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Tumour microenvironment

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https://www.readbyqxmd.com/read/28107546/bone-marrow-stroma-protects-myeloma-cells-from-cytotoxic-damage-via-induction-of-the-oncoprotein-muc1
#1
Michal Bar-Natan, Dina Stroopinsky, Katarina Luptakova, Maxwell D Coll, Arie Apel, Hasan Rajabi, Athalia R Pyzer, Kristen Palmer, Michaela R Reagan, Myrna R Nahas, Rebecca Karp Leaf, Salvia Jain, Jon Arnason, Irene M Ghobrial, Kenneth C Anderson, Donald Kufe, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is a lethal haematological malignancy that arises in the context of a tumour microenvironment that promotes resistance to apoptosis and immune escape. In the present study, we demonstrate that co-culture of MM cells with stromal cells results in increased resistance to cytotoxic and biological agents as manifested by decreased rates of cell death following exposure to alkylating agents and the proteosome inhibitor, bortezomib. To identify the mechanism of increased resistance, we examined the effect of the co-culture of MM cells with stroma cells, on expression of the MUC1 oncogene, known to confer tumour cells with resistance to apoptosis and necrosis...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28104391/na-h-exchanger-mediated-hydrogen-ion-extrusion-as-a-carcinogenic-signal-in-triple-negative-breast-cancer-etiopathogenesis-and-prospects-for-its-inhibition-in-therapeutics
#2
REVIEW
Schammim Ray Amith, Larry Fliegel
Breast cancer is the leading cause of cancer-related death in women in Europe and North America, and metastasis is the primary cause of fatality in patients with breast cancer. While some breast cancers are quite treatable, the triple-negative breast cancers are more metastatic and resistant to chemotherapy. There is clearly an urgent need for better treatments for this form of the disease. Breast cancer is characterized by genetically complex intra-tumour heterogeneity, particularly within the triple-negative clinical subtype...
January 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28098771/breast-cancer-brain-metastases-clonal-evolution-in-clinical-context
#3
REVIEW
Jodi M Saunus, Amy E McCart Reed, Zhun Leong Lim, Sunil R Lakhani
Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#4
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely impact human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of Vascular Endothelial Growth Factor (VEGF), a factor known to promote tumour growth...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28095711/systemic-alkalinisation-delays-prostate-cancer-cell-progression-in-tramp-mice
#5
Simonetta Astigiano, Andrea Puglisi, Luca Mastracci, Stefano Fais, Ottavia Barbieri
The microenvironment of solid tumours is extremely acidic and this condition arises since the precancerous stage. This acidic milieu could therefore provide a useful target for both prophylactic and therapeutic approaches. In TRAMP transgenic mice, an in vivo model of prostate adenocarcinoma (AC), oral administration of alkaline water was devoid of unwanted side effects, and when started from an early age was as effective as NaHCO3 in significantly delaying tumour progression, while when started when prostate tumours were already present, a nonstatistically significant trend in the same direction was detected...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28094262/radiotherapy-and-immunotherapy-a-beneficial-liaison
#6
REVIEW
Ralph R Weichselbaum, Hua Liang, Liufu Deng, Yang-Xin Fu
Investigations into the interaction between radiotherapy and the host immune system have uncovered new mechanisms that can potentially be exploited to improve the efficacy of radiotherapy. Radiation promotes the release of danger signals and chemokines that recruit inflammatory cells into the tumour microenvironment, including antigen-presenting cells that activate cytotoxic T-cell function. By contrast, radiation can attract immunosuppressive cells into the tumour microenvironment. In rare circumstances, the antitumour effect of radiotherapy has been observed outside of the radiation field, known as the abscopal effect...
January 17, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28093297/bottom-up-synthesis-of-carbon-nanoparticles-with-higher-doxorubicin-efficacy
#7
Samer Bayda, Mohamad Hadla, Stefano Palazzolo, Vinit Kumar, Isabella Caligiuri, Emmanuele Ambrosi, Enrico Pontoglio, Marco Agostini, Tiziano Tuccinardi, Alvise Benedetti, Pietro Riello, Vincenzo Canzonieri, Giuseppe Corona, Giuseppe Toffoli, Flavio Rizzolio
Nanomedicine requires intelligent and non-toxic nanomaterials for real clinical applications. Carbon materials possess interesting properties but with some limitations due to toxic effects. Interest in carbon nanoparticles (CNPs) is increasing because they are considered green materials with tunable optical properties, overcoming the problem of toxicity associated with quantum dots or nanocrystals, and can be utilized as smart drug delivery systems. Using black tea as a raw material, we synthesized CNPs with a narrow size distribution, tunable optical properties covering visible to deep red absorption, non-toxicity and easy synthesis for large-scale production...
January 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#8
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28089175/reduction-of-carcinomatosis-risk-using-icodextrin-as-a-carrier-solution-of-intraperitoneal-oxaliplatin-chemotherapy
#9
I Jouvin, H Najah, C Pimpie, C Canet Jourdan, R Kaci, M Mirshahi, C Eveno, M Pocard
There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumour or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumour cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy...
January 9, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28077876/microenvironmental-autophagy-promotes-tumour-growth
#10
Nadja S Katheder, Rojyar Khezri, Fergal O'Farrell, Sebastian W Schultz, Ashish Jain, Mohammed M Rahman, Kay O Schink, Theodossis A Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark, Tor Erik Rusten
As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#11
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28077297/exosomes-key-mediators-of-metastasis-and-pre-metastatic-niche-formation
#12
REVIEW
Richard J Lobb, Luize G Lima, Andreas Möller
While tumour cells are classically known to communicate via direct cell-to-cell contact and the secretion of soluble protein-based factors such as cytokines and growth factors, alternative novel mechanisms that promote tumour progression have recently emerged. Now, new critical components of the secretome thought to be involved in tumour progression are exosomes, small vesicles of endocytic origin that carry a variety of bioactive molecules, including proteins, lipids, RNA, as well as DNA molecules. Cancer cell-derived exosomes have been shown to participate in crucial steps of metastatic spread of a primary tumour, ranging from oncogenic reprogramming of malignant cells to formation of pre-metastatic niches...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28076901/nuclear-factor-one-transcription-factors-as-epigenetic-regulators-in-cancer
#13
REVIEW
Mitchell Fane, Lachlan Harris, Aaron G Smith, Michael Piper
Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state...
January 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28074546/-hypoxia-and-cellular-metabolism-in-tumour-pathophysiology
#14
Scott K Parks, Yann Cormerais, Jacques Pouysségur
Cancer cells are optimized for growth and survival via an ability to outcompete normal cells in their microenvironment. Many of these advantageous cellular adaptations are promoted by the pathophysiological hypoxia that arises in solid tumours due to incomplete vascularisation. Tumour cells are thus faced with the challenge of an increased need for nutrients to support the drive for proliferation in the face of a diminished extracellular supply. Among the many modifications occurring in tumour cells, Hypoxia Inducible Factors (HIFs) act as essential drivers of key pro-survival pathways via the promotion of numerous membrane and cytosolic proteins...
January 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28072762/giving-axl-the-axe-targeting-axl-in-human-malignancy
#15
Carl M Gay, Kavitha Balaji, Lauren Averett Byers
The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers...
January 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28068318/magnesium-silicide-nanoparticles-as-a-deoxygenation-agent-for-cancer-starvation-therapy
#16
Chen Zhang, Dalong Ni, Yanyan Liu, Heliang Yao, Wenbo Bu, Jianlin Shi
A material that rapidly absorbs molecular oxygen (known as an oxygen scavenger or deoxygenation agent (DOA)) has various industrial applications, such as in food preservation, anticorrosion of metal and coal deoxidation. Given that oxygen is vital to cancer growth, to starve tumours through the consumption of intratumoral oxygen is a potentially useful strategy in fighting cancer. Here we show that an injectable polymer-modified magnesium silicide (Mg2Si) nanoparticle can act as a DOA by scavenging oxygen in tumours and form by-products that block tumour capillaries from being reoxygenated...
January 9, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28065864/value-of-ph-regulators-in-the-diagnosis-prognosis-and-treatment-of-cancer
#17
REVIEW
Sara Granja, Diana Tavares-Valente, Odília Queirós, Fátima Baltazar
Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies...
January 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28064435/3d-volume-reconstruction-from-serial-breast-specimen-radiographs-for-mapping-between-histology-and-3d-whole-specimen-imaging
#18
Thomy Mertzanidou, John H Hipwell, Sara Reis, David J Hawkes, Babak Ehteshami Bejnordi, Mehmet Dalmis, Suzan Vreemann, Bram Platel, Jeroen van der Laak, Nico Karssemeijer, Meyke Hermsen, Peter Bult, Ritse Mann
PURPOSE: In breast imaging, radiological in-vivo images, such as X-ray mammography and Magnetic Resonance Imaging (MRI), are used for tumour detection, diagnosis and size determination. After excision, the specimen is typically sliced into slabs and a small subset is sampled. Histopathological imaging of the stained samples is used as the gold standard for characterisation of the tumour microenvironment. A 3D volume reconstruction of the whole specimen from the 2D slabs could facilitate bridging the gap between histology and in-vivo radiological imaging...
January 8, 2017: Medical Physics
https://www.readbyqxmd.com/read/28064102/influence-of-components-of-tumour-microenvironment-on-the-response-of-hct-116-colorectal-cancer-to-the-ruthenium-based-drug-nami-a
#19
Alberta Bergamo, Chiara Pelillo, Angela Chambery, Gianni Sava
Solid tumours are constituted of tumour cells, healthy cells recruited from the host tissues and soluble factors released by both these cell types. The present investigation examines the capacity of co-cultures between the HCEC colon epithelial cells and the HCT-116 colorectal cancer cells (mimicking the primary site of tumour growth) and between IHH hepatocytes and the HCT-116 colorectal cancer cells (metastatic site) to influence the effects of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachloro ruthenate) on the tumour cells themselves...
December 2, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#20
Harvey E Johnston, Matthew J Carter, Kerry L Cox, Melanie Dunscombe, Antigoni Manousopoulou, Paul A Townsend, Spiro D Garbis, Mark S Cragg
Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukaemia (CLL), are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumour, frequently affecting children, whilst CLL typically presents as an indolent, slow-progressing leukaemia affecting the elderly. The B-cell-specific over-expression of the myc and tcl1 oncogenes in mice induce spontaneous malignancies modelling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labelling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumours...
January 4, 2017: Molecular & Cellular Proteomics: MCP
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