Search This Blog

Monday, September 10, 2018

Roche sets up patent hurdle for Bioepis’ Herceptin biosimilar: analyst


Roche is battling competition from Herceptin biosimilars to the bitter end. The Swiss drugmaker has sued Bioepis over its biosimilar as it heads for the finish line, Bernstein analyst Ronny Gal reports.
Bioepis partners Biogen and Samsung are looking for a December approval of their candidate after resubmitting their BLA in June. But Gal said in a note to investors today that Roche has sued the JV over 21 patents, which the two sides agreed should be in contention after a truncated information exchange. He said the suit mainly concerns secondary patents.
Roche sued Pfizer last year over 40 patents on its Herceptin biosimilar, and Mylan has settled with Roche for a mid-2019 launch. But drugmakers are anxious for a cut of the sales of Roche’s second-best-selling drug, with $7.2 billion in worldwide sales and $2.7 billion in the U.S. last year.
“We wonder how long Pfizer and BioEpis will wait before being willing to launch at risk, but 1/1/2019 entry looks unlikely, in our view,” Gal wrote to investors today. Roche and Biogen both declined to comment for this story.

Drugmakers are closing in on Roche’s global cancer fortunes. Bioepis’ Ontruzant already won approval in Europe last year and was launched in May by Merck & Co., which has marketing rights to the biosimilar there. Also last year, Amgen and Allergan won U.S. approval for Mvasi, an Avastin biosim approved in each of the branded drug’s indications. Amgen and Allergan’s approval represents the first cancer biosim nod in the U.S. and a threat to $3 billion in Roche sales in the States.
Gal points out in his note that Roche’s Cabilly patents also expire this year. For nearly 35 years, the so-called Cabilly patents, granted to Roche’s Genentech unit in 1983, have allowed Roche to set up a toll booth collecting royalties from competitors including Eli Lilly, GlaxoSmithKline and AbbVie, which uses the processes to manufacture Humira, the world’s global leader with $16 billion in sales.
Those patents expire in December 2018, a year in which these patents are estimated to generate about $1 billion for Roche and City of Hope, where a team led by scientist Shmuel Cabilly, Ph.D., first developed the manufacturing process.
Posted by at No comments:

Boys and girls share similar math abilities at young ages: study


There has been much speculation about whether lower female participation rates in STEM fields can be traced to an innate male superiority in math and science. But a new University of Chicago study wanted to test whether boys and girls actually show different mathematical abilities at their earliest developmental stages.
UChicago postdoctoral researcher Alyssa Kersey recently co-authored research in the Nature journal Science of Learning that showed the ability to understand numbers is not innately different in boys and girls. Young boys and girls share similar abilities, according to the study, and any differences that show up later are likely learned.
“Across all stages of numerical development, analyses consistently revealed that boys and girls do not differ in early quantitative and mathematical ability,” Kersey and her co-authors wrote. “These findings indicate that boys and girls are equally equipped to reason about mathematics during .”
Kersey and her colleagues point out in their paper that  differences in math and science have been the focus of research for many years, but findings have been inconsistent. Kersey said she relied on her own dissertation—research that focused on how the developing brain represents the idea of number.
“Because of this focus on early-childhood mathematical cognition, we had an opportunity to directly compare the abilities of boys and girls in three foundational areas of mathematical cognition during infancy and early childhood,” she said.
Those areas included the ability to estimate how many things are in a set without knowing the exact number, culturally trained counting, and formal and informal elementary mathematical concepts.
Kersey and her colleagues compiled data from five previously published studies and conducted cross-sectional analysis with unpublished data to examine gender difference in math cognition from more than 500 children.
The researchers found no major differences in numerical processing between genders, noting “these findings indicate that boys and  are equally equipped to reason about  during early childhood.”
They point out that the ability to differentiate between numbers of things in sets emerges in the first year of life, and is even found in nonhuman animals.
“It’s definitely widely shared across species,” Kersey said. “There are examples in the scientific literature of all kinds of animals discriminating numerosities—mammals, birds and fish, just to name a few. So this seems to be an ability with a long evolutionary history.”
Kersey said she and her colleagues are now focused on similarities and differences among genders in the neural mechanisms behind mathematical thinking in early childhood.
“Testing for gender differences in early childhood is important for minimizing the effects of social and cultural influences that can’t be easily teased apart from biological influences in adults,” Kersey said.
Kersey began work at UChicago this summer in the lab of Susan Goldin-Meadow, the Beardsley Ruml Distinguished Service Professor in the Department of Psychology. Kersey said she is looking forward to helping Goldin-Meadow build on her pioneering research on the role of gesture in learning. They will be using neuroimaging to research the role of the nervous system in math learning.
“We’ve discovered that teaching math through gestures is not only effective in getting children to learn how to solve problems on which they were trained, but also helps them generalize what they learned to problems in a different format,” Goldin-Meadow said. “We are going to try to use neuroimaging techniques to figure out why.”
 Explore further: Study highlights gender gap in mental ill-health during early adolescence
More information: Alyssa J. Kersey et al. No intrinsic gender differences in children’s earliest numerical abilities, npj Science of Learning (2018). DOI: 10.1038/s41539-018-0028-7
Posted by at No comments:

Study links widely-used drug azathioprine to skin cancers


A drug used to treat inflammatory bowel disease, arthritis and vasculitis as well as to prevent organ rejection in transplant patients has been identified as an important contributor to skin cancer development, in a research study carried out at the University of Dundee, Queen Mary University of London and the Wellcome Sanger Institute.
The research, published in Nature Communications, identified a `strong case for an association’ between the drug  and the mutational signature found in cases of cutaneous squamous cell carcinoma (cSCC), a common form of skin .
It was already known that use of azathioprine leads to increased photosensitivity to UVA light, probably contributing to development of skin cancers. This new study finds that use of azathioprine leaves a molecular fingerprint in skin cancers, further implicating it in cSCC development.
Charlotte Proby, Professor of Dermatology in the School of Medicine at Dundee, said, “We recommend all physicians give appropriate advice on UVA avoidance including year-round sun protection for their patients on azathioprine.”
Professor Proby and colleagues said they were not necessarily advocating withdrawal of azathioprine.
“As with all medications the risks must be balanced against the benefits, particularly with the need to treat potentially life-threatening diseases with an effective drug,” she said.
“It is important that sun protection, skin surveillance and early diagnosis/lesion removal are part of the routine management of patients on azathioprine.”
cSCC is a common  with more than 40,000 new cases diagnosed annually in the UK, with significant health economic implications.
Sophia Lowes, from Cancer Research UK, said, “It’s important to protect your  from the sun when it’s strong, especially if you burn easily or are taking medications which make you more sun-sensitive. The most effective protection is to spend time in the shade and cover up with a hat, long-sleeved top and sunglasses. For the bits you can’t cover, use sunscreen with at least 4 stars and SPF 15 or higher for protection against both UVA and UVB rays.”
Importantly, this new study also reveals the molecular landscape of cSCC and highlights potential targets that may be developed for future therapeutic approaches to manage cSCC.
Different carcinogens leave a different `mutational signature’ in a cancer. By studying these signatures, researchers can start to determine what the causes of a cancer are.
The researchers in the School of Medicine at Dundee, in collaboration with the Wellcome Sanger Institute and Queen Mary University of London, were able to carry out mutational signature analysis of cSCC tumours from 37 patients, many of whom had been on azathioprine. They found a new mutational signature, Signature 32, which correlated with time on azathioprine therapy.
Professor Gareth Inman, part of the research team at Dundee and now located at the Cancer Research UK Beatson Institute and the University of Glasgow, said, “Although patient numbers were small and these findings should be verified in a larger independent cohort, this molecular study provides a strong case for an association between this novel mutational signature and long-term azathioprine use.”
 Explore further: Researchers identify skin cancer genes
More information: Gareth J. Inman et al, The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature, Nature Communications (2018). DOI: 10.1038/s41467-018-06027-1
Posted by at No comments:

Researchers identify molecule with anti-aging effects on vascular system


A molecule produced during fasting or calorie restriction has anti-aging effects on the vascular system, which could reduce the occurrence and severity of human diseases related to blood vessels, such as cardiovascular disease, according to a study led by Georgia State University.
“As people become older, they are more susceptible to disease, like cancer,  and Alzheimer’s disease,” said Dr. Ming-Hui Zou, senior author of the study, director of the Center for Molecular and Translational Medicine at Georgia State and a Georgia Research Alliance Eminent Scholar in Molecular Medicine. “Age is the most important so-called risk factor for human disease. How to actually delay aging is a major pathway to reducing the incident and severity of human disease.
“The most important part of aging is vascular aging. When people become older, the vessels that supply different organs are the most sensitive and more subject to aging damage, so studying vascular aging is very important. This study is focused on vascular aging, and in old age, what kind of changes happen and how to prevent vascular aging.”
In this study, the research team explores the link between  (eating less or fasting) and delaying aging, which is unknown and has been poorly studied. The findings are published in the journal Molecular Cell.
The researchers identified an important, small molecule that is produced during fasting or calorie restriction conditions. The molecule, β-Hydroxybutyrate, is one type of a ketone body, or a water-soluble molecule that contains a ketone group and is produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation and prolonged intense exercise.
“We found this compound, β-Hydroxybutyrate, can delay vascular aging,” Zou said. “That’s actually providing a chemical link between calorie restriction and fasting and the anti-aging effect. This compound can delay vascular aging through endothelial , which line the interior surface of blood vessels and lymphatic vessels. It can prevent one type of cell aging called senescence, or cellular aging.”
Senescent cells can no longer multiple and divide. The researchers found β-Hydroxybutyrate can promote cell division and prevent these cells from becoming old. Because this molecule is produced during calorie restriction or fasting, when people overeat or become obese this molecule is possibly suppressed, which would accelerate aging.
In addition, the researchers found when β-Hydroxybutyrate binds to a certain RNA-binding protein, this increases activity of a stem cell factor called Octamer-binding transcriptional factor (Oct4) in  and  in mice. Oct4 increases a key factor against DNA damage-induced senescence, which can keep  young.
“We think this is a very important discovery, and we are working on finding a new chemical that can mimic the effect of this ketone body’s function,” Zou said. “We’re trying to take the global approach to reducing cardiovascular disease and Alzheimer’s disease. It’s difficult to convince people not to eat for the next 24 hours to increase the concentration of this compound (β-Hydroxybutyrate), and not everybody can do that, but if we can find something that can mimic this effect and people can still eat, it would make life more enjoyable and help fight disease.
“This stem cell factor (Oct4) could be a pharmaceutical or pharmacological target for slowing down or preventing aging. Then, if the vascular system becomes younger, it is less likely to have cardiovascular disease, Alzheimer’s disease and cancer because all of these diseases are age-related.”
In the future, the researchers would like to target  with the goal of eliminating them and rejuvenating the vascular system to prevent cardiovascular .
 Explore further: How calorie restriction may prolong life
More information: Young-min Han et al. β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4, Molecular Cell (2018). DOI: 10.1016/j.molcel.2018.07.036
Posted by at No comments:

Natural ways to improve insulin sensitivity


Insulin sensitivity refers to how sensitive the body’s cells are in response to insulin. Doctors generally consider a high insulin sensitivity to be healthy. Some lifestyle and dietary changes may help improve this sensitivity.
Insulin is a hormone that helps control the amount of sugar, or glucose, in the blood. The body’s cells respond to insulin by absorbing sugar from the blood.
Low insulin sensitivity is known as insulin resistance. This can cause blood sugar levels to become too high and may lead to type 2 diabetes.
Insulin sensitivity varies between people and can change according to various lifestyle and dietary factors. Improving insulin sensitivity may benefit people who have or are at risk of type 2 diabetes.
In this article, we look at lifestyle and dietary factors that may help a person improve their insulin sensitivity naturally.

Lifestyle

People who wish to increase their insulin sensitivity can try making the following lifestyle changes:

Getting more exercise

Getting more exercise may be one way to improve insulin sensitivity.
In a 2012 study, 55 healthy adults participated in a 16-week exercise program. The researchers found an association between increased physical activity levels and improved insulin sensitivity. This result was dose-dependent, meaning that the more the participants exercised, the more their insulin sensitivity improved.

Combining different exercises

The findings of a 2013 review suggest that certain types of exercise may increase insulin sensitivity more than others. The authors found that a combination of aerobic exercise and strength training was particularly effective for people both with and without diabetes. Based on their findings, the authors recommended that:
  • People without diabetes should do at least 30 minutes of exercise five times a week. This exercise should include high-intensity aerobic exercise three times a week and strength training in all major muscle groups twice a week.
  • People with type 2 diabetes should do at least 30 minutes of exercise five times a week. They should perform long-duration, moderate-intensity aerobic exercise three times a week and high-repetition resistance training in all major muscle groups twice a week.
  • People with type 2 diabetes and limited mobility should do as much exercise as they can manage. They should aim to include low-intensity aerobic exercise combined with low-intensity resistance training in all major muscle groups three times a week.

Getting more sleep

Getting more sleep may also improve a person’s insulin sensitivity.
In a 2015 study, 16 healthy people who were not sleeping for long enough extended their sleep by 1 hour per day for 6 weeks. This extra sleep led to increased insulin sensitivity.

Diet

Some research suggests that making certain dietary changes could increase insulin sensitivity. These changes include:

Fewer carbohydrates, more unsaturated fats

Recent research suggests that replacing carbohydrates with unsaturated fats may improve insulin sensitivity in some people.
A 2012 study investigated the effects of different diets on insulin sensitivity in adults with high blood pressure, which is a risk factor for type 2 diabetes. The researchers concluded that eating a diet low in carbohydrates and high in unsaturated fats for 6 weeks may improve insulin sensitivity.
The study also suggested that this diet was more effective at improving insulin sensitivity than a diet high in carbohydrates or a diet that replaces some carbohydrates with proteins.
A 2016 systematic review of 102 studies concluded that replacing carbohydrate and saturated fat with polyunsaturated fat may improve the body’s blood sugar regulation.

More soluble fiber

Soluble fiber is a type of dietary fiber that comes from plants. Although this fiber is a type of carbohydrate, the body cannot break it down properly. As a result, it does not contribute to spikes in blood glucose levels.
Soluble fiber also delays gastric emptying, which is the time it takes for a meal to leave the stomach and enter the small intestine. A small 2014 study suggests that this delay may help lower blood glucose levels after meals in people with type 2 diabetes.
Another study suggests that eating more soluble fiber may help reduce insulin resistance in healthy women.

Intermittent fasting

Intermittent fasting is a type of diet that focuses on the timing of eating rather than the specific foods in the diet. It may improve insulin sensitivity and reduce the risk of type 2 diabetes for certain people.
A 2014 review investigated the effects of two types of intermittent fasting in overweight and obese adults:
  • Restricting calorie intake for 1–3 days per week and eating freely on the remaining days.
  • Alternating between fast days and feed days. People reduce their regular calorie intake by 75 percent on fast days and do not restrict their diet on feed days.
As with a daily calorie-restricted diet, the researchers found that both types of intermittent fasting reduced insulin resistance. However, this type of eating had no meaningful effect on blood glucose levels. They concluded that more research is necessary.

Dietary supplements

In addition to changing the foods in their diet, people looking to increase their insulin sensitivity may benefit from taking some dietary supplements. According to research, the following supplements could reduce insulin resistance:

Probiotics and omega-3 fatty acids

Taking probiotics or omega-3 fatty acid supplements may improve insulin sensitivity in overweight people.
A 2014 clinical trial investigated the effects of both omega-3 fatty acids and probiotics on insulin sensitivity in 60 adults who were overweight but otherwise healthy.
The researchers reported that taking either a probiotic or omega-3 supplement for 6 weeks led to significant improvements in insulin sensitivity compared to a placebo. The increase in insulin sensitivity was greater still in people who took both supplements together.

Magnesium

Magnesium supplements may also be beneficial for people wanting to improve their insulin sensitivity.
A 2016 systematic review found that taking magnesium supplements for more than 4 months significantly improved insulin resistance in people with and without diabetes.

Resveratrol

Resveratrol is a natural compound that occurs in the skin of red grapes. It is also available as a dietary supplement.
A 2014 meta-analysis of 11 studies found that taking resveratrol supplements significantly improved glucose control and insulin sensitivity in people with diabetes. However, the researchers did not observe the same effects in people without diabetes and concluded that there is a need for more research on the effects of resveratrol supplementation in humans.

Takeaway

Low insulin sensitivity is a risk factor for developing type 2 diabetes. Exercising well, having enough sleep, and eating a healthful diet high in unsaturated fats and soluble fiber may help improve insulin sensitivity in people with and without diabetes.
Certain dietary supplements may also be beneficial. Many of these supplements are available to purchase online:
Posted by at No comments:

Blocking ovarian cancer’s energy supply helps curb spread


It is often the case that an ovarian cancer diagnosis reveals that the tumor has already spread to nearby tissue. Now, scientists have discovered a potential way to cut off the energy supply fueling this invasive stage of ovarian cancer.
A new study, led by the University of Chicago in Illinois, has unraveled the role of glycogen in fueling ovarian cancer spread.
It is the first to reveal how tumor cells interact with support cells called cancer-associated fibroblasts to make this happen.
“No systematic study,” says senior study author Ernst Lengyel, who is a professor of obstetrics and gynecology at the university, “of the signaling pathways initiated by human cancercells and cancer-associated fibroblasts has been performed.”
He and his colleagues report their recent findings in a paper that now features in the journal Cell Metabolism.
“We think this could have significant clinical implications,” claims Prof. Lengyel.

Ovarian cancer and metastasis

The ovaries are female hormone-producing glands that make eggs. Each woman has two ovaries; one on either side of the uterus. About once per month, a mature egg carrying the biological mother’s genes travels through a fallopian tube to the uterus.
There, it is made ready for fertilization by sperm, which carries the biological father’s genes. A fertilized egg then becomes a fetus that has genes from both parents.
Ovarian cancer starts when cells in the ovaries or fallopian tubes grow out of control and form a tumor.
The American Cancer Society (ACS) estimate that around “22,240 women” in the United States will find that they have ovarian cancer and around 14,070 will die of the disease in 2018.
In nearly 4 out of 5 cases of ovarian cancer, the tumor has already invaded the omentum, a curtain of fatty tissue that hangs over the intestines, at the time of diagnosis.
Once the cancer has penetrated this “energy-dense fat pad,” it speeds up. The process of spread, which begins with tissue invasion, is called metastasis and is complex and multistaged.
The next stage is when tumor cells travel through the bloodstream and lymph system to set up new tumors in other parts of the body.
Metastatic cancer is much harder to treat than cancer that is confined to the primary tumor, and it is the main reason for cancer deaths.

Mobilizing energy supplies

In the case of ovarian cancer, as the tumor invades the omentum, it depletes its fat cells and then recruits cells called cancer-associated fibroblasts to help it take the next step.
The fibroblasts speed up metastasis by helping cancer cells get the resources they need to grow and proliferate, such as increasing blood supply to the tumor and mobilizing energy supplies.
Prof. Lengyel and his colleagues investigated the signals that go back and forth between human ovarian cancer cells and cancer-associated fibroblasts.
They did this by growing ovarian cancer cells and fibroblasts together in the laboratory and then using a method called “quantitative phosphoproteomics” to monitor their “cellular crosstalk.”
The investigators found that chemical signals from the fibroblasts trigger the cancer cells to metabolize their own stored glycogen into glucose.
This ready supply of glucose fuels the invasion of other tissues, which, in turn, leads to a more aggressive tumor and rapid metastasis.

Blocking energy supply

The researchers suggest that there could be a way to halt or slow the invasion process. They found that a signaling pathway called p38α MAPK activated glycogen mobilization in the cancer-associated fibroblasts.
They also revealed that disrupting the enzymes involved in this pathway, or blocking the signaling pathways that trigger glycogen metabolism in the cancer cells, “reduced metastasis.”
They suggest that this could be a “therapeutic strategy” for reducing “abdominally metastasizing” tumors following surgery.
“This is the first time that the role of glycogen in cancer metastasis has been thoroughly investigated.”
Prof. Ernst Lengyel
Posted by at No comments:

Approximately 300,000 still at Risk of Developing 9/11 Related Cancers


Dr. Gaetane Michaud, Chief of Interventional Pulmonology at NYU Langone Health and its Perlmutter Cancer Center, emphasize the importance of an overlooked health issue today on SurvivorNet, a newly launched website for cancer patients and survivors, stating that approximately 300,000 people exposed to toxic air after 9/11 are at risk of developing cancer and are not getting the medical screening and attention they need.
The Center for Disease Control and Prevention has long maintained that around 400,000 people in lower Manhattan were exposed to a dangerous mix of substances such as asbestos, lead, and benzene on the day of the attacks and in the weeks and months afterward.
The World Trade Center Health Program was set up by the federal government to help people with health problems related to the attacks obtain and pay for the care they require. To date, just 80,000 people have registered with the program ensuring appropriate screenings and/or care. Dr. Michaud and her team at NYU Langone have seen an increasing number of patients with 9/11 related illnesses and believe that many more people are not getting the help they need and may not even know about the health risks they face. In addition, Dr. Michaud is concerned that physicians caring for these people are also unaware of the concern and/or resources available to their patients.
“I feel heartbroken to know that if at the lowest number, we’re saying there are about 400,000 people that should be benefiting from the World Trade resources, and about 80,000 are actually benefiting from them, that’s a big discrepancy. There’s a lot of people out there that really need help and really need to be vigilant,” said Michaud. “It’s not just lung cancers. It’s lung cancers, breast cancers, esophageal cancers, and thyroid cancers to name a few. These people should be screened and be taken care of. Even if you think beyond cancers, there are all kinds of other World Trade related lung diseases.”
There is no exact consensus on the geographical radius around the World Trade Center site which constitutes a risk to human health. That said, the program radius considered for enrollment in the WTC Health Program is approximately 1.5 miles from Ground Zero.
Common 9/11-linked illnesses include chronic cough, asthma, sinus congestion, certain cancers, stress-related disorders, and many other diseases, according to the WTC Health Program.
“A lot of people that were near Ground Zero at the time, and even lived down there then moved away, have no idea what resources are available or that they should even be screened or are at risk,” Dr. Michaud states.
What to Do If You Are Worried About Exposure From 9/11
If you believe you may be at risk from exposure after the September 11 attacks, you can go to CDC.gov/WTC to enroll in the program. Dr. Michaud strongly urges people to tell their physicians if they believe they may be at risk or were in lower Manhattan at the time.
About SurivorNet
For patients and survivors alike, the wealth and quality of information on the site is invaluable. Users of SurvivorNet have overwhelmingly named it the most valuable source of information available about cancer care. For the majority of people already dealing with the burden and cost of cancer, flying across the country for multiple opinions or securing an appointment with a specialist featured on SurvivorNet is not an option. Through the platform, it brings expertise to all, creating power and comfort through shared information.
Posted by at No comments:
Subscribe to: Posts (Atom)