Posted on Cancer

A new study finds 40 per cent of cancer cases and almost half of all deaths in the US are linked to lifestyle factors.

A new study led by researchers at the American Cancer Society (ACS) finds four in 10 cancer cases and about one-half of all cancer deaths in adults 30 years old and older in the United States (or 713,340 cancer cases and 262,120 cancer deaths in 2019) could be attributed to modifiable risk factors, including cigarette smoking, excess body weight, alcohol consumption, physical inactivity, diet, and infections. Cigarette smoking was by far the leading risk factor, contributing to nearly 20% of all cancer cases and 30% of all cancer deaths. The findings are published today in CA: A Cancer Journal for Clinicians.

“Despite considerable declines in smoking prevalence during the past few decades, the number of lung cancer deaths attributable to cigarette smoking in the United States is alarming. This finding underscores the importance of implementing comprehensive tobacco control policies in each state to promote smoking cessation, as well as heightened efforts to increase screening for early detection of lung cancer when treatment could be more effective,” said Dr Farhad Islami, senior scientific director, cancer disparity research at the American Cancer Society and lead author of the report. “Interventions to help maintain healthy body weight and diet can also substantially reduce the number of cancer cases and deaths in the country, especially given the increasing incidence of several cancer types associated with excess body weight, particularly in younger individuals.”

In this study, researchers used nationally representative data on cancer incidence and mortality and risk factor prevalence to estimate the proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors (excluding non-melanoma skin cancers) for 30 cancer types. These risk factors included cigarette smoking (current and former smoking); secondhand smoke; excess body weight; alcohol consumption; consumption of red and processed meat; low consumption of fruits and vegetables, dietary fibre, and dietary calcium; physical inactivity; ultraviolet (UV) radiation; and infection with Epstein-Barr virus (EBV), Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), human herpes virus-8 (HHV-8; also called Kaposi sarcoma herpesvirus), human immunodeficiency virus (HIV), and human papillomavirus (HPV).

The results showed cigarette smoking had the most considerable population-attributable fraction (PAF) or proportion of cancer cases attributable to risk factors in the population (344,070 cases; 19.3% of all cases), contributing to 56.0% of all potentially preventable cancers in men (206,550 of 368,600) and 39.9% in women (137,520 of 344,740). Excess body weight had the second largest PAF (7.6%), followed by alcohol consumption (5.4%), UV radiation exposure (4.6%), and physical inactivity (3.1%).

By cancer type, the proportion of cases caused by potentially modifiable risk factors ranged from 100% for cervical cancer and Kaposi sarcoma to 4.9% for ovarian cancer. It exceeded 50% for 19 of 30 evaluated cancer types. In addition to cervical cancer and Kaposi sarcoma, more than 80% of all melanomas of the skin (92.2%) and cancers of the anus (94.2%), larynx (89.9%), lung and bronchus (lung; 88.2%), pharynx (87.4%), trachea (85.6%), oesophagus (85.4%), and oral cavity (83.7%) were attributable to evaluated risk factors. Lung cancer had the most significant number of cases attributable to evaluated risk factors in both men (104,410 cases) and women (97,250), followed by skin melanoma (50,570), colorectal cancer (44,310), and urinary bladder cancer (32,000) in men and by breast (83,840), corpus uteri (35,790), and colorectal (34,130) cancer in women.

“These findings show a continued need to increase equitable access to preventive health care and awareness about preventive measures. Effective vaccines are available for hepatitis B virus, which causes liver cancer and HPV, which can cause several cancer types, including cervical, other anogenital, and oropharyngeal cancers,” added Dr Ahmedin Jemal, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “Vaccination at the recommended time can substantially reduce the risk of chronic infection and, consequently, cancers associated with these viruses. HPV vaccination uptake in the United States is suboptimal.”

Posted on Pain Management

Understanding the roots of chronic pain

Image of Piezo2 gene expression (shown in magenta) in lumbar dorsal root ganglion sections from mice.

Image of Piezo2 gene expression (shown in magenta) in lumbar dorsal root ganglion sections from mice. CREDIT Lewin Lab of the Max Delbrück Center

A team of researchers led by Oscar Sánchez-Carranza in Professor Gary Lewin’s lab at the Max Delbrück Center have identified a new function of the PIEZO2 protein in mediating chronic pain hypersensitivity. The research suggests a new target for analgesics and potentially explains why pain medications that target voltage-gated sodium channels have been as disappointing as clinical targets. The study was published in the journal Brain, a leading neurology journal.

“There’s a good correlation between chronic pain and the sensitization of pain receptors, called nociceptors, in humans,” says Lewin. “This study implicates the PIEZO2 channel as a critical mediator of sensory signals that maintain chronic pain.”

PIEZO2 protein forms an ion channel in human sensory receptors. Previous studies have shown that the ion channel communicates the sense of touch to the brain. People with “loss-of-function” mutations in the PIEZO2 gene are hypo-sensitive to gentle touch or vibration. By contrast, patients with “gain-of-function mutations” in PIEZO are often diagnosed with complex developmental disorders. However, whether gain-of-function mutations are responsible for mechanical hypersensitivity has never been proven.

Mutation sensitizes nociceptors dramatically. 

To study the connection, Sánchez-Carranza created two strains of so-called “gain-of-function” mice, each carrying a different version of a mutated PIEZO2 gene. He expected to find the touch receptors of these mice to be highly sensitive. In cell biology experiments, his team found that PIEZO2 mutations have a powerful effect on the activity of the ion channel. One mutation, for example, causes the channel to open with ten times less force than normal non-mutated channels.

Using electrophysiological methods developed in the Lewin lab, Sánchez-Carranza and his colleagues measured electrical activity in sensory neurons isolated from the transgenic mice. They found that in addition to sensitizing touch receptors as expected, the mutations made nociceptive receptors – neurons that detect painful mechanical stimuli – dramatically more sensitive to mechanical stimuli. 

Moreover, the researchers found that the nociceptors were activated by mechanical stimuli typically experienced as light touch.

“You need to crush the skin to activate nociceptors,” Sánchez-Carranza explains. However, the nociceptors from the transgenic mice were triggered by levels of mechanical force that would typically be perceived as a touch. They were susceptible.” 

That a single mutation in PIEZO2 was enough to change the physiology of the nociceptors from one type of neuron to another was especially surprising, says Lewin. More significantly, when the stimulus was removed, the neurons kept firing. The study is the first time anyone has linked gain-of-function mutations in the PIEZO2 gene to pain receptors.

PIEZO2 might be involved in pain syndromes like fibromyalgia

Clinical studies have shown that in patients with chronic pain syndromes such as fibromyalgia and small fibre neuropathies, C-fiber nociceptors, which are the sensory receptors that initiate pain, are hyperactive. When researchers recorded the activity of nociceptors in such people, they found that they were active without any mechanical stimulus. But the mechanism was not precise. 

“We show that just by changing one amino acid in PIEZO2, we can mimic a lot of what happens in chronic pain in the C-fibers,” says Lewin. In humans, “PIEZO2 might be involved in many of these pathologies.” Nociceptive neurons are the largest population of sensory neurons that innervate the skin – humans have four times more pain receptors in the skin than touch receptors.

Up to 20% of the adult population suffers from chronic pain, according to a 2023 study by the U.S. National Institutes of Health, which is poorly treated with existing medications. The same NIH study found that two-thirds of people who reported chronic pain in 2019 were still suffering one year later.

The findings suggest that new pain medications could target a particular aspect of the PIEZO2 channel mechanism of opening. Much effort has been put into developing new analgesics, which have focused on voltage-gated sodium channels with limited success, says Lewin. “By addressing the root cause of nociceptor sensitization, new drugs could provide better relief for chronic pain sufferers.”

Posted on Pain Management

Light-activated drugs against neuropathic pain

Zebrafish larvae

Zebrafish larvae CREDIT

institute for Bioengineering of Catalonia (IBEC)

Light can be used to activate drugs in specific parts of the body through photopharmacology. This innovative approach involves modifying the chemical structure of a drug by adding a light-activated molecular switch, such as azobenzene. This allows the drug to be activated only when exposed to a specific light colour rather than in the dark.

Based on these principles, a team of researchers led by the Institute for Bioengineering of Catalonia (IBEC) has developed photoswitchable derivatives of carbamazepine, an anti-epileptic drug widely used in medicine to combat some types of neuropathic pain, such as trigeminal neuralgia. These compounds, which have an analgesic effect when activated by light, can inhibit nerve signals locally and on demand. The derivatives synthesised by the researchers are activated at wavelengths corresponding to the amber colour, which allows them to pass through tissue and bone using conventional halogen lamps.

The two synthesised compounds, carbazopine-1 and carbadiazocine, show photopharmacological activity, allowing the activity of hippocampal neurons and the locomotion of zebrafish larvae to be reversibly controlled by light. These in vivo experiments allow observing anxiety-related behaviours reflected in sudden swimming movements. IBEC researcher Luisa Camerin, the study’s first author, explains: “When we illuminate larvae that have uptaken these compounds with a certain wavelength, the drug is activated and the larvae move faster. If we change the wavelength, their movement slows down again, demonstrating the reversible effect of the compound on the nervous system.

Carbadiazocine has also been shown to have analgesic properties: “In rat models developed in the laboratory of Esther Berrocoso at the University of Cadiz, we have observed that carbadiazocine has an analgesic effect on neuropathic pain without any signs of anaesthesia, sedation or toxicity. These results demonstrate a simple and convincing treatment with non-invasive illumination,” explains Pau Gorostiza, ICREA research professor, principal investigator at IBEC and member of CIBER-BBN.

Neuropathic pain is caused by lesions or diseases of the somatosensory system, such as lumbar radiculopathy (“sciatica”), diabetic neuropathy and chronic post-operative pain. The treatment of this type of pain often requires opioids, which are stronger analgesics than the usual NSAIDs – such as paracetamol and ibuprofen. However, their use is controversial due to their inconsistent efficacy, the need for high doses that can lead to tolerance and addiction, and systemic side effects such as constipation, nausea, dizziness and drowsiness.

Posted on Arthritis

Nanorobots are capable of travelling through synovial fluid to fight arthritis

Samuel Sánchez, ICREA Research Professor at the Institute of Bioengineering of Catalonia (IBEC), will lead the OrthoBots project, which focuses on treating joint diseases using nanorobots.

Arthritis, an inflammatory disease that affects millions of people worldwide, is mainly characterised by osteoarthritis, a chronic degenerative disease that worsens with age and represents a significant economic burden for healthcare systems.

A promising alternative to current treatments is platelet-rich plasma (PRP) therapy. PRP harnesses the regenerative potential of growth factors, proteins found in the blood that play a key role in injury repair, to stimulate tissue repair processes, particularly in cartilage and bone cells. However, it is common for these proteins to be rapidly degraded upon contact with synovial fluid, limiting their therapeutic efficacy and distribution.

To overcome these obstacles, scientists are exploring advanced drug delivery systems that use nanoparticles as transporters. Although promising, passive diffusion of nanoparticles across viscous biological barriers, such as synovial fluid, remains a significant obstacle.

OrthoBots is presented as an answer to this problem. The project aims to develop enzyme-powered nanoparticles, known as nanorobots, to improve the transport and delivery of these growth factors, facilitating targeted cartilage regeneration.

“This innovative approach has transformative potential, potentially revolutionising arthritis therapy by overcoming current limitations and offering more effective and personalised treatment strategies,” says project leader Samuel Sánchez. Through systematic in vitro studies and in vivo proof of concept, OrthoBots aims to pave the way for the next generation of arthritis therapies, addressing unmet clinical needs and improving patient outcomes.

To carry out the project, Sánchez was awarded an ERC Proof of Concept Grant. This is a prestigious grant awarded by the European Research Council (ERC) to explore the commercial and societal potential of research projects that are or have been funded by the ERC. Applicants use this type of funding to test the practical feasibility of scientific concepts, explore business opportunities or prepare patent applications. This is the sixth grant Samuel Sánchez has received from the European Research Council and the third in the Proof of Concept category.

Posted on Diabetes, Diet

Blood fat profiles confirm the health benefits of replacing butter with high-quality plant oils

Plant oils and butter

CAPTION

Blood fat profiles confirm health benefits of replacing butter with high-quality plant oils CREDIT Chalmers University of Technology | Emma Fry

Switching from a diet high in saturated animal fats to one rich in plant-based unsaturated fats affects the fat composition in the blood, which in turn influences long-term disease risk. A recent study published in Nature Medicine, conducted by a team of researchers from Chalmers University of Technology, Sweden, the German Institute of Human Nutrition, Germany and several other universities, shows that it is possible to accurately measure diet-related fat changes in the blood and directly link them to the risk of developing cardiovascular disease and type 2 diabetes.“Our study confirms with even more certainty the health benefits of a diet high in unsaturated plant fats such as the Mediterranean diet and could help provide targeted dietary advice to those who would benefit most from changing their eating habits”, says Clemens Wittenbecher, research leader at Chalmers University of Technology and the study’s senior author. The World Health Organisation (WHO) highlights the importance of healthy diets in preventing chronic diseases, recommending the replacement of saturated fats with plant-based unsaturated fats to reduce cardiometabolic risk.

“We summarised the effects on blood lipids with a multi-lipid score (MLS). A high MLS indicates a healthy blood fat profile, and a high intake of unsaturated plant fat and low intake of saturated animal fat can help achieving such positive MLS levels”, says Fabian Eichelmann from the German Institute of Human Nutrition Potsdam-Rehbruecke and first author of the study.These MLS results from the dietary intervention study were then statistically related to the occurrence of cardiovascular disease and type 2 diabetes in large observational studies that had previously been carried out. These large cohort studies followed initially healthy participants for several years. This analysis of data from both sets of studies showed that participants with a higher MLS, which indicates a beneficial dietary fat composition, had a substantially reduced risk of developing cardiometabolic diseases. Switching to a healthier diet, can have the most pronounced health benefits Additionally, the study examined whether individuals with low MLS levels, indicating high saturated fat content of the diet, specifically benefited from a healthier diet. The Mediterranean diet focuses on providing more unsaturated plant fats and was used in one of the large intervention trials, known as the PREDIMED trial. Using this study, the researchers found that diabetes prevention was indeed most pronounced in individuals with low MLS levels at the start of the study.“Diet is so complex that it is often difficult to draw conclusive evidence from a single study. Our approach of using lipidomics to combine intervention studies with highly controlled diets and prospective cohort studies with long-term health tracking can overcome current limitations in nutrition research,” explains Clemens Wittenbecher.