Tag: 6/8/21

Categories : CancerTags :

How Cancer Cells Develop Resistance to Chemotherapy

On By ModernMedia
Source: National Cancer Institute on Unsplash

Researchers have found some answers as to why cancer cells can develop resistance to the cytotoxic drugs used in chemotherapy.

“We haven’t understood very much about how this resistance to chemotherapy develops and even less about how the microenvironment in cancer can affect the process,” said Kaisa Lehti, a professor at the Norwegian University of Science and Technology’s (NTNU) Department of Biomedical Laboratory Science.

Lehti has led this study into how cancerous tissues develop resistance to a particular form of chemotherapy, the results of which appear in Nature Communications.

If ovarian cancer is picked up early, almost all patients survive the first five years, while chances of survival are much worse if detected later. Finding effective treatment is therefore very important.

Platinum chemotherapy is one of the standard treatments for ovarian cancer, but cancer cells often develop resistance to this particular treatment. The reason lies in how the platinum-based cytotoxin itself can change the cancer cells and their environment.

Cytotoxin influences cancer cells and their environment
Lehti summed up the process: “The cytotoxin can change the way the cancer cells send and perceive signals and can modify the microenvironment around the cells.”

This change allows the cancer cells to withstand the damage caused by the cytotoxin—and can thus survive the chemotherapeutic attack. The researchers have found this key to the puzzle in a layer of tissue that often surrounds cancer cells.

“A fibrotic network of proteins, known as the extracellular matrix or ECM, surrounds the cancer cells, particularly the most aggressive ones,” said Lehti.

The fibrotic tissue, with the ECM network around the cancer cells, is mainly produced by normal connective tissue cells. But the cancer cells and connective tissue cells in the network can alter this tissue themselves.

“Previously, we haven’t known how the communication between the cancer cells and the extracellular matrix is affected by, or even itself influences, the development of cancer and its response to chemotherapy,” said Prof Lehti.

But it is now known that chemical and mechanical signals in the surrounding ECM tissue help cancer develop its ability to spread and to resist treatment.

“Certain signals from the ECM can critically change the cancer cells’ resistance to platinum-based cytotoxic drugs,” Prof Lehti explained.

In this way, the cytotoxin itself helps change both the microenvironment around the cancer cells and the ability of the cancer cells to sense their environment, and so resist the cytotoxin. By understanding this process, better therapies can be developed.

Source: MedicalXpress

Categories : COVIDTags :

Western Cape Third Wave Peak Expected Anytime Now

On By ModernMedia
Image by Quicknews

Western Cape premier Alan Winde said that the province is at the peak of its third wave of COVID infections.

“We are beginning to see the flattening of the curve at our peak as new case infections start to plateau again,” he said in a briefing on Thursday. “This happened after an initial plateau two weeks ago, and then a subsequent increase the week thereafter.

“This is largely explained by a disruption in testing caused by the taxi violence in the Cape Metro during that time.”

Winde supplied the following information:

The ‘R’ number is currently 1.1 and the test positivity rate is 41.5%. New hospital admissions are at 339 per day, with a slight downturn. Deaths have increased, with about 108 deaths per day and will be the last indicator to fall.

Winde said that provincial authorities are simultaneously monitoring the number of trauma admissions to hospitals to ensure that there is sufficient capacity in the province’s hospitals and that it can proactively identify any risks so that they can be addressed.
Senior CSIR researcher Ridhwaan Suliman, PhD, who was been analysing COVID data tweeted an update on Friday night, indicating that there was still no sign of the peak passing just yet:

https://twitter.com/rid1tweets/status/1423718531208785921

Source: BusinessTech

Categories : PoliticsTags :

A Look Back at Mkhize’s Tenure as Health Minister

On By ModernMedia
Image by Hush Naidoo from Unsplash
Image by Hush Naidoo from Unsplash

With Dr Joseph Phaahla being promoted from his position as Deputy Health Minister to replace the embattle, Dr Zweli Mkhize, Spotlight reviews Dr Mkhize’s tenure, writing that the very reason he was brought in to that post — to roll out National Health Insurance — would likely suffer a considerable setback as a result of his exit.

His appointment as South Africa’s Minister of Health in May 2019 came as a surprise for some. As one of the ANC’s top officials, the health portfolio seemed a meagre choice in the pre-COVID days.

However, Mkhize’s seniority signalled that health was being given high priority in the new administration. Theoretically, his greater political clout meant he would have a better chance of bringing much-needed reforms to provincial healthcare systems. Spotlight were also “cautiously hopeful that Mkhize’s firmer hand would help better organise and direct the National Health Department and the various national health entities.”

A string of procurement scandals during his time as KwaZulu-Natal’s Premier was cause for concern but was not direct evidence that he was corrupt.

The Digital Vibes scandal had the side effect of making Mkhize anathema to the very project he was originally brought in for, implementing National Health Insurance.

Even with Mkhize gone, the ANC will have a hard time convincing the public that we will not see more such looting once NHI is implemented. There has, after all, been little willingness from ANC members in Parliament to engage seriously with people’s concerns about the proposed NHI structure and governance arrangements set out in the NHI Bill.

Mkhize tackled COVID from a scientific standpoint, which is fortunate for the nation considering the anti-scientific stance of the former Minister of Health Dr Manto Tshabalala-Msimang. However, the decision not to use AstraZeneca vaccines remains contentious. Meanwhile, a purge of scientists, starting with Professor Glenda Gray, let Mkhize surround himself with allies, according to Spotlight.

However, entering the third wave with vaccinations lagging so far behind was a governance disaster possibly even worse than the Digital Vibes scandal.

From an outside perspective, the past two years have not seen great progress in the department, despite some competent individuals, with infighting, under-capacity and most seriously, poor management. The procurement department

Source: Spotlight

Categories : CancerTags :

Powering Up NK Cells With Magnetism

On By ModernMedia
NK cells attack a cancer cell (centre). Source: NIH

Powering up natural killer cells with magnetic nanoparticles could enhance cancer immunotherapy, according to a Northwestern Medicine study published in ACS Nano.

This method could allow for the unleashing of natural killer (NK) cells on a variety of solid tumours, according to senior author Dong-Hyun Kim, PhD, associate professor at Northwestern.

“People have had trouble applying NK cells to solid tumours,” said Prof Kim. “If we can provide an easy path to modulate NK cells, perhaps this can become a useful therapy.”

Most cell-based immunotherapies involve T-cells, but these chimeric antigen receptor (CAR) T-cell therapies are costly and have a long incubation period and strong side effects.

On the other hand, NK cells belong to the innate immune system and are quicker to respond to pathogens. NK cell immunotherapy has been explored, according to Prof Kim, but that too has barriers.

“It’s pretty hard for these cells to penetrate inside the tumours which have thick barrier tissues,” Prof Kim said.

Magnetically activated NK cells
Boosting NK cell function with cytokines have proven unsuccessful and, like CAR T-cell therapy, have a high cost and lengthy manufacturing time. However, Prof Kim’s previous work with nanoparticles inspired a different approach.

Prof Kim and colleagues developed a magnetic nanocomplex that binds with NK cells and, when activated with an alternating magnetic field, exerts force on the exterior of the cell, promoting secretion of cytotoxic compounds. Testing this nanocomplex in animal models of hepatocellular carcinoma, the investigators found that magnetic activation increased the cancer-killing ability of NK cells when injected into solid tumours.

As a bonus, these nanoparticles show up with MRI, allowing for precise monitoring of NK cell distribution during and after injection.

“This creates a stronger NK cell, and can hopefully enhance the efficacy of the treatment,” Prof Kim said.

Source: Northwestern University

Categories : New Compounds and TreatmentsTags :

New Molecules Provide Deeper UV Protection

On By ModernMedia
Photo by rfstudio on Pexels

Two new molecules that release tiny quantities of hydrogen sulfide have been found to prevent skin from ageing after being exposed to ultraviolet light found in sunlight. The study was published in Antioxidant and Redox Signalling.

For the study, the researchers exposed adult human skin cells and the skin of mice to ultraviolet radiation (UVA). UVA causes skin ageing by turning on collagenases, enzymes which eat away at the natural collagen, causing the skin to lose elasticity, sag and wrinkle. UVA also penetrates deeper into skin than the UV radiation that causes sunburns (UVB), and it also damages cellular DNA, leading to mutations that can contribute to some skin cancers. Typical sun creams sit on top of the skin and absorb UV radiation, but they do not penetrate the skin where the long-lasting damage occurs.

For deeper protection, the researchers came up with a new way to protect the deeper layers of skin using two compounds invented at the University of Exeter: AP39 and AP123. The compounds do not protect the skin in the same way traditional sun creams prevent sunburn, but instead penetrate the skin to correct how skin cells’ energy production and usage was turned off by UVA exposure. This then prevented the activation of skin-degrading collagenase enzymes. 

The compounds used in this study were previously shown to have impressive effects in reducing skin inflammation and skin damage after burn injury and atopic dermatitis (eczema). In an anti-ageing context, they prevented human skin cells in test tube experiments from ageing, but this is the first time the effects of photo-ageing have been seen in animals.

The important observation noted was that the compounds only regulated energy production, PGC-1α and Nrf2 in skin that was exposed to UVA. This suggests a novel approach to treating skin that has already been damaged by UV radiation, and could potentially reverse, as well as limit, that damage.

While further research is needed, there could be medical as well as cosmetic implications from this work, where protecting skin from UV light is important. For example, not only premature skin ageing and skin cancers, but UV light allergies, solar urticaria and rare hereditary skin diseases such as xeroderma pigmentosum. The researchers are currently partway through testing newer and more potent molecules able to do the same task using newer approaches.

Source: University of Exeter

Categories : Diseases, Syndromes and ConditionsTags :

Host Genes Can Hinder H. Pylori Eradication

On By ModernMedia

Helicobacter pylori is a strong risk factor for gastric cancer and other gastrointestinal disorders, and efforts to eradicate it using a combination of antibiotics and proton pump inhibitors (PPIs) often fail.

A new study has linked this eradication failure with genetic variations that increase the activity of the CYP2C19 enzyme, which metabolises first-generation PPIs.

These so-called ‘fast metabolisers’ may prevent PPIs from suppressing gastric acid production, which is necessary for successful H. pylori eradication.

Analysing 57 studies from 11 countries, the researchers found that the failure rate of H. pylori eradication more than doubled in people with a version of the CYP2C19 gene that increased its metabolic activity. Their results were published in Gastroenterology.

However, CYP2C19 variants were not linked to eradication failure if the fast metabolisers were treated with newer PPIs such as esomeprazole and rabeprazole, which are less metabolised by the enzyme or which bypass CYP2C19 metabolism.

Further well-designed studies are needed to determine whether eradication rates could be improved with higher or more frequent dosages of first-generation PPIs to people with the fast metaboliser gene variant, noted the paper’s corresponding author, Shailja Shah, MD, MPH.
“Even small improvements in H. pylori eradication rates would likely translate to substantial collateral health, economic and societal benefits,” the researchers concluded.

Source: Vanderbilt University