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Tumour microenvironment

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https://www.readbyqxmd.com/read/29149107/treponema-denticola-chymotrypsin-like-proteinase-may-contribute-to-orodigestive-carcinogenesis-through-immunomodulation
#1
Mikko T Nieminen, Dyah Listyarifah, Jaana Hagström, Caj Haglund, Daniel Grenier, Dan Nordström, Veli-Jukka Uitto, Marcela Hernandez, Tülay Yucel-Lindberg, Taina Tervahartiala, Mari Ainola, Timo Sorsa
BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29146005/bone-marrow-adipocytes-in-haematological-malignancies
#2
Ewa Frączak, Mateusz Olbromski, Aleksandra Piotrowska, Natalia Glatzel-Plucińska, Piotr Dzięgiel, Jarosław Dybko, Kazimierz Kuliczkowski, Tomasz Wróbel
Bone marrow adipocytes (BMAs) derived from mesenchymal stem cells (MSC) are an active and significant element of the bone marrow microenvironment. They are involved in metabolic functions, complex interactions with other stromal cells, and in the development and progression of tumours. Currently, there is little data regarding the role of BMAs in haematological malignancies. Due to this, we have attempted to characterise the BMAs in these malignancies in terms of quantity and morphology. Our study included 30 patients aged 22-76 with myelo- (n=17) and lymphoproliferative malignancies (n=13), both with and without bone marrow infiltration...
November 13, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29142217/fbxo32-promotes-microenvironment-underlying-epithelial-mesenchymal-transition-via-ctbp1-during-tumour-metastasis-and-brain-development
#3
Sanjeeb Kumar Sahu, Neha Tiwari, Abhijeet Pataskar, Yuan Zhuang, Marina Borisova, Mustafa Diken, Susanne Strand, Petra Beli, Vijay K Tiwari
The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29140428/hpv-negative-but-not-hpv-positive-oropharyngeal-carcinomas-induce-fibroblasts-to-support-tumour-invasion-through-micro-environmental-release-of-hgf-and-il-6
#4
Robert Bolt, Bernadette Foran, Craig Murdoch, Daniel W Lambert, Sally Thomas, Keith D Hunter
Human papillomavirus (HPV) infection is causally related to a subset of oropharyngeal carcinomas (OPC) and is linked to a more favourable prognosis compared to HPV-negative OPC. The mechanisms underlying this effect on prognosis are not fully understood, but interactions with the tumour microenvironment may be pivotal. Here, we investigated the role of the tumour microenvironment in HPV-positive compared to HPV-negative cancer using 2D and 3D modelling of OPC interactions with stromal fibroblasts. HPV-negative, but not HPV-positive, OPC-derived cell lines induced a rapid fibroblast secretory response that supported 2D cancer cell migration and invasion in vitro...
November 13, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29138507/systems-pathology-by-multiplexed-immunohistochemistry-and-whole-slide-digital-image-analysis
#5
Sami Blom, Lassi Paavolainen, Dmitrii Bychkov, Riku Turkki, Petra Mäki-Teeri, Annabrita Hemmes, Katja Välimäki, Johan Lundin, Olli Kallioniemi, Teijo Pellinen
The paradigm of molecular histopathology is shifting from a single-marker immunohistochemistry towards multiplexed detection of markers to better understand the complex pathological processes. However, there are no systems allowing multiplexed IHC (mIHC) with high-resolution whole-slide tissue imaging and analysis, yet providing feasible throughput for routine use. We present an mIHC platform combining fluorescent and chromogenic staining with automated whole-slide imaging and integrated whole-slide image analysis, enabling simultaneous detection of six protein markers and nuclei, and automatic quantification and classification of hundreds of thousands of cells in situ in formalin-fixed paraffin-embedded tissues...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133316/study-protocol-for-think-a-multinational-open-label-phase-i-study-to-assess-the-safety-and-clinical-activity-of-multiple-administrations-of-nkr-2-in-patients-with-different-metastatic-tumour-types
#6
Caroline Lonez, Bikash Verma, Alain Hendlisz, Philippe Aftimos, Ahmad Awada, Eric Van Den Neste, Gaetan Catala, Jean-Pascal H Machiels, Fanny Piette, Jason B Brayer, David A Sallman, Tessa Kerre, Kunle Odunsi, Marco L Davila, David E Gilham, Frédéric F Lehmann
INTRODUCTION: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3ζ signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29126088/in-the-immuno-oncology-era-is-anti-pd-1-or-anti-pd-l1-immunotherapy-modifying-the-sensitivity-to-conventional-cancer-therapies
#7
Sandrine Aspeslagh, Margarida Matias, Virginia Palomar, Laurent Dercle, Emilie Lanoy, Jean-Charles Soria, Sophie Postel-Vinay
INTRODUCTION: The advent of anti-programmed death receptor-1/ligand-1 antibodies (anti-PD(L)1) is profoundly changing the therapeutic strategy of oncology. As anti-PD(L)1 modulate tumour microenvironment, it might impact sensitivity to conventional cancer therapy (CCT). Therefore, we explored whether sensitivity to CCT was different before and after anti-PD(L)1 therapy. METHODS: Patients who started anti-PD(L)1 treatment at Gustave Roussy Cancer Centre between February 2012 and December 2015, and who received at least one line of CCT immediately before and immediately after anti-PD(L)1, were eligible...
November 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29123322/hypoxia-induced-reactive-oxygen-species-mediate-n-cadherin-and-serpine1-expression-egfr-signalling-and-motility-in-mda-mb-468-breast-cancer-cells
#8
Iman Azimi, Rosalie M Petersen, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith
One of the hallmarks of the tumour microenvironment is hypoxia resulting from increased oxygen consumption by proliferative cancer cells and altered vasculature. Hypoxic tension initiates various cellular signals and can drive epithelial to mesenchymal transition (EMT), a process important in cancer progression. In this study, using the antioxidant N-acetylcysteine (NAC), we show that hypoxia-induced reactive oxygen species (ROS) in MDA-MB-468 breast cancer cells, selectively regulate hypoxia-induced increases in N-cadherin and SERPINE1, two proteins involved in cell adhesion...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29123260/combining-dna-damaging-therapeutics-with-immunotherapy-more-haste-less-speed
#9
REVIEW
Jessica S Brown, Raghav Sundar, Juanita Lopez
The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical work has now demonstrated that in addition to direct cytotoxic effects on cancer cells, a proportion of DNA damaging agents may actually promote immunogenic cell death, alter the inflammatory milieu of the tumour microenvironment and/or stimulate neoantigen production, thereby activating an antitumour immune response...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29123259/tumour-infiltrating-inflammatory-and-immune-cells-in-patients-with-extrahepatic-cholangiocarcinoma
#10
Yuki Kitano, Hirohisa Okabe, Yo-Ichi Yamashita, Shigeki Nakagawa, Yoichi Saito, Naoki Umezaki, Masayo Tsukamoto, Takanobu Yamao, Kensuke Yamamura, Kota Arima, Takayoshi Kaida, Tatsunori Miyata, Kosuke Mima, Katsunori Imai, Daisuke Hashimoto, Yoshihiro Komohara, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba
BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29115712/proteomic-profiling-of-exosomes-secreted-by-breast-cancer-cells-with-varying-metastatic-potential
#11
Lahiru Gangoda, Michael Liem, Ching-Seng Ang, Shivakumar Keerthikumar, Christopher G Adda, Belinda S Parker, Suresh Mathivanan
Cancer cells actively release extracellular vesicles, including exosomes, into the surrounding microenvironment. Exosomes play pleiotropic roles in cancer progression and metastasis, including invasion, angiogenesis, and immune modulation. However, the proteome profile of exosomes isolated from cells with different metastatic potential and the role of these exosomes in driving metastasis remains unclear. Here, we conducted a comparative proteomic analysis of exosomes isolated from several genetically related mouse breast tumour lines with different metastatic propensity...
November 8, 2017: Proteomics
https://www.readbyqxmd.com/read/29115428/inhibition-of-p21-activated-kinase-enhances-tumour-immune-response-and-sensitizes-pancreatic-cancer-to-gemcitabine
#12
Kai Wang, Nhi Huynh, Xiao Wang, Graham Baldwin, Mehrdad Nikfarjam, Hong He
Pancreatic ductal adenocarcinoma (PDA) is one of the major types of cancer that exhibit high mortality worldwide because of the late diagnosis and the lack of effective treatment. Immunotherapy appears to be ineffective in PDA treatment due to the existence of a unique immune-suppressive microenvironment in PDA. Gemcitabine-based therapy is still the most commonly used chemotherapy to treat PDA patients with only marginal increased survival rates. This prompted us to continue the search for more effective therapy for PDA treatment...
November 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113105/the-molecular-and-phenotypic-basis-of-the-glioma-invasive-perivascular-niche
#13
REVIEW
Mohammed Diksin, Stuart J Smith, Ruman Rahman
Gliomas are devastating brain cancers that have poor prognostic outcomes for their patients. Short overall patient survival is due to a lack of durable, efficacious treatment options. Such therapeutic difficulties exist, in part, due to several glioma survival adaptations and mechanisms, which allow glioma cells to repurpose paracrine signalling pathways and ion channels within discreet microenvironments. These Darwinian adaptations facilitate invasion into brain parenchyma and perivascular space or promote evasion from anti-cancer defence mechanisms...
November 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29111978/the-eukaryotic-translation-initiation-factor-eif4e-harnesses-hyaluronan-production-to-drive-its-malignant-activity
#14
Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic, Audrey Emond, Filippa Pettersson, Ronald Midura, Mark Lauer, Sonia Del Rincon, Valbona Cali, Sarit Assouline, Wilson H Miller, Vincent Hascall, Katherine Borden
The microenvironment provides a functional substratum supporting tumour growth. Hyaluronan (HA) is a major component of this structure. While the role of HA in malignancy is well-defined, the mechanisms driving its biosynthesis in cancer are poorly understood. We show that the eukaryotic translation initiation factor eIF4E, an oncoprotein, drives HA biosynthesis. eIF4E stimulates production of enzymes that synthesize the building blocks of HA, UDP-Glucuronic acid and UDP-N-Acetyl-Glucosamine, as well as hyaluronic acid synthase which forms the disaccharide chain...
November 7, 2017: ELife
https://www.readbyqxmd.com/read/29111325/inhibition-of-tissue-factor-signaling-in-breast-tumour-xenografts-induces-widespread-changes-in-the-microrna-expression-profile
#15
Esterina D'Asti, G Mark Anderson, Janusz Rak
Tissue factor (TF) is a transmembrane receptor for coagulation factor VII/VIIa that is frequently overexpressed by cancer cells. The TF/VIIa complex acts as the main initiator of the clotting cascade in blood and a trigger of intracellular signaling that changes gene expression and the cellular phenotype. However, pathways mediating these changes are still poorly characterized and especially the impact of TF signals on regulatory microRNA (miR) networks in cancer remains unknown. We show that the monoclonal antibody that selectively neutralises the signaling (but not coagulant) function of human TF (CNTO 2559) inhibits progression of MDA-MB-231 breast cancer xenografts in mice and prolongs animal survival...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29106767/phagocyte-extracellular-matrix-crosstalk-empowers-tumour-development-and-dissemination
#16
REVIEW
Chen Varol, Irit Sagi
Phagocytes, such as tumour-associated macrophages (TAMs) and tumour-associated neutrophils (TANs), are abundant in the stroma of experimental and human tumours and are locally educated to mediate important biological functions that profoundly affect tumour initiation, growth and dissemination. Of considerable importance is the non- cellular component of the tumour microenvironment, namely - the extracellular matrix (ECM). This milieu is often overlooked due to its complexity and vast heterogeneity. Biophysical and biomechanical cues provided by the dynamically evolving tumourigenic ECM fundamentally modulate every behavioral facet of the cancer cells and of associated stromal cells...
November 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29104494/pathogenic-role-of-exosomes-in-epstein-barr-virus-ebv-associated-cancers
#17
REVIEW
Sin-Yeang Teow, Kitson Liew, Alan Soo-Beng Khoo, Suat-Cheng Peh
Exosomes are 40- to 100-nm membrane-bound small vesicles that carry a great variety of cellular cargoes including proteins, DNA, messenger RNAs (mRNAs), and microRNAs (miRNAs). These nanovesicles are detected in various biological fluids such as serum, urine, saliva, and seminal fluids. Exosomes serve as key mediators in intercellular communication by facilitating the transfer and exchange of cellular components from cells to cells. They contain various pathogenic factors whereby their adverse effects have been implicated in multiple viral infections and cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29104277/heparan-sulfate-biosynthetic-system-is-inhibited-in-human-glioma-due-to-ext1-2-and-hs6st1-2-down-regulation
#18
Victor S Ushakov, Alexandra Y Tsidulko, Gabin de La Bourdonnaye, Galina M Kazanskaya, Alexander M Volkov, Roman S Kiselev, Vyacheslav V Kobozev, Diana V Kostromskaya, Alexey S Gaytan, Alexei L Krivoshapkin, Svetlana V Aidagulova, Elvira V Grigorieva
Heparan sulfate (HS) is an important component of the extracellular matrix and cell surface, which plays a key role in cell-cell and cell-matrix interactions. Functional activity of HS directly depends on its structure, which determined by a complex system of HS biosynthetic enzymes. During malignant transformation, the system can undergo significant changes, but for glioma, HS biosynthesis has not been studied in detail. In this study, we performed a comparative analysis of the HS biosynthetic system in human gliomas of different grades...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29102042/the-prognostic-value-of-cancer-stem-like-cell-markers-sox2-and-cd133-in-stage-iii-colon-cancer-is-modified-by-expression-of-the-immune-related-markers-foxp3-pd-l1-and-cd3
#19
T J Miller, M J McCoy, C Hemmings, M K Bulsara, B Iacopetta, C F Platell
Cancer stem-like cells are highly tumourigenic cells that can repopulate entire tumours after apparent successful treatment. Recent evidence suggests they interact with other cells in the tumour microenvironment, including immune cell subsets, to enhance their survival. The aim of this study was to determine whether the expression of immune cell markers in primary colon cancer impacts the prognostic significance of cancer stem-like cell marker expression. Immunohistochemistry was used to assess the expression of putative stem cell markers (ALDH1, CD44v6, CD133, Lgr5, SOX2) and immune cell related markers (CD3, CD8, FoxP3, PD-L1) in 104 patients with stage III colon cancer...
October 25, 2017: Pathology
https://www.readbyqxmd.com/read/29101800/pharmacotherapeutic-potential-of-phytochemicals-implications-in-cancer-chemoprevention-and-future-perspectives
#20
REVIEW
Varinder Kaur, Manish Kumar, Ajay Kumar, Kamaldeep Kaur, Varinderpal Singh Dhillon, Satwinderjeet Kaur
Cancer is a leading cause of disease burden throughout the world. Many cancers develop as a result of exposure to both lifestyle and environmental factors that are potentially modifiable. In the last few years, much of the scientific attention has drawn to the discovery of new and effective chemopreventive agents from natural sources. A multitude of phytoconstituents have been explored for their potential to prevent the occurrence of carcinogenesis both in vitro and in vivo by means of diverse cellular and molecular approaches...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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