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
January 5,2020

Washington D.C., Jan 5: After a woman filed a lawsuit against a diet soda company, the California court has declared that the beverage does not promise to help buyers in losing weight.

The woman had gulped down the drink for over a decade but did not lose inches as a result.

The three-judge panel declared during the hearing: "The prevalent understanding of the term in (the marketplace) is that the 'diet' version of a soft drink has fewer calories than its 'regular' counterpart."

However, the members of the US 9th circuit court have felt that the consumers tend to make out something of their own that is unreasonable and eventually hamper the reputation of brands through a deceptive allegation, reports Fox News.

The response was due to a misleading case filed against Diet Dr Pepper by Shana Becerra from Santa Rosa, California. Shana claimed that she has been addictively purchasing the low-calorie beverage for the past 13 years hoping for losing some fat but failed to lose even a single inch.

The woman also stated that the attractive and fit models misled her into believing that drink will help her in perfecting her body like them.

However, the court's decision was that advertisements are for representational purposes only. "Cannot be reasonably understood to convey any specific meaning at all," as written by Judge Jay Bybee.

Shana had last week made such allegation against Diet coke as well where the court came to a similar verdict. She claimed that she had found various studies where it is evident that the artificial sweetener aspartame used in diet beverages actually boosts weight gain.

But the artificial sweetener is approved in by the concerned administrative department and thus is used in most American drinks.

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News Network
February 21,2020

Washington, Feb 21: The fat around arteries may play an important role in keeping the blood vessels healthy, according to a study in rats that may affect how researchers test for treatments related to plaque buildup, as seen in conditions leading to heart attack.

The study, published in the journal Scientific Reports, noted that the fat, known as perivascular adipose tissue, or PVAT, helps arteries let go of muscular tension while under constant strain.

According to the researchers, including Stephanie W. Watts from the Michigan State University in the US, this feature is similar to how the bladder expands to accommodate more liquid, while at the same time keeping it from spilling out.

"In our study, PVAT reduced the tension that blood vessels experience when stretched," Watts said.

"And that's a good thing, because the vessel then expends less energy. It's not under as much stress," she added.

According to Watts and her team, PVAT has largely been ignored by researchers believing its main job was to store lipids and do little more.

Until now, she said, scientists only divided blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media, and the outermost layer called the tunica adventitia.

Watts believes PVAT is the fourth layer, which others have called tunica adiposa.

Tunica, she said, meant a membranous sheath enveloping or lining an organ, and adiposa is a synonym for fat.

"For years, we ignored this layer -- in the lab it was thrown out. In the clinic it wasn't imaged. But now we're discovering it may be integral to our blood vessels," Watts said.

"Our finding redefines what the functional blood vessels are, and is part of what can be dysfunctional in diseases that afflict us, including hypertension. We need to pay attention to this layer of a blood vessel because it does far more than we originally thought," she added.

Earlier studies, Watts said, had shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

In the current study, the researchers decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

They tested the thoracic aorta in rats, and found those with intact PVAT had more stress relaxation than those without.

The study revealed that the pieces of artery with surrounding fat had measurably relaxed more than those without.

Watts and her colleagues then tested other arteries, and were able to duplicate the same response.

"It's not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it's a general phenomenon," she said.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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