Tag: 26/3/21

Categories : Cancer Immune SystemTags :

Insights into How CAR T Cancer Treatment Works

On By ModernMedia

Researchers have uncovered why some patients respond strongly to chimeric antigen receptor T-cell therapy (CAR T), 

CAR T is a new development in cancer therapy, a treatment approved to treat many types of aggressive B cell leukaemias and lymphomas. Moffitt Cancer Center researchers use mathematical modeling to help explain why CAR T cells work in some patients and not in others, with the response instead tapering off and the disease continuing its progression.

CAR T is a type of personalised immunotherapy that uses a patient’s own T cells to target cancer cells. Many patients have strong responses to CAR T; however, some have only a short response and develop disease progression quickly. The procedure involves T cells from a patient being genetically modified to include a specific receptor targeting cancer cells. 

hemotherapy then lowers some of the patient’s existing normal immune cells to help deal with the influx of CAR T cells that are infused back into the patient, where they can get to work and attack the tumour.

“Treatment success critically depends on the ability of the CAR T cells to multiply in the patient, and this is directly dependent upon the effectiveness of lymphodepletion that reduces the normal T cells before CAR T infusion,” explained co-lead author Frederick Locke, MD, Vice Chair, Blood and Marrow Transplant and Cellular Immunotherapy Department, Moffitt.

In their model, the researchers discovered that tumour eradication is effectively random, but can happen with high probability. The researchers showed that differences in the timing and probability of cures are determined largely by variability among patient and disease factors. The model confirmed that cures tends to happen 20 to 80 days before the CAR T cells decline, while disease tends to progress over a wider time range between 200 to 500 days after treatment.

“Our model confirms the hypothesis that sufficient lymphodepletion is an important factor in determining durable response. Improving the adaptation of CAR T cells to expand more and survive longer in vivo could result in increased likelihood and duration of response,” explained lead author Philipp Altrock, PhD, and assistant member of the Integrated Mathematical Oncology Department at Moffitt.

Source: News-Medical.Net

Journal information: Kimmel, G.J., et al. (2021) The roles of T cell competition and stochastic extinction events in chimeric antigen receptor T cell therapy. Proceedings of the Royal Society B: Biological Sciences. doi.org/10.1098/rspb.2021.0229.

Categories : Cancer COVIDTags :

Despite COVID, Cancer Screenings in the US Picked Up

On By ModernMedia
Woman Receives Mammogram. An Asian female technician positions an African-American woman at an imaging machine to receive a mammogram. Creator: Rhoda Baer

In an encouraging sign, the RAND corporation reports that despite COVID, cancer screenings in the United States rebounded in the wake of the first wave.

There has been concern since the COVID pandemic was keeping people from going in for routine cancer screening, resulting in more undetected cancers to progress unchecked and an increase in cancer deaths. As some 600 000 Americans were expected to die of cancer in 2020, any impact on screening is a considerable health concern.

In a statement, Ryan McBain, PhD, of the RAND Corp. in Santa Monica, California, said: “These are the first findings to show that, despite real fears about the consequences of drop off in cancer screens, health facilities figured out how to pick this back up after the initial pandemic restrictions. Our study shows that health systems were able to recalibrate resources and protocols in a relatively short interval to deliver these important services.”

In Spain, cancer diagnoses were down 38% in the first half of 2020, according to one study. The pandemic’s impact on cancer screening that required in-person examinations, such as mammography and colonoscopy, were a particular concern, McBain and co-authors noted. Moreover, little was known about the magnitude of the decline in screening rates or longer-term trends in screen.

Using data on Castlight Health beneficiaries from January 15 to July 31, 2020, the researchers calculated weekly screening rates per 10 000 eligible beneficiaries. Before the declaration of national emergency in the US on March 13, screening mammography weekly rate was 87.8 per 10 000, falling to a low of 6.9 per 10 000 in April. Thereafter, screening rates began a steady recovery, to 88.2 per 10 000 at the end of July.

Over the same time period, weekly colonoscopy screenings fell from 15.1 to 0.9 per 10 000, before rebounding to a weekly median of 12.6 per 10 000 by July 31, 2020.

Multivariable regression analyses confirmed the significant declines in screening mammography and colonoscopy. A larger decline in colonoscopy was observed in high-income counties. Otherwise, the analyses showed no significant demographic variations.

Laura Makaroff, DO, of the American Cancer Society in Atlanta, said that the pandemic’s ultimate impact on cancer screening and cancer care is still largely unknown.

“We have seen similar data showing some rebound in cancer screening rates last summer and fall, but even those turnarounds show an approximate 30% decrease in cancer screening compared with pre-pandemic rates,” she said to MedPage Today in an email. “We also don’t yet know the full impact of the late fall and winter surges on disruptions in cancer screening and diagnosis.”

“The COVID-19 pandemic has had numerous consequences secondary to the disease itself, including reduced access to care for other illnesses,” Dr Makaroff added. “While these measures were necessary, delays in cancer screening, diagnosis, and treatment due to reduced healthcare access will likely result in a short-term drop in cancer diagnoses followed by increases in late-stage diagnoses and preventable cancer deaths.

“The full impact of the COVID-19 pandemic on cancer prevention and early detection will not be known until population-based nationwide data become available in the years to come,” she said.

Source: MedPage Today

Journal information: McBain RK, et al “Decline and rebound in routine cancer screening rates during the COVID-19 pandemic” J Intern Med 2021; DOI: 10.1007/s11606-021-06660-5.

Categories : Pain ManagementTags :

Cannabinoid Effectiveness in Pain Management Questioned

On By ModernMedia

The effectiveness of cannabinoids as pain management has been brought into question by experts reviewing clinical evidence.

Researchers from the University of Bath’s Centre for Pain Research leading experts from around the world reviewed existing data into cannabinoids, including that on so-called ‘medicinal cannabis’ and ‘medicinal cannabis extracts’.

Their findings suggest that while preclinical data supports the hypothesis of cannabinoid analgesia, uncertainties especially in clinical evidence do not reach the certainty in efficacy and safety necessary for the IASP to endorse their general use for pain control.
 The studies and the statement from the IASP are limited to the use of cannabinoids to treat pain, and not for other conditions for which cannabinoids are used.

Dr Emma Fisher who led the review of the clinical evidence said: “Cannabis, cannabinoids, and cannabis-based medicines are becoming an increasingly popular alternative to manage pain. However, our review shows that there is limited evidence to support or refute their use for the management of any pain condition. The studies we found were poor quality (high risk of bias) and the evidence was of very low-certainty, meaning that we are very uncertain of the findings and more research is needed.”

Professor Christopher Eccleston, Director of the Centre for Pain Research / Department for Health, said: “Cannabis seems to attract strong opinions. If ever a field needed evidence and a rigorous scientific opinion it is this one. For many this will be an unpopular conclusion, but we need to face up to the fact that the evidence is simply lacking. Science is not about popularity but keeping people safe from false claims. The challenge in this field will be for governments to fund independent research, and to ensure balance and equipoise.

“Coming close on the heels of The Lancet Commission on children’s pain and the WHO guidelines on treating chronic pain, this further contribution also found no evidence to support the use of cannabis, cannabinoids, and cannabis-based medicines for children with chronic pain. We need to invest in real solutions to the very real problem of chronic pain in children.”

Source: Medical Xpress

Journal information: IASP Presidential Task Force on Cannabis and Cannabinoid Analgesia. Pain. journals.lww.com/pain/pages/co … picalCollectionId=23

Categories : Cardiovascular DiseaseTags :

Genetic Clues to ‘Silent Strokes’ Uncovered

On By ModernMedia

After years of research, scientists have uncovered genetic clues to ‘silent strokes’, a major cause of vascular dementia, opening up new pathways to prevention and treatment.

Lacunar strokes are caused by the weakening of the walls of small blood vessels in the brain that can be only a millimetre in diameter. Such strokes by these can often happen in a stepwise progression, only to be detected when symptoms are noticeable and damage has been done. Few drugs are available to prevent or treat these kinds of strokes.  

Thus far, only one genetic fault has been linked to lacunar strokes. Professor Hugh Markus, BHF-funded researcher and neurologist at the University of Cambridge led a study working with researchers around the world to investigate the genetics behind lacunar strokes. They believe their breakthrough can yield treatments for lacunar stroke and vascular dementia.

Recruiting participants from around the world after they attended hospital and had an MRI or CT brain scan., the researchers scanned and compared the genetic code of 7338 patients who had a lacunar stroke with 254 798 people who had not. They found 12 genetic regions associated with lacunar strokes

The researchers found that these 12 genetic regions are linked to vascular control, and dysfunctions make the blood-brain barrier more permeable to toxins, and messages sent around the brain slow down or fail to arrive completely.

“These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to,” said study leader Prof Hugh Markus. “Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

First author Dr Matthew Traylor, of the study at Queen Mary University of London, said: “Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation and cardiologist, said: “This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35 000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the future.”

Source: Medical Xpress

Journal information: The Lancet Neurology (2021). DOI: 10.1016/S1474-4422(21)00031-4

Categories : Immune SystemTags :

Newly Discovered ‘Goldilocks’ Protein Keeps the Immune System in Check

On By ModernMedia

A newly discovered ‘Goldilocks’ protein may be responsible for helping keep the immune system from running amok, according to researchers at the Lunenfeld-Tanenbaum Research Institute (LTRI).

This protein, known as WAVE2, is expressed in all immune cells and plays a critical role in keeping the immune system in balance. To test its role, researchers knocked out the WAVE2 protein in a subset of immune cells in mice, leading to severe autoimmunity and inflammation, as well as an inability to mount an immune response to a viral infection.

Senior author Dr Kathy Siminovitch, said the team also found that in the absence of WAVE2, another protein, known as mTOR, became overly active, sending the immune system into overdrive and leading to immune cell exhaustion.

“Much like Goldilocks, a proper immune response requires such a delicate balance,” said Dr  Siminovitch. “You have to get it just right. By developing a mouse strain in which T cells, key players in immunity, lack WAVE2, we have shown that this protein is absolutely required for balanced immune responses.”

The question of how to keep the immune system in balance is of key importance in the pandemic, where many deaths occur due to cytokine storms as the immune system overreacts, especially in the elderly. 
As part of her work exploring the mechanisms balancing the immune system, Dr Siminovitch helped trace the complex molecular steps that turn a rare gene mutation into Wiskott-Aldrich syndrome, a potentially lethal disease which impairs the immune system of boys.

Future research would look at how the contribution of the WAVE2-mTOR pathway to specific autoimmune, inflammatory and other conditions, such as Alzheimer’s disease.

Source: News-Medical.Net

Journal information: Liu, M., et al. (2021) WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity. Science. doi.org10.1126/science.aaz4544.

Categories : COVIDTags :

EU and UK Aim for ‘Win-win Situation’ to End Vaccine Row

On By ModernMedia

After weeks of tensions over Covid vaccine supplies, the UK and the European Union have said they are working together to improve their relationship, to “create a win-win situation and expand vaccine supply for all”.

The EU’s Internal Market Commissioner Thierry said that the disputes were with AstraZeneca, not the UK. “I know that there’s some tension… but as long as we have transparency, I think [relations] will be able to be normalised,” he said.

Some 19 EU countries have reported a rise in infections, giving their vaccine rollout an even greater urgency,The joint UK-EU statement said that “openness and global co-operation” would be key to tackling the pandemic.

“We are all facing the same pandemic and the third wave makes co-operation between the EU and UK even more important,” it said. “We will continue our discussions.”
EU Health Commissioner Stella Kyriakides rejected any notion of punishing the UK. “We’re dealing with a pandemic and this is not seeking to punish any countries,” she said.

Responding to the question of whether the UK might retaliate, Mr Johnson told MPs he did not believe “that blockades of either vaccines or of medicines, of ingredients for vaccines” would be “sensible”. It is possible that companies might draw conclusions about future investments “in countries where arbitrary blockades are imposed”, he added.
The EU’s Internal Market Commissioner Thierry Breton insisted the contention was with AstraZeneca and not the UK government. “I know that there’s some tension… but as long as we have transparency, I think [relations] will be able to be normalised,” he said.

Had AstraZeneca supplied the 120 million doses to the EU as was agreed, its member states would have achieved the same vaccination rates as the UK: “We have been heavily penalised and we just want to understand why”.

Source: BBC News