New potential breast cancer drug identified

Agencies
August 10, 2018

Scientists, including an Indian-American researcher, have identified a molecule that can help treat breast cancer, giving hope to patients who have become resistant to traditional therapies.

The first-in-class molecule shuts down oestrogen-sensitive breast cancer in a new way, researchers said.

First-in-class drugs are those that work by a unique mechanism - in this case a molecule that targets a protein on the oestrogen receptor of tumour cells.

The potential drug offers hope for patients whose breast cancer has become resistant to traditional therapies.

"This is a fundamentally different, new class of agents for oestrogen-receptor-positive breast cancer," said Ganesh Raj, professor at the University of Texas Southwestern (UT Southwestern) Simmons Cancer Center.

"Its unique mechanism of action overcomes the limitations of current therapies," Raj said.

All breast cancers are tested to determine if they require oestrogen to grow and about 80 per cent are found to be oestrogen-sensitive, researchers said.

These cancers can often be effectively treated with hormone therapy, such as tamoxifen, but as many as a third of these cancers eventually become resistant, they said.

The new compound is a potential highly effective, next-line treatment for these patients, said Raj.

Traditional hormonal drugs, such as tamoxifen, work by attaching to a molecule called the oestrogen receptor in cancer cells, preventing oestrogen from binding to the receptor, a necessary step for cancer cells to multiply.

However, the oestrogen receptor can mutate and change its shape over time so that the treatment drug no longer fits neatly with the receptor. When this happens, the cancer cells start multiplying again.

"There has been intense interest in developing drugs that block the ability of the oestrogen receptor - the prime target in most breast cancers - from interacting with the co-regulator proteins that cause a tumour's growth," said David Mangelsdorf, professor at UT Southwestern.

"Blocking such "protein-protein interactions" has been a dream of cancer researchers for decades.

The drug works by blocking other molecules - proteins called co-factors - that also must attach to the oestrogen receptor for cancer cells to multiply.

 

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Agencies
June 30,2020

Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes, said Paul Zimmet, Professor of Diabetes, Monash University, Australia.

Zimmet, who is President International Diabetes Federation, added that the actual mechanism as to why COVID-19 may cause diabetes is as yet unknown, however, several possibilities exist. "COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues including the lungs and pancreas," said Zimmet. Below are excerpts from an exclusive chat with IANS.

Why do you say Diabetes is dynamite if a person has been infected with COVID-19?

There have been many deaths in many countries, e.g. Italy, China, the UK and US among people with diabetes after infection with COVID-19 (SARS-Cov-2).

The mortality tends to be mainly in older Type 2 diabetics. Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes. This outcome and other complications from the virus, particularly pneumonia, are more likely in people with diabetes which is poorly controlled with high blood sugars (poor metabolic control).

Diabetes is often associated with other chronic conditions, including obesity, hypertension and heart disease compounding the risk. These latter conditions all convey higher risk to COVID-19 infections.

ACE-2, which binds to SARS-Cov-2 and allows the virus to enter human cells is also located in organs and tissues involved in glucose metabolism. Is there solid evidence that virus after entering tissues may cause multiple and complex impairment of glucose metabolism?

The actual mechanism as to why COVID-19 may cause diabetes is as yet unknown.

However, several possibilities exist. Firstly, COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues, including the lungs and pancreas.

A new study just published showed that in miniature lab-grown pancreas, and other cells such as liver, made using human stem cells, COVID-19 caused destruction of the pancreas beta cells that produce insulin.

It is possible that the virus causes disruption of the cells by disrupting cellular metabolism. This is possibly the way it brings about new-onset diabetes. ACE-2 exists in high concentration in the lung as this also explains the terrible lung side effects of COVID-19 infections.

Can COVID-19 lead to a new mechanism of diabetes? Probably a new form of diabetes or a new form of disease?

The COVID-19 virus has only been with us for about 5 months and there is a huge amount that we still must learn about its cunning and devastating ways. The purpose of the Global COVIDIAB Diabetes Registry, a joint initiative of Monash University in Australia, and King’s College London is to gain a much better understanding of how common is the appearance of COVID-19 related diabetes, what form does it take be it type 1 or type 2 or a new form, and how common are the complications that we already know e.g. diabetic keto-acidosis, hyperosmolar coma and high insulin requirements are causing high rates of ill health and mortality worldwide. The knowledge gained will aid our understanding for developing strategies to prevent and treat this terrible virus that has caused destruction globally.

Diabetes is one of the most prevalent chronic diseases in India. According to a recent study, sugar levels of diabetic persons increased by 20 per cent during nationwide lockdown in India to contain COVID-19 outbreak. Even after lockdown was lifted, many people are confined within their home. Do you think lack of physical activity will create more problems for diabetics?

My own major research has been on studying populations with high rates of diabetes, including ethnic Indian communities including India, Mauritius, and Fiji so I am very well aware of this. It is now well established that along with diabetes, that associated poor metabolic control of their diabetes places these people at the highest risk for COVID infection and its devastating complications and the associated morbidity and mortality. And these communities have high prevalence of heart disease as well.

Lockdown not only has deleterious effects on metabolic control of the diabetes through reduced opportunities for exercise to be protective serious consequences of SARS-CoV-2 infection, lockdown usually results in disruption of the regular medical care and the regular monitoring of metabolic control. This may also be partly due to the stress and poor compliance, or inability to afford their medications such as insulin. It may also be compounded by inability to access the care during the pandemic. Nevertheless, we now know that poor metabolic control heightens their risk as described above.

You have said diabetes is itself a pandemic just like Covid-19, and the two pandemics could be clashing. How could governments address this problem?

These are “The Times of COVID-19”. Most nations of the world were totally unprepared for a pandemic of this magnitude. They underestimated its potential impact and the destructive nature of the viral infection. This should prompt all countries to upgrade their guidelines to take into account the lessons learnt on infection control including training of staff specialising in infectious diseases and improved public education and taking their communities into their confidence about the terrible nature of COVID-19. The risks of COVID-19 infection need a much higher priority in the general community, particularly for people with chronic conditions such as diabetes, obesity, and cardiac conditions.

Governments are faced with chronic diseases (NCDs) like diabetes and communicable diseases (CDs) like viral and enteric diseases and TB. In general WHO gives the highest priority to communicable diseases and much less attention and funding to chronic diseases like diabetes (I was an adviser to WHO for many years (about 30) on diabetes and obesity and it was very frustrating to deal with this situation).

This attitude to diabetes, for example, has a flow down effect so that diabetes funding in countries by governments, rich and poor, suffered and was insufficient.

So now we have a COVID-19 pandemic and who are those at highest risk, yes people with diabetes and other NCDs, it is very important that now the two, Diabetes and COVID-19 are clashing face-to-face. This is a major issue that WHO and national governments have to face with equal priority’

Stressed people suffering from diabetes run a greater risk of poor blood glucose levels, what do you suggest to these people?

As mentioned in the answer above, stress is an important factor in upsetting the blood sugar (metabolic) control of diabetes. Additive to this is poor compliance with medications and diet. These and potential associated comorbidities due to other chronic conditions are part of the dynamic dynamite mixture.

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Agencies
July 14,2020

UN, Jul 14: There will be no return to the "old normal" for the foreseeable future as a result of the ongoing COVID-19 pandemic, and too many countries were still headed in the wrong direction, the chief of the World Health Organization (WHO) warned.

"The virus remains public enemy number one, but the actions of many governments and people do not reflect this," Xinhua news agency quoted WHO Director-General Tedros Adhanom Ghebreyesus at as saying a regular briefing on Monday.

He noted that mixed messages from leaders are undermining trust, which is the most critical ingredient of any response, while the only aim of the virus is to find people to infect.

Things are going to "get worse and worse and worse", he warned, unless governments communicate clearly with their citizens and roll out a comprehensive strategy focused on suppressing transmission and saving lives, while populations follow the basic public health principles of physical distancing, hand washing, wearing masks, coughing etiquette and staying home when sick.

COVID-19 has been gaining its momentum lately.

According to Tedros, Sunday saw a record of 230,000 cases reported to WHO, of which almost 80% were from just 10 countries and about half from just two countries.

"But it does not have to be this way," he said, asking every single leader, government and individual "to do their bit to break the chains of COVID-19 transmission and end the collective suffering".

To control the disease and get on with people's lives, Tedros said, three things are required. The first is to focus on reducing mortality and suppressing transmission; the second is to focus on an empowered, engaged community that takes individual behaviour measures in the interest of each other.

And the third is a strong government leadership and coordination of comprehensive strategies that are communicated clearly and consistently.

"We weren't prepared collectively, but we must use all the tools we have to bring this pandemic under control. And we need to do it right now," he added.

At the WHO briefing on Monday, health experts also said there was evidence to suggest that children under the age of 10 were only very mildly affected by Covid-19, while those over 10 seemed to suffer similar mild symptoms to young adults.

To what extent children can transmit the virus, while it appears to be low, remains unknown.

On Tuesday, the number of global coronavirus cases cross the 13 million mark, according to the Johns Hopkins University.

The total number of cases currently stood at 13,070,097, while the fatalities rose to 572,411, the University's Center for Systems Science and Engineering (CSSE) revealed in its latest update.

The US accounted for the world's highest number of infections and fatalities at 3,363,056 and 135,605, respectively, according to the CSSE.

Brazil came in the second place with 1,884,967 infections and 72,833 deaths.

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Agencies
May 8,2020

As Europe and the US loosen their lockdowns against the coronavirus, health experts are expressing growing dread over what they say is an all-but-certain second wave of deaths and infections that could force governments to clamp back down.

"We are risking a backslide that will be intolerable," said Dr Ian Lipkin of Columbia University's Center for Infection and Immunity.

Around the world, German authorities began drawing up plans in case of a resurgence of the virus. Experts in Italy urged intensified efforts to identify new victims and trace their contacts. And France, which has not yet eased its lockdown, has already worked up a "reconfinement plan" in the event of a new wave.

"There will be a second wave, but the problem is to which extent. Is it a small wave or a big wave? It is too early to say," said Olivier Schwartz, head of the virus unit at France's Pasteur Institute.

In the US, with about half of the states easing their shutdowns to get their economies restarted and cellphone data showing that people are becoming restless and increasingly leaving home, public health authorities are worried.

Many states have not put in place the robust testing that experts believe is necessary to detect and contain new outbreaks. And many governors have pressed ahead before their states met one of the key benchmarks in the Trump administration's guidelines for reopening -- a 14-day downward trajectory in new illnesses and infections.

"If we relax these measures without having the proper public health safeguards in place, we can expect many more cases and, unfortunately, more deaths," said Josh Michaud, associate director of global health policy with the Kaiser Family Foundation in Washington.

Cases have continued to rise steadily in places such as Iowa and Missouri since the governors began reopening, while new infections have yo-yoed in Georgia, Tennessee and Texas.

Lipkin said he is most worried about two things: the reopening of bars, where people crowd together and lose their inhibitions, and large gatherings such as sporting events, concerts and plays. Preventing outbreaks will require aggressive contact tracing powered by armies of public health workers hundreds of thousands of people strong, which the US does not yet have, Lipkin said.

Worldwide the virus has infected more than 36 lakh people and killed over a quarter-million, according to a tally by Johns Hopkins University that experts agree understates the dimensions of the disaster because of limited testing, differences in counting the dead and concealment by some governments.

The US has recorded over 70,000 deaths and 12 lakh confirmed infections, while Europe has reported over 140,000 dead.

This week, the researchers behind a widely cited model from the University of Washington nearly doubled their projection of deaths in the US to around 134,000 through early August, in large part because of the easing of state stay-at-home restrictions. Newly confirmed infections per day in the US exceed 20,000 and deaths per day are running well over 1,000.

In hard-hit New York City, which has managed to bring down deaths dramatically even as confirmed infections continue to rise around the rest of the country, Mayor Bill de Blasio warned that some states may be reopening too quickly.

"My message to the rest of the country is learn from how much effort, how much discipline it took to finally bring these numbers down and follow the same path until you are sure that it is being beaten back," he said on CNN, "or else, if this thing boomerangs, you are putting off any kind of restart or recovery a hell of a lot longer."

A century ago, the Spanish flu epidemic's second wave was far deadlier than its first, in part because authorities allowed mass gatherings from Philadelphia to San Francisco.

"It is clear to me that we are in a critical moment of this fight. We risk complacency and accepting the preventable deaths of 2,000 Americans each day," epidemiologist Caitlin Rivers, a professor at Johns Hopkins, told a House subcommittee in Washington.

President Donald Trump, who has pressed hard to ease the restrictions that have throttled the economy and thrown more than three crore Americans out of work, pulled back Wednesday on White House plans revealed a day earlier to wind down the coronavirus task force.

He tweeted that the task force will continue meeting indefinitely with a "focus on SAFETY & OPENING UP OUR COUNTRY AGAIN".

Underscoring those economic concerns, the European Union predicted the worst recession in its quarter-century history. And the US unemployment rate for April, which comes out on Friday, is expected to hit a staggering 16 per cent, a level last seen during the Great Depression of the 1930s.

Governors continue to face demands, even lawsuits, to reopen. In Michigan, where armed demonstrators entered the Capitol last week, the Republican-led Legislature sued Democratic Governor Gretchen Whitmer, asking a judge to declare invalid her stay-at-home order, which runs at least through May 15.

In hard-hit Italy, which has begun easing restrictions, Dr Silvio Brusaferro, president of the Superior Institute of Health, urged "a huge investment" of resources to train medical personnel to monitor possible new cases of the virus, which has killed about 30,000 people nationwide.

He said that contact-tracing apps which are being built by dozens of countries and companies are not enough to manage future waves of infection.

German Chancellor Angela Merkel said after meeting with the country's 16 governors that restaurants and other businesses will be allowed to reopen in the coming weeks but that regional authorities will have to draw up a "restriction concept" for any county that reports 50 new cases for every 100,000 inhabitants within a week.

Lothar Wieler, head of Germany's national disease control centre, said scientists "know with great certainty that there will be a second wave" of infections.

Britain, with over 30,000 dead, the second-highest death toll in the world behind the US, plans to extend its lockdown but has begun recruiting 18,000 people to trace contacts of those infected.

In other developments, the US Centers for Disease Control and Prevention said nearly 5,000 coronavirus illnesses and at least 88 deaths have been reported among inmates in American jails and prisons. An additional 2,800 cases and 15 deaths were reported among guards and other staff members.

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