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Fungal Invasion May Drive Some Pancreatic Cancers

By EJ Mundell
HealthDay Reporter

FRIDAY, Oct. 4, 2019 (HealthDay News) — Fungi living in the gut can move into the pancreas, triggering changes to normal cells that can result in cancer, a new study suggests.

The finding could advance the prevention and treatment of pancreatic cancer, which is usually fatal because it’s often detected too late. The disease has been in the news lately because “Jeopardy!” host Alex Trebek is waging a battle against an advanced form of the illness.

The new research focuses on a particular form of the cancer, called pancreatic ductal adenocarcinoma, which can be fatal within two years.

While the exact causes of pancreatic cancer remain unclear, the American Cancer Society has long recognized that viruses, bacteria and parasites can help spur pancreatic tumors, the authors of the new study noted.

But fungi haven’t been shown to play a role — until now.

“While past studies from our group have shown that bacteria travel from the gut to the pancreas, our new study is the first to confirm that fungi, too, make that trip, and that related fungal population changes promote tumor inception and growth,” study co-author Dr. George Miller said in a news release from NYU Langone Health.

Miller is co-leader of the Tumor Immunology Research Program at Perlmutter Cancer Center at NYU Langone Health, in New York City.

Pancreatic ductal adenocarcinoma is cancer of the tube in the pancreas where digestive juices drain into the intestines. This exchange causes fungal populations in the gut and pancreas — the “mycobiome” — to become abnormal, the NYU team explained. That change may cause pancreatic cells to turn malignant.

In the new study, the researchers first looked at fungal transfer from the gut to the pancreas in mice that already had pancreatic tumors.

In those experiments, the researchers found that treating the rodents with an antifungal drug shrunk the weight of tumors from between 20% to 40% over 30 weeks.

Investigating further, the team catalogued the species of fungi in the poop of mice with or without pancreatic cancer. They even tagged the fungi with “glowing” proteins to watch the microbes travel from the gut to the pancreas.

Continued

Certain patterns emerged, with some populations of fungal species increasing at a far higher rate in the cancerous pancreases versus the non-cancerous ones.

One such cancer-linked species is called Malassezia.

“We have long known that Malassezia fungi — generally found on the skin and scalp — are responsible for dandruff and some forms of eczema, but recent studies have also linked them to skin and colorectal cancer,” study senior co-author Deepak Saxena noted in the news release.

“Our new findings add evidence that Malassezia is abundant in pancreatic tumors as well,” said Saxena, who is professor of basic science and craniofacial biology at NYU College of Dentistry. Pancreatic cancers in the mice grew about 20% faster when Malassezia was allowed to grow unchecked, the team noted.

The researchers theorized that fungi spur growth of the cancer by affecting immune system mechanisms that lead to abnormal tissue growth.

Study co-first author Smruti Pushalkar, a research scientist at NYU College of Dentistry, added, “Moving forward, one goal for our team is to determine which species are most relevant to cancer, as doing so could guide future attempts to slow tumor growth with targeted antifungal medications, and to avert side effects.”

The results of the study add evidence to the theory that fungi increase the risk for cancer by activating an ancient part of the immune system, the researchers said. This immune response fights infections but also increases cell growth as the infection is cured. Past studies have shown that aggressive tissue growth can cause cancer when it’s combined with genetic flaws.

The report was published Oct. 2 in the journal Nature.

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SOURCE:Nature,  news release, Oct. 2, 2019

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Many Advanced Colon Cancers Were ‘Born’ Ready to Spread

TUESDAY, June 18, 2019 — In most patients with metastatic colon cancer, the disease may have begun spreading throughout the body very early on — when the original tumor was no bigger than a poppy seed, a new study suggests.

Metastatic refers to the most advanced stage of cancer, when the original tumor has spread to distant sites in the body.

Traditionally, that’s been seen as a “late” event — the result of a cancer accumulating many mutations that allow it to invade various tissues in the body, said Christina Curtis, lead researcher on the new study.

Her team’s findings turn that viewpoint on its head.

Through genetic analysis of tumor samples, researchers traced the origins of metastases in 21 patients with advanced colon cancer. They found that for 80%, those metastases likely occurred very early — before the cancer was even diagnosed.

Essentially, that means some cancers are “born to be bad,” said Curtis, an assistant professor of medicine and genetics at Stanford University in California.

While that might sound demoralizing, she said the results can actually be viewed in a positive light.

One day, Curtis explained, doctors might be able to use tumors’ genetic characteristics to figure out which patients with early-stage colon cancer need more aggressive treatment.

That could mean, for example, giving chemotherapy after surgeons have removed the colon tumor — to try to wipe out tumor cells that have traveled to other sites in the body.

Plus, Curtis said, discovering which genetic “drivers” cause cancer to spread early could allow researchers to develop new drugs that target those mechanisms.

According to Dr. Martin Weiser, a colon cancer specialist at Memorial Sloan Kettering Cancer Center in New York City, “These findings are very important. This is top-notch work.”

Many researchers and doctors have suspected metastases often get their start early on, he noted, but this is actual proof from patient tumor samples.

“This is showing there are molecular changes that happen early,” Weiser said. That early occurrence, he added, should make it easier to pinpoint the particular genetic culprits.

“Maybe we can figure out which patients need additional treatment early on, and which ones don’t,” Weiser said.

For the study, published June 17 in Nature Genetics, Curtis and her colleagues started with tumor samples from 21 patients with colon cancer that had spread to the liver or the brain.

For each patient, the researchers compared the pattern of genetic mutations in the original colon tumor with that in the metastases.

The investigators found that in 17 patients, the metastases seemed to originate from just one cell — or a small group of genetically similar cells — that had broken away from the original colon tumor early in its development.

Next, researchers combed through data on more than 900 patients with metastatic colon cancer, and 1,800 whose cancer had not spread. All had had their original tumor analyzed to detect changes in genes known to be linked to cancer.

The researchers found that certain combinations of gene mutations were strongly related to the odds of metastases.

“It wasn’t any single mutation, but specific combinations of mutations, that seemed to tip the balance,” Curtis said.

For example, mutations in a gene called PTPRT, in combination with certain other mutations, were found almost exclusively in patients with metastatic cancer. Past research has shown that when PTPRT’s function is lost, a “cell survival” protein called STAT3 becomes more active.

Curtis said it’s possible that a drug that would inhibit STAT3 could prevent metastases.

More research is needed to better understand what genetic drivers cause early metastases — and why some cancer patients never develop metastases, Curtis said.

The study authors are also looking at whether this same phenomenon is true of other types of cancer.

Curtis stressed that the findings do not diminish the importance of colon cancer screening to catch the disease early. Treating the disease in its early stages is always critical.

Weiser made another point: Patients newly diagnosed with colon cancer often feel they have to rush into treatment, thinking the risk of it spreading rises with each day. But if that risk has more to do with tumor genetics than with time, patients may feel less pressure to make an immediate decision.

“You can take the time to consider the options and make sure you get the right treatment,” Weiser said.

More information

The American Cancer Society has more on treating colon cancer.

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Posted: June 2019

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9-11 Responders Report More Head, Neck Cancers

By Robert Preidt

HealthDay Reporter

FRIDAY, Feb. 1, 2019 (HealthDay News) — Head and neck cancers among a group of first responders to the 9/11 World Trade Center terrorist attacks are significantly higher than expected, a new study says.

Rutgers University researchers found that diagnoses of these cancers increased 40 percent in a group of WTC workers and volunteers over a four-year period.

The findings suggest there are emerging health risks among those first responders that require ongoing monitoring and treatment, according to the study.

“This excess occurrence in head and neck cancers is plausible since first responders inhaled debris clouds containing many known carcinogens,” said study author Judith Graber. She’s an associate professor in Rutger’s School of Public Health and a researcher in the Environmental and Occupational Health Sciences Institute.

“In addition, these carcinogenic exposures might add to or increase the effect of known personal risk factors for some head and neck cancers, such as tobacco smoking, heavy alcohol use and oral HPV infection,” Graber added in a university news release.

Graber’s team compared the incidence of head and neck cancers from 2003 to 2012 among 73 first responder workers and volunteers enrolled in the World Trade Center Health Program with the number of expected cases based on the N.J. State Cancer Registry. (The health program involves nearly 34,000 in all).

They found a 40 percent increase in diagnoses of head and neck cancers among first responders between 2009 and 2012, according to the study. The results were published recently in the International Journal of Cancer.

Since cancers develop over time, the findings of significant excess cancer in this period “point to a newly emerging trend that requires ongoing monitoring and treatment of WTC-exposed persons,” Graber said.

The findings stem from a two-year study examining whether WTC first responders were at greater risk of human papillomavirus (HPV)-related throat and tongue cancer because of their Ground Zero exposure. The U.S. Centers for Disease Control and Prevention funded the study.

The most notable increases were seen in throat cancers often associated with HPV infection, but not in mouth and nasal cancers.

The study also found that head and neck cancers were most common among first responders who were over 55, white, or members of the military or protective services and involved in rescue and recovery and maintaining the perimeter after the terrorist attacks.

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SOURCE: Rutgers University, news release, Jan. 17, 2019

Copyright © 2013-2018 HealthDay. All rights reserved.

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Head, Neck Cancers Up Among 9-11 Responders: Study