Findings About Dostarlimab, A New Antibody Drug, Very Encouraging, Says Expert In Cancer Treatment

Representational image. Image Credit: Kidney Research UK

According to New York Times, in a small clinical trial, 18 patients took a drug called Dostarlimab for around six months, and in the end, every one of them saw their tumours disappear. The findings concerning dostarlimab, an antibody drug, in experimental treatment of rectal cancer patients is very encouraging but there is need for long-term studies to understand the real impact, an expert in cancer treatment has said.

“This new trial at MSKCC in a small number of patients, with locally advanced rectal cancer patients who had MMR (MisMatch repair) deficiency, have shown total disappearance of tumour without any additional treatment in all 100 percent of them. This is very encouraging but we must note that long term studies are required to understand the real impact,” Dr. (Col.) R. Ranga Rao, Chairman, Oncology, of Paras Hospitals in Gurugram said.

“The drug is still investigational and the trial is limited to patients of a specific type , that constitute about 4 to 5 per cent of rectal cancers. While this is highly encouraging, we must not prematurely jump to conclusions that we have found a cure for all cancers, all stages, and no chemotherapy, surgery is ever required,” he added.

He said it is well recognized that Immunotherapy with PDL 1 blockers in MMRd patients is effective. “Already immunotherapy has made a big difference in the field of cancer of all types. Several earlier trials have shown encouraging responses,” Dr Rao said.

In what appears to be a miracle and ‘first time in history’, a small clinical trial has found that every single rectal cancer patient who received an experimental treatment found that their cancer had vanished.

According to New York Times, in the small clinical trial conducted by Memorial Sloan Kettering Cancer Center, 18 patients took a drug called Dostarlimab for around six months, and in the end, every one of them saw their tumours disappear. Dr Luis A. Diaz J. of New York’s Memorial Sloan Kettering Cancer Center (MSKCC) said this was “the first time this has happened in the history of cancer”.

According to experts, Dostarlimab is a drug with laboratory-produced molecules and it acts as substitute antibodies in the human body. The cancer is undetectable by physical exam; endoscopy; positron emission tomography or PET scans or MRI scans, added Experts. This proves that Dostarlimab can be a ‘potential’ cure for one of the most deadly common cancers.

According to New York Times, patients involved in the clinical trial earlier underwent treatments such as chemotherapy, radiation, and invasive surgery that could result in bowel, urinary, and even sexual dysfunction. The 18 patients went into the trial expecting to have to go through these procedures as the next step. However, to their surprise, no further treatment was needed.

The findings of this trial have shocked experts and they have pointed out that complete remission in every single patient is “unheard-of”. Dr Alan P. Venook, who is a colorectal cancer specialist at the University of California, said that the complete remission in every single patient is “unheard-of”. He hailed the research as a “world-first”. Experts stated that the research was impressive as not all of the patients suffered significant complications from the drug trial.

Critics:

Tesaro, a biotech company based out of Massachusetts developed the drug. Tesaro was acquired by GlaxoSmithKline in 2019, dostarlimab is also known by the brand name Jemparli. Dostarlimab was developed to treat women with recurrent or advanced endometrial cancer.

On August 17, 2021, the FDA approved dostarlimab-gxly (brand name Jemperli) for adult patients with mismatch repair-deficient recurrent or advanced solid tumours, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

Rectal cancer remission

According to reports, 18 patients in the clinical trial took Dostarlimab for around six months and after over 12 months the doctors found that their cancer disappeared. While it’s a small trial so far, the results have been impressive; they were published in The New England Journal of Medicine and featured at the nation’s largest gathering of clinical oncologists in June 2022.

In every case, rectal cancer disappeared after immunotherapy — without the need for the standard treatments of radiation, surgery, or chemotherapy — and cancer has not returned in any of the patients, who have been cancer-free for up to two years.

It’s incredibly rewarding to get these happy tears and happy emails from the patients in this study who finish treatment and realise, ‘Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery,’ expressed Dr Andrea Cercek, Medical Oncologist, Memorial Sloan Kettering Cancer Center (MSK).

Dr Cercek added, “The most exciting part of this is that every single one of our patients has only needed immunotherapy. We haven’t radiated anybody, and we haven’t put anybody through surgery.” She continued, “They have preserved normal bowel function, bladder function, sexual function, fertility. Women have their uterus and ovaries. It’s remarkable.”

This clinical trial could pave the way for treating other forms of cancer in the future. As the trial continues at MSK, Dr Luis Alberto Diaz, Medical Oncologist, Memorial Sloan Kettering Cancer Center (MSK) said, “It’s the tip of the iceberg.” He explains, “We are investigating if this same method may help other cancers where the treatments are often life-altering and tumours can be MMRd. We are currently enrolling patients with gastric (stomach), prostate, and pancreatic cancers.”

Dostarlimab clinical trial reception by the Indian medical community

Since the trial results have been published, it has created a lot of buzz and has got the entire medical community discussing how it could pave the path for future treatment for various cancers, ETHealthWorld spoke to few experts on the drug trial. Commenting on the trial, “It is definitely a big step towards efficient cancer care. The preliminary data on Dostarlimab PD1 monotherapy has been very encouraging in high-risk rectal cancer patients and has been recently presented at the ASCO meeting in Chicago and subsequently published in NEJM.

We would definitely need further studies on larger groups of patients across the globe to establish it as a standard of care for rectal cancer. Trials are also being conducted to study its effectiveness for cervical cancer, and endometrial cancer amongst others,” said Dr Pankaj Kumar Panda, Senior Research Officer, Apollo Proton Cancer Centre.

Source: Findings about Dostarlimab, a new antibody drug, very encouraging, says expert in cancer treatment

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00:42 Thu, 27 Octpigenetic field defects in progression to cancer” Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression”.pigenetic modifications in cancer”.

Epigenetics Offer New Horizons for Colorectal Cancer Prevention”. Epigenetics and colorectal cancer”.DNA Methylation in Cancer and Aging”Mutator pathways unleashed by epigenetic silencing in human cancer”. “Epigenetic field defects in progression to cancer”

“Colorectal Cancer”Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer”.The consensus molecular subtypes of colorectal cancer”.“Colorectal Cancer”Colon, Rectosigmoid, and Rectum Equivalent Terms and Definitions C180-C189, C199, C209,

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Ice Shards In Antarctic Clouds Heat Up The Southern Ocean

Clouds come in a large variety of shapes, sizes, and types. All of these features control the effect they have on the climate. For instance, a new study led by the University of Washington (UW) has found that splintering of frozen liquid droplets to form ice shards inside Antarctic clouds dramatically affect these clouds’ ability to reflect sunlight back into the atmosphere, leading to a substantial warming of the Southern Ocean.

“Southern Ocean low clouds shouldn’t be treated as liquid clouds,” said study lead author Rachel Atlas, a doctoral student in Atmospheric Sciences at UW. “Ice formation in Southern Ocean low clouds has a substantial effect on the cloud properties and needs to be accounted for in global models.”

Atlas and her colleagues used observations from a 2018 field campaign focused on an in-depth investigation of Southern Ocean clouds, as well as data collected by NASA’s CERES satellite and the Japanese satellite Himawari-8.Their analyses revealed that the peculiar nature of Antarctic clouds has a strong impact on the Southern Ocean and climate in general.

Since ice particles form, grow, and fall out of the clouds very efficiently, the clouds’ coverage and reflectance are significantly reduced, allowing more sunlight to reach the waters.“The ice crystals deplete much of the thinner cloud entirely, therefore reducing the horizontal coverage. Ice crystals also deplete some of the liquid in the thick cores of the cloud.

So the ice particles both reduce the cloud cover and dim the remaining cloud,” Atlas explained.Since in February – which is summer in the Southern Ocean – approximately 90 percent of the sky is covered with clouds, and at least 25 percent of these clouds are affected by the type of ice formation that decreases their reflectance, a massive amount of solar radiation can reach the ocean, substantially warming its upper layers.

“The Southern Ocean is a massive global heat sink, but its ability to take heat from the atmosphere depends on the temperature structure of the upper ocean, which relates to the cloud cover,” Atlas concluded.

By Andrei Ionescu

Source: Ice shards in Antarctic clouds heat up the Southern Ocean • Earth.com.Critics:

Polar regions are foci of climate change, because of more-than-expected warming, problematic remote-sensing retrievals, and large uncertainties about cloud effects on radiation budgets. Antarctica is the world’s most remote, coldest, and driest location. Until recently, researchers have assumed that low-level clouds over the frozen Antarctic Plateau consist mainly of ice crystals.

Now, measurements with a unique tethered balloon system and a ground-based lidar show that nearly 50% of clouds in the austral summer contain supercooled water which has a significant impact on the radiative properties of Antarctic clouds. Modifying a global climate model to relax the freezing below −20 °C results in a strong simulated radiative (cooling) effect, affecting the entire Antarctic Continent and extending out into the Southern Ocean.

Precious little is known about the composition of low-level clouds over the Antarctic Plateau and their effect on climate. In situ measurements at the South Pole using a unique tethered balloon system and ground-based lidar reveal a much higher than anticipated incidence of low-level, mixed-phase clouds (i.e., consisting of supercooled liquid water drops and ice crystals).

The high incidence of mixed-phase clouds is currently poorly represented in global climate models (GCMs). As a result, the effects that mixed-phase clouds have on climate predictions are highly uncertain. We modify the National Center for Atmospheric Research (NCAR) Community Earth System Model (CESM) GCM to align with the new observations and evaluate the radiative effects on a continental scale.

The net cloud radiative effects (CREs) over Antarctica are increased by +7.4 Wm−2, and although this is a significant change, a much larger effect occurs when the modified model physics are extended beyond the Antarctic continent. The simulations show significant net CRE over the Southern Ocean storm tracks, where recent measurements also indicate substantial regions of supercooled liquid. These sensitivity tests confirm that Southern Ocean CREs are strongly sensitive to mixed-phase clouds colder than −20 °C.

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Hydrogen 11 Times Worse Than CO2 For Climate, Says New Report

 

Over a 100-year time period, a tonne of hydrogen in the atmosphere will warm the Earth some 11 times more than a tonne of CO2, with an uncertainty of ± 5

Hydrogen will be one of humanity’s key weapons in the war against carbon dioxide emissions, but it must be treated with care. New reports show how fugitive hydrogen emissions can indirectly produce warming effects 11 times worse than those of CO2.

Hydrogen can be used as a clean energy carrier, and running it through a fuel cell to produce electricity produces nothing but water as a by-product. It carries far more energy for a given weight than lithium batteries, and it’s faster to refill a tank than to charge a battery, so hydrogen is viewed as a very promising green option in several hard-to-decarbonize applications where batteries won’t cut the mustard – for example, aviation, shipping and long-haul trucking.


But when it’s released directly into the atmosphere, hydrogen itself can interact with other gases and vapors in the air to produce powerful warming effects. Indeed, a new UK Government study has put these interactions under the microscope and determined that hydrogen’s Global Warming Potential (GWP) is about twice as bad as previously understood; over a 100-year time period, a tonne of hydrogen in the atmosphere will warm the Earth some 11 times more than a tonne of CO2, with an uncertainty of ± 5.

How does hydrogen act like a greenhouse gas?

One way is by extending the lifetime of atmospheric methane. Hydrogen reacts with the same tropospheric oxidants that “clean up” methane emissions. Methane is an incredibly potent greenhouse gas, causing some 80 times more warming than an equivalent weight of CO2 over the first 20 years. But hydroxyl radicals in the atmosphere clean it up relatively quickly, while CO2 remains in the air for thousands of years, so CO2 is worse in the long run.

When hydrogen is present, however, those hydroxyl radicals react with the hydrogen instead. There are fewer cleanup agents to go around, so there’s a direct rise in methane concentrations, and the methane stays in the atmosphere longer.

What’s more, the presence of hydrogen increases the concentration of both tropospheric ozone and stratospheric water vapor, boosting a “radiative forcing” effect that also pushes temperatures higher.

How does hydrogen escape into the atmosphere?

A lot of it is leakage, according to a second report from Frazer-Nash Consultancy. Store hydrogen in a compressed gas cylinder, and you can assume you’ll lose between 0.12 percent and 0.24 percent of it every day. It’ll leak out of pipes and valves if you distribute it that way, losing some 20 percent more volume than the methane gas that’s now running through municipal pipelines – although since hydrogen is so much lighter than methane, this larger volume equates to just 15 percent of the weight.

Where hydrogen is transported as a cryogenic liquid, boil-off is unavoidable, and you can expect to lose an average of about 1 percent of it per day. Currently, this is vented to the atmosphere.

Indeed, venting and purging operations are currently common across the hydrogen life cycle. They occur during electrolysis, during compression, during refueling, and during the process of conversion back into electricity through a fuel cell.

Where there is venting or purging, the percentages tend to dwarf what’s lost through simple leakage – for example, current electrolysis procedures using venting and purging are assumed to lose between 3.3-9.2 percent of all hydrogen produced, depending largely on how often the process starts up and shuts down – this is a bit of a worry in situations where hydrogen production is seen as a way to store excess renewable energy that’s not being snapped up by immediate demand.

Purging and venting emissions can be cleaned up significantly by adding systems to recombine the vented or purged hydrogen back into water and feed it back into the process – but it’ll be a while before these kinds of operations are economically viable.

In all, the Frazer-Nash report expects that between 1-1.5 percent of all hydrogen in its central modeling scenario will be emitted into the atmosphere, with transport emissions responsible for around half of that, and emissions at the production and consumption ends taking up roughly a quarter each.

Meanwhile, operating under different assumptions, the first report linked expects somewhere between 1 percent and 10 percent of all hydrogen in its global scenario will be emitted into the atmosphere,

Does this mean “green hydrogen” should be avoided in the race to zero emissions?

No. The UK Government report explains that “the increase in equivalent CO2 emissions based on 1 percent and 10 percent H2 leakage rate offsets approximately 0.4 and 4 percent of the total equivalent CO2 emission reductions, respectively,” so even assuming the worst leakage scenario, it’s still an enormous improvement.

“Whilst the benefits from equivalent CO2 emission reductions significantly outweigh the disbenefits arising from H2 leakage,” it continues, “they clearly demonstrate the importance of controlling H2 leakage within a hydrogen economy.”

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Ozone Layer, Lauded Climate Success Story, Threatened by Wildfires

Wildfire smoke may slow progress on one of the most widely hailed climate success stories: healing the ozone layer.

In the 1980s, researchers discovered that a class of household chemicals called chlorofluorocarbons (CFCs) were eating a hole in the ozone layer, which protects Earth from cancer-causing radiation. A 10% decrease in ozone levels would result in an additional 300,000 skin-cancer cases worldwide, according to a World Health Organization estimate.

World governments banded together to phase CFCs out of household products, like refrigerators and hairspray, when they signed the Montreal Protocol in 1987. CFC emissions fell, and the ozone hole over the Antarctic began to close. Now the ozone layer is on track to fully recover by 2060, according to a scientific assessment from the United Nations and the World Meteorological Association.

But an unexpected new threat — wildfire smoke — might slow that recovery, a pair of recent studies suggest. Researchers discovered that Australia’s “Black Summer” wildfires in late 2019 and early 2020 created a cloud of smoke so large that it rose into the stratosphere, circled the southern hemisphere, and triggered a chain of chemical reactions that destroyed ozone.

“Smoke was not supposed to do this,” Peter Bernath, an atmospheric chemist at the University of Waterloo, who co-authored one of the studies and led the other, told Insider. “It was completely unexpected that smoke made these atmospheric changes. So this is new chemistry.”

The smoke was associated with a 1% decrease in ozone at southern midlatitudes in March 2020, according to calculations in one of the studies, published this month in the Proceedings of the National Academy of Sciences. One percent may sound small, but it’s significant, considering the ozone layer is rebuilding itself by about 1-3% every decade.

The second study found that the smoke led to a rise in compounds, like hypochlorous acid, which react with ozone molecules to break them apart. Researchers aren’t sure how the smoke causes an increase in these reactive compounds, but they are confident that this is what caused the ozone levels to dip in March 2020. That paper was published in the journal Science on Thursday.

Within about nine months, the smoke had cleared from the stratosphere, and ozone had recovered to pre-wildfire levels. But the researchers suspect that other major wildfire events, like the 2017 and 2020 blazes across the Pacific Northwest, could have a similar ozone-depleting effect.

Smoke probably won’t undo the ozone layer’s healing, Bernath said, but it could slow it down. In recent global climate and wildfire reports, the United Nations warned that fires will become more frequent and more severe as global temperatures rise. That could mean more enormous smoke clouds that reach into the stratosphere and destroy ozone.

“As severe wildfires increase in number, they will play an increasingly important role in the global ozone budget,” Bernath’s study concludes.

Australia had the first ‘super outbreak’ of fire-driven thunderstorms

When wildfires burn hot enough, under the right conditions, their smoke creates its own weather. It billows up into anvil-shaped thunderstorms called pyrocumulonimbus clouds, or “pyroCbs” for short.

Smoke cools and expands as it quickly rises miles high, allowing water vapor to condense on the ash particles and create a cloud sitting atop the smoke column. The fires below fuel hot updrafts that sustain the thunderstorm and funnel smoke into the upper atmosphere, like a chimney.

That’s what happened above Australia in the final months of 2019 and beginning of 2020. As fires consumed about 50 million acres of land, they created about 38 pyrocumulonimbus clouds, which persisted for days.

More than half of those clouds reached the stratosphere, according to research led by David Peterson, a meteorologist who studies pyrocumulonimbus clouds at the Naval Research Laboratory.

“That’s why we refer to it as the first pyroCb super outbreak,” Peterson, who is not affiliated with the new studies on ozone, told Insider.

It’s unclear how often fires will shoot ozone-destroying smoke into the stratosphere

Pyrocumulonimbus clouds that reach into the stratosphere could become more common as the climate warms, but for now, that’s hard to forecast.

“It’s not just the fire. You need a certain atmospheric condition that allows for the thunderstorm to develop,” Peterson said, adding, “Just because you have more wildfires doesn’t necessarily mean you’ll get more pyroCbs. It’s really, how often do you have this synergy of the weather and the fire at the same time?”

That’s an area of ongoing research — a “frontier topic,” in Peterson’s words. Nobody knows the future of wildfire-smoke storms and their ozone-destroying potential.

Bernath and his colleagues aren’t even sure how wildfire smoke leads to compounds that react with ozone. They think that the hydrated, acidic surface of the smoke particles triggers chemical reactions that wouldn’t otherwise take place in the stratosphere, creating new compounds.

“The smoke particles have a reactive surface, and that surface catalyzes this chemistry that destroys the ozone,” Bernath said, adding, “So we kind of know what the smoke is doing. And we have some clue what the surface of the smoke particles looks like. But we don’t actually know what particular reactions are taking place on the surface.”

Laboratory research that inserts smoke particles into a stratosphere-like environment, and documents ensuing chemical reactions, could fill in the blanks.

Bernath and his colleagues are also studying satellite data from the fires that engulfed the West Coast of the US and Canada in 2020. Those blazes created pyrocumulonimbus clouds, and Bernath suspects that smoke had its own effect on ozone levels.

“This field of research into pyroCbs and their effects is relatively new, especially compared to other types of wildfire impacts,” Peterson said, adding, “We learn a lot, but then we get a lot of new questions.”

By:

Source: Ozone Layer, Lauded Climate Success Story, Threatened by Wildfires

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Russian Seizure of Ukraine Nuclear Plant Sparks Worries About Radiation

Russia’s seizure of a Ukrainian nuclear power plant has raised fears about access to data, atomic experts said, although they stressed they did not see immediate radiological risks and a U.N. watchdog said its reactors were undamaged.

Russian forces captured the Zaporizhzhia plant – Europe’s largest – after attacking it in the early hours of Friday, setting an adjacent five-storey training facility on fire

Russian forces captured the Zaporizhzhia plant – Europe’s largest – after attacking it in the early hours of Friday, setting an adjacent five-storey training facility on fire, Ukrainian authorities said. Russia has blamed the attack on the plant on Ukrainian saboteurs.

In a press conference on Friday, Atomic Energy Agency (IAEA) chief Rafael Grossi said no damage had been done to the Zaporozhzhia reactors and Ukrainian staff continued to operate the nuclear facilities while Russian forces controlled the area.

The monitoring system at the site was functioning normally and there had been no release of radioactive material, Grossi said.

Park Jong-woon, a professor at the energy and electric engineering department of Dongguk University, said he did not think there was an immediate radiological threat posed by the plant’s seizure, but added Russia could disrupt public access to data to sow confusion.

“They can make people wonder, freak them out and spread fear,” said Park, who worked at state-run power operators between 1996 and 2009, helping build nuclear reactors.

The fire at the Zaporizhzhia facility has since been extinguished but it had raised “a very real concern” about the potential for disaster, Edwin Lyman, director of nuclear power safety at the Union of Concerned Scientists in Washington D.C., said.

“For example, the prospect of a widespread fire, although that appears not to be the case, could disable the plant’s electrical systems and lead to an event very much like Fukushima if cooling is not restored in time,” he said.

More broadly, experts expressed worries about access to real time data necessary for gauging the radiation situation on the ground.

The official website for radiation readings at the Zaporizhzhia site was not immediately accessible as of Friday afternoon, Lyman said.

Since last week’s takeover by Russian forces of Chernobyl – the site of the world’s worst nuclear disaster and now a defunct power plant – monitoring of radiation levels there has been more difficult, according to Kenji Nanba, who heads Fukushima University’s Institute of Environmental Radioactivity and has been involved in a joint research project with Ukrainian scientists.

He said an official Ukrainian website with hourly radiation measurements from Chernobyl’s exclusion zone had been down for days and that another site had gradually lost most of its real-time readings.

Although the damaged Chernobyl reactor is stable and is covered under a large new containment structure, Nanba said it was still crucial for researchers like himself to track radiation data at the site to make sure there were no sudden changes.

Elevated radiation readings were recorded near Chernobyl after it was taken over by Russian forces last week, but experts say those were most likely caused by military activity that kicked up irradiated dirt and earth into the air.

The fourth reactor at Chernobyl exploded in April 1986 during a botched safety test, sending clouds of radiation billowing across much of Estimates for the numbers of direct and indirect deaths from the disaster vary from the low thousands to as many as 93,000 extra cancer deaths worldwide.

Source: Russian seizure of Ukraine nuclear plant sparks worries about radiation | Business Standard News

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