Statins may block an inflammation pathway involved in the development of cancer

Published

4 months ago

May 30, 2024

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May 30 2024 Massachusetts General Hospital

A new study led by investigators from Mass General Cancer Center, a founding member of the Mass General Brigham healthcare system, reveals that statins-;commonly used cholesterol-lowering drugs-;may block a particular pathway involved in the development of cancer that results from chronic inflammation. The findings are published in Nature Communications.

"Chronic inflammation is a major cause of cancer worldwide," said senior author Shawn Demehri, MD, PhD, a principal investigator at the Center for Cancer Immunology and Cutaneous Biology Research Center of Massachusetts General Hospital and an associate professor of Dermatology at Harvard Medical School. "We investigated the mechanism by which environmental toxins drive the initiation of cancer-prone chronic inflammation in the skin and pancreas," says Demehri, who is also the Bob and Rita Davis Family MGH Research Scholar 2023-2028. "Furthermore, we examined safe and effective therapies to block this pathway in order to suppress chronic inflammation and its cancer aftermath."

Demehri and his colleagues' study relied on cell lines, animal models, human tissue samples and epidemiological data. The group's cell-based experiments demonstrated that environmental toxins (such as exposure to allergens and chemical irritants) activate two connected signaling pathways called the TLR3/4 and TBK1-IRF3 pathways. This activation leads to the production of the interleukin-33 (IL-33) protein, which stimulates inflammation in the skin and pancreas that can contribute to the development of cancer.

When they screened a library of U.S. Food and Drug Administration–approved drugs, the researchers found that a statin, pitavastatin, effectively suppresses IL-33 expression by blocking the activation of the TBK1-IRF3 signaling pathway. In mice, pitavastatin suppressed environmentally-induced inflammation in the skin and the pancreas and prevented the development of inflammation-related pancreatic cancers.

In human pancreas tissue samples, IL-33 was over-expressed in samples from patients with chronic pancreatitis (inflammation) and pancreatic cancer compared with normal pancreatic tissue. Also, in analyses of electronic health records data on more than 200 million people across North America and Europe, use of pitavastatin was linked to a significantly reduced risk of chronic pancreatitis and pancreatic cancer.

The findings demonstrate that blocking IL-33 production with pitavastatin may be a safe and effective preventive strategy to suppress chronic inflammation and the subsequent development of certain cancers. Next, we aim to further examine the impact of statins in preventing cancer development in chronic inflammation in liver and gastrointestinal tract and to identify other novel, therapeutic approaches to suppress cancer-prone chronic inflammation"

Shawn Demehri, MD, PhD, senior author Source:

Massachusetts General HospitalJournal reference:

Park, J. H., et al. (2024). Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression. Nature Communications. doi.org/10.1038/s41467-024-48441-8.

Sports

Sources: Nats demote All-Star after all-nighter

Published

2 hours ago

September 21, 2024

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Sources: Nats demote All-Star after all-nighter

Jeff Passan, ESPNSep 21, 2024, 01:47 PM ET
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The Washington Nationals demoted All-Star shortstop CJ Abrams to the minor leagues after he stayed out all night at a Chicago-area casino, leaving only hours before a Friday day game against the Chicago Cubs, sources told ESPN’s Jesse Rogers.

The 23-year-old Abrams led off for the Nationals and went 0 for 3 with a walk and strikeout in Friday’s game, which started at 1 p.m. CT. He was informed of the demotion Friday night, sources said. He will be sent to West Palm Beach, home of the Nationals’ minor league complex.

Because Abrams has been with Washington for the entirety of the season, the demotion will not affect his service time. Players earn a full year of service with 172 days on the major league roster, and Abrams already has exceeded that threshold.

Abrams could, however, file a grievance through the Major League Baseball Players Association to fight for lost pay if he believes the demotion unjust. He would lose around $30,000 of his $752,000 salary for missing the season’s final week. Abrams will be arbitration-eligible this winter, entering the system for the first of four times as a Super 2.

Acquired as one of the centerpieces of the Juan Soto trade two years ago, Abrams parlayed a breakout first-half into an All-Star selection, hitting .268/.343/.489 with 15 home runs and 15 stolen bases over the Nationals’ first 89 games. He struggled significantly in the second half, slashing .203/.260/.326, and Abrams’ defense has been a weakness throughout the season.

Still, the Nationals did not intend to send him to the minor leagues until they learned of his time spent at the casino, which was first reported Friday by CHGO.

“I just want it to be known it wasn’t performance-based,” Nationals manager Dave Martinez told reporters Saturday. “It’s an internal issue. I’m not going to give specifics.”

World

At least 44 people killed in Israel strikes on Lebanon and Gaza in last 24 hours

Published

2 hours ago

September 21, 2024

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At least 44 people killed in Israel strikes on Lebanon and Gaza in last 24 hours

At least 44 people have been killed in Israeli strikes on Lebanon and Gaza in the last 24 hours.

A strike on the Lebanese capital Beirut killed at least 31 people including three children and seven women, the country’s health minister Firas Abiad said.

Fifteen of the 68 wounded in the attack remain in hospital.

Ali Harake, the head of the rescue team searching through the rubble, told Sky News his team is still looking for between 17 and 18 missing people – though he fears none have survived.

Follow the latest updates on the Middle East

It is understood two apartment blocks in a densely populated southern neighbourhood collapsed in the strike – the deadliest attack on Beirut in decades.

Top Hezbollah commanders are believed to have been meeting in the basement of one of the buildings.

Hezbollah has confirmed two of its senior commanders, Ibrahim Aqil and Ahmed Wahbi, died in the strike while an Israeli military spokesperson said that at least 16 Hezbollah militants were killed.

Wahbi oversaw the military operations of the Radwan special forces – a commando unit that seeks to infiltrate and carry out attacks in Israel – until early 2024. Aqil was also a top commander for the Iran-backed group.

The Palestinian militant group Hamas has described the killing of Aqil as a “crime” and a “folly”, adding Israel will “pay the price”.

Meanwhile, at least 13 people have been killed in Israeli strikes on Gaza City, according to a local report.

The strikes are believed to have hit several schools sheltering displaced people in the southern part of the city.

The strikes come after Hezbollah launched one of its most intense bombardments of northern Israel in nearly a year of fighting, largely targeting Israeli military sites.

Israel’s Iron Dome missile defence system intercepted most of the Katyusha rockets.

Hezbollah said its latest wave of rocket attacks was a response to past Israeli strikes on southern Lebanon.

It came days after mass explosions of Hezbollah pagers and walkie-talkies killed at least 37 people, including two children. Some 2,900 others were wounded in the assault which has been widely attributed to Israel.

World

Fire rips through arms depot deep inside Russia after huge Ukrainian drone attack – as Zelenskyy prepares to meet Trump

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2 hours ago

September 21, 2024

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Fire rips through arms depot deep inside Russia after huge Ukrainian drone attack - as Zelenskyy prepares to meet Trump

A fire has ripped through a Russian missile depot in the Tver region deep inside the country after it was targeted in a Ukrainian drone attack, the defence ministry in Moscow has said.

Footage shows a second Ukrainian drone attack on the southwestern Russian region of Krasnodar also triggered a fire and caused a series of explosions.

Russia’s defence ministry has claimed its forces shot down 101 Ukrainian drones over Russian territory and occupied Crimea during the overnight attacks.

The drone strikes were carried out as Ukrainian leader Volodymyr Zelenskky said he is hoping to meet Donald Trump next week when he travels to the US – where he will present US President Joe Biden with a “victory plan” in relation to the war.

Meanwhile, Ukraine’s foreign minister said Russia appears to be planning strikes on Ukrainian nuclear facilities before the winter.

Posts on local Telegram channels said a Ukrainian drone attack struck an arms depot near the town of Toropets, in Russia’s Tver region – which is about 380 kilometres (240 miles) northwest of Moscow and about 500 kilometres (300 miles) from the Ukrainian border on Saturday.

Russian authorities closed a 100-kilometre (62-mile) stretch of a highway and evacuated passengers from a nearby rail station.

The depot appeared to be just miles from a Russian weapons arsenal storing missiles, bombs and ammunition in Tver that was struck by Ukrainian drones early Wednesday, injuring 13 people and also causing a huge fire.

Meanwhile, at least 1,200 people were evacuated from Russia’s southwestern Krasnodar region after an ammunition depot and missile arsenal were struck in the second drone attack overnight, the local governor has said.

Most of those evacuated were staying with friends and relatives, Veniamin Kondratyev, the governor of Krasnodar region, said on the Telegram messaging app.

There were no immediate reports of casualties in either Tver or Krasnodar.

Ukraine warning of attacks on nuclear sites

It comes as Kyiv is urging the International Atomic Energy Agency (IAEA) and Ukraine’s allies to establish permanent monitoring missions at the country’s nuclear plants as it warns they could be targeted in Russian attacks.

“In particular, it concerns open distribution devices at (nuclear power plants and) transmission substations, critical for the safe operation of nuclear energy,” foreign minister Andriy Sybiha wrote on X.

Zelenskyy prepares for US trip

Meanwhile, the Ukrainian leader has said he plans to meet Republican presidential candidate Mr Trump on either Thursday or Friday next week.

During the trip, Mr Zelenskyy will present Mr Biden with a so-called victory plan as he hopes to bring about an end to the conflict.

The Ukrainian president has said the plan will include long-range striking capabilities and other weapons long sought by Kyiv, and will serve as the basis for any future negotiation with Russia.

He is also expected to push Washington to lift restrictions on long-range missile strikes inside Russia.

Mr Zelenskyy will attend sessions of the UN Security Council and General Assembly and also plans to meet vice president Kamala Harris, the Democratic candidate in this year’s US election, in separate meetings on 26 September.

The developments come as three sources have told Reuters that Iran did not include mobile launchers with the close-range ballistic missiles that Washington has accused Tehran of delivering to Russia for use against Ukraine.

The sources – a European diplomat, a European intelligence official and a US official – said it was not clear why Iran did not supply launchers with the Fath-360 missiles, raising questions about when and if the weapons will be operational.