Podcasts about microenvironment

A new editorial paper was published in Oncotarget's Volume 14 on August 10, 2023, entitled, “Inhibition of glutamine metabolism: acting on tumoral cells or on tumor microenvironment?” Cancer cell growth and survival relies on metabolites and metabolic routes different from those used by healthy cells. Glucose and glutamine (Gln) uptake and consumption is increased by many cancer types in order to support their high growth rate. Besides being metabolized to tricarboxylic acid (TCA) cycle precursors, Gln is necessary also for the generation of nitrogen-containing metabolites, such as nucleotides, glucosamine-6-phosphate or nonessential amino acids. Indeed, nitrogen supply has been widely described as limiting for cell cycle progression. As mitochondrial glutaminase (GLS) directs Gln into the TCA cycle, its inhibition has been suggested as a potential strategy for targeting and blocking Gln metabolism in cancer cells. In fact, GLS inhibitors block cancer cell growth in vivo and in vitro. Based on this premise, several clinical studies have been conducted to test if Gln dysregulation increases cancer patients' survival. So far, these treatments have not been able to induce a great overall benefit for patients due to the ability of tumor cells to alter their metabolism. Different authors have described an increase in the oxidative stress after alterations in Gln metabolism in vivo, suggesting the possibility to combine glutamine dysregulation strategies with some other therapies increasing reactive oxidative species to promote cancer cell death. In his new editorial, researcher Raul Peña from Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) discusses a novel mechanism by which Gln, usually concentrated at the tumor periphery, acts as a chemoattractant for cancer-associated fibroblasts (CAFs), enhancing extracellular matrix degradation and facilitating epithelial cancer cell migration and metastasis in vivo. “Recently, we described a new action of Gln on cancer-associated fibroblasts (CAFs) in breast cancer. [...] In our study, we determined that mesenchymal-like epithelial breast tumor cells and CAFs present a higher dependence on Gln than tumor epithelial breast cancer cells.” DOI - https://doi.org/10.18632/oncotarget.28443 Correspondence to - Raúl Peña - rpena@imim.es Video short - https://www.youtube.com/watch?v=HcI9CpUdbys Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28443 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, glutamine, tumor microenvironment, fibroblasts, CAF, snail1 About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Join Kristin Gilmour as she interviews Julianne Grant to discuss the immune system implications within the tumour microenvironment. This podcast explores the unique immune environment that is slowly established through the stages of cancer cell growth and spread. Julianne, an experienced Melbourne-based Naturopath who focuses her clinic on supporting immune health, discusses the important role of specific phytomedicines and medicinal mushrooms in modulating the tumour microenvironment to promote a less favourable terrain for cancer cell survival. ---- DISCLAIMER: All information provided via OptimalRx is for educational and informational purposes only.  The information provided is not, nor is it intended to be, a substitute for independent professional advice.  Please seek the advice of a qualified health care professional in the event something you learn here raises questions or concerns regarding your health. Thank you.www.optimalrx.com.au

In this week's episode, we'll learn more about ventricular arrhythmias in sickle cell anemia, discuss the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders, and uncover the role of the bone marrow microenvironment as a driver of myeloid disorders.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.27.550884v1?rss=1 Authors: Jury-Garfe, N., You, Y., Martinez, P., Redding-Ochoa, J., Karahan, H., Johnson, T. S., Zhang, J., Kim, J., Troncoso, J. C., Lasagna-Reeves, C. A. Abstract: Asymptomatic Alzheimer 's disease (AsymAD) describes the status of subjects with preserved cognition but with identifiable Alzheimer 's disease (AD) brain pathology (i.e. A {beta}-amyloid deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD cases to gain insight into the underlying mechanisms of resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit an enrichment of core plaques and decreased filamentous plaque accumulation, as well as an increase in microglia surrounding this last type. In AsymAD cases we found less pathological tau aggregation in dystrophic neurites compared to AD and tau seeding activity comparable to healthy control subjects. We used spatial transcriptomics to further characterize the plaque niche and found autophagy, endocytosis, and phagocytosis within the top upregulated pathways in the AsymAD plaque niche, but not in AD. Furthermore, we found ARP2, an actin-based motility protein crucial to initiate the formation of new actin filaments, increased within microglia in the proximity of amyloid plaques in AsymAD. Our findings support that the amyloid-plaque microenvironment in AsymAD cases is characterized by microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared to AD. These two mechanisms can potentially provide protection against the toxic cascade initiated by A {beta} that preserves brain health and slows down the progression of AD pathology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.04.547746v1?rss=1 Authors: Ly, C. H., Chung, J. D., Nguyen, J. H., Tian, L., Schroeder, J., Knaupp, A. S., Su, S., Trieu, J., Salmi, T. M., Zalcenstein, D., Jabbari, J. S., Boughton, B. A., Cox, A. G., Naik, S. H., Polo, J. M., Ritchie, M. E., Lynch, G. S., Ryall, J. G. Abstract: Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use metabolomics and mass spectrometry imaging (MSI) to identity a state of localized hyperglycaemia following skeletal muscle injury. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal in regenerating skeletal muscle. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment during skeletal muscle regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.23.546317v1?rss=1 Authors: Tharp, K., Park, S., Timblin, G. A., Richards, A., Berg, J., Twells, N., Riley, N. M., Peltan, E., Shon, D. J., Stevenson, E., Tsui, C. K., Palomba, F., Lefebvre, A. E., Soens, R., Ayad, N., ten Hoeve-Scott, J., Healy, K., Digman, M., Dillin, A., Bertozzi, C., Mahal, L. K., Swaney, D., Cantor, J. R., Paszek, M., Weaver, V. Abstract: Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.21.545899v1?rss=1 Authors: Turiel, G., Desgeorges, T., Masschelein, E., Birrer, M., Zhang, J., Engelberger, S., De Bock, K. Abstract: BackgroundPeripheral artery disease (PAD) is caused by atherosclerosis and chronic narrowing of lower limb arteries leading to decreased muscle perfusion and oxygenation. Current guidelines for treating PAD include endovascular strategies or bypass surgery but long-term outcomes have been suboptimal. This is likely due to our limited understanding of the contribution of the microvasculature as well as other cell types, in particular macrophages, to PAD skeletal muscle pathophysiology. We used single cell sequencing to investigate cellular and transcriptional heterogeneity of the skeletal muscle microenvironment in PAD. MethodsSamples from the medial head of the gastrocnemius muscle of individuals undergoing either lower limb aneurysm surgery (controls) or PAD bypass surgery (PAD) were collected. Samples were either frozen for histological evaluation (control: n=4; PAD: n=6) or were immediately processed for single cell RNA sequencing of mononuclear cells (control: n=4; PAD: n= 4). Bioinformatic tools were used to annotate cell types and their subpopulations, to study transcriptional changes and to analyze cellular interactions. ResultsWe generated a dataset comprised of 106,566 high-quality, deep-sequenced cells that compose the muscle microenvironment. Focusing on endothelial cells (ECs) and macrophages, we confirmed the presence of ATF3/4+ ECs with angiogenic and immune regulatory capacities in human muscle and found that their transcriptional profile profoundly alters during PAD. Also, capillary ECs display features of endothelial to mesenchymal transition. Furthermore, we identified LYVE1hiMHCIIlow resident macrophages as the dominant macrophage population in human muscle, even under a chronic inflammatory condition such as PAD. During PAD, LYVE1hiMHCIIlow macrophages get activated and acquire a more pro-inflammatory profile. Finally, we map strong intercellular communication in the muscle microenvironment, which is significantly altered in PAD. ConclusionsThe dataset we present here provides a highly valuable resource for gaining deeper insights into the critical roles that cells in the muscle microenvironment may play in PAD skeletal muscle pathology. We propose that targeting the crosstalk between ECs and macrophages could provide novel insights for developing effective treatments against this disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.20.537710v1?rss=1 Authors: Kwon, S. H., Parthiban, S., Tippani, M., Divecha, H. R., Eagles, N. J., Lobana, J. S., Williams, S. R., Mark, M., Bharadwaj, R. A., Kleinman, J. E., Hyde, T. M., Page, S. C., Hicks, S. C., Martinowich, K., Maynard, K. R., Collado-Torres, L. Abstract: Neuropathological lesions in the brains of individuals affected with neurodegenerative disorders are hypothesized to trigger molecular and cellular processes that disturb homeostasis of local microenvironments. Here, we applied the 10x Genomics Visium Spatial Proteogenomics (Visium-SPG) platform, which measures spatial gene expression coupled with immunofluorescence protein co-detection, in post-mortem human brain tissue from individuals with late-stage Alzheimer's disease (AD) to investigate changes in spatial gene expression with respect to amyloid-{beta} (A{beta}) and hyperphosphorylated tau (pTau) pathology. We identified A{beta}-associated transcriptomic signatures in the human inferior temporal cortex (ITC) during late-stage AD, which we further investigated at cellular resolution with combined immunofluorescence and single molecule fluorescent in situ hybridization (smFISH) co-detection technology. We present a workflow for analysis of Visium-SPG data and demonstrate the power of multi-omic profiling to identify spatially-localized changes in molecular dynamics that are linked to pathology in human brain disease. We provide the scientific community with web-based, interactive resources to access the datasets of the spatially resolved AD-related transcriptomes at https://research.libd.org/Visium_SPG_AD/. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.12.536447v1?rss=1 Authors: Kaminska, P., Ovesen, P. L., Jakiel, M., Obrebski, T., Schmidt, V., Bieniek, M., Anink, J., Paterczyk, B., Draminski, M., Jensen, A. M. G., Piatek, S., Andersen, O. M., Aronica, E., Willnow, T. E., Kaminska, B., Dabrowski, M. J., Malik, A. R. Abstract: SorLA, encoded by the gene SORL1, is an intracellular sorting receptor of the VPS10P domain receptor gene family. Although SorLA is best recognized for its ability to shuttle target proteins between intracellular compartments in neurons, recent data suggest that also its microglial expression can be of high relevance for the pathogenesis of brain diseases, including glioblastoma (GBM). Here we interrogated the impact of SorLA on the functional properties of glioma-associated microglia and macrophages (GAMs). In the GBM microenvironment, GAMs are re-programmed and in turn lose the ability to elicit anti-tumor responses. Instead, they acquire glioma-supporting phenotype, which is a key mechanism promoting glioma progression. Our analysis of scRNA-seq data from GBM patients revealed that the pro-tumorigenic and pro-inflammatory properties of GAMs are linked to high and low SORL1 expression, respectively. Using cell models, we confirm that SorLA levels are differentially regulated by the presence of glioma cells and by inflammatory cues. We further show that SorLA acts as a sorting receptor for the pro-inflammatory cytokine TNFalpha to restrain its secretion from microglia. As a consequence, loss of SorLA enhanced the pro-inflammatory potential of microglia, having a remarkable impact on glioma progression. In a murine model of glioma, SorLA-deficient mice develop smaller tumors and show hallmarks of anti-tumor response including altered microglia morphology, enhanced necroptosis, and massive neutrophil influx into the tumor parenchyma. Our findings indicate that SorLA is a key player in shaping the phenotype of GAMs, and its depletion can unlock an anti-tumor response. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new review paper was published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Crosstalk between triple negative breast cancer and microenvironment.” Although many advances have been made in the treatment of breast cancer, for triple negative breast cancer (TNBC) these therapies have not significantly increased overall survival. Tumor microenvironment (TME) plays an essential role to develop and control TNBC progression. Many preclinical and clinical studies are ongoing to treat patients with TNBC disease, but effective therapies are currently not available. In their new review, researchers Karly Smrekar, Artem Belyakov and Kideok Jin from Albany College of Pharmacy and Health Science discuss recent progress in our understanding of TNBC, advancements in defining mechanisms of TNBC therapies and potential therapeutic strategies to overcome TNBC. “Technological advancements such as genomics and epigenomics have provided us with vast insight about the complexity of breast cancer. However, one thing has remained the same, the need for the evaluation of three markers. These three markers; the expression of estrogen, progesterone, and HER2, are all molecular targets for treatment regimens, and are relied on by clinicians [1]. Chemotherapy is the staple treatment for TNBC patients. However, they lack the expression of three key therapeutic markers. The lack of therapeutic markers leads to poorer outcomes in TNBC.” DOI: https://doi.org/10.18632/oncotarget.28397 Correspondence to: Kideok Jin - kideok.jin@acphs.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28397 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - triple negative breast cancer, tumor microenvironment, current therapy About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534302v1?rss=1 Authors: Yordanov, T. E., Martinez, M. A. E., Esposito, T., Tefft, J. B., Labzin, L. I., Stehbens, S. J., Rowan, A., Hogan, B. M., Chen, C. S., Lauko, J., Lagendijk, A. K. Abstract: Cerebral Cavernous Malformations (CCMs) are vascular lesions that predominantly form in blood vessels of the central nervous system (CNS) upon loss of the CCM multimeric protein complex. The endothelial cells (ECs) within CCM lesions are characterised by overactive MEKK3 kinase and KLF2/4 transcription factor signalling, leading to pathological changes such as increased EC spreading and reduced junctional integrity. Concomitant to aberrant EC signalling, non-autonomous signals from the extracellular matrix (ECM) have also been implicated in CCM lesion growth and these factors might explain why CCM lesions mainly develop in the CNS. Here, we adapted a three dimensional (3D) microfluidic system to examine CCM1 deficient human micro-vessels in distinctive ECMs. We validate that EC pathological hallmarks are maintained in this 3D model. We further show that supplementing the ECM with distinct forms of Hyaluronic Acid (HA), a major ECM component of the CNS, alters CCM1 biology, independent of KLF2/4. This study provides a proof-of-principle that ECM embedded 3D microfluidic models are ideally suited to identify how changes in ECM structure and signalling impact vascular malformations. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.16.520731v1?rss=1 Authors: Bartlome, S., Xiao, Y., Ross, E., Dalby, M. J., Berry, C. C. Abstract: Breast cancer is the leading cause of cancer mortality in women worldwide and commonly metastasizes to the bone marrow, drastically reducing patient prognosis and survival. In the bone marrow niche, metastatic cells can enter into a dormant state, thereby evading immune surveillance and treatment, and can be reactivated to enter a proliferative state due to poorly understood cues. Mesenchymal stromal cells (MSCs) maintain cells in this niche partly by secreting extracellular matrix and paracrine factors and by responding to regenerative cues. MSCs also produce extracellular vesicles (EVs) that carry a range of cargoes, some of which are implicated in cell signalling. Here, we investigate if the changing metabolic state of MSCs alters the cargoes they package into EVs, and how these changing cargoes act on dormant breast cancer cells (BCCs) using an in vitro BCC spheroid model and a scratch assay to create a regenerative demand on MSCs. Our findings show that EVs produced by standard MSCs contain glycolytic metabolites that maintain BCC dormancy. When MSCs are placed under a regenerative demand and increase their respiration to fuel differentiation, these metabolites disappear from the EV cargo and their absence encourages rapid growth in the BCC spheroids. This work implicates EVs in cancer cell dormancy in the bone marrow niche and indicates that pressures on the niche, such as regeneration, can be a driver of BCC activation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.12.520033v1?rss=1 Authors: Wu, Y., Huang, J., Ding, N., Lu, M., Wang, F. Abstract: Non-obstructive azoospermia is the most serious cause of male infertility. The testis has a special immunological environment, but the relationship between immune cells in the testicular microenvironment is still unclear. Therefore, it is urgent to identify the interaction mechanism and molecular determinants of immune cells in the testicular microenvironment. To further elucidate the etiology of azoospermia and provide a reference for the treatment of azoospermia. The GSE145467 and GSE9210 datasets were analyzed by Limma package, and then the differential genes were analyzed by enrichment analysis and protein-protein interaction analysis. In addition, we combined single-cell analysis(scRNA) to identify immune cell types and verified the expression of Hub genes in these immune cells. Finally, CellChat was used for cell-to-cell communication analysis. We found the distribution of immune cells in the microenvironment of Y chromosome AZF region microdeletions (AZFa_Del), idiopathic NOA (iNOA), and Klinefelter syndrome (KS) was significantly different from that of normal adults, especially monocytes/macrophages. In normal subjects, monocytes/macrophages mainly played the role of the signal source, while in patients with azoospermia, monocytes/macrophages mainly received signals from other immune cells. Monocytes/macrophages in AZFa_Del, iNOA, and KS communicated with other immune cells mainly through MDK-LRP1, PTN-NCL, and MDK-NCL ligand-receptor pairs respectively. Our research provides new ideas for the pathogenesis and treatment of azoospermia. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The 19th International Workshop on Non-Hodgkin Lymphoma (iwNHL) 2022 took place in Barcelona, Spain, and brought together leading experts in... The post iwNHL Session II: Understanding and harnessing the immune microenvironment against lymphoma appeared first on VJHemOnc.

The 19th International Workshop on Non-Hodgkin Lymphoma (iwNHL) 2022 took place in Barcelona, Spain, and brought together leading experts in... The post iwNHL Session II: understanding and harnessing the immune microenvironment against lymphoma appeared first on VJHemOnc.

Hyaluronic acid is a well-known skincare active. While most people are aware of its function in moisturizing the skin, what is equally important but lesser-known is that it participates in very meaningful cell-to-cell interactions, which is known as cell talk. The key here is that not all forms of hyaluronic acid is able to perform this function of enhancing the cellular processes that are beneficial in the anti-aging process. Multi weighted hyaluronic acid which includes macro and micro hyaluronic acid ensures that there are different depths of penetration where the molecules also exert various effects on skin. The term natural moisturizing factor is helpful in the understanding of this concept. It helps to regulate the skin microenvironment which ensures an optimal state of balance. These are crucial processes that make our skin resilient to environmental and lifestyle assaults that can accelerate photoaging. Want more of our podcast? Episode Recaps and Notes:https://www.scienceofbeauty.net/; Instagram: @drteowanlin; Youtube: http://bit.ly/35rjbve

In this week's episode, we will review a report on a clinical prognostic tool that identifies which group of older, fit acute myeloid leukemia patients may derive survival benefit from intensive induction and consolidation chemotherapy, learn more about how pediatric acute myeloid leukemia cells connect with mesenchymal stromal cells and the potential to exploit these cell-cell contacts in AML treatments, and examine the effects of eltrombopag and romiplostim in elderly patients with immune thrombocytopenia.

Recent progress in the field of immunotherapy presents an exciting alternative to standard chemotherapy treatments for patients with non-Hodgkin lymphoma.... The post iwNHL 2021: immunotherapy and the microenvironment appeared first on VJHemOnc.

Recent progress in the field of immunotherapy presents an exciting alternative to standard chemotherapy treatments for patients with non-Hodgkin lymphoma.... The post iwNHL 2021: immunotherapy and the microenvironment appeared first on VJHemOnc.

In this week's episode, we will review a study that addresses the issue of reconstitution of immunity to cytomegalovirus in transplant patients receiving the antiviral drug letermovir, learn more about the role extracellular vesicles play in forming a tumor supportive stromal cell niche in follicular lymphoma, and finally, look at a report identifying a mechanism that couples the treatment of acute ischemic stroke with tissue plasminogen activator to the development of intracerebral hemorrhage.

This episode, supported by Bethyl, delves into the realm of the tumor microenvironment (TME), exploring the cells that reside there and how they interact to promote tumor growth and metastasis. Discover how immune cells are attracted and manipulated by tumor cells enabling the cancer to invade neurons where they can then travel throughout the body. Providing an expert's insight into this topic is Moran Amit, Assistant Professor at the MD Anderson Cancer Center (TX, USA). Moran exposes the nebulous interactions in the TME and describes the techniques that he uses to interrogate it, in the hope that by further understanding these interactions we will be able to design more successful, targeted therapies for neurotropic cancers. Contents: ·      Introductions: 00:00-01:20 ·      The key cells of the TME:  01:20-02:50 ·      How cells of the TME  support the tumor: 02:50-05:45 ·      How cancer cells influence and impact immune cells: 05:45-07:25 ·      The invasion of cancers into the neurons: 07:27-9:45 ·      Recruitment of neurons to the TME: 09:45-10:55 ·      The evolution of neuron recruitment to the TME: 10:55-15:00 ·      Techniques involved in the study of the TME: 15:00-17:00 ·      Tips for best practice: 17:00-18:00 ·      Tumors with neural networks: 18:00-20:05 ·      Clinical impact of research: 20:05-21:50 ·      The cancers impacted the most by this research: 21:50-23:25 ·      The impact of neural invasion on patients and neurons: 23:25-25:30 ·      One thing to improve our understanding of the TME: 25:30-28:00

How can cancer cells be understood through a lens other than strictly biological? Mechanical factors may serve a function in the genes never before understood. Press play to learn: How normal cells respond to stressors on the body If organs as a whole change in response to the presence of cancer How an encapsulated tumor affects surgery Xi Huang, assistant professor in the department of molecular genetics at the University of Toronto, discusses his research on the mechanical aspects of cancer cells. Cancer tissue in an organ can alter the rigidity of the tissue around it. A more rigid environment can be conducive to forming new growths of cancer if the pathways in the area allow for it. Different stiffnesses in tissue can give clues into the stem cells of that specific cancer. If tumors of the same kind vary in stiffness, they may behave differently or have different impacts on the surrounding area. To learn more, visit http://www.moleculargenetics.utoronto.ca/faculty/2015/7/2/xi-huang. Episode also available on Apple Podcasts: apple.co/30PvU9C

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Elisabet E. Manasanch, MD Anderson Cancer Center, Houston, US, and Taxiarchis Kourelis, Mayo Clinic, Rochester, US. They discuss new findings regarding the role of the immune microenvironment presented at ASH 2020In this podcast, Manasanch and Kourelis describe two studies on immune microenvironment changes in myeloma. The first study is a preliminary analysis of peripheral blood and bone marrow samples from patients with smoldering myeloma. This included identifying changes to immune cell composition and using RNA/DNA sequencing to identify biomarkers associated with immune changes in patients with disease progression. From the data, they outline possible new avenues in immune cell profiling for the prognosis of high-risk precursor patients, as well as therapeutic targeting, including the potential for curing at the precursor stage. The second study for discussion compared major components of tumor ecosystems in patients with newly diagnosed/relapsed myeloma that are triple-class refractory. Kourelis brings attention to unhealthy T-cell compartments in more heavily pretreated patients compared with patients with newly diagnosed/relapsed disease and the implications for their response to T-cell-based immunotherapies. Hosted on Acast. See acast.com/privacy for more information.

Professor Jacintha O'Sullivan joins me this week to chat about her Translational Oncology research group in the Trinity Translational Medicine Institute at St James's hospital. She talks to me about her work on gastrointestinal cancers, both Colorectal and Oesophageal and how her studies on tumour microenvironment, metabolism and angiogenesis could impact GI cancer treatments and diagnosis. Jacintha also talks to me about spending nearly a decade in the US and the importance of working with patients and clinical teams to further our knowledge of cancer pathogenesis.Follow Jacintha: JacinthaOSFollow me: MeganHanlon4 This season is kindly sponsored by Bio-Sciences Ltd

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.31.362988v1?rss=1 Authors: Christensen, E. R., Naidas, A., Husic, M., Shooshtari, P. Abstract: Tumour microenvironments (TME) contain a variety of cells including but not limited to stromal fibroblasts, endothelial cells, immune cells, malignant cells, and cells of the tissues of origin, whose interactions likely influence tumour behaviour and response to cancer treatment. The specific composition of the TME can be elucidated using single-cell RNA sequencing (scRNA-seq) by measuring the expression profiles of individual cells. Several scRNA-seq datasets from multiple cancer types have been published in recent years, yet we still lack a comprehensive database for the collection and presentation of TME data from these studies in an easily accessible format. We have thus built a database of TME scRNA-seq data, containing 21 TME scRNA-seq datasets from 12 different cancer types. We have also created an R package called TMExplorer, which provides an interface to easily search and access all available datasets and their metadata. Data and metadata are kept in a consistent format across all datasets, with multiple expression formats available depending on the use case. Users can view a table of metadata and select individual datasets or filter them by specific characteristics. Users may also select a specific type of cancer and view all published scRNA-seq data for that cancer type available in our database. Users are provided with an option to save the data in multiple formats in order to view or process it outside of R. Thus, the TMExplorer database and search tool allow for thorough examination of the TME using scRNA-seq in a way that is streamlined and allows for easy integration into already existing scRNA-seq analysis pipelines. Copy rights belong to original authors. Visit the link for more info

There are 6 pillars to creating deep health. The 6 pillars represent the Marriage, Microenvironment, Movement, Mood, Meaning and Mental. To feel fulfilled in life, we need all of the above. To listen to this podcast choose your favourite platform in the comment below. I help you build long-term sustainable habits so you can feel amazing in your skin. I am an anti-diet activist. I cultivate anti-diet cultures and non-diet nutrition. I create lifestyle change using short-term methodologies. I encourage long-term weight loss results for optimal health. I improve your relationship with food. I enhance your self-confidence. I promote self-compassion and self-care. I deliver the above through my Anti-Diet Challenge. In 30 days I help you lose up to 10lbs WITHOUT following diets, taking pills or drinking shakes. Some of my ladies have achieved up to 5 lbs loss in the first week and are loving the process. Are you struggling with the weight you may have put on while being in lockdown? Let me help you to shift this… Stop wishing and start living the life you deserve. If this message resonates with you and you would like to lose your first (or next 10 pounds) then take my 30-Day Anti-Diet Challenge™ Now, click here to sign up, https://www.30dayantidietchallenge.com Everyday, I will bring you evidence-based nutrition tips that will help you to lose weight and keep it off without counting calories, macros and points. Each week we will have a guest that will enlighten us with their expertise.

"I will always ask myself, what can I do with my knowledge in science to be able to bridge that to patients?" - Michel Detheux, co-founder and CEO of iTeos Therapeutics

Full Text- https://tinyurl.com/yavmxbxt The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested. In addition, there were sets of differentially-expressed genes in AML-exposed BM-MSC that were unique to the particular AML genotype or Trp53 status. Our findings support the hypothesis that leukemia cells alter the transcriptome of surrounding BM stromal cells, in both common and genotype-specific ways. These changes are likely to be advantageous to AML cells, affecting disease progression and response to chemotherapy, and suggest opportunities for stroma-targeting therapy, including those based on AML genotype. Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N www.Oncotarget.com

In this podcast, Editor Anna Berghoff speaks to Professor Eric Tartour (Department of Immunology; Hôpital Européen Georges Pompidou) about new therapeutic targets in the inflammatory microenvironment. The introduction of immune checkpoint inhibitors introduced a new era of oncology. The CTLA4 or PD1/PDL1 axis targeting immune checkpoint inhibitors have shown remarkable and long lasting responses in a variety of tumor types, Here, the biology of immune checkpoint inhibitors is outlined including the main site of action for the different immune checkpoint inhibitor types. Further, other possible immune checkpoints like LAG3 and other cells types including macrophages and NK cells as future directions for immune modulating therapies are discussed. Combination approaches including immune checkpoint inhibitors and chemotherapy or radiotherapy are currently investigated for their synergistic efficacy and preliminary data has shown promising results. Read the Abstract on the ESMO Open website: http://esmoopen.bmj.com/content/3/1/e000310.

Dr Sergei Grivennikov speaks with ecancertv at AACR 2016 on the mechanisms by which a tumour can modulate its environment to promote inflammation for its own benefit. Normally an immune response to infection, tumour upregulation of the inflamed environment attracts cell repair and growth factors that would otherwise heal a wound, contributing to further cancer growth. Dr Grivennikov reviews different therapeutic prospects in treating cancer by destabilising the microenvironment, from aspirin to targeted molecules.

Prof Jorge Moscat speaks with ecancertv at AACR 2016 about signalling pathways involving p62. He describes the role of p62-regulated detoxification, and how this can be subverted to promote cancer cell survival and proliferation. Currently his work focuses on molecular targeting of p62, which has prevented hepatocarcinoma in mouse models.

Prof de Castro talks to ecancertv at IAOO 2015 about head and neck squamous cell carcinoma and the impact of the microenvironment on immune tolerance with particular reference to PD-1.

Dr Jan Burger speaks with ecancertv at BSH 2016 about the crosstalk targeting therapies presenting an alternative to chemotherapy in treating CLL. These include kinase inhibitors, which enable signals from the microenvironment which upregulate B and T Cell presence towards tumours. With regards to drug resistance, Dr Burger describes the need for strategies in novel treatment schemes to manage and reduce risk to patients.

Prof Lei Zheng speaks with ecancer and his research into vaccine therapies to treat pancreatic cancer. Pancreatic cancer is notoriously resistant to many treatments, including checkpoint inhibitors. Prof Zheng reports that using combined vaccine alongside anti-PD1 therapies primes the tumour microenvironment, increasing sensitivity and drug uptake.

Dr George Follows speaks with ecancertv at BSH 2016 about the UKCLL session he chaired, reviewing the data presented, the background, and potential clinical applications of current research. He describes the microenvironment required to sustain CLL in research, having previously been difficult to model and maintain cancer cells in situ.

A lot of very aggressive forms of cancer seem to metastasize to the bone. Now, researchers at the Lawrence Livermore National Laboratory and University of California campuses at Merced and Davis have joined forces to figure out what’s going on in the bone microenvironment between cancer cells and bone cells. Gabriela Loots, a biomedical scientist at the Livermore Lab, says they’re onto something. "There are certain molecules, for example, that once secreted by the bone they seem to create this environment that’s very attractive to the cancer cells to go there and to grow." Loots and her team are studying prostate cancer in particular because the aggressive form of the disease spreads primarily to the skeleton. They’ve identified a bone protein called Sclerostin, which had an inhibitory effect on prostate cancer invasion. "So, basically our next step now is really trying to understand how we can manipulate the environment of the tumor, so we can prevent it from forming bone metastases."

Sat, 6 Feb 2016 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19273/ https://edoc.ub.uni-muenchen.de/19273/1/Grziwok_Sandra.pdf Grziwok, Sandra ddc:590, ddc:50

Dr Lisa Coussens talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about inflammation and cancer and how this can be used in the tumour microenvironment. By studying transgenic mouse models of skin, lung, breast and pancreas cancer development, Dr Coussens lab found that adaptive leukocytes differentially regulate myeloid cell recruitment, activation, and behaviour, by organ-dependent mechanisms. This has been translated into a recent clinical trial involving triple negative breast cancer.

Dr Ansell talks to ecancertv at ASCO 2013 about the tumour microenvironment and stroma and its role in cancer. He covers antibodies and immunotherapy tackling lymphnodes and ALK positive cells.

Metastasis

Animal life has adapted to survive in the most unlikely and inhospitable habitats. This unit looks at the surprisingly diverse desert climates throughout the world and mammals, birds, lizards and amphibians that survive there. It splits these animals into three groups according to their strategy for survival: evaders, evaporators and endurers, then discusses how these strategies work on a biochemical and physiological level. This study unit is just one of many that can be found on LearningSpace, part of OpenLearn, a collection of open educational resources from The Open University. Published in ePub 2.0.1 format, some feature such as audio, video and linked PDF are not supported by all ePub readers.

John F. DiPersio, MD, PhD Chief, Division of Oncology Deputy Director, Alvin J. Siteman Cancer Center Professor of Medicine, Pathology & Immunology Section of BMT & Leukemia Barnes-Jewish Hospital and Washington University School of Medicine St. Louis, Missouri

John F. DiPersio, MD, PhD   Chief, Division of Oncology Deputy Director, Alvin J. Siteman Cancer Center Professor of Medicine, Pathology & Immunology

Introduction: Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration. The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1 beta activates the transcription factor nuclear factor-KB (NF-KB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1 beta-induced activation of NF-KB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1 beta-induced NF-KB signalling pathway in MSCs during chondrogenic differentiation. Methods: MSCs were either cultured in a ratio of 1:1 with primary chondrocytes in high-density culture or cultured alone in monolayer with/without curcumin and/or IL-1 beta. Results: We demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1 beta-induced activation of NF-KB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes. In IL-1 beta stimulated co-cultures, four-hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans (CSPGs), beta 1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2. Conclusions: Curcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.

Dans cet exposé nous présentons un travail qui est mené conjointement par deux équipes du laboratoire IBISC : l'équipe DYNAMIC, constituée de biologistes expérimentaux, et l'équipe TADIB, spécialisée en traitement de données et d'images. L'objectif final de ce travail est de proposer aux biologistes un logiciel d'analyse automatique d'images qui, à partir de vues prises sur un microscope apotome ZEISS, permette d'évaluer le pourcentage de cellules appartenant à des classes prédéterminées. En effet, l'équipe DYNAMIC étudie les occurrences de cellules morphologiquement différentes et potentiellement plus invasives. Pour cela ils travaillent sur la potentialité de migration de cellules cancéreuses mises en culture. A ce stade, les cellules saines ayant évolué vers l'état cancéreux peuvent opter pour deux types de migration cellulaire : la migration mésenchymateuse, migration lente caractérisée par des cellules de forme allongée, ou la migration amiboïde, migration rapide caractérisée par des cellules de forme ronde et "blebbante" qui est conjointe à un échappement cellulaire de la tumeur primaire avec comme pronostic une forte probabilité de création de métastase. La question qui se pose aux biologistes est de savoir pourquoi des cellules passent du mode de migration mésenchymateuse au mode de migration amiboïde. L'hypothèse faite par l'équipe DYNAMIC est que cette évolution du comportement est liée au micro-environnement cellulaire et en particulier à la présence de la molécule PAI-1 (Plasminogen Activator Inhibitor-1) qui "encouragerait" ce comportement "métastatique". La validation d'une telle hypothèse permettrait d'envisager de modifier le micro-environnement d'une tumeur primaire pour éviter la multiplication des sites cancéreux à travers le développement de métastases. Le problème est que, pour valider cette hypothèse, de nombreuses observations sont nécessaires. Ces observations se font sur des cultures de cellules vivantes photographiées au microscope. Sur ces images, on va compter le nombre de cellules de chaque classe : non migrante (ronde et lisse), mésenchymateuse (allongée) et amiboïde (ronde et blebbante), et évaluer les pourcentages de chaque classe en fonction de la composition du micro-environnement et de la durée écoulée. Le travail de culture est déjà long et délicat. Rajouter à cela des opérations de comptage et de classification "manuelle" rendent le travail particulièrement fastidieux. Après avoir exposé le mode opératoire permettant d'acquérir les images, nous nous attarderons sur les différentes difficultés liées à ces images : gradient de luminosité d'orientation variable, faible rapport signal à bruit, éclairage rasant provoquant une rupture des contours. Si chacun de ces problèmes peut être résolu, la présence de l'ensemble de ces difficultés nécessite la mise en place d'une chaîne complète de prétraitements permettant d'obtenir une image correcte des écarts-types, image servant de support au calcul des composantes connexes présentes dans l'image. Par ailleurs, un filtrage par une différence de gaussiennes appliqué sur l'image des écarts-type permet d'obtenir une image dite de "halo" mettant en évidence la position du centre des cellules et rendant possible l'opération de comptage. Cette approche par filtrage est comparée à une approche par transformée de Hough. Les résultats présentés illustrent les limites respectives de chaque méthode. Enfin, une segmentation par Ligne de Partage des Eaux (LPE) est opérée sur une carte des distances réalisée sur chaque composante connexe, les germes de la LPE étant les centres précédemment obtenus. Il est ainsi possible d'isoler un maximum de cellules sur lesquelles seront calculés cinq paramètres morphologiques utilisés dans l'étape de classification. D'où l'intérêt du développement d'un logiciel automatique de traitement et analyse des images qui dégage les biologistes de cette tâche et leur permet de prétendre à une validation de leur hypothèse sur une analyse d'une population cellulaire de grande taille. Ce travail est réalisé en collaboration avec T.Q. Syed, A. Cartier-Michaud, V. Vigneron, C. Charrière-Bertrand, C. Montagne, G. Barlovatz-Meimon, M. Malo. Référence : M. Malo, C. Charrière-Bertrand, E. Chettaoui, C. Fabre-Guillevin, F. Maquerlot, A. Lackmy, A. Vallée, F. Delaplace, and G. Barlovatz-Meimon. The PAI-1 swing: Microenvironment and cancer cell migration. Accepté aux "Comptes Rendus Biologie", 2006. V. Vigneron, S. Lelandais, C. Charriere-Bertrand, M. Malo, A. Ugon, and G. Barlovatz-Meimon. Pro or cons local vs. global imagery information for identifying cell migratory potential. In 15th European Signal Processing Conference (EUSIPCO 2007), pages 443-448, Poznan, Poland, September 2007. Sylvie Lelandais. Université d'Evry-Val-D'Essonne. Vous pouvez entendre l'intervention, tout en visualisant le Power Point, en cliquant sur ce lien : http://epn.univ-paris1.fr/modules/ufr27statim/UFR27STATIM-20090122-Lelandais/UFR27STATIM-20090122-Lelandais.html. Ecouter l'intervention : Bande son disponible au format mp3 Durée : 54 mn

Der Tissue Factor (TF) der Gefäßwand gilt heute als der wichtigste Starter der menschlichen Blutgerinnung. Es wird davon ausgegangen, dass die Lokalisation von TF innerhalb der Gefäßwand unter physiologischen Verhältnissen eine strikte Trennung von den plasmatischen Gerinnungsfaktoren gewährleistet, so dass es unter physiologischen Bedingungen nur nach Wegfallen der endothelialen Barriere zur Bildung des TF/VIIa-Komplexes und dort zur Auslösung der Blutgerinnung kommt. Nach der bisherigen Lehrmeinung stellen Monozyten die einzigen bekannten Blutzellen dar, die nach Langzeitstimulationsbedingungen in der Lage sind, TF zu synthetisieren und zu exprimieren. Der monozytäre TF spielt vor allem bei der Pathogenese der Sepsis und der damit assoziierten Disseminierten Intravasalen Gerinnung (DIC) eine wichtige Rolle. In der vorliegenden Arbeit zeigte sich, dass TF bereits nach einer fünf minütigen Stimulation von Vollblut mit fibrillärem Kollagen in Monozyten-Plättchen-Komplexen und Neutrophilen-Plättchen-Komplexen gemessen wurde. Die TF Präsentation in den Leukozyten-Plättchen-Komplexen war streng abhängig von der vorhandenen Plättchenzahl. Mit Hilfe von Vollblutgerinnungsmodellen und prokoagulatorischen Assays konnte gezeigt werden, dass der schnell präsentierte Tissue Factor funktionell aktiv war und somit die Fibrinbildung auslöste. Elektronenmikroskopische Aufnahmen zeigten, dass das TF Antigen auf der Oberfläche von Plättchen vorhanden war, die sich in Konjugaten mit Leukozyten befanden. Um die Frage nach dem Ursprung dieses intravaskulären TF zu klären, wurden Monozyten, Neutrophile Granulozyten und Plättchen auf ihren Gehalt an TF Protein mit einem Double-Sandwich-ELISA untersucht. Dabei konnte nur in den Plättchen TF Antigen nachgewiesen werden. Weitergehende Untersuchungen zeigten, dass TF in der Tat in den a-Granula und dem „open cannanicular system“ der Plättchen lokalisiert ist. In den Plättchen und in deren Vorläuferzellen war keine m-RNA für TF vorhanden. So bleibt die letztendliche Quelle des intravaskulären TF bis auf weiteres ungeklärt. Durch Hemmung von Adhäsionsproteinen, die die Interaktion von Plättchen mit Leukozyten vermitteln, wie P-Selektin und CD40L, konnte die TF-Präsentation in den Plättchen-Leukozyten-Komplexen inhibiert werden. Daher ist davon auszugehen, dass mehrere Adhäsionsproteine an dem Prozess der Präsentation von intravaskulärem TF beteiligt sind. Ein aus den Ergebnissen der vorliegenden Arbeit abgeleitetes Modell der Aktivierung des intravaskulären TF geht davon aus, dass in dem zwischen Leukozyten und Plättchen entstandenen Microenvironment ein von dem Plasma weitgehend unabhängiger Raum entsteht. In diesem Microenvironment wird möglicherweise der von den aktivierten Plättchen sezernierte TFPI durch die leukozytenassoziierte Elastase sowie weitere Proteasen und reaktive Sauerstoffspezies inaktiviert. TF kann damit zusammen mit FVIIa und FXa die Gerinnung starten. Die Ergebnisse lassen vermuten, dass die gesamte Blutgerinnung auf der Oberfläche von Plättchen stattfinden kann. Der intravaskuläre TF spielt vermutlicherweise eine Rolle bei der Aufrechterhaltung der Gerinnung innerhalb des lumenwärts wachsenden Thrombus. Somit kann die Fibrinbildung gezielt dort aktiviert werden, wo sie benötigt wird, um den Thrombus zu stabilisieren. Das Vorhandensein eines schnell aktivierbaren, intra-vaskulären Tissue Factor Systems stellt ein neues Konzept dar, um sowohl den physiologischen als auch den pathologischen Gerinnungsstart besser zu verstehen.