Tobacco use makes precancerous cells that fertilize cancer growth: Study

Agencies
April 3, 2019

Apr 3: A recent study has found that tobacco consumption leads to the formation of precancerous cells that fertilize cancer growth. There have been a lot of studies dedicated to cancer-related topics, exactly how this precancerous field influences cancer has been often overlooked. As part of the study, the researchers wanted to understand how these precancerous cells may impact neighboring cancer.

The study explores this communication between precancerous and cancer cells in the context of an enzyme called PI3K. The enzyme PI3K is activated in many or even most cancers, with some researchers considering PI3K over-activation an essential feature driving the disease. Attractively, PI3K is a “kinase” and the class of drugs known as kinase inhibitors has proven effective against a host of cancer types. Kinase inhibitors have been developed against PI3K as well, and by and large they do a lovely job of killing cancer cells in dishes.

The ongoing question has been why PI3K inhibitors do not necessarily work in patients – what are cancer cells doing to resist this therapy that should kill them? The current study offers an intriguing hint: “These cancer cell lines in culture are sensitive to PI3K inhibition, but when you put them next to precancerous cells, they become resistant,” Young says. “These cancer cell lines in culture are sensitive to PI3K inhibition, but when you put them next to precancerous cells, they become resistant,” said Christian Young, senior author of the study discussed in AACR Annual Meeting 2019.

To explore this observation, the team of researchers including first author Khoa Nguyen, grew head and neck cancer cells in the same dish as precancerous cells (called NOK cells), and then hit the cells, alone and together, with PI3K inhibitors. Cancer cells grown with NOK cells grew faster and resisted PI3K inhibition compared with cancer cells grown alone. When the researchers grew NOK cells alone, then removed the cells, and “fertilized” cancer cells with the culture medium in which NOK cells had grown, they saw similar cancer cell growth and PI3K inhibitor resistance. Additionally, the NOK cells were stimulating cancer stem cell-like features in the recipient cancer cells. This means that in addition to resisting PI3K therapy, cancer cells that sit alongside precancerous cells may themselves become more dangerous, for example, more able to restart the disease.

“What this means is that some properties of cancer cells may not necessarily be intrinsic. In our study, cancer cells were given some of their cancer-like and stem cell-like properties by nearby, precancerous cells,” Young says. Continuing the line of study, Young and his team asked what these precancerous cells were giving to head and neck cancer cells that allowed them to resist PI3K therapy and gain cancer stem cell-like traits. What they found is a dramatic increase in EGFR ligands – think of PI3K like an engine driving cancer growth. EGFR is another engine that can work alongside PI3K. In this analogy, EGFR ligands are like fuel, allowing cancer cells, in the absence of PI3K, to power their growth and survival through the engine of EGFR instead.”It was the precancerous cells that were providing this fuel,” Young says.

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Agencies
July 25,2020

The COVID-19 pandemic and the subsequent lockdown saw many people turning chefs overnight, but those who could not turned to online delivery of food. And not just any food, as per a new report, Indians "craved the most for Biryani" during the lockdown.

The "StatEATistics report: The Quarantine Edition" from food delivery platform Swiggy found that Indians ordered biryani over "5.5 lakh times" from their favourite restaurants.

The new normal might have opened a pandora's box of behavioral changes, but some old habits die hard like the love for Biryani, which took the top spot for overall orders. It was followed by butter naan and masala dosa at 3,35,185 and 3,31,423, respectively.

Biryani has topped the list of most ordered dishes for the fourth year in a row, the food delivery platform noted.

Indians didn't forget to indulge their sweet tooth in the uncertain months of lockdown. Their favourite comfort food during the lockdown period was the moist and decadent Choco Lava cake, ordered around 1,29,000 times.

"The humble Gulab Jamun (84,558) and chic Butterscotch Mousse cake (27,317) followed suit," said the report derived from Swiggy's order analysis in the past few months across cities that it is present in.

Also, as birthday parties moved to video calls, and virtual cake cutting sessions, according to the food delivery platform, it delivered nearly "1,20,000 cakes" to complete these celebrations.

According to the report, on average, "65,000 meal orders" were placed by 8 pm each day to make sure food arrived in time for dinner.

"It was the busiest hour for Swiggy delivery partners and restaurants. On average, they (customers) chose to tip Rs.23.65, with one particularly generous customer tipping Rs. 2500!," it added.

For those who only relied on home-made food during the quarantine, Swiggy delivered a whooping 323 million kgs of onions and 56 million kgs of bananas through its grocery section and hence ensured that its consumers were all stocked up.

That said, it also took care of the 'quick-fix meal' tribe -- consumers who resort to the evergreen college hacks of living on instant noodles.

"Around 3,50,000 packets of this ideal easy to cook meal were ordered during the lockdown," it said.

In all, Swiggy delivered 40 million orders across food, groceries, medicines and other household items during India's lockdowns. It also delivered over 73,000 bottles of sanitizers and hand wash along with 47,000 face masks as the definition of essentials' changed during these uncertain times.

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News Network
May 13,2020

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

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Agencies
June 10,2020

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

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