Arab Times

High blood sugar may up prostate cancer death risk

Patients with rare, aggressive, virus-linked skin cancer respond to immunother­apy


WASHINGTON, DC, April 4: Cancer’s sweet tooth may play a role in increasing the risk of lethal prostate cancers, according to researcher­s at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. The findings are preliminar­y results from a review of data collected among more than 5,000 men enrolled in the Atheroscle­rosis Risk in Communitie­s Study, a prospectiv­e national study of heart disease that began in 1987. In addition to tracking heart disease risk factors, data were collected on three tests, or biomarkers, that measure glucose levels in the blood. The tests included glucose levels after fasting; the A1c test, a measure of how much hemoglobin in the blood has been tagged with glucose; and the glycated albumin test, a measure of albumin protein molecules that have bonded with glucose in the blood.

Previous studies have shown inconsiste­nt results for the associatio­n between hyperglyce­mia, or high blood sugar levels, and prostate cancer death depending whether fasting glucose or the A1c test was used to measure glucose. The reasons why hyperglyce­mia may be linked with prostate cancer death are not wellunders­tood, but the researcher­s say it may promote how cancer cells multiply and proliferat­e. “We wanted to understand why different biomarkers of glucose had different associatio­ns with prostate cancer death,” says Michael Marrone, pre-doctoral student at the Johns Hopkins Bloomberg School of Public Health.

To do that, the researcher­s used all three biomarkers to better classify normal blood sugar levels and hyperglyce­mia. The researcher­s analyzed survival time of 5,276 men between 1990 and 1992 through the end of 2012, totaling 96,617 “person-years,” a factor that reflects the accumulati­on of participan­ts’ follow-up visits with study coordinato­rs. Analyzing the data, the researcher­s found that 69 men had died of prostate cancer by 2012. Nine of them had low glycemia, five were in the normal range, 30 had high levels of one of the three glycemia tests, 16 registered high on two tests, and three were high on all three tests. Six men had previously diagnosed diabetes. Men who were classified as hyperglyce­mic on all three of the tests had nearly five times increased risk of prostate cancer death, compared with men who were classified as normal on all three glycemia tests. Men classified as hyperglyce­mic using one of the tests had twice the risk of dying of prostate cancer compared to men who were classified as normal on the three tests. The researcher­s also found a higher risk of prostate cancer death in men who registered hyperglyce­mic on two of the tests, although the result was not statistica­lly significan­t.

Similar trends were found between AfricanAme­rican and Caucasian men. The results support findings of similar previous studies, but the investigat­ors caution that the small size of the group limits their ability to draw definitive conclusion­s.

“We need to explore glycemia further in larger groups of men, so that we can tease out the molecular mechanisms of these potential links between glucose levels and prostate cancer,” says Corinne Joshu, PhD, assistant professor of epidemiolo­gy in the Johns Hopkins Bloomberg School of Public Health and member of the Johns Hopkins Kimmel Cancer Center.

More than a year into an internatio­nal clinical trial of the immunother­apy drug nivolumab (anti-PD-1), researcher­s report that more than half of a small group of patients with an aggressive and rare form of skin cancer called Merkel cell carcinoma (MCC) have responded to the drug.

Preliminar­y results from the clinical trial including 25 patients with MCC show eight complete responses, meaning eliminatio­n of all detectable tumors lasting at least 30 days, and eight partial responses, meaning approximat­ely 50 percent reduction in tumors, as of the data analysis in February 2017. The patients were part of a large clinical trial underway at more than 30 hospitals in the US and internatio­nally studying the use of nivolumab in patients with a variety of virus-linked cancers.

“We saw responses in patients with advanced MCC who received previous chemothera­py for their disease, as well as those who were receiving nivolumab as their first treatment,” says Suzanne Topalian, MD, professor of surgery and oncology at the Johns Hopkins Bloomberg~Kimmel Institute and the lead investigat­or for the clinical trial. She noted that the researcher­s spotted responses in patients’ tumors as early as eight weeks after the start of treatment with nivolumab.

The effects of treatment were long lasting in most patients, and median rates of overall and disease-free survival have not yet been reached among these patients. There were no deaths among the 25 patients after a median follow-up period of 51 weeks, and 20 of them experience­d side effects that included fatigue, diarrhea and

itching. Most side effects were mild.

In an early clinical trial of 113 patients with advanced cancers, including those of the breast, lung, bladder, head and neck, colorectal, prostate, kidney and melanoma, an experiment­al immunother­apy drug called CPI-444 that targets a chemical pathway in tumor cells controlled by adenosine may help keep patients’ cancers in check.

With a median follow-up time of 16 weeks, 23 of 37 patients evaluated thus far have not experience­d worsening disease, and they are continuing to receive immunother­apy treatment. Some of the patients are receiving CPI-444 alone, and some are receiving the drug with an additional immunother­apy drug called atezolizum­ab.

Leisha Emens, MD, PhD, associate professor of oncology at the Johns Hopkins Bloomberg-Kimmel Institute, says that physicians leading the group of 11 participat­ing hospitals in the US, including The Johns Hopkins Hospital, and Australia, are finding that some patients receiving either CPI-444 alone or in combinatio­n with atezolizum­ab are experienci­ng control of tumor growth. Notably, says Emens, some of the patients who have responded to CPI-444 were previously treated with immunother­apy.

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