injected Av-3ROX into the peritoneum of the mice, captured fluorescent images of both Av-3ROX and RFP, and compared the number of metastases identified using both compounds. They found that Av3-ROX had 92 percent sensitivity and 98 percent specificity for the cancer cells.

Because Av-3ROX would cause an immune system reaction in humans, the researchers are now working on a second-generation compound that joins the binding site of avidin - the part that recognizes the cancer cells - to human serum albumin. The authors believe that this approach to molecular imaging “holds promise as a method of optically enhancing surgical or endoscopic procedures,” and may allow for more complete surgical removal of metastatic disease.

Many Protein Kinase Genes Linked to Cancer

Researchers have cataloged the mutations in genes that produce protein kinases, which are enzymes that regulate other proteins and play a role in some cancers. Using DNA from 210 diverse human cancers, the researchers sequenced 518 protein kinase genes. Approximately 120 of the genes carried a mutation related to cancer development and may function as cancer genes, the researchers reported in the March 8 Nature.

Drs. Andrew Futreal and Michael Stratton of the Wellcome Trust Sanger Institute in Cambridge, U.K., and their colleagues identified more than 1,000 mutations in the gene family, but only some of these are so-called “driver” mutations that drive the cancer. The others are “passenger” mutations, which are present in tumors but may not contribute to disease. Their results suggest that most mutations in cancer cells are likely to be passenger mutations.

Mutations were relatively common in cancers of the lung, stomach, ovary, colon, and kidney, and rare in cancers of the testis and breast. “Given that we have studied only 518 genes and limited numbers of each cancer type, it seems likely that the repertoire of mutated human cancer genes is larger than previously envisaged,” the researchers wrote.

Together with another large-scale sequencing study published in September 2006, this study presents a largely unbiased overview of the spectrum of mutations in human cancers, noted an editorial by Drs. Daniel Haber and Jeff Settleman of Massachusetts General Hospital. These studies suggest that “each cancer genome carries many unique abnormalities, and not all mutations identified contribute equally to the manifestation of the associated cancers,” they wrote.

Study Compares Two-Transplant Treatments

An Italian clinical trial has shown that patients with newly diagnosed multiple myeloma (MM) who received a transplant of their own stem cells (an autologous stem cell transplant) and a second stem cell transplant from an “HLA-matched” sibling (an allogeneic stem cell transplant) had superior survival outcomes compared to patients who received two autologous stem cell transplants.

Published in the March 15 New England Journal of Medicine, the trial involved 162 consecutive patients with newly diagnosed MM who were under age 65 and had at least 1 sibling. Patients with a sibling whose blood cells expressed genetically identical surface antigens, human-leukocyte antigens - known as an HLA match - were offered the option of the autologous-allogeneic treatment regimen. The chances of a sibling being an HLA match are one in four.

Both patient groups received the same initial chemotherapy regimen at conventional dosing followed by high-dose myeloablative chemotherapy and an autologous stem cell transplant. Those with an HLA-matched sibling received radiation and an allogeneic stem cell transplant using the siblings’ cells (60 patients); those without an HLA-identical sibling received another round of high-dose chemotherapy and a second autologous stem cell transplant (59 patients). Of these patients, 58 receiving allogeneic transplant and 46 receiving double autologous transplants completed treatment.

Allogeneic stem cell transplants, while they are considered to have greater curative potential because they have a stronger antitumor cell effect, have been associated with high treatment-related mortality rates. Combined regimens like the one used in the Italian trial that employ “reduced-intensity” chemotherapy or radiation before the allogeneic transplant “have lowered transplant-related mortality to approximately 15 percent,” lead author Dr. Benedetto Bruno of the University of Turin and colleagues explained. But it has been unclear whether they offer a survival advantage.

In the trial, there was little difference in treatment-related mortality between the two groups; however, survival outcomes clearly favored those in the autologous-allogeneic transplant group - a 67-percent improvement in overall survival and a 53-percent improvement in event-free survival.

African Americans' Prostate Mortality Rooted in Class

Prostate cancer mortality is twice as high in African American men compared with white men, a fact often attributed to poor education, lack of awareness of the threat, and undiscovered genetic factors.

In fact, according to a study published online March 12 in Cancer, screening, treatment choices, and health behavior are all affected by barriers that “arise directly from the racial disparity in socioeconomic position, not reduced information or culturally based misunderstandings sometimes presumed to arise in its wake.”

Dr. James A. Talcott of the Center for Outcomes Research at Harvard Medical School and colleagues surveyed 207 African American men and 348 white men from North Carolina who were recently diagnosed with prostate cancer. The disparities they found, generally attributed to lower social position, translate “into disadvantages in their medical care that may escape notice in studies that collect less detailed information than ours,” wrote the authors.

For example, the researchers found that African Americans were more aware than white men of their prostate cancer risk and the responsibility to get screened. Yet they were less able to access good medical care because of less convenient health care settings, less public and private insurance coverage, and less flexible work circumstances.

Distrust of their physicians was also rooted in African Americans’ health care experiences. Their lower income, educational level, and social status make them more likely to use public clinics and emergency rooms and less likely to receive continuity of care. They were also less likely to establish ongoing ties with a primary physician, had less frequent regular physical exams, and less follow-up on significant medical complaints. These findings led researchers to conclude that African Americans “are simply less likely to know their physicians and other providers well enough to develop trust.”