PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Team discovers how TKI cancer drugs cause inflammatory side effects

Team discovers how TKI cancer drugs cause inflammatory side effects
2023-03-17
(Press-News.org) Tyrosine kinase inhibitors are a type of targeted cancer medicine that can attack specific types of cancer cells and prevent them from multiplying. Although these inhibitors, called TKIs, can be very useful in fighting certain cancers, they also cause serious inflammatory side effects that limit their use. A Japanese research team has discovered the underlying mechanism that causes this inflammation.

"This study revealed the underlying mechanism by which the TKIs cause inflammation, and therefore provides the molecular basis that is essential to overcome the inflammatory-based side effects," said Atsushi Matsuzawa, a professor at the Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University.

The team's findings were published in The Journal of Immunology on February 6, 2023.

These TKIs are essential anticancer drugs. However, the use of TKIs frequently initiates inflammation in the body, such as the lung disease interstitial pneumonitis. From their earlier studies, the team had learned that a representative TKI called Gefitinib (GF) causes lung inflammation. GF is a helpful cancer medication used in treating certain breast, lung, and other cancers. It works by targeting the epidermal growth factor receptors. When the GF is used to treat the cancer, it can also cause inflammation in the patient's lungs, through the NLRP3 inflammasome. The NLRP3 inflammasome is part of the body's immune system and plays an important role in innate immunity. But when the NLRP3 inflammasome is improperly activated, it can contribute to the development of a wide range of inflammatory diseases.

Until now, scientists have not fully understood why the NLRP3 inflammasome is activated, but the evidence seems to point to mitochondrial dysfunction. When mitochondria are healthy, they work like batteries, producing energy in the body's cells. Mitochondrial dysfunction happens when the mitochondria do not work as they should because of disease. In their earlier study, the team learned that the GF activated the NLRP3 inflammasome through mitochondrial damage that led to the interstitial pneumonitis in patients. However, they had not understood how GF initiates the mitochondrial damage and whether or not other TKIs also shared this mechanism.

To conduct their study, the team looked at the tyrosine kinases, those enzymes that work as a kind of "on" and "off" switch in many of the cells' functions. They specifically studied the Src family kinases, called SFKs. The SFKs are nonreceptor tyrosine kinases that regulate many cell processes. There are 11 types of SFKs in the human genome. Some of these SFKs are in the mitochondria and they play an essential role in the function of the mitochondria. The team found that all the TKIs they tested inhibit the kinase activity of the SKFs in the mitochondria which is responsible for the NLRP3 inflammasome.

The team's comprehensive analysis of the TKIs they tested revealed that these TKIs act as powerful agonists. In addition, the team observed off-target activity that could contribute to the side effects. "As an important finding, all TKIs we tested share a common off-target activity against the mitochondrial SFKs. Therefore, blocking the access of TKIs to mitochondria is a good way to prevent the inflammation," said Matsuzawa. They also noted that the other TKIs that do not affect the activity of the mitochondrial SFKs may overcome the inflammatory-based side effects. As another approach, when effective inhibitors of the NLRP3 inflammasome are developed, administering the TKIs at the same time as the NLRP3 inhibitors can counteract the side effects. The team's results provide insight into both the biological and the clinical significance of the NLRP3 inflammasome and the SFKs.

Looking ahead, the team's next step is to propose a new approach to avoid the inflammatory-based side effects of TKIs. They hope to lead in the development of new TKIs that do not initiate inflammation.

The research team includes Yuto Sekiguchi, Saya Takano, Takuya Noguchi, Tomohiro Kagi, Ryuto Komatsu, Maoko Tan, Yusuke Hirata, and Atsushi Matsuzawa from the Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.

END

[Attachments] See images for this press release:
Team discovers how TKI cancer drugs cause inflammatory side effects Team discovers how TKI cancer drugs cause inflammatory side effects 2 Team discovers how TKI cancer drugs cause inflammatory side effects 3

ELSE PRESS RELEASES FROM THIS DATE:

Numerical simulation of materials-oriented ultra-precision diamond cutting: Review and outlook

Numerical simulation of materials-oriented ultra-precision diamond cutting: Review and outlook
2023-03-17
Publishing in the International Journal of Extreme Manufacturing (IJEM), researchers from Harbin Institute of Technology, Huazhong University of Science and Technology, Guizhou University and Ruhr-University Bochum present a brief review on the application of numerical simulations in addressing the impact of properties and microstructures of workpiece materials on the diamond cutting mechanisms of different types of workpiece materials, such as metallic, hard brittle materials and composite materials. In addition, the effect of applying an external energy field to the diamond cutting of difficult-to-cut materials is also discussed. The anisotropic deformation ...

Better simulations of neutron scattering

2023-03-17
A new simulation approach named eTLE aims to improve the precision of a primary tool for estimating neutron behaviours in 3D space. This study examines the approach in detail – validating its reliability in predicting the scattering of neutrons in crystalline media. Tripoli-4® is a tool used by researchers to simulate the behaviours of interacting neutrons in 3D space. Recently, researchers developed a new ‘next-event estimator’ (NEE) for Tripoli-4®. Named eTLE, this approach aims to increase Tripoli-4®’s precision using Monte ...

New gene-editing technique reverses vision loss in mice

New gene-editing technique reverses vision loss in mice
2023-03-17
Researchers in China have successfully restored the vision of mice with retinitis pigmentosa, one of the major causes of blindness in humans. The study, to be published March 17 in the Journal of Experimental Medicine, uses a new, highly versatile form of CRISPR-based genome editing with the potential to correct a wide variety of disease-causing genetic mutations. Researchers have previously used genome editing to restore the vision of mice with genetic diseases, such as Leber congenital amaurosis, that affect ...

Machine intelligence and humanity benefit from ‘spiral’ of mutual learning, says AI researcher and proponent of ‘cognitive physics’

Machine intelligence and humanity benefit from ‘spiral’ of mutual learning, says AI researcher and proponent of ‘cognitive physics’
2023-03-17
Deyi Li from the Chinese Association for Artificial Intelligence believes that humans and machines have a mutually beneficial relationship. His paper on machine intelligence, which was published Feb. 15 in Intelligent Computing, a Science Partner Journal, builds on five groundbreaking works by Schrödinger, the father of quantum mechanics, Turing, the father of artificial intelligence, and Wiener, the father of cybernetics. Schrödinger and beyond: Machines can think and interact with the world as time goes by. ...

Miracle math determines the dynamically coordinated regulation of edge velocity by Rho GTPases

Miracle math determines the dynamically coordinated regulation of edge velocity by Rho GTPases
2023-03-17
Ikoma, Japan – Rho GTPases have a crucial role in the orchestration of cell movements. Cells use Rho GTPases to coordinate cytoskeletal reorganization in dynamically changing environments. Among these RhoGTPases, Cdc42 and Rac1 promote cytoskeletal formation, whereas RhoA is involved in myosin II-mediated cytoskeletal retraction and formation. Simultaneous live observations of multiple GTPase activities and cell morphology changes by specific biosensors and the resulting spatiotemporal data might help to determine the coordinated regulation of ...

The most beautiful strongly bound dibaryon

The most beautiful strongly bound dibaryon
2023-03-17
Dibaryons are the subatomic particles made of two baryons. Their formations through baryon-baryon interactions play a fundamental role in big-bang nucleosynthesis, in nuclear reactions including those within stellar environments, and provide a connection between nuclear physics, cosmology and astrophysics. Interestingly, the strong force, which is the key to the existence of nuclei and provides most of their masses, allows formations of numerous other dibaryons with various combinations of quarks. However, we do not observe them abound -- deuteron is the only known stable dibaryon. To resolve this apparent dichotomy, it is essential to investigate ...

New machine-learning approach enables to identify one molecule in a billion molecules selectively with graphene sensors

New machine-learning approach enables to identify one molecule in a billion molecules selectively with graphene sensors
2023-03-17
Graphene’s 2D nature, single molecule sensitivity, low noise, and high carrier concentration have generated a lot of interest in its application in gas sensors. However, due to its inherent non-selectivity, and huge p-doping in atmospheric air, its applications in gas sensing are often limited to controlled environments such as nitrogen, dry air, or synthetic humid air. While humidity conditions in synthetic air could be used to achieve controlled hole doping of the graphene channel, this does not adequately mirror the situation ...

ETRI introduces AI tutor who teaches foreign language reading

ETRI introduces AI tutor who teaches foreign language reading
2023-03-17
The Electronics and Telecommunications Research Institute(ETRI) has developed a reading comprehension education AI technology that allows you to learn foreign language listening, speaking, and reading by talking to an artificial intelligence (AI) tutor. It is expected to be of great help in the spread of AI-based language education services. The Electronics and Telecommunications Research Institute(ETRI) introduced a reading comprehension AI tutor, an artificial intelligence technology for reading education, that introduced deep learning-based dialog processing technology to reading comprehension education for the first time in the world. Through ...

Burt's Bees nature-based products improve photodamaged and hyperpigmented facial skin

2023-03-17
DURHAM, N.C., March 17, 2023 – Burt’s Bees, the #1 dermatologist recommended natural skin care brand,* announced its latest research findings on the benefits of a topical bakuchiol-containing sunscreen in treating redness and pigmentation of photodamaged facial skin. Burt’s Bees also published research findings on a topical treatment in improving the appearance of post-inflammatory hyperpigmentation associated with acne. These studies, available online via ePoster, have been developed for the American Academy of Dermatology 2023 Annual Meeting (AAD) Mar. 17–21, 2023, ...

Resistant bacteria are a global problem. Now researchers may have found the solution

2023-03-17
Staphylococcus aureus. You may have had it in connection with a wound infection. In most cases, it will pass without treatment, while severe cases may require antibiotics, which kills the bacteria. This is the case for the majority of the population. In fact, many of us – though we feel perfectly fine – carry staphylococci in the nose, a good, moist environment in which the bacteria thrive. However, more and more staphylococci are becoming resistant to antibiotics (also known as multi resistant staphylococcus aureus or MRSA), and these infections can be difficult to treat. “Antibiotics resistance ...

LAST 30 PRESS RELEASES:

Modesty and boastfulness – perception depends on usual performance

Do sweeteners increase your appetite? New evidence from randomised controlled trial says no 

Women with obesity do not need to gain weight during pregnancy, new study suggests

Individuals with multiple sclerosis face substantially greater risk of hospitalisation and death from COVID-19, despite high rates of vaccination

Study shows obesity in childhood associated with a more than doubling of risk of developing multiple sclerosis in early adulthood

Rice Emerging Scholars Program receives $2.5M NSF grant to boost STEM education

Virtual rehabilitation provides benefits for stroke recovery

Generative AI develops potential new drugs for antibiotic-resistant bacteria

Biofuels could help island nations survive a global catastrophe, study suggests

NJIT research team discovering how fluids behave in nanopores with NSF grant

New study shows association of historical housing discrimination and shortfalls in colon cancer treatment

Social media use may help to empower plastic surgery patients

Q&A: How to train AI when you don't have enough data

Wayne State University researchers uncover potential treatment targets for Zika virus-related eye abnormalities

Discovering Van Gogh in the wild: scientists unveil a new gecko species

Small birds spice up the already diverse diet of spotted hyenas in Namibia

Imaging detects transient “hypoxic pockets” in the mouse brain

Dissolved organic matter could be used to track and improve the health of freshwaters

Indoor air quality standards in public buildings would boost health and economy, say international experts

Positive associations between premenstrual disorders and perinatal depression

New imaging method illuminates oxygen's journey in the brain

Researchers discover key gene for toxic alkaloid in barley

New approach to monitoring freshwater quality can identify sources of pollution, and predict their effects

Bidirectional link between premenstrual disorders and perinatal depression

Cell division quality control ‘stopwatch’ uncovered

Vaccine protects cattle from bovine tuberculosis, may eliminate disease

Andrew Siemion to receive the SETI Institute’s 2024 Drake Award

New study shows how the Crimean-Congo hemorrhagic fever virus enters our cells

Neoadjuvant chemotherapy proves effective for locally advanced penile squamous cell carcinoma

Study flips treatment paradigm in bilateral Wilms tumor, shows resistance to chemotherapy may point toward favorable outcomes

[Press-News.org] Team discovers how TKI cancer drugs cause inflammatory side effects