Antibiotic may may kill dangerous skin cancer cells, says study

Agencies
October 7, 2018

London, Oct 7: An existing antibiotic may selectively kill dangerous cells within melanoma, the deadliest type of skin cancer, a study claims.

The research, published in the journal Cell Chemical Biology, found the drug, called nifuroxazide, showed promise for complementing existing melanoma therapies.

Researchers at the University of Edinburgh in the UK tested the drug’s effect on melanoma cells in mice and samples from human tumours.

They caution more research is needed to determine if it will be effective in people.

Within a single tumour there can be variation in the properties of the cells, with some more dangerous than others, in terms of their potential to support growth or become resistant to drug treatment.

Many of the more dangerous cells in melanoma tumours produce a lot of an enzyme called aldehyde dehydrogenase 1 (ALDH1).

Current research into therapies has focused on blocking ALDH1, but in this study the researchers went a step further and aimed to selectively kill cells producing high ALDH1.

They used the drug nifuroxazide, an antibiotic, that is activated by the enzyme ALDH1, which means that it only becomes toxic once it is inside cells producing ALDH1.

Using samples of human melanomas implanted in mice the researchers showed that the nifuroxazide therapy killed the tumour cells that produced a lot of ALDH1, without significant toxicity to other cells in the body.

The researchers hope that the strategy may complement existing melanoma treatments, called BRAF and MEK inhibitors.

Currently, some people’s tumours develop resistance to BRAF and MEK inhibitors and the researchers found that some of these resistant tumours were high in ALDH1.

In the lab, the researchers simulated this by treating cancer cells lines with BRAF and MEK inhibitors, which increased the number of cells with high levels of ALDH1 and made the cells especially sensitive to nifuroxazide treatment.

“We’ve shown this antibiotic that’s used mostly to target intestinal bacteria can also target and kill cancer cells high in the enzyme ALDH1,” said Liz Patton from the University of Edinburgh.

“It’s great that this antibiotic is approved for use in humans, but it wasn’t designed as a cancer drug, so we still need to find out if it’s safe and effective for cancer in humans — for example, can it get to the cancer in the body and are the doses needed safe,” said Patton.

“We may need to take the concept for how this antibiotic works and re-design it to make it better at killing cancer,” Patton 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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Agencies
May 30,2020

Drinking coffee may help reduce the risk of certain digestive disorders, including gallstone disease and pancreatitis, a new study has suggested.

The study from the Institute for Scientific Information on Coffee (ISIC) also highlighted other beneficial effects that coffee consumption may have on the process of digestion, including supporting gut microflora and promoting gut motility.

"Data indicates benefits against common digestive complaints such as constipation, as well as a potential reduction in the risk of more serious conditions like chronic liver diseases," said study author Carlo La Vecchia from the University of Milan in Italy.

Gallstone disease is a common digestive disorder, caused by the accumulation of gallstones in the gallbladder or bile duct, which affects approximately 10-15 per cent of the adult population.

While the mechanism by which coffee may protect against gallstone disease is not yet known, it has been observed that the risk for the condition declines with increasing daily consumption of coffee, the researchers said.

Caffeine is thought to play a role in these associations, as the same effect is not observed with decaffeinated coffee.

A common question among consumers and focus area for research is whether coffee is associated with heartburn or gastro-oesophageal reflux disease (GORD).

While a small number of studies have suggested an association between coffee drinking and GORD, the majority of studies reviewed suggest that coffee is not a major trigger of these conditions.

The report also reviewed a growing area of health and nutrition research, namely: the effect of coffee on the gut microflora (microorganism populations).

Recent studies suggest that populations of the beneficial gut bacteria Bifidobacterium spp, increase after drinking coffee.

The findings showed the dietary fibre and polyphenols found in coffee, support the healthy growth of microflora populations.

Additional research findings highlighted that coffee consumption is thought to stimulate digestion by encouraging the release of gastric acid, bile and pancreatic secretions.

Coffee is one of the most widely researched components of the diet, and its effect on digestion remains a growing area of research, the researchers noted.

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Agencies
May 2,2020

Clinician-scientists have found that Irish patients admitted to hospital with severe coronavirus (COVID-19) infection are experiencing abnormal blood clotting that contributes to death in some patients.

The research team from the Royal College of Surgeons in Ireland found that abnormal blood clotting occurs in Irish patients with severe COVID-19 infection, causing micro-clots within the lungs.

According to the study, they also found that Irish patients with higher levels of blood clotting activity had a significantly worse prognosis and were more likely to require ICU admission.

"Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focussed within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19," said Professor James O'Donnell from St James's Hospital in Ireland.

In addition to pneumonia affecting the small air sacs within the lungs, the research team has also hundreds of small blood clots throughout the lungs.

This scenario is not seen with other types of lung infection and explains why blood oxygen levels fall dramatically in severe COVID-19 infection, the study, published in the British Journal of Haematology said.

"Understanding how these micro-clots are being formed within the lung is critical so that we can develop more effective treatments for our patients, particularly those in high-risk groups," O'Donnell said.

"Further studies will be required to investigate whether different blood-thinning treatments may have a role in selected high-risk patients in order to reduce the risk of clot formation," Professor O'Donnell added.

According to the study, emerging evidence also shows that the abnormal blood-clotting problem in COVID-19 results in a significantly increased risk of heart attacks and strokes.

As of Friday morning, the cases increased to 20,612 cases in Ireland, with 1,232 deaths so far, according to the Johns Hopkins University.

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