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Tumour microenvironment

Caroline Wilson
The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine) or from distant sites (endocrine). Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones...
September 2016: Journal of Bone Oncology
Penelope D Ottewell
The primary role of osteoblasts is to lay down new bone during skeletal development and remodelling. Throughout this process osteoblasts directly interact with other cell types within bone, including osteocytes and haematopoietic stem cells. Osteoblastic cells also signal indirectly to bone-resorbing osteoclasts via the secretion of RANKL. Through these mechanisms, cells of the osteoblast lineage help retain the homeostatic balance between bone formation and bone resorption. When tumour cells disseminate in the bone microenvironment, they hijack these mechanisms, homing to osteoblasts and disrupting bone homeostasis...
September 2016: Journal of Bone Oncology
Emma V Morris, Claire M Edwards
Adipocytes are a significant component of the bone marrow microenvironment. Although bone marrow adipocytes were first identified more than 100 years ago, it is only in recent years that an understanding of their complex physiological role is emerging. Bone marrow adipocytes act as local regulators of skeletal biology and homeostasis, with recent studies suggesting that marrow adipose tissue is metabolically active, and can function as an endocrine organ. As such, bone marrow adipocytes have the potential to interact with tumour cells, influencing both tumour growth and bone disease...
September 2016: Journal of Bone Oncology
Anjali P Kusumbe
The vasculature of the skeletal system regulates osteogenesis and hematopoiesis, in addition to its primary function as a transportation network. Recent studies suggest that the vasculature in bone regulates multiple steps involved in the metastatic cascade. Matrix and growth factor abundant vascular microenvironments in bone not only provide a fertile soil for the metastatic growth but also support the dormancy of Disseminated Tumour Cells (DTCs). Interestingly, vasculature also seems to direct the reactivation of dormant DTCs...
September 2016: Journal of Bone Oncology
Andrew J Highton, Adam Girardin, Georgia M Bell, Sarah M Hook, Roslyn A Kemp
BACKGROUND: Vaccination generating a robust memory population of CD8(+) T cells may provide protection against cancer. However, immune therapies for cancer are influenced by the local tumour immune microenvironment. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis. METHODS: We used an intracaecal mouse model of cancer to determine whether a protective immune response against a mucosal gut tumour could be generated using a systemic intervention...
October 18, 2016: BMC Immunology
Darren Rodenhizer, Dan Cojocari, Bradly G Wouters, Alison P McGuigan
The tumour microenvironment is heterogeneous and consists of multiple cell types, variable extracellular matrix (ECM) composition, and contains cell-defined gradients of small molecules, oxygen, nutrients and waste. Emerging in vitro cell culture systems that attempt to replicate these features often fail to incorporate design strategies to facilitate efficient data collection and stratification. The tissue roll for analysis of cellular environment and response (TRACER) is a novel strategy to assemble layered, three-dimensional tumours with cell-defined, graded heterogeneous microenvironments that also facilitates cellular separation and stratification of data from different cell populations from specific microenvironments...
October 18, 2016: Biofabrication
Yoshihiro Komohara, Motohiro Takeya
Many non-tumour host cells such as inflammatory cells, fibroblasts and endothelial cells are present in the tumour microenvironment and affect the malignant potential and chemo-resistance of the tumour cells. Macrophages and fibroblasts are the main components of infiltrating stromal cells and are referred to as tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively. TAMs and CAFs are reported to be involved in tumour progression, although their functions change to those of an anti-tumour phenotype under specific conditions...
October 18, 2016: Journal of Pathology
Antonino Carbone, Annunziata Gloghini, Arnaldo Caruso, Paolo De Paoli, Riccardo Dolcetti
The pathogenesis of classical Hodgkin lymphoma (cHL) is still enigmatic, largely because its tumor cells, the so-called Hodgkin and Reed-Stenberg (HRS) cells, invariably reside in a prominent reactive microenvironment, are rare and therefore difficult to analyze. On the other hand, the broadly investigated cHL-derived cell lines are not unequivocally considered as suitable and representative models for this puzzling disease. Based on current knowledge, it appears that the cross talk between the tumour cells and the reactive infiltrate of the microenvironment is complex and that multiple mechanisms occur, making cHL a very heterogeneous disease...
October 17, 2016: International Journal of Cancer. Journal International du Cancer
Christian Manegold, Anne-Marie C Dingemans, Jhanelle E Gray, Kazuhiko Nakagawa, Marianne Nicolson, Solange Peters, Martin Reck, Yi-Long Wu, Odd Terje Brustugun, Lucio Crino, Enriqueta Felip, Dean Fennell, Pilar Garrido, Rudolf M Huber, Aurelien Marabelle, Marcin Moniuszko, Francoise Mornex, Silvia Novello, Mauro Papotti, Maurice Pérol, Egbert F Smit, Kostas Syrigos, Jan P van Meerbeeck, Nico van Zandwijk, James Chih-Hsin Yang, Caicun Zhou, Everett Vokes
Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced non-small cell lung cancer (NSCLC), particularly those who have progressed on or during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab and nintedanib). It is hypothesised that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments...
October 8, 2016: Journal of Thoracic Oncology
Jian-Fei Tu, Ya-Hui Ding, Xi-Hui Ying, Fa-Zong Wu, Xin-Mu Zhou, Deng-Ke Zhang, Hai Zou, Jian-Song Ji
Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3(+), CD4(+), and CD8(+) cytotoxic lymphocytes (CTLs) as well as CD56(+) NK cells and CD68(+) macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3(+) (FOXP3(+)) Tregs were found in intratumoural tissue...
October 11, 2016: Scientific Reports
Patrícia Oliveira, Joana Carvalho, Sara Rocha, Mafalda Azevedo, Inês Reis, Vânia Camilo, Bárbara Sousa, Sofia Valente, Joana Paredes, Raquel Almeida, David Huntsman, Carla Oliveira
Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown...
October 10, 2016: Scientific Reports
Briony E Forbes
The last two years of insulin-like growth factor (IGF) research has yielded a vast literature highlighting the central role IGFs factors play in processes such as development, growth, aging and neurological function. It also provides our latest understanding of how IGF system perturbation is linked to diseases including growth deficiency, cancer, and neurological and cardiovascular diseases. A snapshot of the highlights is presented in this review, focussing on the topics of IGFs and growth, comparative and structural biology to understand insulin-like peptide function, IGFs and cancer, and IGFs and neurological function...
September 30, 2016: Growth Hormone & IGF Research
Katherine Hughes, Maximilian Blanck, Sara Pensa, Christine J Watson
Mammary gland regression at the cessation of lactation (involution) is an exquisitely orchestrated process of cell death and tissue remodelling in which Stat3 signalling has an essential role. The involution microenvironment of the mammary gland is considered to be pro-tumourigenic and a proportion of cases of pregnancy-associated breast cancer are suggested to originate in tandem with involution. However, the apparent paradox that STAT3 is required for cell death in normal mammary gland, but is associated with breast cancer cell survival, has not been resolved...
October 6, 2016: Cell Death & Disease
Ahmed Boujelben, Michael Watson, Steven McDougall, Yi-Fen Yen, Elizabeth R Gerstner, Ciprian Catana, Thomas Deisboeck, Tracy T Batchelor, David Boas, Bruce Rosen, Jayashree Kalpathy-Cramer, Mark A J Chaplain
Patients diagnosed with glioblastoma, an aggressive brain tumour, have a poor prognosis, with a median overall survival of less than 15 months. Vasculature within these tumours is typically abnormal, with increased tortuosity, dilation and disorganization, and they typically exhibit a disrupted blood-brain barrier (BBB). Although it has been hypothesized that the 'normalization' of the vasculature resulting from anti-angiogenic therapies could improve drug delivery through improved blood flow, there is also evidence that suggests that the restoration of BBB integrity might limit the delivery of therapeutic agents and hence their effectiveness...
October 6, 2016: Interface Focus
Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, Enrique Fuentes-Mattei, Lesley G Ellies, C Michael Knudson, Mong-Hong Lee, Sai-Ching J Yeung, Suzanne L Cassel, Fayyaz S Sutterwala, Weizhou Zhang
Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis...
October 6, 2016: Nature Communications
Mahdi Nabil, Paolo Zunino
The application of hyperthermia to cancer treatment is studied using a novel model arising from the fundamental principles of flow, mass and heat transport in biological tissues. The model is defined at the scale of the tumour microenvironment and an advanced computational scheme called the embedded multiscale method is adopted to solve the governing equations. More precisely, this approach involves modelling capillaries as one-dimensional channels carrying flow, and special mathematical operators are used to model their interaction with the surrounding tissue...
September 2016: Royal Society Open Science
Leona Rohrbeck, Jia-Nan Gong, Erinna F Lee, Andrew J Kueh, Andreas Behren, Lin Tai, Guillaume Lessene, David C S Huang, Walter D Fairlie, Andreas Strasser, Marco J Herold
A large proportion of melanomas harbour the activating BRAF(V600E) mutation that renders these cells dependent on MAPK signalling for their survival. Although the highly specific and clinically approved BRAF(V600E) kinase inhibitor, PLX4032, induces apoptosis of melanoma cells bearing this mutation, the underlying molecular mechanisms are not fully understood. Here, we reveal that PLX4032-induced apoptosis depends on the induction of the pro-apoptotic BH3-only protein PUMA with a minor contribution of its relative BIM...
September 30, 2016: Cell Death and Differentiation
Caroline Wilson, Hannah Brown, Ingunn Holen
Multiple factors influence the survival of disseminated breast tumour cells (DTCs) in bone. Whilst gene signature studies have identified genes that predict a propensity of tumours to metastasise to bone, the bone environment is key in determining the fate of these tumour cells. Breast cancer cells locate to specific niches within the bone that support their survival, regulated by host factors within the bone microenvironment including bone cells, cells of the bone micro vasculature, immune cells and the extracellular matrix...
September 29, 2016: Endocrine-related Cancer
Hsin-I Hung, Oliver J Klein, Sam W Peterson, Sarah R Rokosh, Sam Osseiran, Nicholas H Nowell, Conor L Evans
Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce "dark toxicity" through light-independent mechanisms...
September 30, 2016: Scientific Reports
James R Bradford, Angela Cox, Philip Bernard, Nicola J Camp
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes and diseases such as cancer; however, their functions remain poorly characterised. Several studies have demonstrated that lncRNAs are typically disease and tumour subtype specific, particularly in breast cancer where lncRNA expression alone is sufficient to discriminate samples based on hormone status and molecular intrinsic subtype. However, little attempt has been made to assess the reproducibility of lncRNA signatures across more than one dataset...
2016: PloS One
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