Day: August 17, 2022

Categories : CancerTags :

Cancer-associated Fibroblasts Sometimes Aid Certain Drugs

On By ModernMedia
Cancer-associated fibroblasts surrounding a prostate tumour. Credit: Moscat and Diaz Meco labs

Cancer-associated fibroblasts in the tumour environment have typically been linked to tumour progression and therapy resistance, but some studies suggest that these fibroblasts may also sensitise cancer cells to therapy. In a new article published in Science Signaling, researchers shed light on these conflicting studies and demonstrate that cancer associated fibroblasts can promote or inhibit drug sensitivity based on the type of tumour cell and the drug used for treatment.

Through a series of laboratory experiments, the research team from Moffitt Cancer Center determined the impact of cancer associated fibroblasts on drug responses among different non-small cell lung cancer (NSCLC) cell lines. They discovered that the presence of cancer-associated fibroblasts had varying effects on tumour cells based on both the type of NSCLC and the drug used for treatment. For example, the presence of cancer associated fibroblasts induced resistance to two different MEK inhibitors in non-small cell lung cancer cell lines with a mutant KRAS protein. However, cancer associated fibroblasts sensitised NSCLC cell lines with a mutant EGFR protein to EGFR inhibitors. Interestingly, normal lung associated fibroblasts never sensitised cells to drug treatment, suggesting that cancer associated fibroblasts secrete a factor that causes differential responses to drug treatment in a cell-context manner.

The researchers compared cancer associated fibroblasts to normal fibroblasts to identify factors that would produce these disparate effects. They found that cancer associated fibroblasts had alterations in the levels of secreted proteins that are part of the insulin-like growth factor (IGF) signalling pathway, which is involved in cell growth, death and migration. Specifically, cancer-associated fibroblasts secreted higher levels of proteins called IGF binding proteins (IGFBPs), which inhibit IGF signalling, and lower levels of IGFs, which activate IGF signalling. In combination, these alterations result in inhibitory effects on the IGF signalling pathway.

In further analyses, the researchers found that IGFBPs sensitised lung cancer cell lines to EGFR inhibitor treatment, while IGF proteins induced resistance to EGFR inhibitor treatment. They identified that survival signalling in response to EGFR inhibitor treatment was dependent on the proteins IGF1R and FAK, which are both part of the IGFBP signalling pathway. Importantly, they discovered that drugs that blocked the activity of IGF1R and FAK sensitised mutant EGFR lung cancer cells to EGFR inhibitors, suggesting that this combination approach may be effective in the clinic.

“These results highlight tumour suppressive effects competing with otherwise tumour promoting effects of cancer associated fibroblasts and add to the growing evidence that eliminating cancer associated fibroblasts in an undifferentiated way may be detrimental to cancer therapy,” said lead study author Lily Remsing Rix, PhD

“We show that mechanistic understanding not just of cancer associated fibroblast-mediated resistance, but also of their tumour suppressive pathways, can lead to rational design of improved therapeutic approaches that mimic these effects and may delay the onset of drug resistance,” added Uwe Rix, PhD, principal investigator of the study.

Source: H. Lee Moffitt Cancer Center & Research Institute

Categories : Expert Opinion Medical IndustryTags :

Act Now to Stop the Bleed on Medical Schemes Industry

On By ModernMedia

By Junior Biola

Last year, fraud and abuse of medical aids resulted in a loss of R22 billion for medical scheme funds according to The Board of Healthcare Funders – a loss which could be avoided with the implementation of fraud mitigation services.

Medical aid fraud is certainly nothing new: for years, medical schemes have railed against members collaborating with medical practitioners – from doctors to pharmacists – for personal gain. There are the members who convince practitioners to admit them to hospital, for example, and pocket the monies received from their hospital cash back plans; the pharmacists who bill their customers for ‘medicine’, when their baskets are in fact filled with non-medicinal items; or even the practitioners who bill patients for treatments which never take place.

Since the advent of the Covid pandemic, such activities have escalated. In fact, it is no longer rogue pharmacists or practitioners taking advantage of medical aids; the industry is now affected by dishonest members and criminals using stolen cards to deplete medical savings accounts or take advantage of benefits.

The results are catastrophic for an industry which is frequently accused of charging members exorbitant fees. In truth, players are under siege from the steeply rising costs of healthcare, and while they are doing their best to limit the impact on members, this is no easy task when those very members are, in effect, stealing from the scheme through fraudulent claims.

The impacts are far-reaching for all stakeholders. Medical funds have no choice but to raise the price of contributions – after all, they need to maintain a steady pool of funds in order to be able to pay out claims, and if members are dipping into that pool for illicit reasons, it needs to be replenished. Naturally, this affects members severely, especially as many are already challenged by the rising cost of living. On the other side of the equation, practitioners also take a hit: when the pool of medical funds decreases, a less profitable practice is inevitable.

The prevalence of fraud is understandable when you consider that few controls are in place to prevent it. Think of the average consumer entering a retail chain pharmacy, for example: they may be asked to present their loyalty card, and while this may be considered a form of identification, the reality is that it is rather ineffective as a verification tool. The absence of an identification photo means that the purchaser could well be someone besides the patient for whom the script was written; nor is there anything to stop them from adding over-the-counter items to purchase and claiming them from their savings.

The good news? Fraud mitigation is both effective, and simple to implement. Establishing a ‘safety net’ of identity and biometric recognition makes it possible for medical schemes to ensure that members claim only for medicines and treatments they have been prescribed, while also protecting against scripts that have been falsified.

The result? A healthier medical aid industry – for the benefit of all.

Junior Biola is CEO of Johannesburg-based fintech company, Bitventure, a provider of state-of-the-art real-time automated verification and payment solutions. www.bitventure.co.za

Categories : Medical Research & TechnologyTags :

Spider Silk Woven into New Biomedical Applications

On By ModernMedia
Photo by Anthony Ievlev on Unsplash

Researchers have discovered that spider silk proteins can be fused to biologically active proteins and then converted into a gel at body temperature. This could allow for injectable protein solutions that form a gel inside the body, which could be used in tissue engineering and for drug release. Their study is published in Nature Communications.

“We have developed a completely new method for creating a three-dimensional gel from spider silk that can be designed to deliver different functional proteins,” says Anna Rising, research group leader at the Department of Biosciences and Nutrition, Karolinska Institutet (KI) and professor at the Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences (SLU). “The proteins in the gel are very close together and the method is so mild that it can be used even for sensitive proteins.”

An injectable protein solution

In the future, the researchers hope to develop an injectable protein solution that forms a gel inside the body. The ability to design hydrogels with specific functions opens up for a range of possible applications, for example, achieving a controlled release of drugs into the body. In the chemical industry, it could be fused to enzymes, a form of proteins used to speed up various chemical processes.

“In the slightly longer term, I think injectable gels can become very useful in regenerative medicine,” says the study’s first author Tina Arndt, PhD student in Prof Rising’s research group at Karolinska Institutet. “We have a long way to go, but the fact that the protein solution quickly forms a gel at body temperature and that the spider silk has been shown to be well tolerated by the body is promising.”

Mimics spider silk spinning

The researchers have been particularly interested in the spiders’ ability to keep proteins soluble so that they do not clump together before the spinning of the spider silk. They have previously developed a method for the production of valuable proteins which mimics the process the spider uses to produce and store its silk proteins.

“We have previously shown that a specific part of the spider silk protein called the N-terminal domain is produced in large quantities and can keep other proteins soluble, and we can exploit this for medical applications,” said Anna Rising. “We have let bacteria produce this part of the protein linked to functional proteins, including various drugs and enzymes.”

Transformed into a gel

The new study shows that the N-terminal domain also has the ability to change shape and transition to small fibrils that cause the protein solution to be converted into a gel if incubated at 37 °C. In addition, it can be fused to functional proteins that preserve their function in the gel.

Source: Karolinska Institutet

Categories : Diet and Nutrition ExerciseTags :

IV Nutrition is a Growing and Potentially Dangerous Trend among Athletes

On By ModernMedia
Intravenous IV drip
Source: Marcelo Leal on Unsplash

Once a last resort solution, intravenous (IV) nutrition is threatening to become the norm for competitive athletes, despite no scientific evidence that it works or that it is safe, warn experts in an editorial in the British Journal of Sports Medicine.

To halt this trend, the experts urge that ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and their support teams.

The authors, who interact with professional team players in European and American leagues and their support teams on a regular basis, have become increasingly aware of the practice.

While it is not known how common it is, anecdotally, some players are hooked up to IV nutrition drips as often as every week as part of a pre- or post-game routine, they say. 

So-called ‘drip bars’ and concierge IV nutrition services claim to boost health and performance, restore hydration and speed up recovery. These services offer a menu of B vitamins, amino acids, glutathione, vitamin C and electrolytes, which could potentially boost levels beyond any therapeutic range.

These services seemed to have slipped under the regulatory radar despite being quite visible, and there is no guidance on their use for players or practitioners, the authors pointed out.

The principle of reducing needle use in sport and a ‘food first’ approach is taught in sports nutrition courses around the world, and a ban on needle use by athletes at the Olympic Games, except for appropriate medical use, and where a therapeutic use exemption (TUE) is obtained, has been in place for all recent Games, they highlight.

IV nutrition drips have traditionally been reserved for serious clinical conditions, such as anaemia, symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in a desert, for example. But they are now being used for tiredness, fatigue, or recovery, say the authors.

“But the evidence is sparse and not supportive. We are aware of just two studies assessing vitamin injections in otherwise healthy participants, neither of which yielded an effect for the injection group,” note the authors.

They add that these drips are risk-free, potentially interfering with the liver and gut microbes with implications for detoxification and immunity.

“Bypassing these mechanisms appears foolhardy unless there is a significant clinical rationale,” they write, adding that IV drips also carry risks of infection at the needle site and of blood clots.

Excessive vitamin B6 is associated with peripheral neuropathy, while athletes regularly receiving IV iron risk liver disease, they point out.

“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they write. 

“More than this is the reputational risk to sport if it is normalised for athletes to regularly partake in self-directed IV [nutrition] use with a worrying shift away from what ‘works’ (according to scientific standards), to that which is unproven. 

“Furthermore, some athletes risk an anti-doping violation by participating in self-directed IV [nutrition] use.”

Figures on the prevalence of IV nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of IV nutrition use, say the authors.

“The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams to avoid what was previously a ‘last resort’ treatment becoming normal without scientific evidence of benefit,” they warn.

Source: EurekAlert!

Categories : Surgeries & ProceduresTags :

Remove All Secondary Kidney Stones, Study Suggests

On By ModernMedia
Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

A new study showed, during kidney stone removal procedures, leaving small asymptomatic stones behind significantly increases the risk of a patient’s relapse in the following five years. The study findings appear in the New England Journal of Medicine.

Typically, stones < 6mm in diameter that are not a procedure’s primary target are not removed but monitored, since ‘secondary’ stones have high rates of successful passage if they move into the ureter, explained Dr Mathew Sorensen, a urologist at the University of Washington School of Medicine and the study’s lead author.

“Before this study, the clinical views were pretty mixed on whether some of these stones should be treated,” he said. “Most clinicians would decide, based on the size of the stone, whether it hit the bar for treatment, and if it did not, you would often ignore the little stones.”

The researchers studied 75 patients who were treated at multiple institutions over 2015 to 2021. About half of the patients had only their large primary stone treated, while the others had primary and secondary stones removed. Relapse was defined as having to go to the emergency room or undergo an additional procedure due to a recurrence or if a follow-up CT scan showed that the secondary stones grew.

Removal of the secondary stones reduced the relapse rate by 82%, the researchers found, leading the authors to recommend that smaller stones should not be left behind.

“Results of our trial support the removal of small asymptomatic renal stones at the time of surgery with a larger stone,” their paper concluded. The authors noted that while removal of smaller stones could add to the procedure’s duration and cost, those costs would likely be less than those associated with a patient’s repeat procedure or visit to the emergency room. Some patients in the study visited the emergency department multiple times and then required surgery, the report noted.

Dr Sorensen said he would share the study results with colleagues with the hope of changing their sensibility toward smaller stones. Further study is needed to determine whether treatment of small stones alone is justified, as technology improves and the costs and risks of intervention diminish, he said.

“I think we have proven through this rigorous study that removal of the small asymptomatic stones is beneficial when feasible and in patients that are candidates to have all their stones treated in one procedure,” he noted. “Leaving the stones behind risk trouble in the future.”

Source: University of Washington School of Medicine/UW Medicine