'Intelligent' nanoparticles could help treat cancer patients

Scientists from the University of Surrey have developed 'intelligent'  nanoparticles which heat up to a temperature high enough to kill  cancerous cells - but which then self-regulate and lose heat before they get hot enough to harm healthy tissue.

The self-stopping nanoparticles could soon be used as part of  hyperthermic-thermotherapy to treat patients with cancer, according to  an exciting new study reported in Nanoscale. Thermotherapy has long been used as a treatment method for cancer, but it is difficult to treat patients without damaging healthy cells. However, tumor cells can be weakened or killed without affecting normal tissue if temperatures can be controlled accurately within a range of 42°C to 45 °C.

This could potentially be a game changer in the way we treat people who have cancer . If we can keep cancer treatment sat at a temperature level high enough to kill the cancer, while low enough to stop harming healthy tissue, it will prevent some of the serious side effects of vital treatment.

It's a very exciting development which, once again, shows that the University of Surrey research is at the forefront of nanotechnologies - whether in the field of energy materials or, in this case, healthcare. Dr. Wei Zhang, Associate Professor from Dalian University of Technology said Magnetic induced hyperthermia is a traditional route of treating  malignant tumors. However, the difficulties in temperature control has significantly restricted its usage If we can modulate the magnetic  properties of the nanoparticles, the therapeutic temperature can be  self-regulated, eliminating the use of clumsy temperature monitoring and controlling systems.

By making magnetic materials with the Curie temperature falling in the range of hyperthermia temperatures, the self-regulation of therapeutics can be achieved. For the most magnetic materials, however,  the Curie temperature is much higher than the human body can endure. By  adjusting the components as we have, we have synthesized the nanoparticles with the Curie temperature as low as 34 °C. This is a major nanomaterials breakthrough.

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'Intelligent' nanoparticles could help treat cancer patients

FDA Approves Once-Weekly Bydureon BCise (exenatide) for Patients with Type-2 Diabetes

 In continuation of my update on exenatide. AstraZeneca announced that the US Food and Drug Administration (FDA) has approved Bydureon® BCise™ (exenatide extended-release) injectable suspension, a new formulation of Bydureon (exenatide extended-release) injectable suspension in an improved once-weekly, single-dose autoinjector device for adults with type-2 diabeteswhose blood sugar remains uncontrolled on one or more oral medicines inaddition to diet and exercise, to improve glycemic control.

Unlike other glucagon-like peptide-1 (GLP-1) receptor agonists, Bydureon BCise has a unique, continuous-release microsphere delivery system designed to provide consistent therapeutic levels of the active ingredient, exenatide, to help patients reach and maintain steady state. The new formulation in the innovative Bydureon BCise device is proven to reduce blood sugar levels, with the added benefit of weight loss, although not a weight loss medicine.

Across two clinical trials, average HbA1c reductions of up to 1.4% and average weight loss of up to 3.1 pounds were achieved when used as  monotherapy or as an add-on to metformin, a sulfonylurea, a thiazolidinedione, or any combination of two of these oral anti-diabetic medicines at 28 weeks. The most common adverse reactions reported in ≥5% of patients in clinical trials were nausea (8.2%) and adverse events associated with injection-s te nodules (10.5%).

Bydureon BCise is designed for ease and patient convenience in a once-weekly, pre-filled device with a pre-attached hidden needle. The medication is administered in three simple steps – mix, unlock, inject.

New molecule could become first treatment against chemotherapy-induced neuropathy

IDIBELL Researchers of the Neuro-Oncology Unit of Bellvitge University Hospital - Catalan Institute of Oncology, led by Dr. Jordi Bruna, have successfully tested a new molecule capable of preventing the development of peripheral neuropathy induced by chemotherapy in cancer patients, especially in colon cancer cases, the third most common neoplasm in the world. The molecule, which has a completely novel mechanism of action, would be the first treatment against this neurological complication, for which no effective treatment has yet been approved.

One of the main adverse effects of certain chemotherapeutics used in the treatment of cancers is peripheral neuropathy, which can cause tingling, numbness, pain or alterations in the functionality of patients, among others. This complication, so far, has been regarded as a "price to pay" despite having a demonstrated negative impact on the quality of life of the patient, increasing their care expenses and often preventing the complete and effective administration of the cytostatic treatment, with the potential decrease of survival chances that entails.

Researchers at the HUB-ICO-IDIBELL Unit identified a new molecule - developed by the Catalan laboratory Esteve - as a candidate to prevent  the onset of this adverse effect. "Through a public-private partnership, we have been able to design a Phase 2b clinical trial (randomized with placebo), which has allowed us to get a great deal of scientific information - effect on pain, pathophysiology - and draw conclusions as to the potential of the drug in the prevention of neuropathies during cytostatic treatment", explains Dr. Bruna, who led the trial.

The results of the study prove a decrease in the appearance of disorders associated with nerve dysfunction in those cancer patients who took the new drug. "When the trial was designed, safety data from the previous trials limited the duration of treatment with the new molecule and this meant that we had to work at low doses in relation to the duration of the chemotherapy treatment, but we have nevertheless obtained positive results and now we have enough information to be able to extend the duration of the treatment. Therefore, we hope to obtain even more satisfactory results" the IDIBELL researcher comments.

"Given the usual pace of clinical trials and drug agencies following fast-track approval processes in severe or orphan pathologies, this new drug could potentially reach the market soon, since it would be the first available treatment to avoid this type of neuropathy. In addition,  it has other medical uses as a non-opioid analgesic", adds Bruna. In any case, improving pain control and reducing the occurrence of severe neuropathy is undoubtedly the most prominent benefit of the development of this novel drug.

Yoga can be beneficial to people with lung cancer and their caregivers

In a feasibility trial of people with advanced lung cancer receiving radiation therapy, and their caregivers, yoga was beneficial to both parties. These findings will be presented at the upcoming 2017 Palliative and Supportive Care in Oncology Symposium in San Diego, California.

"It is never too late to engage in exercise, and we know from earlier studies that people can exercise while being treated with chemotherapy or radiation," said lead study author, Kathrin Milbury, PhD, an assistant professor of cancer medicine in the Department of Palliative Care and Rehabilitation Medicine, University of Texas MD Anderson Cancer Center in Houston, Texas. "Caregivers sometimes have more anxiety and sleeping problems than patients. Therefore, we thought that having the patient and caregiver go through yoga instruction together would be beneficial for both partners."

Prior research showed that women with breast cancer benefit from an exercise regimen. Because people with lung cancer  usually have more symptoms, are older, and in worse physical shape than women with breast cancer, researchers believed yoga was a low-impact exercise that patients could perform easily. Additionally, yoga has a strong emphasis on breathing, an important issue for people with lung
cancer who often have shortness of breath.

"Choosing yoga as the form of exercise to use in this study was important because it is a gentle form of exercise readily modifiable for patients' needs, and it easily allowed for partners to participate in the yoga practices," said Dr. Milbury. "Among the yoga poses we chose to include in this study are what are known as chest openers - exercises that emphasize stretching the chest area along with deep breathing."

FDA Approves Ascor (Ascorbic Acid Injection, USP) for the Treatment of Scurvy

McGuff Pharmaceuticals, Inc., a wholly owned subsidiary of McGuffCompany, Inc. announces the United States Food and Drug Administration’s New Drug Approval (NDA) of Ascor (Ascorbic Acid Injection, USP). Ascor is provided in a 50 mL vial labeled as a Pharmacy Bulk Package with a strength of 500mg/mL.

Ascor is vitamin C indicated for the short term (up to 1 week) treatment of scurvy in adult and pediatric patients age 5 months and older for whom oral administration is not possible, insufficient or contraindicated.

Ascor is the first single moiety ascorbic acid drug approved for the US market and is the result of a multi-year development effort.

Ronald McGuff, CEO said "The FDA approval of Ascor Ascorbic Acid
Injection USP will allow McGuff Pharmaceuticals, Inc. to deliver this
medically necessary drug to US hospitals and pharmacies to improve
patient health. In addition, McGuff Pharmaceuticals, Inc. currently
holds Ascorbic Acid Injection USP approvals in multiple other
countries."

FDA Approves Verzenio (abemaciclib) for Certain Advanced or Metastatic Breast Cancers

 

We know that, Abemaciclib is a kinase inhibitor for oraladministration. It is a white to  yellow powder with the empirical formula C₂₇H₃₂F₂N₈

and a molecular weight 506.59.

The chemical name for abemaciclib is 2-Pyrimidinamine,
N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-Abemaciclib  has the above  structure:

The U.S. Food and Drug Administration today approved Verzenio (abemaciclib) to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negativeadvanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy). Verzeniois approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It isalso approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer hadspread (metastasized).

"Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alonetreatment to patients who were previously treated with endocrine therapy and chemotherapy," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Dietary supplement could be promising therapeutic target for seizure disorders

We know that, Glucosamine  is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, as well as the cell walls of fungiand many higher organisms. Glucosamine is one of the most abundant monosaccharides.

Seizure disorders -- including epilepsy are associated with pathological hyperexcitability in brain neurons. Unfortunately, there are limited available treatments that can prevent this hyperexcitability. However, University of Alabama at Birmingham researchers have found that inducing a biochemical alteration in brain proteins via the dietary supplement glucosamine was able to rapidly dampen that pathological hyperexcitability in rat and mouse models.

These results represent a potentially novel therapeutic target for the treatment of seizure disorders, and they show the need to better understand the physiology underlying these neural and brain circuit changes.

Proteins are the workhorses of living cells, and their activities are tightly and rapidly regulated in responses to changing conditions. Adding or removing a phosphoryl group to proteins is a well-known regulator for many proteins, and it is estimated that human proteins may have as many as 230,000 sites for phosphorylation.

A lesser-known regulation comes from the addition or removal of N-acetylglucosamine to proteins, which is usually controlled by glucose, the primary fuel for neurons. Several years ago, neuroscientist Lori McMahon, Ph.D., professor of cell, developmental and integrative biology at UAB, found out from her colleague John Chatham, D.Phil., a UAB professor of pathology and a cardiac physiologist, that brain cells had the second-highest amounts of proteins with N-acetylglucosamine, or O-GlcNAcylation, in the body.

At the time, very little was known about how O-GlcNAcylation might affect brain function, so McMahon and Chatham started working together. In 2014, McMahon and Chatham, in a study led by graduate student Erica Taylor and colleagues, reported that acute increases in protein O-GlcNAcylation caused long-term synaptic depression, a reduction in neuronal synaptic strength, in the hippocampus of the brain. This was the first time acute changes in O-GlcNAcylation of neuronal proteins were shown to directly change synaptic function.

Since neural excitability in the hippocampus is a key feature of seizures and epilepsy, they hypothesized that acutely increasing protein O-GlcNAcylation might dampen the pathological hyperexcitability associated with these brain disorders.

That turned out to be the case, as reported in the Journal of Neuroscience study, "Acute increases in protein O-GlcNAcylation dampen epileptiform activity in hippocampus." The study was led by corresponding author McMahon and first author Luke Stewart, a doctoral student in the Neuroscience Theme of the Graduate Biomedical Sciences Program. Stewart is co-mentored by McMahon and Chatham.

"Our findings support the conclusion that protein O-GlcNAcylation is a regulator of neuronal excitability, and it represents a promising target for further research on seizure disorder therapeutics," they wrote in their research significance statement. The researchers caution that the mechanism underlying the dampening is likely to be complex.

Research details

Glucose, the major fuel for neurons, also controls the levels of protein O-GlcNAcylation on proteins. However, high levels of the dietary supplement glucosamine, or an inhibitor of the enzyme that removes O-GlcNAcylation, leads to rapid increases in O-GlcNAc levels.

In experiments with hippocampal brain slices treated to induce a stable and ongoing hyperexcitability, UAB researchers found that an acute increase in protein O-GlcNAcylation significantly decreased the sudden bursts of electrical activity known as epileptiform activity in area CA1 of the hippocampus. An increased protein O-GlcNAcylation in normal cells also protected against a later induction of drug-induced hyperexcitability.

The effects were seen in slices treated with both glucosamine and an inhibitor of the enzyme that removes O-GlcNAc groups. They also found that treatment with glucosamine alone for as short a time as 10 minutes was able to dampen ongoing drug-induced hyperexcitability.

In common with the long-term synaptic depression provoked by increased O-GlcNAcylation, the dampening of hyperexcitability required the GluA2 subunit of the AMPA receptor, which is a glutamate-gated ion channel responsible for fast synaptic transmission in the brain. This finding suggested a conserved mechanism for the two changes provoked by increased O-GlcNAcylation -- synaptic depression and dampening of hyperexcitability.

The researchers also found that the spontaneous firing of pyramidal neurons in another region of hippocampus, area CA3, was reduced by increased O-GlcNAcylation in normal brain slices and in slices with drug-induced hyperexcitability. This reduction in spontaneous firing of CA3 pyramidal neurons likely contributes to decreased hyperexcitability in area CA1 since the CA3 neurons directly excite those in CA1.

Similar to the findings for brain slices, mice that were treated to increase O-GlcNAcylation before getting drug-induced hyperexcitability had fewer of the brain activity spikes associated with epilepsy that are called interictal spikes. Several drug-induced hyperexcitable mice had convulsive seizures during the experiments -- this occurred in both the increased O-GlcNAcylation mice and the control mice. Brain activity during the seizures differed between these two groups: The peak power of the brain activity for the mice with increased O-GlcNAcylation occurred at a lower frequency, as compared with the control mice. 

Ref : http://www.uab.edu/news/innovation/item/8796?utm_source=eurekaalert&utm_medium=referral&utm_campaign=&utm_content=

Dietary supplement could be promising therapeutic target for seizure disorders