First comprehensive survey of virus DNA found within cancer cells

Researchers from the University of East Anglia have helped to carry out the first comprehensive survey of viruses found within different types of cancer.

An international team systematically investigated the DNA found within more than 2,600 tumour samples from patients with 38 different types of cancer.
They discovered traces of viruses in 13 per cent of the samples studied, and also further identified some of the mechanisms that viruses use to trigger carcinogenic mutations.
The findings come after UEA scientists pioneered a new way of finding the bacteria and viruses associated with cancer.
Dr. Daniel Brewer, from UEA’s Norwich Medical School and a Visiting Worker at the Earlham Institute (EI), said: “We already knew of some strong associations between infections and cancer. For example, the presence of Helicobacter pylori in the digestive tract can lead to stomach ulcers and is associated with stomach cancer.
“Meanwhile some types of the HPV virus can cause cervical cancer.
“Human tissue is increasingly being whole genome sequenced as we transition into an era of genomic medicine.
“When tumour samples are whole genome sequenced, DNA from any pathogens present are also sequenced, making it possible to detect and quantify viruses.
“This has given us a fantastic opportunity to collect data to find new associations between viruses and different types of cancer.
“This is the first time that a systematic study of the majority of cancer types for viruses has been made.
“It is important because finding new links between infection and cancer types has the potential to provide vaccines, such as the HPV vaccine, which could reduce the global impact of cancer.”
To date, 11 pathogens have been identified as cancer causing—including Helicobacter pylori, some types of the HPV virus, Hepatits B, Hepatits C and the Epstein-Barr Virus.
Throughout the world, a total of 640,000 cancers each year are caused by human papillomaviruses (HPV) alone, with a vaccine expected to prevent the vast majority of cervical cancers.
The new research provides an overview of which viruses play a role in which cancers.
The researchers also looked for viruses that have not previously been associated with carcinogenesis or even ones that were completely unknown.
Dr. Marc Zapatka from DKFZ said: “The issue of which viruses are linked to cancer is highly relevant in medicine, because in virus-related cancers, real prevention is possible.
“If a carcinogenic virus is identified, there is a chance of avoiding infection with a vaccine to prevent cancer developing.”
The research was led by the German Cancer Research Center (DKFZ) and is part of the Pan-Cancer Analysis of Whole Genomes (PCAWG), a consortium of more than 1,300 researchers who have teamed up to establish which genetic mutations or patterns of DNA mutations play a role in several types of tumors. It is an initiative launched by the International Cancer Genome Consortium (ICGC).
For this meta-analysis, they carried out a comprehensive bioinformatic analysis of the sequencing data of more than 2,600 tumor genomes from 38 different types of cancer.
The team discovered traces of 23 different virus types in 356 cancer patients. And as expected, the known viral drivers of tumor initiation and growth were the most common.
The genome of Epstein-Barr viruses (EBV), which are known to cause a number of different types of cancer (particularly lymphoma, stomach cancer and nasopharyngeal cancer), was found in 5.5 per cent of the cancer genomes investigated. Hepatitis B virus (HBV) DNA was found in 62 of the 330 cases of liver cancer.
The team found human papillomaviruses, most commonly HPV16, in 19 of 20 cervical cancers cases and in 18 of 57 head and neck tumors.
Dr. Brewer said: “We found that the presence of HPV is mutually exclusive to some of the important changes seen in head and neck cancer, which means that the HPV virus can help the cancer develop without additional changes to its genome.”
The team also ruled out a connection between some viruses, including adenoviruses and baculoviruses, and cancer.
In a few cases, the team found other viruses already known to cause cancer, such as a retrovirus in kidney carcinoma. Other pathogens were occasionally found in tumors of the tissue type that they normally infect, such as cytomegaloviruses in gastric cancer.
In some of the tumors linked to HPV and EBV, the researchers observed that the characteristic driver mutations that the cells of these cancer types normally depend on for growth were missing. The presence of the virus presumably supports malignant cell degeneration through other factors.
Viral integration into the host genome was found as the most important mechanism that leads to mutations caused by viruses, particularly HVB and papillomaviruses.
Dr. Brewer said: “We also found that the presence of a virus in a tumour is associated with a pattern of changes in the genome that has been associated with faulty DNA damage repair mechanisms in the human cell. This suggests a role of impaired antiviral defence as driving force in cervical, bladder and head-and-neck carcinoma.”
Prof Peter Lichter from the German Cancer Research Center (DKFZ) said: “When analyzing the whole cancer genome, we discovered traces of viruses in considerably more tumors than in earlier studies that were based on investigating the RNA only. Nevertheless, we were not able to confirm the common speculation that other, as yet unknown viruses are associated with cancer.
“However, in many cases we now have a clearer idea of how the pathogens cause malignant mutations in cells.”
The research was funded in the UK by the Bob Champion Cancer Trust, Cancer Research UK, the Dallaglio Foundation, The Masonic Charitable Foundation, The King Family and the Hargrave Foundation.
Prof David Dearnaley from the Bob Champion Cancer Trust said: “This is a formidable international collaborative enterprise cataloguing the viral associations of human cancer.
“Deep whole genome sequencing from over 2600 cancers and paired normal tissue using robust methodology to avoid “false discovery” have shown about 16 per cent of cancers to be virus associated—higher than previous estimates.
“Known associations of a range of viruses with for example cervix, head and neck, liver and gastric cancers have been confirmed but putative associations with brain tumours refuted.
“The researchers have explored mechanistic explanations for associations showing for example that viral integration may drive high telomerase expression which is tumourogenic and emphasised the potential importance of viral integration to the immune response.
“Novel viral isolate ‘hits’ were uncommon. The results give important new insights into tumour classification and hold future promise for developing novel cancer targeting strategies.”

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Viruses and cancer: DNA sequencing reveals viral components in malignant tumor samples

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More information: ‘The landscape of viral associations in human cancers’ is published in the journal Nature Genetics on February 5, 2020.

https://medicalxpress.com/news/2020-02-comprehensive-survey-virus-dna-cancer.html

‘Severe’ hospital bed shortage at China virus epicentre: officials

Authorities in China warned Wednesday they faced a severe shortage of hospital beds and equipment needed to treat a growing number of patients stricken by the new coronavirus, as cities far from the epicentre tightened their defences.

Central Hubei province reported 3,156 new infections, its biggest single-day jump in the outbreak that has spiralled into a global health emergency with cases reported in over 20 countries.
Among those new cases was a newborn, who was diagnosed just 30 hours after being born.
Despite authorities building a hospital from scratch and converting public buildings to accommodate thousands of extra patients, there was still a “severe” lack of beds, said Hu Lishan, an official in Wuhan, the quarantined city where the virus first appeared—and where doctors are now overwhelmed with cases.
There was also a shortage of “equipment and materials,” he told reporters, adding that officials were looking to convert other hotels and schools in the city into treatment centres.
As the number of confirmed infections nationwide exceeded 24,000, a growing number of cities have imposed a range of restrictions far from Hubei, as authorities battle to contain the virus that has killed nearly 500 people.
Millions of people, from the eastern industrial heartlands to near the northern border with Russia, have been ordered to stay indoors as authorities battle to curb the outbreak.

Global concerns have risen after the World Health Organization declared an international health emergency last week.
The WHO called for $675 million (613 million euros) in donations for a plan to fight the novel coronavirus, mainly through investment in countries considered particularly “at risk”.
The Bill and Melinda Gates Foundation pledged to commit up to $100 million.
New cases emerged abroad, with 10 people testing positive for the virus on a cruise ship quarantined off the coast of Japan with thousands on board.
Italy announced that passengers from every international flight would be scanned for fevers, while Vietnam, which has detected 10 cases, joined a growing list of countries banning arrivals from China.
And Hong Kong, which reported its first coronavirus death this week, said anyone arriving from the mainland will face a mandatory two-week quarantine from Saturday.

‘Don’t go out!’
In Hangzhou, some 175 kilometres (110 miles) southwest of Shanghai, fences blocked streets near the headquarters of Chinese tech giant Alibaba—one of the world’s most valuable companies—as a fighter jet circled overhead.
The building appeared to be shut down, while deliverymen moved in and out of nearby fenced-in residential areas to drop off groceries. Many people were also seen going out.
The firm is based in one of three Hangzhou districts subject to new restrictions that allow only one person per household to go outside every two days to buy necessities.
“Please don’t go out, don’t go out, don’t go out!” blared a message on a loudspeaker urging people to wear masks, wash their hands regularly and report any people who are from Hubei—reflecting a common fear that people from the province might infect others.
At least three other cities in Zhejiang province—Taizhou, Wenzhou and parts of Ningbo—have imposed the same measures, affecting 18 million people.

In the central city of Zhumadian, authorities said one person would be allowed to leave each household only every five days.
Residents of the city of seven million were also offered cash rewards for informing on people who came from neighbouring Hubei province.
Authorities in Beijing said restaurants could no longer accept reservations for parties from Wednesday.
Jitters
The disease is believed to have emerged in December in a Wuhan market that sold wild animals, and spread rapidly as people travelled for the Lunar New Year holiday in January.
The Ministry of Public Security said “political security” was the “top priority” in confronting the epidemic.
“We should take strict precautions against and crack down on all kinds of disruptive activities by hostile forces,” security minister Zhao Kezhi said in a briefing.

The statement came days after the top leadership admitted “shortcomings” in its handling of the outbreak—local authorities in Hubei have been criticised for initially downplaying the situation.
The death toll has steadily increased, rising to 490 in China on Wednesday.
But officials have noted that the death rate, at around two percent, is well below the mortality rate of SARS, which killed some 800 people in 2002-2003.
Two fatalities have been reported outside the mainland, in Hong Kong and the Philippines.
Several governments have imposed travel restrictions while major airlines have suspended flights to and from China.
United and American Airlines said Wednesday they have added Hong Kong to their China flight suspensions.
Thousands of Chinese tourists risked being stranded in Bali after the Indonesian government suspended flights to and from mainland China.

China has reacted angrily against travel bans, noting that the WHO does not advise imposing them.
It has accused the US of spreading “panic” in its response to the coronavirus, including its ban on Chinese travellers, and on Wednesday, it took another swipe at Washington.
“Panic is more deadly and contagious than any virus,” foreign ministry spokeswoman Hua Chunying said at a press briefing.
https://medicalxpress.com/news/2020-02-severe-hospital-bed-shortage-china.html

Qiagen expects coronavirus test to be ready this month: CEO

Genetic testing specialist Qiagen (QIA.DE) should have a targeted test for the coronavirus ready this month and is extremely active in providing products to disease control institutions in China, its interim CEO said on Wednesday.
But while Qiagen could boost profits by focusing on products identifying the coronavirus it will continue to bet on growth in its molecular diagnostics business, rather than uncertain one-off gains, CEO Thierry Bernard told a results conference call.
The company headquartered in the Netherlands, which makes diagnostic kits for cancer and tuberculosis as well as products for identifying viruses, reported better than expected quarterly sales and profit growth late on Tuesday.
Qiagen shares were up 5.6% at 1555 GMT on Wednesday, set for their best day in three months.
Bernard said in a results statement on Tuesday that Qiagen had not included global demand for products that can be used to recognise the coronavirus in its 2020 outlook, given the uncertainties around broader business trends in China.
The company is looking into different variants of coronavirus testing solutions, including options using QIAsymphony, NeuMoDx or a syndromic solution, Bernard told the call on Wednesday.
Qiagen’s increased focus on its molecular diagnostics division is one of the reasons why its adjusted operating margin of 33.5% in the fourth-quarter came in well above its own forecast and the market consensus, analysts have said.

Bernard said the division’s QIAsymphony automation system could become a important source of new growth after its long-established major growth driver, the tuberculosis test QuantiFERON, saw a slowdown in the fourth quarter.
After Qiagen reached a new milestone with more than 2,500 cumulative placements of QIAsymphony in January, the product has become a steady and consistent growth engine and it is planning for more than 200 new placements in 2020, he said.
Thanks to its expanded partnership with DiaSorin, Qiagen should be able to grow QuantiFERON by double digits again in 2020, Berenberg analysts said.
https://www.reuters.com/article/us-china-health-qiagen/qiagen-expects-coronavirus-test-to-be-ready-this-month-ceo-idUSKBN1ZZ2J9

Nonalcoholic Liver Disease ‘an Epidemic of the 21st Century’

The way Christos S. Mantzoros, MD, DSc, PhD, sees it, nonalcoholic steatohepatitis (NASH) is an epidemic of the 21st century that can trigger a cascade of reactions.
“If more than 5.8% of fat is in the liver, we call it nonalcoholic fatty liver disease [NAFLD],” Dr. Mantzoros, professor of medicine at Harvard Medical School, Boston, and Boston University, explained at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “If inflammation develops to remove the fat, we call it NASH. If this progresses to decompensated reaction and fibrosis and cirrhosis, then we call it nonalcoholic steatohepatitis with fibrosis. That can lead to liver cirrhosis, hepatocellular carcinoma, and liver failure.”
The underlying problem stems from the rise in obesity prevalence, according to Dr. Mantzoros, who is also chief of endocrinology at the Boston Veterans Affairs Healthcare System. For 75%-80% of individuals with metabolically unhealthy obesity, the storage space in their adipose tissue is exceeded. “Fat is deposited into muscle, causing insulin resistance, and into the liver,” he explained. “If it’s more than 5.8%, it causes NAFLD. Most of us don’t realize that most of the patients with diabetes we have in our clinics also have nonalcoholic fatty liver disease. That’s because we don’t have an easy diagnostic tool or an easy treatment. It’s an unmet clinical need.” (There are currently no drugs approved for the treatment of NASH or NAFLD. Current recommended first-line treatment is weight loss through diet and exercise and control of diabetes, if it is present.)
“Assuming the rate of increase in cost due to NAFLD parallels the growth in obesity, the 10-year projection for direct cost is $1.005 trillion,” said Dr. Mantzoros, who is also editor in chief of the journal Metabolism. “Obesity, NAFLD, and insulin resistance are each independently associated with a twofold risk for diabetes. If all three are present, there is a 14-fold risk for diabetes. Insulin resistance promotes an increase in free fatty acid traffic to the liver, which can trigger hepatic lipotoxicity. Hyperinsulinemia enhances free fatty acid uptake and activates de novo lipogenesis. Hyperglycemia can also activate de novo lipogenesis.”

About 85 million Americans have NAFLD, he continued. Most (80%) are cases of steatosis, but 20% have NASH. Of those, 20% develop advanced fibrosis, which leads to liver failure and transplantation or death. A study of data from the National Health and Nutrition Examination Survey found that diabetes was the strongest predictor of advanced fibrosis in patients with NAFLD (odds ratio, 18.20), followed by a body mass index of 30 kg/m² or greater (OR, 9.10), hypertension (OR, 1.20), and age (OR, 1.08; Ailment Pharmacol Ther. 2017;46:974-80). “Most of the patients who come to our clinics with diabetes have nonalcoholic fatty liver disease – 75%-80% in our clinics, and about 10% have advanced fibrosis,” Dr. Mantzoros said. “Most of them go undiagnosed.”
Patients with type 2 diabetes and NAFLD progress faster to fibrosis and end-stage liver disease, compared with those who do not have diabetes. One study of 108 patients with biopsy-proven NALFD showed that 84% of those with fibrosis progression had type 2 diabetes (J Hepatol. 2015;62:1148-55). Other findings have shown that patients with type 2 diabetes are at increased risk of chronic NAFLD and hepatocellular carcinoma (Gastroenterol. 2001;126:460-8). “We are doing more liver transplantations because of NAFLD and NASH than because of hepatitis C,” Dr. Mantzoros said. “What we need to keep in mind is that, although liver morbidity and mortality is important, this is a component of the cardiometabolic syndrome. So, people have all the risk factors for cardiovascular disease. Because CVD is much more common, people with NAFLD suffer from and die from CVD. The more advanced the NAFLD, the higher the risk of death from cardiovascular disease.”
https://www.medscape.com/viewarticle/924818

Puma Bio shorts squeezed?

Two factors may be behind this abrupt, double-digit uptick in Puma’s stock today. First, the biotech has consistently been one of the most heavily shorted equities in the industry over the prior 12 months. Short-sellers have piled on to this name due to the worrisome side effects associated with the company’s breast cancer drug, Nerlynx. Although Nerlynx is targeting a fairly large commercial opportunity, it has also seen an alarmingly high discontinuation rate due to severe diarrhea. This noteworthy pop, in turn, could be nothing more than a bout of covering on the part of one or more short-sellers.
Second, Puma may be fetching some takeover interest — which short-sellers might have caught wind of before the general public. Several big biopharmas have already announced plans this year to boost their pipelines through merger and acquisition activity, after all. Puma, for its part, might be an especially attractive target, given that its shares are trading at a small fraction of Nerlynx’s commercial potential.

Should investors jump on this surging biotech stock today? Unfortunately, the answer is probably not. Stated bluntly, Puma’s shares could quickly give back these impressive gains due to the lack of a clear-cut catalyst. And that’s simply not an attractive setup for long-term investors.
https://www.fool.com/investing/2020/02/05/why-puma-biotechnology-is-soaring-today.aspx

UPS reaches deal with pilots on flying to China

The UPS (NYSE:UPS) pilots union says it reached an agreement with the company for pilots to make a voluntary decision on whether they will fly to China or not.

“This joint effort addresses crewmember concerns over safety during the coronavirus health crisis,” reads a statement from the union.

Shares of UPS are down 9.0% over the last month.

https://seekingalpha.com/news/3538745-ups-reaches-deal-pilots-on-flying-to-china

NEJM Coronavirus Transmission Research Questioned

Asymptomatic transmission of the novel coronavirus in Germany was called into doubt on Monday when an article appeared to question the research behind it.
Science magazine detailed errors in the New England Journal of Medicine (NEJM) research letter published last Thursday. The letter reported that asymptomatic transmission of novel coronavirus occurred in Bavaria, Germany, when several co-workers of an asymptomatic woman traveling from China contracted the virus.

The letter, and several media reports, said that the woman wasn’t sick when she was in Germany and only began to feel ill on the plane ride home. Turns out that wasn’t quite true.
Researchers who wrote the NEJM letter did not speak to the woman herself, according to Science. But after she spoke to officials from the Robert Koch Institute, Germany’s public health agency, and Bavarian officials, she said that she “felt tired, suffered from muscle pain,” and took fever-lowering medication while in Germany.
While Germany’s health agency spokespeople would only confirm that the woman had symptoms, the Robert Koch Institute has submitted a letter to NEJM, presumably to correct the record.
China has claimed to have data showing asymptomatic transmission occurring within the country, but U.S. health officials previously said that they did not have enough data to make that claim. That appeared to change after the publication of the NEJM letter.
Indeed, asymptomatic transmission outside China was alluded to when the U.S. declared a public health emergency for novel coronavirus on Friday. And on Saturday, the World Health Organization (WHO) reported “third-generation” transmission of the virus in Germany.
Science said that WHO officials and European partner agencies have been notified with the new information. As of Tuesday, NEJM has not published a letter of correction.
https://www.medpagetoday.com/infectiousdisease/publichealth/84688