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Tumour microenvironment

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https://www.readbyqxmd.com/read/29346540/blood-and-lymphatic-vessels-contribute-to-the-impact-of-the-immune-microenvironment-on-clinical-outcome-in-non-small-cell-lung-cancer
#1
Giovanna Armani, Denise Madeddu, Giulia Mazzaschi, Giovanni Bocchialini, Francesco Sogni, Caterina Frati, Bruno Lorusso, Angela Falco, Costanza Annamaria Lagrasta, Stefano Cavalli, Chiara Mangiaracina, Rocchina Vilella, Gabriella Becchi, Letizia Gnetti, Emilia Corradini, Eugenio Quaini, Konrad Urbanek, Matteo Goldoni, Paolo Carbognani, Luca Ampollini, Federico Quaini
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29345578/searching-for-new-targets-and-treatments-in-the-battle-against-squamous-cell-carcinoma-of-the-head-and-neck-with-specific-focus-on-tumours-of-the-tongue
#2
Nicola Sgaramella, Xiaolian Gu, Linda Boldrup, Philip J Coates, Robin Fahraeus, Luigi Califano, Gianpaolo Tartaro, Giuseppe Colella, Lena Norberg Spaak, Adrian Strom, Torben Wilms, Lorenzo Lo Muzio, Giovanni Dell'Aversana Orabona, Mario Santagata, Lotta Loljung, Riccardo Rossiello, Karin Danielsson, Klas Strindlund, Sandra Lillqvist, Karin Nylander
Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide an increasing number of people ? 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group...
January 16, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29345283/regulation-of-programmed-death-ligand-in-the-human-head-and-neck-squamous-cell-carcinoma-microenvironment-is-mediated-through-matrix-metalloproteinase-mediated-proteolytic-cleavage
#3
Mayuko Hira-Miyazawa, Hiroyuki Nakamura, Mariko Hirai, Yutaka Kobayashi, Hiroko Kitahara, George Bou-Gharios, Shuichi Kawashiri
Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. According to recent clinical studies, tumour growth can be effectively reduced and survival can be improved by blocking the programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD‑L1) pathway. PD-L1 expression has been proposed as a potential causative mechanism, as HNSCC is highly immunosuppressive. However, anti-PD-1 treatment is beneficial only for certain patients...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345251/cancer-associated-cachexia
#4
REVIEW
Vickie E Baracos, Lisa Martin, Murray Korc, Denis C Guttridge, Kenneth C H Fearon
Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells...
January 18, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29342186/doxorubicin-provoked-increase-of-mitotic-activity-and-concomitant-drain-of-g0-pool-in-therapy-resistant-be-2-c-neuroblastoma
#5
Isabell Hultman, Linnea Haeggblom, Ingvild Rognmo, Josefin Jansson Edqvist, Evelina Blomberg, Rouknuddin Ali, Lottie Phillips, Bengt Sandstedt, Per Kogner, Shahrzad Shirazi Fard, Lars Ährlund-Richter
In this study chemotherapy response in neuroblastoma (NB) was assessed for the first time in a transplantation model comprising non-malignant human embryonic microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi-resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT model and the tumour growth was exposed to single or repeated treatments with doxorubicin, and thereafter evaluated for cell death, apoptosis, and proliferation...
2018: PloS One
https://www.readbyqxmd.com/read/29339539/the-hippo-pathway-component-taz-promotes-immune-evasion-in-human-cancer-through-pd-l1
#6
Helena J Janse van Rensburg, Taha Azad, Min Ling, Yawei Hao, Brooke Snetsinger, Prem Khanal, Lori M Minassian, Charles H Graham, Michael J Rauh, Xiaolong Yang
The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ) is a transcriptional co-activator and an oncogene in breast and lung cancer. Transcriptional targets of TAZ that modulate immune cell function in the tumour microenvironment are poorly understood. Here, we perform a comprehensive screen for immune-related genes regulated by TAZ and its paralog YAP using NanoString gene expression profiling. We identify the immune checkpoint molecule PD-L1 as a target of Hippo signaling. The upstream kinases of the Hippo pathway, mammalian STE20-like kinase 1 and 2 (MST1/2) and large tumour suppressor 1 and 2 (LATS1/2), suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and lung cancer cell lines...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29337962/the-relationship-between-right-sided-tumour-location-tumour-microenvironment-systemic-inflammation-adjuvant-therapy-and-survival-in-patients-undergoing-surgery-for-colon-and-rectal-cancer
#7
Meera Patel, Stephen T McSorley, James H Park, Campbell S D Roxburgh, Joann Edwards, Paul G Horgan, Donald C McMillan
BACKGROUND: There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer...
January 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29332937/improving-immune-vascular-crosstalk-for-cancer-immunotherapy
#8
REVIEW
Yuhui Huang, Betty Y S Kim, Charles K Chan, Stephen M Hahn, Irving L Weissman, Wen Jiang
The vasculature of tumours is highly abnormal and dysfunctional. Consequently, immune effector cells have an impaired ability to penetrate solid tumours and often exhibit compromised functions. Normalization of the tumour vasculature can enhance tissue perfusion and improve immune effector cell infiltration, leading to immunotherapy potentiation. However, recent studies have demonstrated that the stimulation of immune cell functions can also help to normalize tumour vessels. In this Opinion article, we propose that the reciprocal regulation between tumour vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumour immune microenvironment to induce durable antitumour immunity...
January 15, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29328436/role-of-exosomes-and-exosomal-micrornas-in-hepatocellular-carcinoma-potential-in-diagnosis-and-antitumour-treatments-review
#9
Jing-Hua Pan, Hong Zhou, Xiao-Xu Zhao, Hui Ding, Wei Li, Li Qin, Yun-Long Pan
Communication between hepatocellular carcinoma (HCC) cells and their environment is essential for the development and progression of HCC. Exosomes, which are microvesicles secreted by a number of cell types, are carriers of intercellular information and regulate the tumour microenvironment. Studies have demonstrated that exosomes are involved in the communication between HCC cells, endothelial cells and stem cells, and that they serve important roles in the metastasis and invasion, immune evasion and immunotherapy of HCC...
January 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29326431/impact-of-oncogenic-pathways-on-evasion-of-antitumour-immune-responses
#10
REVIEW
Stefani Spranger, Thomas F Gajewski
Immunotherapeutic interventions are showing effectiveness across a wide range of cancer types, but only a subset of patients shows clinical response to therapy. Responsiveness to checkpoint blockade immunotherapy is favoured by the presence of a local, CD8+ T cell-based immune response within the tumour microenvironment. As molecular analyses of tumours containing or lacking a productive CD8+ T cell infiltrate are being pursued, increasing evidence is indicating that activation of oncogenic pathways in tumour cells can impair induction or execution of a local antitumour immune response...
January 12, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29323709/osteosarcoma-derived-extracellular-vesicles-induce-a-tumour-like-phenotype-in-normal-recipient-cells
#11
Enrica Urciuoli, Ezio Giorda, Marco Scarsella, Stefania Petrini, Barbara Peruzzi
Osteosarcoma is the most common primary bone cancer and the most frequent cause of bone cancer-related deaths in children and adolescents. Osteosarcoma cells are able to establish a crosstalk with resident bone cells leading to the formation of a deleterious vicious cycle. We hypothesized that osteosarcoma cells can release, in the bone microenvironment, transforming Extracellular Vesicles (EVs) involved in regulating bone cell proliferation and differentiation, thereby promoting tumour growth. We assessed EV production by three osteosarcoma cell lines with increasing aggressiveness in order to investigate their roles in the communication between osteosarcoma cells and normal recipient cells...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29322326/heparan-sulfate-accumulation-and-perlecan-hspg2-up-regulation-in-tumour-tissue-predict-low-relapse-free-survival-for-patients-with-glioblastoma
#12
Galina M Kazanskaya, Alexandra Y Tsidulko, Alexander M Volkov, Roman S Kiselev, Anastasia V Suhovskih, Vyacheslav V Kobozev, Alexei S Gaytan, Svetlana V Aidagulova, Alexei L Krivoshapkin, Elvira V Grigorieva
Glycosaminoglycans are major components of brain extracellular matrix (ECM), although heparan sulfate (HS) contribution in brain physiology and carcinogenesis remains underinvestigated. This study examined HS content and distribution in glioblastoma multiforme (GBM) tissues in the context of potential molecular mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue samples and paraffin-embedded tissues for 31 patients with different prognosis were investigated. HS expression was demonstrated in 50-55% of the GBM tumours by immunohistochemistry (IHC), while almost no HS content was detected in the surrounding paratumourous brain tissues...
January 10, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29317710/chemokine-receptor-7-overexpression-promotes-mesenchymal-stem-cell-migration-and-proliferation-via-secreting-chemokine-ligand-12
#13
Ling Liu, Jian-Xiao Chen, Xi-Wen Zhang, Qin Sun, Lan Yang, Airan Liu, Shuling Hu, Fengmei Guo, Songqiao Liu, Yingzi Huang, Yi Yang, Hai-Bo Qiu
Great interest has been shown in mesenchymal stem cell (MSC) therapy in a wide variety of clinical domains. However, the therapeutic efficiency depends on the proliferation and migration of MSCs. Chemokine receptors are involved in regulating the proliferation and migration to the specific organs of MSCs in different microenvironments. CXC receptor seven (CXCR7), a newly discovered Chemokine ligand 12 (CXCL12) receptor, has organ specificity for tumour migration. We hypothesized that CXCR7 expression affects proliferation and migration of MSCs...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311580/lsd1-activation-promotes-inducible-emt-programs-and-modulates-the-tumour-microenvironment-in-breast-cancer
#14
T Boulding, R D McCuaig, A Tan, K Hardy, F Wu, J Dunn, M Kalimutho, C R Sutton, J K Forwood, A G Bert, G J Goodall, L Malik, D Yip, J E Dahlstrom, A Zafar, K K Khanna, S Rao
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29305721/paragangliomas-arise-through-an-autonomous-vasculo-angio-neurogenic-program-inhibited-by-imatinib
#15
Fabio Verginelli, Silvia Perconti, Simone Vespa, Francesca Schiavi, Sampath Chandra Prasat, Paola Lanuti, Alessandro Cama, Lorenzo Tramontana, Diana Liberata Esposito, Simone Guarnieri, Artenca Sheu, Mattia Russel Pantalone, Rosalba Florio, Annalisa Morgano, Cosmo Rossi, Giuseppina Bologna, Marco Marchisio, Andrea D'Argenio, Elisa Taschin, Rosa Visone, Giuseppe Opocher, Angelo Veronese, Carlo T Paties, Vinalogu K Rajasekhar, Cecilia Söderberg-Nauclér, Mario Sanna, Lavinia Vittoria Lotti, Renato Mariani-Costantini
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts...
January 5, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29300334/understanding-the-progression-of-bone-metastases-to-identify-novel-therapeutic-targets
#16
REVIEW
Annie Schmid-Alliana, Heidy Schmid-Antomarchi, Rasha Al-Sahlanee, Patricia Lagadec, Jean-Claude Scimeca, Elise Verron
Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue...
January 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29300332/role-of-microenvironment-in-glioma-invasion-what-we-learned-from-in-vitro-models
#17
REVIEW
Ivana Manini, Federica Caponnetto, Anna Bartolini, Tamara Ius, Laura Mariuzzi, Carla Di Loreto, Antonio Paolo Beltrami, Daniela Cesselli
The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo...
January 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29285690/using-single-cell-multiple-omics-approaches-to-resolve-tumor-heterogeneity
#18
REVIEW
Michael A Ortega, Olivier Poirion, Xun Zhu, Sijia Huang, Thomas K Wolfgruber, Robert Sebra, Lana X Garmire
It has become increasingly clear that both normal and cancer tissues are composed of heterogeneous populations. Genetic variation can be attributed to the downstream effects of inherited mutations, environmental factors, or inaccurately resolved errors in transcription and replication. When lesions occur in regions that confer a proliferative advantage, it can support clonal expansion, subclonal variation, and neoplastic progression. In this manner, the complex heterogeneous microenvironment of a tumour promotes the likelihood of angiogenesis and metastasis...
December 28, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29285324/focus-on-periodontal-disease-and-colorectal-carcinoma
#19
REVIEW
D Lauritano, L Sbordone, M Nardone, A Iapichino, L Scapoli, F Carinci
Diagnosis of focal disease, the theory that the human oral microbial (HOM) could affect the onset and development of systemic diseases, was very popular in the past, but the lack of scientific evidence has led to the abandonment of this idea. Interestingly, increasing evidence over the past 3 or so decades suggests that HOM can indeed serve as a reservoir for systemic dissemination of pathogenic bacteria and their toxins in distant body sites, favouring the developments of malignant tumours. Malignant tumours are complex communities of oncogenically transformed cells with aberrant genomes, associated non-neoplastic cells including immune and stromal cells, and sometimes HOM, including bacteria and viruses...
July 2017: Oral & Implantology
https://www.readbyqxmd.com/read/29282685/key-factors-in-breast-cancer-dissemination-and-establishment-at-the-bone-past-present-and-future-perspectives
#20
Sioned Owen, Catherine Zabkiewicz, Lin Ye, Andrew J Sanders, Chang Gong, Wen G Jiang
Bone metastases associated with breast cancer remain a clinical challenge due to their associated morbidity, limited therapeutic intervention and lack of prognostic markers. With a continually evolving understanding of bone biology and its dynamic microenvironment, many potential new targets have been proposed. In this chapter, we discuss the roles of well-established bone markers and how their targeting, in addition to tumour-targeted therapies, might help in the prevention and treatment of bone metastases...
2017: Advances in Experimental Medicine and Biology
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