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October 10, 2006 • Volume 3 / Number 39 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Antibiotic May Be Effective Against an Ocular Lymphoma


Special Issue on Cancer Survivorship

Next week, the NCI Cancer Bulletin will publish a special issue. Among other things, the issue will highlight the 10th anniversary of NCI's Office of Cancer Survivorship and provide information on NCI research in the areas of childhood cancer survivors, mental and physical health of cancer survivors, and issues facing cancer caregivers. The issue will also contain a list of resources and links for researchers, clinicians, patients, and families.

A new study suggests that a common antibiotic may be an effective treatment for a rare form of lymphoma that occurs in and around the eyelid, even if the patient is not infected with the bacterium that has been linked to this particular cancer.

Published in the October 4 Journal of the National Cancer Institute (JNCI), the 27-patient prospective clinical trial by Italian researchers found that the antibiotic doxycycline could induce complete or partial tumor regression in patients with ocular adnexal MALT lymphoma (OAL), including those with newly diagnosed cancer or who had relapsed after previous radiation or chemotherapy treatments.

Some of the same researchers, including lead author Dr. Andres J. M. Ferreri of the San Raffaele H. Scientific Institute in Milan, had previously shown a link between OAL and infection with Chlamydia psittaci (Cp). In this study, however, some patients responded to a 3-week course of treatment with doxycycline even if they were Cp-negative. Of the Cp-positive patients, 7 of the 11 responded to doxycycline treatment, while 6 of the 16 Cp-negative patients responded.

Two years after treatment, 66 percent of patients were disease free. Because of the short follow-up with some patients and the fact that "a sizeable fraction of OAL patients experienced slow and gradual tumor regression" after treatment, the authors argued that the results may underestimate doxycycline's true impact.

The responses seen in Cp-negative patients could have multiple interpretations, the authors noted. It could mean the patients are truly Cp-positive but the bacterium's DNA levels were too low and could not be detected by the PCR test they used, or it could be that other doxycycline-sensitive bacteria are associated with OAL.

The findings, they concluded, need to be confirmed in larger studies.

NPRL2 Gene Influences Cisplatin Resistance

New research from the University of Texas M.D. Anderson Cancer Center and Southwestern Medical Center suggests that loss of function of the tumor-suppressor gene NPRL2 may play an important role in cisplatin resistance in non-small-cell lung cancer (NSCLC). The study was published in the October 1 Cancer Research.

In 40 NSCLC cell lines, expression of the NPRL2 protein correlated with cisplatin sensitivity; most cell lines that had little or no NPRL2 protein expression were resistant to the chemotherapy drug. The authors then used nanoparticle-mediated gene transfer to force the expression of NPRL2 in several of the cell lines, both in the presence and absence of cisplatin. The combination of NPRL2 and cisplatin synergistically inhibited tumor-cell growth in cisplatin-resistant cell lines. The combination also caused a significant and synergistic increase in cell death.

The investigators then tested the combination of nanoparticle-delivered NPRL2 and cisplatin in mice bearing NSCLC xenografts established from cisplatin-resistant cell lines. Again, the combination significantly and synergistically inhibited tumor growth and increased cell death, more so than either the NPRL2 nanoparticles or cisplatin delivered alone. Total tumor volumes were reduced more than 90 percent in mice receiving the combination of treatments.

"Our results suggest that NPRL2 has potential…as a molecular therapeutic agent for enhancing and resensitizing the response of nonresponders to cisplatin treatment," stated the authors. They also suggest that expression of the gene may have potential as a biomarker for the prediction of cisplatin response in NSCLC.

Fanconi Anemia Gene Linked to Breast Cancer Risk

A gene that is mutated in some patients with the blood disease Fanconi anemia may also be a risk factor for breast cancer. Researchers estimate that certain mutations in the gene BRIP1 result in a twofold increase in breast cancer risk. This puts the gene in a class with two other breast cancer susceptibility genes, CHEK2 and ATM, which may predispose a woman to cancer only in the presence of other genetic or environmental risk factors. By comparison, mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and TP53 confer a 10- to 20-fold increased risk of the disease.

Dr. Nazneen Rahman of the Institute of Cancer Research in Sutton, U.K., and her colleagues discovered the gene by analyzing proteins that interact with the proteins of known breast cancer susceptibility genes. The BRIP1 protein interacts with the breast-cancer associated protein BRCA1, according to findings published online October 10 in Nature Genetics.

The researchers screened for BRIP1 mutations in 1,212 women with breast cancer who lacked mutations in BRCA1 and BRCA2. They found 9 women who had "truncating" mutations in BRIP1, which probably inactivate the BRIP1 protein; only 2 of 2,081 women without breast cancer in a comparison group had such mutations. Several of the BRIP1 mutations they detected had been reported in patients with Fanconi anemia.

Like other breast cancer susceptibility genes, BRIP1 may play a role in repairing damaged DNA. The researchers predict that "other genes involved in DNA repair processes may also be involved in breast cancer susceptibility." Together, the known breast cancer susceptibility genes are estimated to account for up to 25 percent of the familial, or inherited, risk of the disease, leaving most of the risk unexplained.

New Estimate: Smoking Reduction Central to Cancer Mortality Decline in Men

Between 1991 and 2003, the nation's overall cancer death rate decreased by nearly 12 percent. Now, in a paper published in the October 1 Tobacco Control, researchers from the American Cancer Society provide an estimate of the contribution of decreased smoking to this important trend.

Drs. Michael Thun and Ahmedin Jemal first compared the observed overall cancer death rate to the lung cancer death rate between 1991 and 2003. In men, the overall cancer death rate dropped by 16 percent, but the lung cancer death rate dropped even more precipitously (by 20 percent); 40 percent of men's decreased overall cancer death rate can be attributed to their decreased rate of lung cancer. In contrast, while the overall cancer death rate among women decreased by 11.6 percent, the lung cancer rate increased by 9.6 percent, preventing a larger drop in the overall female cancer rate.

Lung cancer death rates largely reflect smoking prevalence from decades past. While male smoking prevalence began a steady decline in the mid-1960s, female smoking prevalence began declining steadily only in the mid-1980s. Reflecting this, the male lung cancer death rate has been declining for some time, while the lung cancer death rate for women is still climbing, although at a slower rate than in the past.

Drs. Thun and Jemal also estimate that about 146,000 lung cancer deaths among men were prevented or postponed between 1991 and 2003 because of earlier declines in smoking rates. They conclude that "the payoff from past investments in tobacco control has only just begun," but caution that "sustained progress in tobacco control is essential if we are to continue to make progress against cancer."

Racial Disparities Persist in Endometrial Cancer

African American women with advanced stage endometrial cancer have lower survival rates than white women with the disease even when both groups receive similar treatments, according to a study published online September 25 in Cancer.

Previous studies on the disparities in outcomes and survival for African American women with endometrial cancer have suggested that the poorer prognosis was due to differences in treatment, noted researchers led by Dr. G. Larry Maxwell of Walter Reed Army Medical Center. "The objective of the current study was to determine whether race influenced the survival of patients with advanced endometrial cancer," they note.

The retrospective study analyzed data from 169 African American women and 982 white women who were participants in 4 randomized treatment trials conducted by the Gynecologic Oncology Group, where the patients received "contemporary chemotherapy regimens that included doxorubicin." The pooled data revealed that African American women were more likely to have papillary serous histology Stage IV disease and higher tumor grade compared with white women; survival was also worse among African American women than among white women (median survival: 10.6 months vs. 12.2 months, respectively). The study results were initially presented at a gynecological cancer conference in 2005 (See NCI Cancer Bulletin, March 29, 2005).

"Our findings suggest that, even when patients with advanced endometrial cancer receive similar therapy, black women have a worse overall survival compared with white women," the researchers comment. "Although the causes of racial disparity in endometrial cancer remain to be elucidated, socioeconomic, biologic, and cultural factors should be investigated to identify the etiologic origins of this multifactorial health care problem."