Turkey Formally Requests To Join BRICS, Citing Frustration In EU Bid

 Via The Cradle

Turkey has formally requested to join the BRICS group of emerging economies, Bloomberg cited informed sources as saying on Monday. 

Ankara "seeks to bolster its global influence and forge new ties beyond its traditional Western allies," the sources said. President Recep Tayyip Erdogan believes “that the geopolitical center of gravity is shifting away from developed economies" and that the push to join BRICS "reflects its aspirations to cultivate ties with all sides in a multipolar world, while still fulfilling its obligations as a key member of NATO."

Turkish Foreign Minister Hakan Fidan said in early June that BRICS serves as a good alternative to the EU. Later that month, he confirmed that dialogue between Ankara and BRICS nations was ongoing – coming as Turkish frustration continued to grow due to stalled efforts to join the EU. 

While Turkey has long been a member of NATO, accession talks for EU membership have faced several obstacles since they began in 2005. Turkey had applied to join the EU predecessor organization, the EEC, in 1987.  

"Turkey submitted an application to join BRICS some months ago amid frustration over a lack of progress in its decades-old bid to join the EU," Bloomberg’s sources went on to say. 

After Russia became the most sanctioned nation in the world following the start of the war in Ukraine in 2022, the BRICS bloc began seriously pursuing the creation of a common currency to de-dollarize trade and circumvent western sanctions. 

A coalition initially made up of Brazil, Russia, India, China, and South Africa, BRICS at the start of this year expanded for the first time since 2010 to include Egypt, Iran, Ethiopia, and the UAE.

Palestine’s ambassador in Moscow, Abdel Hafeez Nofal, said on August 26 that the Palestinian Authority (PA) is planning to apply to join BRICS.

"The different and beautiful thing about BRICS compared to the EU is that it includes all civilizations and races. If it can become a little more institutional, it will produce serious benefits," Fidan said in early June.

Fidan confirmed in an interview later that month that his country may apply for an upgraded dialogue partnership with the Association of South East Asian Nations (ASEAN). 

Erdogan has also shown interest in joining China’s Shanghai Cooperation Council (SCO). In early, he attended the SCO summit in Kazakhstan. 

"We do not have to choose between the EU and the SCO as some people claim. On the contrary, we have to develop our relations with both these and other organizations on a win-win basis," the Turkish president said over the weekend. 

"Turkiye can become a strong, prosperous, prestigious and effective country if it improves its relations with the East and the West simultaneously. Any method other than this will not benefit Turkiye, but will harm it," he added. 

https://www.zerohedge.com/markets/turkey-formally-requests-join-brics-citing-frustration-eu-bid

Exosomes secreted by living cells may successfully target TKI-resistant cancer

 In a new study, clinician-scientists and researchers from the National Cancer Center Singapore (NCCS) have demonstrated the use of exosomes to successfully target squamous cell cancer tumors that are usually resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).

Their research is the first where exosomes have been applied to target TKI-resistant cancers in Singapore. The findings were published in the journal Developmental Cell.

Epidermal growth factor receptor, also known as EGFR, is a biomarker frequently implicated in cancer and EGFR-TKIs are a class of drugs commonly used to target EGFR and treat the disease. However, the success of these cancer therapeutics has been variable, and many tumors with high levels of EGFR are resistant to TKIs.

The discovery

One of the biggest groups of EGFR-implicated cancers are squamous cell cancers, one of the deadliest cancers worldwide. Professor Gopal Iyer, Head of the Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and NCCS, treats head and neck squamous cell cancers (HNSCC) in which over 80–90% of tumors have overexpressed EGFR.

While treating patients in the clinic at NCCS, he observed that the majority do not respond to drugs targeting EGFR.

In 2017, Prof Iyer and his research team identified mutations in a rare subset of HNSCC patients that conferred sensitivity to EGFR-TKIs. The mutation resulted in a number of changes: low expression of EGFR-AS1 and high expression of EGFR isoform D. Only 3–5% of HNSCC harbor these mutations, leaving the rest of the patient group without an effective treatment.

Using exosomes in cancer treatment

Since the initial discovery in 2017, Prof Iyer and team have worked on extending their initial findings for application to a larger group of patients.

In their most recent work, they found that the EGFR isoform D produced by sensitive tumors had certain characteristics that allowed it to be secreted. Using patient-derived HSNCC cell lines in the lab, they were able to show that EGFR isoform is carried as a cargo in exosomes, and these were taken up by adjacent cancer cells and made them sensitive to TKIs.

Exosomes, which are excreted by all living cells, contain cell parts such as DNA, RNA, lipids, and proteins. They are secreted into circulation and affect the function and behavior of other cells they encounter. This communication has been shown to influence the development of various diseases, including inflammatory diseases, neurodegenerative diseases and cancer, which has made using exosomes a new and promising field for medical treatments.

The team then tested whether this characteristic of sensitivity conferred by high levels of the EGFR isoform D, was transferrable from a sensitive cancer to a resistant cancer. They produced large volumes of exosomes producing EGFR isoform D in the lab and treated a number of cell lines that were resistant to TKIs.

The exosomal treatment was able to increase the sensitivity of the resistant cell lines to many different types of TKIs. Remarkably, they were able to achieve the same result in vivo using a mouse model, confirming that it is possible to target EGFR TKI-resistant tumors with this strategy.

Opening a treasure chest

Professor Iyer, who is also Head of the translational research Division of Medical Sciences at NCCS said, "Our findings provide new hope for patients as we can potentially target a large population who previously had poor prognosis for their cancer. We're excited to partner industry to move this research to the next phase so that we can start offering therapeutic solutions to our patients in the clinic."

"We have opened a treasure chest of how exosomes can potentially be applied to transfer treatment-sensitivity for other cancers. The possibilities are endless for the future of exosomes as yet another weapon in the fight against cancer."

The research team plans to scale up exosome production so that the findings can be taken into early-stage clinical trials. They are currently in discussions with various industry and academic partners to achieve this goal.

More information: Shen Yon Toh et al, Therapeutic application of extracellular vesicular EGFR isoform D as a co-drug to target squamous cell cancers with tyrosine kinase inhibitors, Developmental Cell (2024). DOI: 10.1016/j.devcel.2024.07.003

https://medicalxpress.com/news/2024-09-scientists-exosomes-secreted-cells-successfully.html

Proof-of-principle study uncovers promising treatment for incurable prostate cancer

 Researchers from Flinders University and University of South Australia have unveiled a promising new strategy that could be used to treat the most aggressive forms of prostate cancer. Their study, published in British Journal of Cancer, explores the role of a novel drug, CDKI-73, to tackle drug-resistant prostate cancer that defies conventional therapies.

Prostate cancer is the most commonly diagnosed cancer in Australian men and causes more than 3,300 deaths each year. The disease frequently evolves into aggressive forms that do not respond to standard hormone therapies.

Despite this, prostate cancer remains a sensitive and often under-discussed topic.

The study, led by Associate Professor Luke Selth from Flinders University and Professor Shudong Wang from University of South Australia, investigated the potential of targeting a protein called Cyclin-Dependent Kinase 9 (CDK9), which plays a crucial role in the growth and survival of prostate cancer cells.

More specifically, the researchers tested whether an inhibitor of CDK9, CDKI-73, could overcome the cancer's resistance to current treatments.

"Our research demonstrates that CDKI-73 potently blocks the growth of prostate cancer, even aggressive subtypes of the disease that are resistant to current treatments," says Associate Professor Selth. "Importantly, CDKI-73 targets cancer cells specifically without harming normal cells and its potential as an oral capsule makes it an attractive treatment option."

Using advanced technologies, the study examined the effects of CDKI-73 using an array of prostate cancer models, including patient tumor samples, which revealed not only the effectiveness of the inhibitor but also provided new insights into its mode of action.

"This study represents a significant step forward in understanding the role of CDK9 in aggressive prostate cancer," adds Associate Professor Selth. "Having said that, we still need to do a lot more work to fully understand the potential of CDK9 inhibitors and to deliver a new treatment for patients."

CDKI-73 is currently being investigated in Phase 2 clinical trials in patients with relapsed and therapy-resistant acute myeloid leukemia, an aggressive blood cancer.

"This study demonstrates that CDKI-73 is a promising candidate for treating solid tumors such as prostate cancer," says Professor Wang, who developed CDKI-73.

"Our proof-of-principle study is an important step towards future clinical trials and these findings will inform future studies in the use and efficacy of CDKI-73 as a prostate cancer treatment," adds Professor Wang.

More information: Razia Rahman et al, CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer, British Journal of Cancer (2024). DOI: 10.1038/s41416-024-02810-8

https://medicalxpress.com/news/2024-09-proof-principle-uncovers-treatment-incurable.html

'New technique allows comprehensive genetic examination of embryos with single test'

 Researchers from Karolinska Institutet and Maastricht University have developed a technique that enables the examination of embryos for all known genetic abnormalities with a single test. The new method is more accurate and faster than existing techniques, increasing the chance of a healthy child for parents at increased risk of inherited conditions.

The research was published today (Sept. 2) in Nature Communications.

Prospective parents who are at risk of having a child with a serious hereditary condition or repeated miscarriages due to chromosomal abnormalities may opt for pre-implantation genetic testing (PGT), also known as embryo selection. It is an IVF treatment in which embryos are screened for known genetic abnormalities, and only embryos without the abnormality are placed in the womb.

Led by geneticist Masoud Zamani Esteki, an affiliated researcher at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, researchers at Maastricht UMC+ have developed a technique that can analyze the entire genome—all genes and chromosomes—in a single test. This means that any hereditary condition for which help is sought can now be detected faster and more effectively.

Multiple tests are replaced by a single test

Genetic abnormalities can occur in different places. For example, a change in a single gene can increase the risk of hereditary breast cancer, while a chromosomal abnormality can lead to repeated miscarriages because the embryos are not viable.

Previously, different tests were required to detect different types of abnormalities, meaning that each couple needed to undergo a separate genetic examination to decide which test to use.

With the new test, which can detect all known types of abnormalities, the preliminary procedure is the same for everyone and much faster.

"With the available tests, we could only examine specific parts of the genetic information in an embryo. This new technique maps all the genetic information in an embryo, which means we do not need to develop a PGT test for each individual condition.

"In addition, this technique can also detect specific genetic abnormalities, namely those in the DNA outside the cell nucleus (mitochondrial DNA), such as in MELAS syndrome," says Esteki.

WGS-PGT as an all-in-one method. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-51508-1

More embryos

In addition to being more complete, the new technique is also more accurate than current methods and reveals even the smallest errors in the genetic material.

Esteki explains, "In the past, prospective parents had to wait a long time for the test to develop and some embryos could not be transferred because the PGT result was unclear. Now we can determine this quickly and with more than 99% certainty, which means that more embryos can be considered for transfer."

The new technique is now being used at Maastricht UMC+, the only PGT center in the Netherlands. PGT centers in other countries are expected to adopt the technique.

Ethical questions remain

As the new technology makes it possible to examine the entire genetic material, new possibilities arise.

"In principle, we can look beyond the condition for which help is sought and better determine which embryos have the best chance of succeeding in pregnancy and giving birth to a healthy child. As a result, fewer placement procedures would be needed," says Esteki.

He emphasizes that a number of ethical issues must first be resolved for these applications. For example, there should be an agreement on which unexpected abnormalities we have solid evidence, such that we do not select embryos for transfer and which can be considered normal genetic variation. So both ethical consideration and new data are required to define these guidelines in the clinic.

More information: Anouk E. J. Janssen et al, Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing, Nature Communications (2024). DOI: 10.1038/s41467-024-51508-1

https://medicalxpress.com/news/2024-09-technique-comprehensive-genetic-embryos.html

False-positive mammograms discourage some women from future screenings

 Early detection of breast cancer through mammography screening continues to save lives. However, abnormal findings on mammograms can lead to women being recalled for additional imaging and biopsies, many of which turn out to be "false positives," meaning they do not result in a cancer diagnosis. False positives can also have financial implications for patients and cause significant emotional anxiety.

A major, new study led by the UC Davis Comprehensive Cancer Center has found that women who received a false-positive result that required additional imaging or biopsy were less likely to return for that follow-up screening.

The research was published in the Annals of Internal Medicine on Sept. 3. It analyzed data on more than 3.5 million screening mammograms nationwide performed between 2005–2017 on over 1 million patients aged 40 to 73.

"The finding raises concerns about the potential unintended consequence of false-positive results, where women may avoid screening mammograms in the future," said lead author Diana Miglioretti, cancer center researcher and chief of the Division of Biostatistics at UC Davis.

Findings are worrisome to researchers

The study found that 77% of women with a negative result from a mammogram returned for subsequent screening. But this percentage dropped to 61% after a false-positive finding requiring another mammogram in six months to confirm the results and 67% if a biopsy was recommended.

The impact was even more pronounced for women who received false-positive results on two consecutive mammograms recommending short-interval follow-up—only 56% returned their next screening mammogram.

The high rate of women who don't return for future screening is concerning to the research team.

"It is important for women with false-positive results to continue screening every one to two years," Miglioretti said, "Having a false-positive result, especially if it results in a diagnosis of benign breast disease, is associated with an increased risk of being diagnosed with breast cancer in the future."

The research also showed that Asian and Hispanic/Latinx women were the least likely to return for future screening mammograms after a false positive result, which may contribute to existing health disparities.

False-positive results are common, especially among younger women. They occur in 10–12% of mammograms in women 40–49 years of age. After 10 years of annual screenings, 50–60% of women can expect at least one false-positive and 7–12% at least one false-positive with a biopsy recommendation.

"It's important to understand that most women recalled for additional imaging due to a finding on a screening mammogram do not have breast cancer," Miglioretti said. "They should try not to be worried if they are recalled for additional work-up. It is a normal and common part of the screening process."

It is important for women to understand that about 10% of the time, additional imaging is necessary to get a better look at a finding on a screening mammogram.

Steps to consider

Miglioretti said women who feel anxious while waiting for their screening mammography results might consider requesting an on-the-spot interpretation of their mammogram. Some facilities provide this service along with same-day diagnostic work-up, if there is a suspicious finding.

She said it is also important for physicians to carefully explain false-positive results to their patients to reassure them that the result was negative and stress the importance of continued screening.

More information: Impact of False-Positives on Future Screening, Annals of Internal Medicine (2024). DOI: 10.7326/M24-0123

https://medicalxpress.com/news/2024-09-false-positive-mammograms-discourage-women.html

Two of three trials fail, but Sanofi will still file MS drug

 Sanofi has said it plans to start discussions about filing its oral BTK inhibitor tolebrutinib for multiple sclerosis, even though the drug only achieved its primary objective in one of three phase 3 trials.

The good news for the company was that tolebrutinib was able to achieve a statistically significant reduction in disability accumulation in non-relapsing secondary progressive MS (nrSPMS) in the HERCULES study – becoming the only drug in the class to do so, according to the drugmaker.

On the other hand, two studies of the drug in relapsing forms of MS – GEMINI 1 and 2 – were unable to show any improvement with tolebrutinib compared to Sanofi's current oral MS therapy Aubagio (teriflunomide) on the main endpoint of reducing the annualised relapse rate.

Tolebrutinib was one of three oral BTK inhibitors that Sanofi acquired as part of its $3.7 billion buyout of Principia Biopharma in 2020, and was abandoned as a treatment for myasthenia gravis - another neuromuscular disorder – last year for what the company said at the time were commercial reasons.

Sanofi is banking on the totality of data from the three phase 3 trials supporting potential filings for tolebrutinib, with the HERCULES result backed up by secondary endpoint data from the GEMINI studies showing that the drug was able to achieve a "considerable delay" in the worsening of disability compared to Aubagio.

A fourth phase 3 trial called PERSEUS in patients with primary progressive MS (PPMS) is still ongoing, with results due next year.

There is a much greater need for new therapies for progressive forms of MS than in relapsing forms of the disease, so Sanofi's decision to proceed based on the HERCULES result makes sense.

While relapsing forms are characterised by sudden attacks associated with advancing disability, in non-relapsing patients the decline tends to be more continuous and driven by underlying nerve inflammation. For that reason, focusing on disease progression and the time to disability – rather than the relapse rate – is a more logical measure for progressive forms.

Despite treatment, most patients with relapsing MS eventually go on to develop SPMS, so having an additional treatment option for this group could be a big step forward.

Earlier this year, Houman Ashrafian, Sanofi's head of R&D, said that while the annualised relapse rate remains the endpoint of choice currently, "most of the [patient] community and most of the physicians that are looking after these patients will point you to the fact that […] confirmed disability progression is much more important."

The question now is what wording on tolebrutinib's label Sanofi will go after if – based on feedback from regulators – it files the drug for approval in MS.

The drug is one of several oral BTK drugs that have been in clinical development for MS, alongside Merck KGaA's evobrutinib, Roche's fenebrutinib, Novartis' remibrutinib, and InnoCare Pharma's orelabrutinib.

Evobrutinib was the first BTK inhibitor to show proof-of-concept in a phase 2 trial, but failed two phase 3 trials in relapsing MS last year and was shelved. Fenebrutinib is in phase 3 for PPMS, with results due in 2026, while remibrutinib is in phase 3 for relapsing MS. China's InnoCare was partnering with Biogen on the development of orelabrutinib, which is in a phase 2 trial in relapsing MS, but the US firm handed back rights last year.

The rationale for targeting BTK is that it allows selective inhibition of the auto-reactive B-cells that are behind the pathologies of MS, myasthenia gravis, and other autoimmune disorders.

That could give the drugs an advantage over CD20-targeting therapies like Roche's Ocrevus (ocrelizumab) – which inhibit B-cells across the board, leaving patients prone to infections and other side effects – and are also less likely to cross the blood-brain barrier into the central nervous system.

Last year, GlobalData suggested that tolebrutinib would be the leading BTK inhibitor for MS by 2030, with forecasted sales of approximately $2.6 billion across seven of the largest pharma markets.

https://pharmaphorum.com/news/two-three-trials-fail-sanofi-will-still-file-ms-drug

Hundreds of rabid anti-Israel protesters storm NYC on Labor Day, light flares, set off smoke bombs

 Hundreds of rowdy anti-Israeli protesters stormed through the Big Apple on Labor Day, lighting flares and setting off smoke bombs as they marched toward the heart of the city.

The mob gathered at Union Square in the early afternoon and began their raucous march north towards Grand Central Terminal, according to footage posted online Freedom TV and others.

Police officers detain an anti-Israel protester as people march with a demand of a ceasefire and the end of Israeli attacks on Gaza, amid the Israel-Hamas conflict, in New York City, New York, September 2, 2024.REUTERS

Video footage shows an NYPD officials attempting to halt the march, only to be shoved aside by a few of the demonstrators.

Blue and red flares fill the air with smoke as the group moves through the city.

Anti-Israel demonstrators march as they demand a ceasefire and the end of Israeli attacks on Gaza, amid the Israel-Hamas conflict, in New York City, New York, September 2, 2024.REUTERS
The mass protest is just the latest show of disorder by anti-Israeli marchers since the Jewish State retaliated for a sneak attack on Israel by Hamas terrorists on Oct. 7 — with protests spreading to college campuses in the city and throughout the nation.

The Post reported this weekend that the demonstrations are costing corporations across the globe billions of dollars.

https://nypost.com/2024/09/02/us-news/hundreds-of-rabid-anti-israel-protesters-storm-nyc-on-labor-day-light-flares-and-set-off-smoke-bombs/