scholarly journals Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kelda Chia ◽  
Marcus Keatinge ◽  
Julie Mazzolini ◽  
Dirk Sieger

Previously we described direct cellular interactions between microglia and AKT1+ brain tumour cells in zebrafish (Chia et al., 2018). However, it was unclear how these interactions were initiated: it was also not clear if they had an impact on the growth of tumour cells. Here, we show that neoplastic cells hijack mechanisms that are usually employed to direct microglial processes towards highly active neurons and injuries in the brain. We show that AKT1+ cells possess dynamically regulated high intracellular Ca2+ levels. Using a combination of live imaging, genetic and pharmacological tools, we show that these Ca2+ transients stimulate ATP-mediated interactions with microglia. Interfering with Ca2+ levels, inhibiting ATP release and CRISPR-mediated mutation of the p2ry12 locus abolishes these interactions. Finally, we show that reducing the number of microglial interactions significantly impairs the proliferation of neoplastic AKT1 cells. In conclusion, neoplastic cells repurpose the endogenous neuron to microglia signalling mechanism via P2ry12 activation to promote their own proliferation.

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv11-iv12
Author(s):  
Kerlann Le Calvez ◽  
Peter Treasure ◽  
Matt Williams

Abstract Introduction Access to clinical trials is a common request for patients with brain tumours. However, opening clinical trials requires additional work per centre opened. We have previously shown that surgical and oncology workload varies between centres, and fluctuates over time. There is a trade-off between offering access to clinical trials and increasing costs associated with opening trials in centres that treat few patients. Methods We used two separate datasets from England covering 3 years – one for neurosurgical workload and one for radiotherapy. We only included adult patients and calculated cumulative proportions of the malignant primary brain tumour population (C71) by number of centres. We investigated stability by checking how many patients would have to be added/ removed from a centre to change their rank. Results There were 7061 surgical and 5060 radiotherapy patients. To capture 25% of patients, we would need to open trials in 4 surgical/5 radiotherapy centres; for 50%, 9 surgical/ 13 radiotherapy centres; for 75%, 16 surgical/ 24 radiotherapy centres. Centre rank was fluid: adding 16 surgical/9 radiotherapy patients would change the rank of a centre. Discussion These are the first data to allow for rational planning of trials in brain tumour patients. We have shown that we can reach 75% of the brain tumour population by opening trials in ~50% of surgical and radiotherapy centres. Centre rank alters over year, so we should be cautious about being too prescriptive. Nonetheless, these data should allow some rational planning of trial centre inclusion.


2021 ◽  
Vol 2 (1) ◽  
pp. 10-11
Author(s):  
Sarah Lindsell

Everyone has a role to play in reducing diagnosis times for childhood brain tumours, the biggest cancer killer of children and adults under 40 years old in the UK. The Brain Tumour Charity's HeadSmart campaign aims to inform parents and healthcare professionals about the key early signs and symptoms of brain tumours.


2020 ◽  
Vol 93 (1107) ◽  
pp. 20190237 ◽  
Author(s):  
Damien C Weber ◽  
Pei S Lim ◽  
Sebastien Tran ◽  
Marc Walser ◽  
Alessandra Bolsi ◽  
...  

Proton therapy (PT) has been administered for many years to a number of cancers, including brain tumours. Due to their remarkable physical properties, delivering their radiation to a very precise brain volume with no exit dose, protons are particularly appropriate for these tumours. The decrease of the brain integral dose may translate with a diminution of neuro-cognitive toxicity and increase of quality of life, particularly so in children. The brain tumour patient’s access to PT will be substantially increased in the future, with many new facilities being planned or currently constructed in Europe, Asia and the United States. Although approximately 150’000 patients have been treated with PT, no level I evidence has been demonstrated for this treatment. As such, it is this necessary to generate high-quality data and some new prospective trials will include protons or will be activated to compare photons to protons in a randomized design. PT comes however with an additional cost factor that may contribute to the ever-growing health’s expenditure allocated to cancer management. These additional costs and financial toxicity will have to be analysed in the light of a more conformal radiation delivery, non-target brain irradiation and lack of potential for dose escalation when compared to photons. The latter is due to the radiosensitivity of organs at risk in vicinity of the brain tumour, that photons cannot spare optimally. Consequentially, radiation-induced toxicities and tumour recurrences, which are cost-intensive, may decrease with PT resulting in an optimized photon/proton financial ratio in the end. Advances in knowledge: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.


2020 ◽  
Vol 9 (3) ◽  
pp. 91-96
Author(s):  
Agnieszka Królikowska ◽  
◽  
Piotr Zieliński ◽  
Marek Harat ◽  
Renata Jabłońska ◽  
...  

Introduction. The location of intracranial neoplasms and the process of treating these lesions itself can significantly affect the quality of life of patients. Hence, the aim of the study was to investigate the impact of the location of the brain tumour on the quality of life of surgically treated patients. Aim. The aim of the study was to investigate the influence of the location of the brain tumour on the quality of life of surgically treated patients. Material and Methods. The study included 236 patients with brain tumours operated at the Department of Neurosurgery of the 10th Military Clinical Hospital with the SP ZOZ Polyclinic in Bydgoszcz. Patients with different tumour locations were included: in the temporal lobe, in the frontal lobe, in the parietal lobe, in the ventricles of the brain and in the extra-cerebral locations. The following questionnaires were used to assess the quality of life: EORTC QLQ-C30 and EORTC QLQ-BN20, in which the patients were tested three times: on the day of admission to the Clinic, on the fifth day after brain tumour surgery and 30 days after the surgery. Results. Patients’ quality of life decreased in the early postoperative period in all groups in terms of tumour location, especially in patients with tumours of the frontal lobe (-0.104) and ventricular neoplasms (-0.109) (p > 0.05). On the 30th day, however, an improvement in the quality of life was achieved in all groups, the highest improvement was obtained in patients with tumours located extra-cerebrally (0.115) and tumours of the temporal lobe (0.097) (p > 0.05). Conclusions. There was no effect of the location of the brain tumour on the quality of life of the studied patients. In the early postoperative period, the quality of life decreased, while it improved 30 days after the surgery. (JNNN 2020;9(3):91–96) Key Words: brain tumour, quality of life, tumour location


2017 ◽  
Vol 6 (3) ◽  
Author(s):  
Denis Lacroix

Zammit, Marisa, and Erica Dornbusch. A Friend In Hope: a Story About Hope's Journey with a Brain Tumour. Brain Tumor Foundation of Canada, 2008.Zammit, Marisa, Erica Dornbusch, and Carole Baillargeon. Mon amie Claire: L'histoire de Claire et de sa tumeur cérébrale. Foundation canadienne des tumeurs cérébrales, 2009.Zammit, Marisa, Erica Dornbusch, and Rocco Speranza. La mia amica Speranza : Speranza e il suo tumore cerebrale. Fondazione canadese del tumore cerebrale, 2008.In an interview with Daytime television, available on YouTube, author Marisa Zammit explains how the Brain Tumour Foundation of Canada contacted her as an established freelance copy writer to come up with a positive story of hope for and about children with brain tumours. According to Susan Marshall, executive director of the Foundation, no other storybook existed for elementary school aged children in Canada before 2008, when the book was published. It is the personal connection, having a child diagnosed with a brain tumour at the age of 4,that motivated Sharon to commission the publication of A Friend in Hope. Marisa had worked previously with illustrator Erica Dornbusch, who had published other storybooks (e.g. Finding Kate's shoes , Mrs. Goodstory) in the past. Marisa is now a school teacher librarian at Holy Cross Catholic Secondary School in Strathroy, Ontario and she has read the book to her students.A Friend in Hope has definitely accomplished its main objective of giving children, parents, and friends a positive and hopeful outlook on the brain tumour journey. Amy Mathias, the Online Community Engagement Coordinator of the Foundation, indicated that 15,000 copies of the book had been distributed in time for the organization’s 30th Anniversary in 2012. It is thanks to the Ronald McDonald House Charities that printing and distribution of the book were possible. The book addresses a very real need not only in alleviating young patients’ fears, but also in explaining brain tumours and their medical implications to children’s teachers and classmates. In turn, adults diagnosed with brain tumours may also use the storybook to approach the subject with their children.As for the translated versions of the book, Pia di Bacco helped translate from English into French by enlisting the support of youth and staff at her school in Montreal. Similarly, her godson Rocco Speranza commissioned grades 4, 5, and 6 youth and staff at the École East Hill School’s Italian program to translate the storybook from English and French into Italian. The motivation in both translation cases was a result of a family member or a student being diagnosed with a brain tumour and the belief in educating youth about brain tumours. Schools across the English Montreal School Board and beyond in Italy, Australia, Argentina, and the USA have also benefited from the storybook.The story is written from the perspective of a young brain tumour patient’s best friend, Danny, Daniel, or Daniele in English, French, and Italian respectively. Danny is trying to understand and, most of all, support his “best buddy,” Hope, who begins her brain tumour journey. As the author Marisa Zammit expressed in the Daytime interview, Hope, or in Italian Speranza, received that name because “it is hope [speranza] that buoys the character through the hardships of the story.” In French, the character’s name is Claire, whose Latin origin “clarus” means “clear, bright, celebrated” and by extension the word “clear”. The French name too, therefore, is representative of her personality and journey.Part of the story involves references to some of the medical treatments that Hope undergoes: MRI, pharmaceutical drugs, radiation therapy, a special helmet and mouthguard, a hospital’s child life centre, and the effects of various treatments on Hope. In every instance, the story uses the narrator’s voice and point of view to express Hope’s various experiences, Danny’s reactions to them, and his own fears. It is a child’s imagination which makes this topic bearable and allows the illustrations to become particularly powerful, when, for example, Danny sees Hope take some medication, which she says will help her “feel well enough to play with [him].” The illustration, in this case, represents a mountain scape and the children’s game of climbing pillows and cushions as if they were mountain climbers, because as Hope says the medication she takes is the “same medicine mountain climbers use,” (ie. dexamethasone). Another exceptional illustration is the one representing an oceanic world with an octopus and fish, which is how Hope faces the MRI machine and transforms it into a submarine. The illustrations are identical across the translations and the English source text, except for one image representing a hockey player in what appears to be Toronto Maple Leafs colours; however, in the French and Italian translations, which originated in Montreal, the team colours were changed to those of the Montreal Canadiens. Habs fans will no doubt appreciate the sensitivity of the illustrator.All in all the story is very well written and the language is suitable for children from grades 2 to 4; however the concepts that are addressed also make this book relevant to higher grade levels. That said, some grammatical inaccuracies exist within the French translation. Public and school libraries would benefit from access to this book, as would hospital library patrons and those who use Faculty of Education libraries. The health education elements of the story are presented in a very appropriate yet realistic manner for the target audience, who will appreciate having access to such a unique resource.Highly Recommended: 4 out of 4 stars Reviewer: Denis LacroixDenis Lacroix has worked at the University of Alberta Libraries since 2003. He is the romance languages and classics librarian and enjoys reading in French, Spanish, and Italian.


2018 ◽  
Vol 3 (2) ◽  

There have been a few case reports of head injury leading to brain tumour development in the same region as the brain injury. Here we report a case where the patient suffered a severe head injury with contusion. He recovered clinically with conservative management. Follow up Computed Tomography scan of the brain a month later showed complete resolution of the lesion. He subsequently developed malignant brain tumour in the same region as the original contusion within a very short period of 15 months. Head injury patients need close follow up especially when severe. The link between severity of head injury and malignant brain tumour development needs further evaluation. Role of anti-inflammatory agents for prevention of post traumatic brain tumours needs further exploration.


2020 ◽  
Vol 15 ◽  
Author(s):  
Smita P. Kakad ◽  
Sanjay J. Kshirsagar

Introduction: The infiltration of HIV into the brain alters the functions of the nervous system known as NeuroAIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions. Materials/Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which acts as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination antiretroviral therapy. Results/Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful to treat neuro-AIDS and related disorders effectively.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Bin Jiang ◽  
Hongmei Liu ◽  
Dongling Sun ◽  
Haixin Sun ◽  
Xiaojuan Ru ◽  
...  

Abstract Background and purpose Epidemiological data on primary brain tumours (PBTs) are lacking due to the difficulty in case ascertainment among the population. Thus, we aimed to estimate mortality due to PBTs in China nationwide and the detection rate in people with suspected symptoms. Methods A multistage, complex sampling survey regarding mortality due to PBTs in Chinese individuals was carried out by reviewing all causes of death within a year. The detection rates in people with suspected symptoms were estimated based on PBT symptom screening and neurologist reviews and compared between groups by logistic regression analysis. Results Weighted mortality due to PBT was 1.6 (0.8–3.3) per 100,000 population in Chinese individuals, 1.8 (0.7–4.6) per 100,000 population in men, and 1.5 (0.5–4.5) per 100,000 population in women. Among 14,990 people with suspected symptoms, the PBT detection rate was 306.9 (95% CI 224.7–409.3) per 100,000 population in the total population, 233.0 (95% CI 135.7–373.1) per 100,000 population in men, and 376.9 (95% CI 252.4–546.3) per 100,000 population in women. People with an unsteady gait (OR 2.46; 95% CI 1.09–5.51; P=0.029), visual anomalies (3.84; 1.88–7.85; P<0.001), and headache (2.06; 1.10–3.86; P=0.023) were more likely to have a brain tumour than those without corresponding symptoms, while people with dizziness/vertigo were less likely to have a brain tumour than those without corresponding symptoms (0.45; 0.23–0.87; P=0.017). Conclusions Mortality due to PBT in China was low, with a nationwide estimate of 21,215 (10,427–43,165) deaths attributable to PBTs annually. However, the detection rate of PBTs can be greatly improved based on symptom screening in the population.


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