scholarly journals Biomechanical modelling of cancer: Agent‐based force‐based models of solid tumours within the context of the tumour microenvironment

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Cicely K. Macnamara
Keyword(s):  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Agent Based ◽  
Biomechanical Modelling ◽  
Cancer Agent

scholarly journals Clostridial Spores for Cancer Therapy: Targeting Solid Tumour Microenvironment

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Brittany Umer ◽  
David Good ◽  
Jozef Anné ◽  
Wei Duan ◽  
Ming Q. Wei
Keyword(s):  
Cancer Therapy ◽  
Solid Tumour ◽  
Early Stage ◽  
Treatment Options ◽  
Anaerobic Bacteria ◽  
Past Research ◽  
Tumour Microenvironment ◽  
The Body ◽  
Solid Tumours ◽  
Current Status

Solid tumour accounts for 90% of all cancers. The current treatment approach for most solid tumours is surgery, however it is limited to early stage tumours. Other treatment options such as chemotherapy and radiotherapy are non-selective, thus causing damage to both healthy and cancerous tissue. Past research has focused on understanding tumour cells themselves, and conventional wisdom has aimed at targeting these cells directly. Recent research has shifted towards understanding the tumour microenvironment and it’s differences from that of healthy cells/tissues in the body and then to exploit these differences for treatmeat of the tumour. One such approach is utilizing anaerobic bacteria. Several strains of bacteria have been shown to selectively colonize in solid tumours, making them valuable tools for selective tumour targeting and destruction. Amongst them, the anaerobicClostridiumhas shown great potential in penetration and colonization of the hypoxic and necrotic areas of the tumour microenvironment, causing significant oncolysis as well as enabling the delivery of therapeutics directly to the tumourin situ. Various strategies utilizingClostridiumare currently being investigated, and represent a novel area of emerging cancer therapy. This review provides an update review of tumour microenvironment as well as summary of the progresses and current status of Clostridial spore-based cancer therapies.

scholarly journals Development of a Hypoxia-Activated Trehalose Diester for the Treatment of Solid Tumours

2021 ◽  
Author(s):  
◽  
Amy Jane Foster
Keyword(s):  
Cell Wall ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Great Promise ◽  
Tumour Regression ◽  
Tumour Burden ◽  
Isolation And Identification ◽  
Enzymatic Reduction ◽  
Thesis Work ◽  
Wall Components

<p><b>The potential of bacterial cell wall components in the treatment of various cancers was initially realised in the late 1800s during pioneering work with Coley’s toxins. Since this preliminary work, efforts have been concentrated on the isolation and identification of bacterial components that lead to tumour regression. Trehalose dimycolates (TDMs) are compounds isolated from the M. tuberculosis cell wall and are known to activate macrophages to give a polarised Th1 immune response resulting in reduced tumour burden. Consequently, TDMs have shown great promise in the treatment of solid tumours.</b></p> <p>In this thesis, work is presented towards the synthesis of trehalose glycolipid prodrugs that will be specifically activated inside the hypoxic tumour microenvironment, and thereby lead to a more selective form of cancer therapy. These hypoxia-activated trehalose glycolipids incorporate a nitroimidazole trigger that fragments upon enzymatic reduction (in the absence of oxygen) to give the active glycolipid. Throughout the course of this work, it was determined that the nitroimidazole trigger group could not be directly attached to the glycolipid and thus, an alternative carbonate-linker strategy was explored through the use of a reporter fluoroprobe. The validity of this approach was determined in various enzyme and cell-based assays.</p>

scholarly journals Enhancing co-stimulation of CAR T cells to improve treatment outcomes in solid cancers

2021 ◽  
Author(s):  
Aaron J Harrison ◽  
Xin Du ◽  
Bianca von Scheidt ◽  
Michael H Kershaw ◽  
Clare Y Slaney
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Biology ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract Co-stimulation is a fundamental component of T cell biology and plays a key role in determining the quality of T cell proliferation, differentiation and memory formation. T cell-based immunotherapies, such as chimeric antigen receptor (CAR) T cell immunotherapy, are no exception. Solid tumours have largely been refractory to CAR T cell therapy owing to an immunosuppressive microenvironment which limits CAR T cell persistence and effector function. In order to eradicate solid cancers, increasingly sophisticated strategies are being developed to deliver these vital co-stimulatory signals to CAR T cells, often specifically within the tumour microenvironment. These include designing novel co-stimulatory domains within the CAR or other synthetic receptors, arming CAR T cells with cytokines or using CAR T cells in combination with agonist antibodies. This review discusses the evolving role of co-stimulation in CAR T cell therapies and the strategies employed to target co-stimulatory pathways in CAR T cells, with a view to improve responses in solid tumours.

scholarly journals How and Why Are Cancers Acidic? Carbonic Anhydrase IX and the Homeostatic Control of Tumour Extracellular pH

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1616 ◽  
Author(s):  
Shen-Han Lee ◽  
John R. Griffiths
Keyword(s):  
Carbonic Anhydrase ◽  
Imaging Techniques ◽  
Tumour Microenvironment ◽  
Extracellular Ph ◽  
Solid Tumours ◽  
Carbonic Anhydrase Ix ◽  
Carbonic Anhydrases ◽  
Somatic Evolution ◽  
Ph Imaging ◽  
Ph Stat

The acidic tumour microenvironment is now recognized as a tumour phenotype that drives cancer somatic evolution and disease progression, causing cancer cells to become more invasive and to metastasise. This property of solid tumours reflects a complex interplay between cellular carbon metabolism and acid removal that is mediated by cell membrane carbonic anhydrases and various transport proteins, interstitial fluid buffering, and abnormal tumour-associated vessels. In the past two decades, a convergence of advances in the experimental and mathematical modelling of human cancers, as well as non-invasive pH-imaging techniques, has yielded new insights into the physiological mechanisms that govern tumour extracellular pH (pHe). In this review, we examine the mechanisms by which solid tumours maintain a low pHe, with a focus on carbonic anhydrase IX (CAIX), a cancer-associated cell surface enzyme. We also review the accumulating evidence that suggest a role for CAIX as a biological pH-stat by which solid tumours stabilize their pHe. Finally, we highlight the prospects for the clinical translation of CAIX-targeted therapies in oncology.

scholarly journals PO-263 Assessment of the accumulation of hyaluronan in the tumour microenvironment (TME) of solid tumours

2018 ◽  
Author(s):  
D Taverna ◽  
S Garrovillo ◽  
B Blouw ◽  
B Thompson ◽  
D Kang
Keyword(s):  
Tumour Microenvironment ◽  
Solid Tumours

scholarly journals Depletion of CD206+ tumour macrophages by mUNO targeted nanoconjugate inhibits tumourigenesis and dissemination in triple negative breast cancer

2021 ◽  
Author(s):  
Anni Lepland ◽  
Alessio Malfanti ◽  
Uku Haljasorg ◽  
Eliana Asciutto ◽  
Monica Pickholz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Foxp3 Expression ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Fluorescent Reporter

Abstract Chemotherapy is the standard of care for patients with triple negative breast cancer (TNBC), an aggressive breast cancer subtype with a poor prognosis. In many solid tumours, M2-skewed tumour-associated macrophages (TAMs) are known to promote progression, immunosuppression, relapse, and dissemination of the malignant disease. Although TAM depletion has been explored as an anticancer strategy, the currently available TAM depleting compounds suffer from poor efficacy and dose-limiting side effects. Here, we develop of a novel TAM-depleting agent that specifically targets CD206+ macrophages and show that it is efficacious as an anti-TNBC agent and well tolerated. This new TAM-depleting compound, called “OximUNO”, is a star-shaped polyglutamate decorated with the CD206-targeting peptide mUNO and carrying doxorubicin through a pH-responsive linker. In the orthotopic and experimental metastases of TNBC, fluorescent reporter mUNO-guided polyglutamate construct homed to CD206+ macrophages in the primary cancer lesions and at the sites of metastases. OximUNO displayed enhanced cytotoxicity towards primary M2 macrophages in vitro and exhibited no acute liver or kidney toxicity in vivo. In TNBC mouse models, OximUNO reduced the progression of primary breast cancer lesions and metastatic dissemination of malignant cells. Treatment with OximUNO had an immunomodulatory effect on the tumour microenvironment: besides reducing the number of CD206+ TAMs, it resulted in increased ratio of the CD8/FOXP3 expression. These studies suggest the potential utility of OximUNO based CD206+ TAM depletion strategies for the treatment of TNBC, and possibly, other types of solid tumours.

scholarly journals 15P Tumour PD-L1 expression and blood biomarkers of activity of adaptive immunity and tumour microenvironment in patients with solid tumours

2020 ◽  
Vol 31 ◽  
pp. S1422
Author(s):  
A. Malkova ◽  
R.V. Orlova ◽  
N. Zhukova ◽  
V. Sharoyko ◽  
E. Kaledina ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Blood Biomarkers

scholarly journals An agent-based model for drug-radiation interactions in the tumour microenvironment: Hypoxia-activated prodrug SN30000 in multicellular tumour spheroids

2018 ◽  
Vol 14 (10) ◽  
pp. e1006469 ◽  
Author(s):  
Xinjian Mao ◽  
Sarah McManaway ◽  
Jagdish K. Jaiswal ◽  
Priyanka B. Patel ◽  
William R. Wilson ◽  
...  
Keyword(s):  
Tumour Microenvironment ◽  
Agent Based Model ◽  
Agent Based ◽  
Tumour Spheroids

scholarly journals Identification of PIEZO1 as a potential prognostic marker in gliomas

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wenjianlong Zhou ◽  
Xiangxiang Liu ◽  
Jan Willem Maurits van Wijnbergen ◽  
Linhao Yuan ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Proliferation ◽  
Tumour Cell ◽  
Tumour Progression ◽  
Malignant Gliomas ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
The Cancer Genome Atlas ◽  
Tumour Cell Proliferation ◽  
Genome Atlas

Abstract In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. If and how mechanical cues regulate tumour cell proliferation is currently not fully studied. PIEZO1 has recently been identified as a crucial mechanosensitive cation channel in multiple solid tumours. However, we didn’t find any clinical data describing the association between PIEZO1 expression and glioma. To investigate the role of PIEZO1 in gliomas, we analysed PIEZO1 gene expression at the transcriptome level, genomic profiles and the association of PIEZO1 with clinical practice. In total, 1633 glioma samples with transcriptome data, including data from the Chinese Glioma Genome Atlas RNAseq, the Cancer Genome Atlas RNAseq and GSE16011 databases, were included in this study. Clinical information and genomic profiles including somatic mutations were also obtained. We found that PIEZO1 expression was highly correlated with malignant clinical and molecular subtypes of glioma. Gene ontology analysis showed that expression of PIEZO1 was correlated with tumour microenvironment-related genes that encode proteins involved in extracellular matrix (ECM) organization, angiogenesis and cell migration. Additionally, PIEZO1 was shown to be involved in tumour progression by serving as the central checkpoint of multiple ECM remodelling-related signalling pathways to modulate tumour cell proliferation and the tumour microenvironment in turn. Finally, high PIEZO1 expression was correlated with reduced survival time and acted as a robust biomarker for poor prognosis in gliomas. Taken together, the results indicated that high PIEZO1 expression is closely associated with highly malignant gliomas. Importantly, PIEZO1 serves as a key factor involved in sensing mechanical properties in the tumour and can regulate both tumour cells and their microenvironment to promote glioma progression, and it is also a potential therapeutic target for the treatment of gliomas.

Tumour microenvironment: informing on minimal residual disease in solid tumours

2017 ◽  
Vol 14 (6) ◽  
pp. 325-326 ◽  
Author(s):  
Klaus Pantel ◽  
Catherine Alix-Panabières
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Minimal Residual
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