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What Might be the Best Way to Delivery Nanoparticle Therapy for Cancer? – Genetic Engineering & Biotechnology News

Posted: March 27, 2020 at 1:45 am

Scientists in the cancer nanomedicine community debate whether use of nanoparticles can best deliver drug therapy to tumors passively, allowing the nanoparticles to diffuse into tumors and become held in place, or actively, adding a targeted anti-cancer molecule to bind to specific cancer cell receptors and, in theory, keep the nanoparticle in the tumor longer. Now, new research on human and mouse tumors in mice by investigators at the Johns Hopkins Kimmel Cancer Center suggests the question is even more complicated.

Laboratory studies testing both methods in six models of breast cancer; five human cancer cell lines and one mouse cancer in mice with three variants of the immune system found that nanoparticles coated with trastuzumab, a drug that targets human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells, were better retained in the tumors than plain nanoparticles, even in tumors that did not express the pro-growth HER2 protein. However, immune cells of the host exposed to nanoparticles induced an anti-cancer immune response by activating T cells that invaded and slowed tumor growth. The results of the work Nanoparticle interactions with immune cells dominate tumor retention and induce T cellmediated tumor suppression in models of breast cancer, appears in Science Advances.

The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand (active targeting) is superior to its unlabeled counterpart (passive targeting). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions, write the investigators.

Systemic exposure to either nanoparticle type induced an immune response leading to CD8+ T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.

Its been known for a long time that nanoparticles, when injected into the bloodstream, are picked up by scavenger-like macrophages and other immune system cells, explains senior study author Robert Ivkov, PhD, associate professor of radiation oncology and molecular radiation sciences at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Many researchers in the field have been focused on trying to reduce interactions with immune cells, because they have been trying to increase the circulation time of the nanoparticles and their retention in tumor cells. But our study demonstrates that the immune cells in the tumor collect and react to the particles in such a way to stimulate an anti-cancer response. This may hold potential for advancing beyond drug delivery toward developing cancer immunotherapies.

The investigators conducted a few in vitro experiments in their study. First, they applied some plain starch-coated iron oxide nanoparticles and others coated with trastuzumab to five human breast cancer cell lines, finding that the amount of binding between the trastuzumab-coated nanoparticles and cells depended on how much the cancer cells expressed the oncogene HER2. In people, HER2-positive breast cancers are among the most resistant to standard chemotherapy.

Trastuzumab, sold under the name Herceptin, targets the HER2-positive tumor cells and triggers the immune system as well.

Responses were surprisingly different in animal models, the researchers report. In separate experiments, the team used the nanoparticles in two immune-deficient strains of mice engrafted with cells from five human breast cancer cell linestwo that were HER2 negative and three that were HER2 positive. When they studied the animals tumors 24 hours later, they noticed that nanoparticles coated with trastuzumab were found in a concentration two to five times greater than the plain nanoparticles in all types of tumors, regardless of whether they expressed the HER2 protein. They also found that the number of trastuzumab-coated nanoparticles was even greater (tenfold) in mice that had a fully functional immune system and were bearing mouse-derived tumors.

This led the researchers to suspect that the host animals immune systems were interacting strongly with the nanoparticles and playing a role in determining retention of the particles in the tumor, whether or not a drug was added.

More experiments, the team reports, revealed that tumor-associated immune cells were responsible for collecting the nanoparticles, and that mice bred with an intact immune system retained more of the trastuzumab-coated nanoparticles than mice bred without a fully functioning immune system.

In addition, inflammatory immune cells in the tumors immediate surroundings, or microenvironment, seized more of the coated nanoparticles than the plain ones. Finally, in a series of 30-day experiments, the researchers found that exposure to nanoparticles inhibited tumor growth three to five times more than controls, and increased CD8-positive cancer-killing T cells in the tumors.

Surprisingly, Ivkov notes, the anti-cancer immune activating response was equally effective with exposure to either plain or trastuzumab-coated nanoparticles. Mice with defective T cells did not show tumor growth inhibition. The investigators say this demonstrated that systemic exposure to nanoparticles can cause a systemic host immune response that leads to anti-cancer immune stimulation and does not require nanoparticles to be inside the tumors.

Overall, our work suggests that complex interdependencies exist between the host and tumor immune responses to nanoparticle exposure, Ivkov says. These results offer intriguing possibilities for exploring nanoparticle targeting of the tumor immune microenvironment. They also demonstrate exciting new potential to develop nanoparticles as platforms for cancer immune therapies.

The investigators say they also plan to study whether the same types of immune responses can be generated for noncancer conditions, such as infectious diseases.

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What Might be the Best Way to Delivery Nanoparticle Therapy for Cancer? - Genetic Engineering & Biotechnology News

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Graphene research that breaks the mould – Times Higher Education (THE)

Posted: March 27, 2020 at 1:45 am

Alfaisal Universitys development of polymer nanocomposites is creating new materials with exceptional properties

When we talk about technological advancements transforming the way we live, our focus is often on the digital revolution, such as the effects of artificial intelligence and smart technologies. But within physics and chemistry, research into nanomaterials is creating equally profound and important changes in the physical world.

Edreese Alsharaeh, professor of chemistry at Alfaisal University in Saudi Arabia, works with graphene-based composites that are synthesised with nanoparticulate matter to enhance their physiochemical properties. He believes that every aspect of our lives and almost every product that we use could be transformed by the application of nanomaterials and likens their discovery to the synthesis of the first polymers.

Almost 100 years ago, the use of polymers had a major, major impact on our daily life, he says. We replaced steel. We replaced aluminium. We preserved a lot of natural resources. Nanomaterials nowadays are like polymers 100 years ago. In my line of work, it is the synergetic effect when adding a small percentage of this graphene into the polymer that can do magic.

Of course, there is no magic, but nanomaterials are perhaps as close to sorcery as contemporary chemistry gets. As Professor Alsharaeh explains, nanomaterials have an inordinately high surface-to-volume ratio compared with materials composed of larger particles, and are thus more reactive, with nano-enhanced materials dramatically more efficient in their design. In some respects, nanotechnology builds on the fundamentals already established by the physical sciences, such as Professor Alsharaehs work with graphene and silver composites.

Silver has antimicrobial physiochemical properties capable of killing a wide range of bacteria and fungi, which is why wound dressings often incorporate it as a means of reducing the risk of infection. But by using graphene and silver nanocomposites, these antimicrobial properties can be achieved using far less silver. This, explains Professor Alsharaeh, is a synergetic effect that can make a graphene composite with 5 per cent of silver nanoparticles behave with the same antimicrobial properties as 100 per cent silver. Because graphene is flexible, these composites can be used in biomedical contexts such as engineering next-generation bone cement for hip surgery, where infection can be a major cause of morbidity, because the physical demands placed on hips require super-durable orthopaedic solutions.

We need a product that can stop clinical problems such as infection when you do implants, says Professor Alsharaeh. We chose the silver and the graphene because graphene is stronger than steel yet elastic. In our product, the toughness increases 70 per cent and the elasticity is increased by 150 per cent, all from adding 2 per cent graphene.

With multiple drug resistant bacteria increasingly a problem, finding novel strategies for combatting hospital infections is also a priority for medical science. This is an area where the antimicrobial properties of both graphene and silver might provide the answer; and so it is the focus of extensive research at Professor Alsharaehs lab, where graphene and silver have been found to be effective in disinfecting MDR bacteria and E. coli, with the electronic structure of graphene in particular inhibiting bacteria growth. Everyday medical apparatus could incorporate nanocomposites of graphene and silver to stop the spread of infection.

This composite is very good for coating biomedical devices, which is something that is a major deal when you use a catheter, for example, says Professor Alsharaeh. People are [developing an] infection and I think when we coat [devices] with some kind of material like this, that will change. This is in our product development phase now, in addition to the bone cement.

Graphene has the potential to revolutionise nanocomposite materials. That it can be anchored with any number of nanoparticles only enhances its versatility and increases the number of real-world applications it could be used for. It is strong, flexible and thermoconductive. You can make any device out of it, says Professor Alsharaeh. It can be used as a substrate for multifunctional properties.

As he explains, graphenes structure with carbon atoms bonded in a flat, hexagonal lattice is key. Because it is a two-dimensional structure, it restricts electrons to movements along an X or Y axis, and this confinement creates energy that endows graphene with useful optical and electronic properties. Its electronic properties are actually one of the most attractive things about the graphene, says Professor Alsharaeh, who adds that graphene can conduct electricity up to 150 times faster than silicon, and be used for superconductors and to manufacture dramatically more efficient integrated circuits for computer processing.

The goal for Professor Alsharaehs lab at Alfaisal is to take this research into product development as soon as possible. Besides its medical applications, Alfaisal has a patent with oil and gas giant Saudi Aramco on a graphene-based product that is in the process of commercialisation. The Kingdom puts a lot of resources in, says Professor Alsharaeh. From 2010, since I came to Saudi Arabiathere has been major funding for all scientists, which is a major plan for this energy sector. With agriculture, medicine, energy and textiles sectors all set to reap the benefits of nanotechnology, the commercial potential of graphene nanocomposites is invaluable.

Professor Alsharaeh adds that he is a chemist, and his passion is for discovery and teaching. It is very, very rewarding for me to see [that some students] have now finished their PhDs and are making their way in the world, he says. This is also about building the culture for future scientists. And I think nanotechnology is the future for all future-first technologies.

That future will still be shaped by the digital revolution, but when the smart devices in our pockets, homes, workplaces and hospitals are all enhanced by nanomaterials, perhaps that future should be considered a joint venture with nanotechnology.

Learn moreabout Alfaisal University.

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Graphene research that breaks the mould - Times Higher Education (THE)

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Kanazawa University Research: Insights into the Diagnosis and Treatment of Brain Cancer in Children – PR Newswire UK

Posted: March 27, 2020 at 1:45 am

KANAZAWA, Japan, March 25, 2020 /PRNewswire/ -- In a recent study published in Autophagy, researchers at Kanazawa University show how abnormalities in a gene called TPR can lead to pediatric brain cancer.

Ependymoma is a rare form of brain cancer that implicates children and is often tricky to diagnose. Since effective treatment options can be initiated only after a well-formed diagnosis, there is a dire need among the medical community to identify markers for ependymoma, which in turn, will help oncologists tailor therapy better. Richard Wong's and Mitsutoshi Nakada's team at Kanazawa University has now shown how one gene closely linked to ependymoma can help with not just diagnosis, but also treatment options for the condition.

A gene known as TPR shows an elevated presence in 38% of ependymoma cases. Thus, the team first sought out to investigate how an increase in the TPR gene correlated to the development of cancer cells. Each gene present in a cell contains a code for the creation of a specific protein. The TPR gene contains the code for an eponymous protein. Therefore, cancer samples from patients were assessed for the levels of TPR protein. As expected, levels of TPR were abnormally high in these tumor tissues.

The researchers then moved on to investigate whether these abnormal TPR levels could lead to cancer progression. For this purpose, mice were implanted with human ependymoma cancer tissue into their brains. The TPR gene was then deleted in these tissues so that the mice were unable to create the TPR protein. When the tumor tissues were subsequently analyzed, a reduction of cancer growth was seen. The TPR gene was thus vital for the growth of ependymoma tumors.

Deletion of the TPR protein is known to induce a process called autophagy within cells. Autophagy is initiated when a cell is under undue stress and results in the death of damaged cells. The patient tumor samples, with their high levels of TPR protein, showed little or no presence of autophagy. However, autophagy was remarkably high in the mice with TPR depletion. Ependymoma cells were thus spared of autophagic death due to the increased presence of TPR. These damaged cells continued to grow by circumventing the biological systems set up to keep them in check. The high TPR levels were also accompanied by an increase in HSF-1 and MTOR, molecules which are responsible for cell growth and survival.

Finally, the possibility of lowering TPR levels therapeutically to control the cancer was assessed. The mice were given a drug called rapamycin, which inhibits MTOR. The treatment not only led to decreased TPR levels, but also shrank the tumor tissues within their brains.

"Thus, TPR can serve as a potential biomarker, and MTOR inhibition could be an effective therapeutic approach for ependymoma patients," conclude the researchers. While looking out for increased levels of TPR in patients can help oncologists achieve a more comprehensive diagnosis, reducing TPR levels with the help of drugs can help keep the tumors in check.

Background:

Autophagy: Autophagy, which literally translates to "self-eating" is the self-preservation mechanism of the body to get rid of damaged cells. Autophagy is initiated when an abnormal amount of proteins or toxins build up within a cell, which the cell cannot clear out. Conditions like Alzheimer's disease and Parkinson's disease arise when autophagic mechanisms within the cells start malfunctioning. Impaired autophagy is also known to be implicated in driving various forms of cancer.

Reference

Firli Rahmah Primula Dewi, Shabierjiang Jiapaer, Akiko Kobayashi, Masaharu Hazawa, Dini Kurnia Ikliptikawati, Hartono, Hemragul Sabit, Mitsutoshi Nakada, and Richard W. Wong. "Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma", Autophagy. Published online 24March2020.

DOI 10.1080/15548627.2020.1741318.

About Nano Life Science Institute (WPI-NanoLSI)

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Nano Life Science Institute (NanoLSI), Kanazawa University is a research center established in 2017 as part of the World Premier International Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology. The objective of this initiative is to form world-tier research centers. NanoLSI combines the foremost knowledge of bio-scanning probe microscopy to establish 'nano-endoscopic techniques' to directly image, analyze, and manipulate biomolecules for insights into mechanisms governing life phenomena such as diseases.

About Kanazawa University

http://www.kanazawa-u.ac.jp/e/

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

Further information

Hiroe Yoneda Vice Director of Public AffairsWPI Nano Life Science Institute (WPI-NanoLSI)Kanazawa UniversityKakuma-machi, Kanazawa 920-1192, JapanEmail: nanolsi-office@adm.kanazawa-u.ac.jp Tel: +81-(76)-234-4550

SOURCE Kanazawa University

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Kanazawa University Research: Insights into the Diagnosis and Treatment of Brain Cancer in Children - PR Newswire UK

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Hundreds of research scholars working at chem, bio labs across India want to help test COVID-19. But the govt isn’t letting them – EdexLive

Posted: March 27, 2020 at 1:45 am

Image for representational purpose only (Pic: PTI)

Research scholars working with pieces of equipment that are used for testing the novel Coronavirus at chemistry, biotechnology and even physics labs from across India say they would be able and are willing to help the clinics and personnel with the testing equipment train them properly and also work with them. But they need the government's permission to do so. They have written to various ministries but have not received any reply yet.

Hundreds of researchers from Pune, Mumbai, New Delhi, Hyderabad, Chennai, Varanasi, Kolkata, Mohali and even tier-II and tier-III cities are willing to contribute as volunteers in any way possible. "We have expertise in molecular diagnosis clinical sample handling, RNA isolation, cDNA preparation and RT-PCR data analysis. We handle such complicated equipment day in and day out in our labs. We learn and perform experiments with these types of equipment on a daily basis," said Vikas Shukla, who is working on Nanomedicine and chronic inflammatory diseases at the Department of Zoology of the Delhi University. "If we possess a skill set that can help the nation in a dire situation like this shouldn't we be allowed to help? We need approval so that we can go and help as volunteers. I understand that this involves a virus and we need to know the protocol. We can start our work with a dummy sample as well for the training," he added.

Harsha, a postgraduate in Optoelectronics and Communications from Thrissur in Kerala wants to be a part of this as well. "I want to help out in any way I can," she wrote to the researchers. But she cannot move out. She is a nursing mother of 10-month-old twins. "This is the only way we can give back to our society right now and I want to be a part of the process," she added.

The CSIR-CCMB has been training medical staff to handle the testing process of Coronavirus but Nikhil Gupta, a Research Fellow at the Centre of Biomedical Research, SGPGI, Lucknow says that the researchers can learn the procedures faster. "We already have the training to handle such equipment. We can learn faster and even spread the knowledge. We can train others when we have the know-how of the equipment. So why not trains? Won't it be more efficient?" he asked.

The researchers have written to Dr Harsh Vardhan, the Minister of Science & Technology, Health and Family Welfare and Earth Science and the Principal Scientific Adviser to the Government of India (PSA). He has also written to the Chief Minister of Uttar Pradesh Yogi Adityanath to allow them to participate in this war against the virus that has affected 562 individuals and claimed nine lives till now. They are now waiting for the government's green signal to start their work.

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Hundreds of research scholars working at chem, bio labs across India want to help test COVID-19. But the govt isn't letting them - EdexLive

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What An Herbalist, Midwife & Integrative MD Says About The Coronavirus – mindbodygreen.com

Posted: March 27, 2020 at 1:44 am

In terms of supplements, needless to say, this herbalist is on board. Romm says there's an arsenal of herbs and supplements we can take to support our immune systemsfrom widely recognized players like zinc and vitamin D to ones we might not be familiar with for immunity, like astragalus and lavender oil.

Let's start with those common supplements: "Nutritionally, if you had to pick the top three we can feel confident about in terms of safety, it would bezinc, vitamin D, and vitamin C. They're safe for anyone at any age, safe during pregnancy and breastfeeding," Romm says.

As for the lesser-known herbs, Romm is partial to adaptogens in order to support the immune system (that includes medicinal mushrooms, like reishi and ashwagandha, and holy basil). She also touts echinacea and astragalus as herbs worth trying for immunitywhile there's no data on them for COVID-19 yet, they do have purported benefits for the common cold.

But Romm's favorite herb in her medicine cabinet is none other than lavender oil, as it helps reduce her anxiety (which, as we know, has quite the impact on our immune systems). "One of my favorites right now is lavender oilit's incredibly effective for a good night's sleep, especially when it's disrupted by anxiety," she explains.

With these herbs and supplements, feel free to take them by capsule, tincture, or even add them to soups and smoothies. While they're great to have on hand, Romm emphasizes that they're not totally necessary (hence the term, supplement). "Don't freak out if you can't find them; just do your best," she assures me.

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What An Herbalist, Midwife & Integrative MD Says About The Coronavirus - mindbodygreen.com

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What Is Curcumin? Why This Anti-Inflammatory Active Is A Game-Changer – mindbodygreen.com

Posted: March 27, 2020 at 1:44 am

Your brain has nerve cells called neurons that can multiply within certain areas of your brain. A big factor behind this is a growth hormone called brain-derived neurotrophic factor (BDNF). "BDNF is a protein produced by brain cells that is very important to the function and survival of brain cells," Lin explains. "We used to believe that we are born with a specific number of nerve cells in the brain, and once they die, they don't grow back. We now know that is not true."

Instead, your brain has the ability to regenerate and repair itself, and BDNF is "critical" in the process, Lin says. "Studies show curcumin can increase BDNF levels, and thus support brain healing and regeneration from injury and trauma," she says.* Cognitive decline is a form of inflammation of the brain tissues, and, given that curcumin manages inflammation, it may help protect people from developing cognitive decline, Lin says.*

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What Is Curcumin? Why This Anti-Inflammatory Active Is A Game-Changer - mindbodygreen.com

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