According to the scientists at the University of Michigan Rogel Cancer Center, a small molecule has been identified that blocks a key pathway in brain tumors. But there was a problem: How to get the inhibitor through the bloodstream and into the brain to reach the tumor.
In collaboration with multiple labs, the teams fabricated nanoparticles to contain the inhibitor, and the results were even better than expected. Not only did the nanoparticles deliver the inhibitor to the tumor in mouse models, where the drug successfully turned on the immune system to eliminate cancer, but the process triggered immune memory so that a reintroduced tumor was also eliminated a sign that this potential new approach could not only treat brain tumors but prevent or delay recurrences. “No one could get this molecule into the brain. It’s a huge milestone. Outcomes for patients with glioma have not improved for the last 30 years,” said Maria G. Castro, Ph.D., R.C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Castro is the senior author of the study, published in ACS Nano.
“Despite survival gains in many cancer types, glioma remains stubbornly challenging, with only 5% of patients living five years after their diagnosis,” said study author Pedro R. Lowenstein, M.D., Ph.D., Richard C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Gliomas are often resistant to traditional therapies, and the environment inside the tumor suppresses the immune system, rendering new immune-based therapies ineffective. Add to that the challenge of passing the blood-brain barrier, and it becomes even more difficult to deliver effective treatments to these tumors.
The Castro-Lowenstein lab saw an opportunity. The small-molecule inhibitor AMD3100 was developed to block the action of CXCR12, a cytokine released by the glioma cells that build up a shield around the immune system, preventing it from firing up against the invading tumor. Researchers showed in mouse models of glioma that AMD3100 prevented CXCR12 from binding with immune-suppressive myeloid cells. By disarming these cells, the immune system remains intact and can attack the tumor cells. But AMD3100 was having trouble getting to the tumor. The drug did not travel well through the bloodstream, and it did not pass the blood-brain barrier, a key issue with getting drugs into the brain.
The Castro-Lowenstein lab collaborated with Joerg Lahann, Ph.D., Wolfgang Pauli Collegiate Professor of Chemical Engineering at the U-M College of Engineering, to create protein-based nanoparticles to encapsulate the inhibitor, in the hopes of helping it pass through the bloodstream. Castro also connected with Anuska V. Andjelkovic, M.D., Ph.D., professor of pathology and research professor of neurosurgery at Michigan Medicine, whose research focuses on the blood-brain barrier. They noted that glioma tumors create abnormal blood vessels, interfering with normal blood flow.
The researchers injected AMD3100-loaded nanoparticles into mice with gliomas. The nanoparticles contained a peptide on the surface that binds to a protein found mostly on the brain tumor cells. As the nanoparticles traveled through the bloodstream toward the tumor, they released AMD3100, which restored the integrity of the blood vessels. The nanoparticles could then reach their target, where they released the drug, thus blocking the entry of the immune-suppressive myeloid cells into the tumor mass. This allowed the immune cells to kill the tumor and delay its progression. “If you don’t have blood flow, nothing will get to your target. That’s why tumors are so smart. But AMD3100 restores the conduits, which is what allows the nanoparticles to reach the tumor,” Castro said.
Further studies in mice and patient cell lines demonstrated that coupling the AMD3100 nanoparticles with radiation therapy enhanced the effect beyond either the nanoparticles or radiation alone. Among the mice whose tumors were eliminated, the researchers then reintroduced the tumor, simulating a recurrence.
Without any additional therapy, 60% of mice remained cancer-free. This suggests that, like a vaccine, AMD3100 created immune memory, enabling the immune system to recognize and destroy the reintroduced cells. While it prevented a recurrence in mice, Castro said it bodes well for at least delaying recurrence in people. “Every glioma recurs. It’s very important for glioma therapy to have this immunological memory,” Castro said.
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WARNING SIGNS OF A BRAIN TUMOUR ONE MUST NOT IGNORE
Brain tumour is an abnormal growth of the brain cells. The extra growth inside the brain can exert pressure on the skull, causing life-threatening complications.
Brain tumour is an abnormal growth of the brain cells. The extra growth inside the brain can exert pressure on the skull, causing life-threatening complications. However, not all brain tumours are malignant. Some can be non-cancerous, benign or harmless masses of cancerous cells that mainly target the structural tissue of the brain. It can start either in the brain, or cancer elsewhere in the body can spread to the brain.
According to WHO guidelines brain tumours are categorized into four grades based on the intensity and abnormality of the cells.
· GRADE 1: Cells look benign and grow slowly; survival of the patient is likely.
· GRADE 2: Cells look slightly abnormal. The tumor grows slowly and may spread to other tissues.
· GRADE 3: Cells look abnormal. The tumor grows aggressively and tends to recur.
· GRADE 4: The cells look abnormal and spread quickly. Tumour could be life-threatening.
WARNING SIGNS AND SYMPTOMS OF BRAIN TUMOUR
Depending on the type, location, and stage of the tumor, it can cause both physical and mental symptoms. Some of the commonly observed signs and symptoms of brain tumors are
Unusual headache: Headache can be a common symptom. If someone is experiencing an unusual headache, especially a new one that feels localized to a specific part of the head it could be an early indication of a brain tumor. The headache tends to be more severe in the morning. A brain tumor increases the pressure inside the skull, which can lead to inflammation and tissue damage. Hence, severe, persistent headaches can occur. If there are changes in the frequency or intensity of the headaches, one must consult a doctor.
Seizures: They are one of the most common symptoms of brain tumors. The seizures occur when the brain’s normal patterns of electrical impulses are disrupted. It is reported that brain tumor-related epilepsy (BTE) is common in low- and high-grade gliomas. The risk of seizures varies between 60% and 100% among low-grade gliomas and between 40% and 60% in glioblastomas.
Memory loss, Speech difficulties and hearing loss: Brain tumors can affect the stages of creating, storing and recalling of memory. Retrograde amnesia, a state where one can’t recall memories that were formed before the event that caused the amnesia and anterograde amnesia, where one can’t form new memories after the event that caused the amnesia can occur in people with brain tumor. A brain tumor can affect the communication capabilities of a person and can cause difficulties in uttering or producing sounds, finding the correct word, and understanding what others are saying. It can also have an impact on reading and writing. Also, the pressure exerted by a tumor on surrounding nerves may cause hearing loss and imbalance.
Weakness in the hands and legs: Weakness or numbness in the face, arms or legs is a common occurrence in brain tumors. It is caused by brain tumors located in the frontal lobes or the brainstem. Weakness in one foot/leg or both feet/legs can cause difficulty in walking. Hence, one may experience loss of balance while walking.
Sudden shifts in mood or personality: Mood changes are commonly associated with brain tumors located in the frontal lobe. This part of the brain is highly involved in regulating personality and behaviour and it also helps controls a person’s behavior and emotions. Sudden mood change can be seen in persons whose pituitary gland has been affected by tumors. It can cause the gland to under-or overproduce hormones, leading to a hormonal imbalance. Getting to know about one’s diagnosis of brain tumor can greatly affect the mental and emotional state.
WHEN TO SEE A DOCTOR
The above symptoms are a clear indication that one must immediately seek medical help. Upon diagnosis and conducting a range of neurological tests, your doctor will be able to identify and tell you what’s causing the symptoms.
If diagnosed with a tumor, one can identify the types and follow the doctor’s advice. Always remember that early diagnosis and treatment are important to help prevent the tumour from growing.
The writer is the Lead Consultant Neurosurgery & Program Director – Global Centre of Excellence in Neurosciences, Aster Hospitals Bengaluru.
SHOULD YOU PRACTISE YOGA ON AN EMPTY STOMACH?
If practising yoga on an empty stomach works for you, do that. On the other hand, if you feel like eating something to get a better start to your day, consider something light.
In this fast-paced world, where we are all trying to cope with the hectic lifestyle, Yoga has become a preferred choice of exercise for many, not only to stay fit, active and agile but also to reduce stress and promote relaxation of the body and mind. With physical exercise, it becomes important to focus on the right nutrition and right diet as well.
So can you or should you practice Yoga on an empty stomach?
Well, there are many claims doing the rounds, with some saying it’s necessary to do yoga on an empty stomach and other’s saying it’s not. Some also consider eating the right breakfast is necessary. However, remember you and only you will know and understand your body, so make sure you listen to it, protect it and celebrate it.
While it is believed, working out in the morning on an empty stomach is the best approach, as you can get the best of your breath work and your yoga practice, nourishing your body allows a deeper yoga practice. It is necessary to have something light before you exercise in the morning to help jumpstart your metabolism. However, remember to avoid eating anything heavy for at least 4 hours before performing any asanas.
If you are looking for a great way to lose more weight, try practising Yoga while on intermittent fasting. It is one of the best morning workouts as it allows the body to use the stored fat as energy and is easy on the body. If you first eat something and then workout, your body will focus more on burning the food you just put into your body instead of your stored fat. Also doing high impact or cardio workouts while on fasts, requires you to burn a lot of energy because of the high intensity workouts.
In the end, remember everyone’s body is different and reacts differently. What may work for us, will not work for others. It really comes down to observing and understanding your body, listening to what it likes and what it dislikes and what deems fit for you. If practising yoga on an empty stomach works for you, do that. On the other hand, if you feel like eating something to get a better start to your day, consider something light.
The writer is a fitness expert.
HIGH OPTIMISM LEVELS ARE LINKED WITH LONGER LIFESPAN
A new study led by researchers at Harvard T.H. Chan School of Public Health has found that higher levels of optimism were associated with longer lifespan and living beyond age 90 in women across racial and ethnic groups.
The study was published in the Journal, ‘American Geriatrics Society’. “Although optimism itself may be affected by social structural factors, such as race and ethnicity, our research suggests that the benefits of optimism may hold across diverse groups,” said Hayami Koga, a PhD candidate in the Department of Social and Behavioral Sciences at Harvard Chan School and lead author of the study. “A lot of previous work has focused on deficits or risk factors that increase the risks for diseases and premature death. Our findings suggest that there’s value to focusing on positive psychological factors, like optimism, as possible new ways of promoting longevity and healthy ageing across diverse groups.”
In a previous study, the research group determined that optimism was linked to a longer lifespan and exceptional longevity, which was defined as living beyond 85 years of age. Because they had looked at mostly white populations in that previous study, Koga and her colleagues broadened the participant pool in the current study to include women from across racial and ethnic groups. According to Koga, including diverse populations in research is important to public health because these groups have higher mortality rates than white populations, and there is limited research about them to help inform health policy decisions.
For this study, the researchers analyzed data and survey responses from 159,255 participants in the Women’s Health Initiative, which included postmenopausal women in the U.S. The women enrolled at ages 50-79 from 1993 to 1998 and were followed for up to 26 years.
Of the participants, the 25 per cent who were the most optimistic were likely to have a 5.4 per cent longer lifespan and a 10 per cent greater likelihood of living beyond 90 years than the 25 per cent who were the least optimistic. The researchers also found no interaction between optimism and any categories of race and ethnicity, and these trends held true after taking into account demographics, chronic conditions, and depression. Lifestyle factors, such as regular exercise and healthy eating, accounted for less than a quarter of the optimism-lifespan association, indicating that other factors may be at play.
Koga said that the study’s results could reframe how people view the decisions that affect their health.
“We tend to focus on the negative risk factors that affect our health,” said Koga. “It is also important to think about the positive resources such as optimism that may be beneficial to our health, especially if we see that these benefits are seen across racial and ethnic groups.”
Social isolation is a key reason for dementia
Scientists have found that a major reason for dementia is social isolation, which causes changes in the brain structures associated with memory, according to a study by the University of Warwick.
Setting out to investigate how social isolation and loneliness were related to later dementia, researchers at the University of Warwick, University of Cambridge and Fudan University used neuroimaging data from more than 30,000 participants in the UK Biobank data set. Socially isolated individuals were found to have lower gray matter volumes of brain regions involved in memory and learning.
The results of the study are published online today (June 8, 2022) in Neurology, the medical journal of the American Academy of Neurology, in a paper entitled “Associations of social isolation and loneliness with later dementia” by Shen, Rolls, Cheng, Kang, Dong, Xie, Zhao, Sahakian and Feng.
Based on data from the UK Biobank, an extremely large longitudinal cohort, the researchers used modelling techniques to investigate the relative associations of social isolation and loneliness with incident all-cause dementia. After adjusting for various risk factors (including socio-economic factors, chronic illness, lifestyle, depression and APOE genotype), socially isolated individuals were shown to have a 26% increased likelihood of developing dementia.
Loneliness was also associated with later dementia, but that association was not significant after adjusting for depression, which explained 75% of the relationship between loneliness and dementia. Therefore, relative to the subjective feeling of loneliness, objective social isolation is an independent risk factor for later dementia. Further subgroup analysis showed that the effect was prominent in those over 60 years old.
Professor Edmund Rolls, the neuroscientist from the University of Warwick Department of Computer Science, said: “There is a difference between social isolation, which is an objective state of low social connections, and loneliness, which is subjectively perceived social isolation.
“Both have risks to health but, using the extensive multi-modal data set from the UK Biocomputational scbank, and working in a multidisciplinary way linking sciences and neuroscience, we have been able to show that it is social isolation, rather than the feeling of loneliness, which is an independent risk factor for later dementia. This means it can be used as a predictor or biomarker for dementia in the UK.
“With the growing prevalence of social isolation and loneliness over the past decades, this has been a serious yet underappreciated public health problem. Now, in the shadow of the COVID-19 pandemic, there are implications for social relationship interventions and care — particularly in the older population.”
Professor Jianfeng Feng, from the University of Warwick Department of Computer Science, said: “We highlight the importance of an environmental method of reducing the risk of dementia in older adults through ensuring that they are not socially isolated. During any future pandemic lockdowns, it is important that individuals, especially older adults, do not experience social isolation.”
Professor Barbara J. Sahakian, of the University of Cambridge Department of Psychiatry, said: “Now that we know the risk to brain health and dementia of social isolation, it is important that the government and communities take action to ensure that older individuals have communication and interactions with others on a regular basis.”
Controlling body weight in early life can prevent male infertility later
Controlling body weight more carefully during childhood and adolescence can be helpful in preventing male infertility later in life, suggests the findings of a recent study.
The researchers will be presented at the Endocrine Society’s annual meeting in Atlanta, Ga. The study finds that children and adolescents with overweight or obesity, or those who have high levels of insulin or insulin resistance tend to have smaller testicles compared with their peers with normal weight and insulin levels.
“More careful control of body weight in childhood and adolescence may help to maintain testicular function later in life,” said lead researcher Rossella Cannarella, M.D., of the University of Catania in Italy.
The prevalence of male infertility is increasing, and the average sperm count has been reduced by half in the past 40 years worldwide for no apparent reason, she said.
Testicular volume (a measure of testicle size) is directly related to sperm count. This means smaller testicles tend to produce less sperm. Up to one-quarter of young men aged 18-19 have low testicular volume or smaller-than-normal testicles. This puts their future fertility at risk, Cannarella said. At the same time, the prevalence of childhood obesity has increased.
“This evidence suggests a possible link between childhood obesity and the high prevalence of low testicular volume in youngsters,” she said.
To look for a possible link between low testicular volume and obesity, the researchers assessed testicular volume in 53 children and teens with overweight and 150 with obesity. Their results were compared to 61 age-matched healthy peers. The boys and teens with normal weight had a significantly higher testicular volume compared to their peers with obesity or overweight.
The study also looked at the relationship between obesity-related metabolic abnormalities, such as insulin resistance and hyperinsulinemia, on testicular volume. Insulin resistance is an impaired response of the body to insulin, resulting in elevated levels of glucose in the blood.
Hyperinsulinemia is abnormally high levels of insulin in the body. Children and teens with normal insulin levels had significantly higher testicular volume compared to those with hyperinsulinemia. Post-puberty teens with insulin resistance had lower testicular volume compared to those without insulin resistance.
“These findings help to explain the reason for the high prevalence of decreased testicular size in young men,” Cannarella said.
‘Inadequate nutrition puts male runners at risk of stress fractures’
Male runners who do not receive enough energy from their diet can be at risk for stress fractures, according to a new study.
The findings of the study will be presented at the Endocrine Society’s annual meeting in Atlanta, Ga. “Our findings indicate that male runners, including recreational runners, should be counselled on the importance of adequate nutrition and caloric intake to optimize hormones, body composition, and bone health and to prevent stress fractures,” said lead researcher Melanie S. Haines, M.D., of Massachusetts General Hospital in Boston, Mass.
Female athletes with undernutrition are at risk for low bone density and stress fractures, Haines noted. “However, it is unclear whether a similar process occurs in male athletes,” she added.
The researchers enrolled 15 male runners and 16 male non-athlete controls, aged 16-30 years. They assessed their bone density, body composition and blood hormone levels. They found that bone density of the tibial cortex, or outer shell of bone of the lower leg, was lower in athletes than controls. This may increase the risk for stress fractures in male runners, which occur in this outer shell of bone. Lower weight and muscle mass, and lower levels of hormone associated with fat mass (such as leptin and estrogen) were associated with lower bone strength in the lower leg.
“We suspect that a subset of male runners may not be fueling their bodies with enough nutrition and calories for their high level of physical activity. The undernutrition that results negatively affects hormones and bone. Just getting enough calcium and vitamin D is not enough to overcome other macronutrient and micronutrient deficiencies,” Haines notes. Hormones are very important for bone health and strength. Abnormal hormone levels in the body can contribute to low bone density and increased fracture risk. The Endocrine Society recognizes that there are a number of risk factors for poor bone strength in young men, including low body weight or losing too much weight, diets low in calcium, low vitamin D and testosterone levels, and eating disorders.
Male runners, including recreational runners, should be counselled on the importance of adequate nutrition and caloric intake.
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