Tag Archives: cancer

Molecular ‘Switch’ Reverses Chronic Inflammation And Aging

Chronic inflammation, which results when old age, stress or environmental toxins keep the body’s immune system in overdrive, can contribute to a variety of devastating diseases, from Alzheimer’s and Parkinson’s to diabetes and cancer.

Now, scientists at the University of California, Berkeley, have identified a molecularswitch” that controls the immune machinery responsible for chronic inflammation in the body. The finding, which appears online  in the journal Cell Metabolism, could lead to new ways to halt or even reverse many of these age-related conditions.

My lab is very interested in understanding the reversibility of aging,” said senior author Danica Chen, associate professor of metabolic biology, nutritional sciences and toxicology at UC Berkeley. “In the past, we showed that aged stem cells can be rejuvenated. Now, we are asking: to what extent can aging be reversed? And we are doing that by looking at physiological conditions, like inflammation and insulin resistance, that have been associated with aging-related degeneration and diseases.”

In the study, Chen and her team show that a bulky collection of immune proteins called the NLRP3 inflammasome — responsible for sensing potential threats to the body and launching an inflammation response — can be essentially switched off by removing a small bit of molecular matter in a process called deacetylation.

Overactivation of the NLRP3 inflammasome has been linked to a variety of chronic conditions, including multiple sclerosis, cancer, diabetes and dementia. Chen’s results suggest that drugs targeted toward deacetylating, or switching off, this NLRP3 inflammasome might help prevent or treat these conditions and possibly age-related degeneration in general.

This acetylation can serve as a switch,” Chen said. “So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off.”

Source: https://news.berkeley.edu/

Ultrasound Can Selectively Kill Cancer Cells

A new technique could offer a targeted approach to fighting cancer: low-intensity pulses of ultrasound have been shown to selectively kill cancer cells while leaving normal cells unharmed.

Ultrasound wavessound waves with frequencies higher than humans can hear—have been used as a cancer treatment before, albeit in a broad-brush approach: high-intensity bursts of ultrasound can heat up tissue, killing cancer and normal cells in a target area. Now, scientists and engineers are exploring the use of low-intensity pulsed ultrasound (LIPUS) in an effort to create a more selective treatment.

A study describing the effectiveness of the new approach in cell models was published in Applied Physics Letters. The researchers behind the work caution that it is still preliminary—it still has not been tested in a live animal let alone in a human, and there remain several key challenges to address—but the results so far are promising.

The research began five years ago when Caltech‘s Michael Ortiz, Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering, found himself pondering whether the physical differences between cancer cells and healthy cells—things like size, cell-wall thickness, and size of the organelles within them—might affect how they vibrate when bombarded with sound waves and how the vibrations might trigger cancer cell death.

I have my moments of inspiration,” Ortiz says wryly.

And so Ortiz built a mathematical model to see how cells would react to different frequencies and pulses of sound waves. Together with then-graduate student Stefanie Heyden (PhD ’14), who is now at ETH Zurich, Ortiz published a paper in 2016 in the Journal of the Mechanics and Physics of Solids showing that there was a gap in the so-called resonant growth rates of cancerous and healthy cells. That gap meant that a carefully tuned sound wave could, in theory, cause the cell membranes of cancerous cells to vibrate to the point that they ruptured while leaving healthy cells unharmed. Ortiz dubbed the process “oncotripsy” from the Greek oncos (for tumor) and tripsy (for breaking).

Source: https://www.caltech.edu/

Nanoparticles Act As Immunotherapy Agents

University of Wisconsin–Madison researchers have developed nanoparticles that, in the lab, can activate immune responses to cancer cells. If they are shown to work as well in the body as they do in the lab, the nanoparticles might provide an effective and more affordable way to fight cancer.

They are cheaper to produce and easier to engineer than the antibodies that underlie current immunotherapies, which as drugs cost tens of thousands of dollars a month.

The nanoparticles were made of sections of the T cell protein PD-1 (in blue) attached to a branched core called a dendrimer (in gray). The branches in the core of the nanoparticle allowed many chunks of the PD-1 protein to bind to the nanoparticle, increasing its effectiveness.

Immunotherapy basically boosts the patient’s own immune system to fight against cancer cells better,” says Seungpyo Hong, a professor in the UW–Madison School of Pharmacy. “The antibodies that are used right now are large, they’re expensive, they’re hard to engineer, and they don’t always show the highest level of efficacy either. So we wanted to explore other ways to activate the immune system.

Hong and postdoctoral associate Woo-jin Jeong led the study, published online Jan. 2 in the Journal of the American Chemical Society, with collaborators at the University of Illinois at Chicago. It’s the first demonstration that nanoparticles can act as immunotherapy agents.

More research is needed to understand their effectiveness in the body, but Hong has applied for a patent on the new nanoparticles and is now testing them in animal models.

In tests against lab-grown strains of cancer, the nanoparticles boosted production of the immune stimulating protein interleukin-2 by T cells, one kind of immune cell in the body, by about 50 percent compared to no treatment. They were just as effective as antibodies. The nanoparticles were also able to improve the effectiveness of the chemotherapy drug doxorubicin in similar tests.

Normally, T cells produce a protein named PD-1 that acts like an off switch for immune responses. This “checkpoint” helps keep T cells from improperly attacking healthy cells.

Source: https://news.wisc.edu/

Copper-based Nanomaterials Kill Cancer Cells

An interdisciplinary team of scientists from KU Leuven (Belgium), the University of Bremen (Germany), the Leibniz Institute of Materials Engineering (Germany), and the University of Ioannina (Greece) has succeeded in killing tumour cells in mice using nano-sized copper compounds together with immunotherapy. After the therapy, the cancer did not return.

Recent advances in cancer therapy use one’s own immunity to fight the cancer. However, in some cases, immunotherapy has proven unsuccessful. The team of biomedical researchers, physicists, and chemical engineers found that tumours are sensitive to copper oxide nanoparticles – a compound composed of copper and oxygen. Once inside a living organism, these nanoparticles dissolve and become toxic. By creating the nanoparticles using iron oxide, the researchers were able to control this process to eliminate cancer cells, while healthy cells were not affected.

Any material that you create at a nanoscale has slightly different characteristics than its normal-sized counterpart,” explain Professor Stefaan Soenen and Dr Bella B. Manshian from the Department of Imaging and Pathology, who worked together on the study. “If we would ingest metal oxides in large quantities, they can be dangerous, but at a nanoscale and at controlled, safe, concentrations, they can actually be beneficial.

As the researchers expected, the cancer returned after treating with only the nanoparticles. Therefore, they combined the nanoparticles with immunotherapy. “We noticed that the copper compounds not only could kill the tumour cells directly, they also could assist those cells in the immune system that fight foreign substances, like tumours,” says Dr Manshian.

The combination of the nanoparticles and immunotherapy made the tumours disappear entirely and, as a result, works as a vaccine for lung and colon cancer – the two types that were investigated in the study. To confirm their finding, the researchers injected tumour cells back into the mice. These cells were immediately eliminated by the immune system, which was on the lookout for any new, similar, cells invading the body.

Source: https://nieuws.kuleuven.be/

Turning Light Energy Into Heat To Fight Disease

An emerging technology involving tiny particles that absorb light and turn it into localized heat sources shows great promise in several fields, including medicine. For example, photothermal therapy, a new type of cancer treatment, involves aiming infrared laser light onto nanoparticles near the treatment site. Localized heating in these systems must be carefully controlled since living tissue is delicate. Serious burns and tissue damage can result if unwanted heating occurs in the wrong place. The ability to monitor temperature increases is crucial in developing this technology. Several approaches have been tried, but all of them have drawbacks of various kinds, including the need to insert probes or inject additional materials.

In this week’s issue of APL Photonics,, scientists report the development of a new method to measure temperatures in these systems using a form of light known as terahertz radiation. The study involved suspensions of gold nanorods of various sizes in water in small cuvettes, which were illuminated by a laser focused on a small spot within the cuvette. The tiny gold rods absorbed the laser light and converted it to heat that spread through the water by convection.

 

We are able to map out the temperature distribution by scanning the cuvette with terahertz radiation, producing a thermal image,” co-author Junliang Dong said.

The study also looked at the way the temperature varied over time. “Using a mathematical model, we are able to calculate the efficiency by which the gold nanorod suspensions converted infrared light to heat,” said co-author Holger Breitenborn.

The smallest gold particles, which had a diameter of 10 nanometers, converted laser light to heat with the highest efficiency, approximately 90%. This value is similar to previous reports for these gold particles, indicating the measurements using terahertz radiation were accurate. Although the smaller gold rods had the highest light-to-heat conversion efficiency, the largest rods — those with a diameter of 50 nanometers — displayed the largest molar heating rate. This quantity has been recently introduced to help evaluate the use of nanoparticles in biomedical settings.

By combining measurements of temperature transients in time and thermal images in space at terahertz frequencies, we have developed a noncontact and noninvasive technique for characterizing these nanoparticles,” co-author Roberto Morandotti said. This work offers an appealing alternative to invasive methods and holds promise for biomedical applications.

Source:  https://aip.scitation.org/
A
ND
https://www.eurekalert.org/

Simple Urine Test To Spot Cancer

A Japanese firm is poised to carry out what it hailed as the world’s first experiment to test for cancer using urine samples, which would greatly facilitate screening for the deadly disease. Engineering and IT conglomerate Hitachi developed the basic technology to detect breast or colon cancer from two years ago. It will now begin testing the method using some 250 urine samples, to see if samples at are suitable for analysis, Hitachi spokesman Chiharu Odaira told AFP.

If this method is put to practical use, it will be a lot easier for people to get a cancer test, as there will be no need to go to a medical organisation for a ,” he said. It is also intended to be used to detect paediatric cancers.

That will be especially beneficial in testing for ” who are often afraid of needles,” added Odaira. Research published earlier this year demonstrated that a new blood test has shown promise towards detecting eight different kinds of tumours before they spread elsewhere in the body.

Usual diagnostic methods for breast cancer consist of a mammogram followed by a biopsy if a risk is detected. For , screening is generally conducted via a stool test and a colonoscopy for patients at high risk. The Hitachi technology centres around detecting waste materials inside urine samples that act as a “biomarker“—a naturally occurring substance by which a particular disease can be identified, the company said in a statement.

The procedure aims to improve the early detection of cancer, saving lives and reducing the medical and social cost to the country, Odaira explained.

The experiment is now completed in cooperation with Nagoya University in central Japan. “We aim to put the technology in use in the 2020s, although this depends on various things such as getting approval from the authorities,” Odaira said.

Source: https://medicalxpress.com/

New Vaccine Brings Revolution In Preventing Chronic Inflammation Related To 60% Of Death

As we learn more and more about health, well-being, and all the factors that affect both, inflammation has become a major player in the conversation. Linked with symptoms ranging from bloating and acne to more serious things like depression and cancer, chronic inflammation, researchers believe, could continue to increase in prevalence. But a new vaccine offers hope for the future of preventing inflammatory diseases.

The vaccine, which is currently for animals, was developed by Institut Cochin in France. Researchers already knew about a connection between inflammation, gut health, and the protein flagellin: Flagellin essentially allows into the rest of the body, resulting in inflammation, and while antibodies exist within that intestinal barrier to help prevent leaky gut, it’s harder to keep all the bacteria contained if your microbiome is out of balance. Researchers hypothesized they could boost the flagellin antibodies within the gut, thereby keeping harmful bacteria from spreading into the body. They administered a flagellin vaccine to mice by injecting it directly into their intestinal lining, spurring the production of the flagellin-fighting antibodies. Chronic inflammation is thought to be related to 60% of deaths worldwide, due to its connection to stroke, diabetes, cancer, and more. This vaccine could be a game-changer if scientists are able to replicate the findings in a version for humans, which researcher Benoît Chassaing says they’re working on.

This vaccine strategy can be envisaged in humans, because such abnormalities of the microbiota have been observed in patients with inflammatory and metabolic diseases. With this in mind, we are currently working on a means of locally administering flagellin to the intestinal mucosa,” he says.

They’re also looking into testing the vaccine on animals that already have chronic inflammatory diseases, to see if it can be used for inflammatory treatment, as opposed to just prevention. But until such a vaccine for humans exists, there are lots of ways to combat inflammation naturally. If you’re still looking for more information, check out the Ultimate Guide to Inflammation class.. When inflammation was induced, the unvaccinated mice became obese, and the vaccinated mice did not. Immunization quelled intestinal inflammation by lowering levels of the flagellin-expressing bacteria in their microbiota, intestines, and intestinal lining.

Source: https://www.mindbodygreen.com/

53% Of Blood Cancer Treated With CAR-T Cell Immunotherapy Healed

Bristol-Myers Squibb Co on Saturday said that an experimental cancer therapy it acquired as part of its $74 billion deal for Celgene Corp produced positive results in a clinical trial. The company said it will apply for U.S. approval for the treatment for a type of advanced blood cancer by the end of the year.

The treatment, liso-cel, is a newer type of immunotherapy known as CAR-T cell therapy, that takes immune cells from a patient, engineers them to better recognize and attack cancer and infuses them back into the patient.

The study tested three dose levels of liso-cel in the 269 patients with relapsed or refractory large B-cell lymphoma. Nearly three quarters of the patients responded to the one-time treatment, with 53% experiencing a complete response, meaning no detectable sign of the cancer, according to data presented at American Society of Hematology Conference in Orlando.

The data marks a win for Bristol-Myers after its purchase of Celgene met resistance from some investors who thought that it was overpaying for the cancer-focused biotech. It is also a positive sign for Celgene investors, who are entitled to received a contingent value right, or CVR, payment of $9 a share if three treatments in development, including liso-cel, achieve timely approvals.

Source: https://www.reuters.com/

The Rising Of Gene Therapy

After false starts, drugs that manipulate the code of life are finally changing lives. The idea for gene therapy—a type of DNA-based medicine that inserts a healthy gene into cells to replace a mutated, disease-causing variant—was first published in 1972. After decades of disputed results, treatment failures and some deaths in experimental trials, the first gene therapy drug, for a type of skin cancer, was approved in China in 2003. The rest of the world was not easily convinced of the benefits, however, and it was not until 2017 that the U.S. approved one of these medicines. Since then, the pace of approvals has accelerated quickly. At least nine gene therapies have been approved for certain kinds of cancer, some viral infections and a few inherited disorders. A related drug type interferes with faulty genes by using stretches of DNA or RNA to hinder their workings. After nearly half a century, the concept of genetic medicine has become a reality.

These treatments use a harmless virus to carry a good gene into cells, where the virus inserts it into the existing genome, canceling the effects of harmful mutations in another gene.

GENDICINE: China’s regulatory agency approved the world’s first commercially available gene therapy in 2003 to treat head and neck squamous cell carcinoma, a form of skin cancer. Gendicine is a virus engineered to carry a gene that has instructions for making a tumor-fighting protein. The virus introduces the gene into tumor cells, causing them to increase the expression of tumor-suppressing genes and immune response factors.The drug is still awaiting FDA approval.

GLYBERA: The first gene therapy to be approved in the European Union treated lipoprotein lipase deficiency (LPLD), a rare inherited disorder that can cause severe pancreatitis. The drug inserted the gene for lipoprotein lipase into muscle cells. But because LPLD occurs in so few patients, the drug was unprofitable. By 2017 its manufacturer declined to renew its marketing authorization; Glybera is no longer on the market.

IMLYGIC: The drug was approved in China, the U.S. and the E.U. to treat melanoma in patients who have recurring skin lesions following initial surgery. Imlygic is a modified genetic therapy inserted directly into tumors with a viral vector, where the gene replicates and produces a protein that stimulates an immune response to kill cancer cells.

KYMRIAH: Developed for patients with B cell lymphoblastic leukemia, a type of cancer that affects white blood cells in children and young adults, Kymriah was approved by the FDA in 2017 and the E.U. in 2018. It works by introducing a new gene into a patient’s own T cells that enables them to find and kill cancer cells.

LUXTURNA: The drug was approved by the FDA in 2017 and in the E.U. in 2018 to treat patients with a rare form of inherited blindness called biallelic RPE65 mutation-associated retinal dystrophy. The disease affects between 1,000 and 2,000 patients in the U.S. who have a mutation in both copies of a particular gene, RPE65. Luxturna delivers a normal copy of RPE65 to patients’ retinal cells, allowing them to make a protein necessary for converting light to electrical signals and restoring their vision.

STRIMVELIS: About 15 patients are diagnosed in Europe every year with severe immunodeficiency from a rare inherited condition called adenosine deaminase deficiency (ADA-SCID). These patients’ bodies cannot make the ADA enzyme, which is vital for healthy white blood cells. Strimvelis, approved in the E.U. in 2016, works by introducing the gene responsible for producing ADA into stem cells taken from the patient’s own marrow. The cells are then reintroduced into the patient’s bloodstream, where they are transported to the bone marrow and begin producing normal white blood cells that can produce ADA.

YESCARTA: Developed to treat a cancer called large B cell lymphoma, Yescarta was approved by the FDA in 2017 and in the E.U. in 2018. It is in clinical trials in China. Large B cell lymphoma affects white blood cells called lymphocytes. The treatment, part of an approach known as CAR-T cell therapy, uses a virus to insert a gene that codes for proteins called chimeric antigen receptors (CARs) into a patient’s T cells. When these cells are reintroduced into the patient’s body, the CARs allow them to attach to and kill cancer cells in the bloodstream.

ZOLGENSMA: In May 2019 the FDA approved Zolgensma for children younger than two years with spinal muscular atrophy, a neuromuscular disorder that affects about one in 10,000 people worldwide. It is one of the leading genetic

causes of infant mortality. Zolgensma delivers a healthy copy of the human SMN gene to a patient’s motor neurons in a single treatment.

ZYNTEGLO: Granted approval in the E.U. in May 2019, Zynteglo treats a blood disorder called beta thalassemia that reduces a patient’s ability to produce hemoglobin, the protein in red blood cells that contains iron, leading to life-threatening anemia. The therapy has been approved for individuals 12 years and older who require regular blood transfusions. It employs a virus to introduce healthy copies of the gene for making hemoglobin into stem cells taken from the patient.The cells are then reintroduced into the bloodstream and transported to the bone marrow, where they begin producing healthy red blood cells that can manufacture hemoglobin.

The approach called ‘Gene Interference‘ uses a synthetic strand of RNA or DNA (called an oligonucleotide) that, when introduced into a patient’s cell, can attach to a specific gene or its messenger molecules, effectively inactivating them. Some treatments use an antisense method, named for one DNA strand, and others rely on small interfering RNA strands, which stop instruction molecules that go from the gene to the cell’s protein factories.

Source: https://www.nature.com/

How Do Killer Immune Cells Protect Themselves?

White blood cells, which release a toxic potion of proteins to kill cancerous and virus-infected cells, are protected from any harm by the physical properties of their cell envelopes, find scientists from UCL and the Peter MacCallum Cancer Centre in Melbourne. Until now, it has been a mystery to scientists how these white blood cells – called cytotoxic lymphocytesavoid being killed by their own actions and the discovery could help explain why some tumours are more resistant than others to recently developed cancer immunotherapies.

The research, published in Nature Communications, highlights the role of the physical properties of the white blood cell envelope, namely the molecular order and electric charge, in providing such protection.

Cytotoxic lymphocytes, or white blood cells, rid the body of disease by punching holes in rogue cells and by injecting poisonous enzymes inside. Remarkably, they can do this many times in a row, without harming themselves. We now know what effectively prevents these white blood cells from committing suicide every time they kill one of their targets,” according to Professor Bart Hoogenboom (London Centre for Nanotechnology, UCL Physics & Astronomy and UCL Structural & Molecular Biology), co-author of the study.

The scientists made the discovery by studying perforin, which is the protein responsible for the hole-punching. They found that perforin’s attachment to the cell surface strongly depends on the order and packing of the molecules – so-called lipids – in the membrane that surrounds and protects the white blood cells.

Source: https://www.ucl.ac.uk/