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Tumour microenvironment

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https://www.readbyqxmd.com/read/29781548/multi-omics-in-high-grade-serous-ovarian-cancer-biomarkers-from-genome-to-the-immunome
#1
Cole Clifford, Natasha Vitkin, Sarah Nersesian, Gillian Reid-Schachter, Julie-Ann Francis, Madhuri Koti
Epithelial ovarian cancer (EOC) is a lethal gynaecological disease that imposes significant burden on health care and patient quality of life. High-grade serous carcinoma of the ovary (HGSC) is the most prevalent histological type of EOC. A vast majority of HGSC cases are diagnosed at late stages of the disease, limiting the opportunity for clinical intervention and resulting in a 10-year survival rate of <20%. Recent innovations in high-throughput molecular analysis of patient-derived specimens may address these clinical challenges by providing an enhanced understanding of the molecular aetiology of ovarian cancer, in addition to offering several opportunities for rational biomarker and targeted therapy discovery...
May 21, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29776544/two-photon-fluorescent-probe-for-detection-of-nitroreductase-and-hypoxia-specific-microenvironment-of-cancer-stem-cell
#2
Yajing Liu, Wei Liu, Hongjuan Li, Weixiao Yan, Xinjian Yang, Dandan Liu, Shuxiang Wang, Jinchao Zhang
Hypoxia plays a crucial role in cancer progression, and it has great significance for monitoring hypoxic level in biosystems. Cancer stem cells (CSCs) represent a small population of tumour cells that regard as the key to seed tumours. The survival of CSCs depend on the tumour microenvironment, which is distinct region has the hypoxic property. Therefore, the detection of the hypoxic CSC niche plays a pivotal role in the destructing the 'soil' of CSCs, and eliminating CSCs population. Numerous one-photon excited fluorescent probes have been developed to indicate the hypoxic status in tumours through the detection of nitroreductase (NTR) level...
September 18, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29774910/design-of-rgd-atwlppr-peptide-conjugates-for-the-dual-targeting-of-%C3%AE-v-%C3%AE-3-integrin-and-neuropilin-1
#3
Fabien Thoreau, Laetitia Vanwonterghem, Maxime Henry, Jean-Luc Coll, Didier Boturyn
Targeting the tumour microenvironment is a promising strategy to detect and/or treat cancer. The design of selective compounds that co-target several receptors frequently overexpressed in solid tumours may allow a reliable and selective detection of tumours. Here we report the modular synthesis of compounds encompassing ligands of αVβ3 integrin and neuropilin-1 that are overexpressed in the tumour microenvironment. These compounds were then evaluated through cellular experiments and imaging of tumours in mice...
May 18, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29771149/preparation-and-evaluation-of-tumour-microenvironment-response-multistage-nanoparticles-for-epirubicin-delivery-and-deep-tumour-penetration
#4
Jialing Dai, Shangcong Han, Fang Ju, Mei Han, Lisa Xu, Ruoyu Zhang, Yong Sun
Poor tumour penetration became a major challenge for the use of nanoparticles in anticancer therapy. To further enhance the tumour penetration efficiency, we developed a tumour-microenvironment-responsive multistage drug delivery system which was formed layer by layer via electrostatic interaction with cationic drug-loaded nanoparticles, hyaluronidase (HAase) and iRGD-modified gelatin (G-iRGD). The drug-loaded nanoparticles were formed by self-assembling mPEG-PDPA-PG and encapsulation with epirubicin (EPI)...
May 17, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29767411/mek1-2-inhibition-by-binimetinib-is-effective-as-a-single-agent-and-potentiates-the-actions-of-venetoclax-and-abt-737-under-conditions-that-mimic-the-chronic-lymphocytic-leukaemia-cll-tumour-microenvironment
#5
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765774/how-shall-we-treat-early-triple-negative-breast-cancer-tnbc-from-the-current-standard-to-upcoming-immuno-molecular-strategies
#6
REVIEW
Ji Hyun Park, Jin-Hee Ahn, Sung-Bae Kim
Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the 'BRCAness' highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors...
2018: ESMO Open
https://www.readbyqxmd.com/read/29761522/thrombotic-characteristics-of-extracellular-vesicles-derived-from-prostate-cancer-cells
#7
Hassan A Al Saleh, Sandor Haas-Neill, Ali Al-Hashimi, Anil Kapoor, Bobby Shayegan, Richard C Austin, Khalid Al-Nedawi
BACKGROUND: Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor-1 PAI-1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI-1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells...
May 15, 2018: Prostate
https://www.readbyqxmd.com/read/29760523/combination-of-fucoidan-based-magnetic-nanoparticles-and-immunomodulators-enhances-tumour-localized-immunotherapy
#8
Chih-Sheng Chiang, Yu-Jung Lin, Rachel Lee, Yen-Ho Lai, Hung-Wei Cheng, Chia-Hung Hsieh, Woei-Cherng Shyu, San-Yuan Chen
Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex3 ) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex3 can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects...
May 14, 2018: Nature Nanotechnology
https://www.readbyqxmd.com/read/29760166/the-role-of-il-1b-in-breast-cancer-bone-metastasis
#9
Claudia Tulotta, Penelope Dawn Ottewell
Approximately 75% of patients with late stage breast cancer will develop bone metastasis. This condition is currently considered incurable and patients' life expectancy is limited to 2-3 years following diagnosis of bone involvement. IL-1B is a pro-inflammatory cytokine whose expression in primary tumours has been identified as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In this Review, we discuss how IL-1B from both the tumour cells and the tumour microenvironment influence growth of primary breast tumours, dissemination into the bone metastatic niche and proliferation into overt metastases...
May 14, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29759567/epcam-duality-becomes-this-molecule-in-a-new-dr-jekyll-and-mr-hyde-tale
#10
REVIEW
Alejandro Herreros-Pomares, Cristóbal Aguilar-Gallardo, Silvia Calabuig-Fariñas, Rafael Sirera, Eloísa Jantus-Lewintre, Carlos Camps
EpCAM, known as an epithelial cell adhesion molecule, plays an essential role in cell adhesion, migration, metastasis and cell signalling. Rather than acting as an apoptosis antagonist, it induces cellular proliferation that impacts the cell cycle, and as a signalling transducer it uses and enhances the Wnt pathway, which is significantly relevant in cell renewal and cancer. EpCAM has become a marker of circulating tumour cells (CTCs) in lung cancer due to its specificity, and its high and stable expression level...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29753703/ngr-htnf-in-combination-with-best-investigator-choice-in-previously-treated-malignant-pleural-mesothelioma-ngr015-a-randomised-double-blind-placebo-controlled-phase-3-trial
#11
Vanesa Gregorc, Rabab M Gaafar, Adolfo Favaretto, Francesco Grossi, Jacek Jassem, Andreas Polychronis, Paolo Bidoli, Marcello Tiseo, Riyaz Shah, Paul Taylor, Silvia Novello, Alberto Muzio, Alessandra Bearz, Laurent Greillier, Floriana Fontana, Giulia Salini, Antonio Lambiase, Mary O'Brien
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with highly vascularised tumours. It has poor prognosis and few treatment options after failure of first-line chemotherapy. NGR-hTNF is a vascular-targeting drug that increases penetration of intratumoral chemotherapy and T-cell infiltration by modifying the tumour microenvironment. In this trial, we aimed to investigate the efficacy and safety of NGR-hTNF in patients with malignant pleural mesothelioma who had progressed during or after a first-line treatment...
May 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29750997/the-role-of-spatial-variations-of-abiotic-factors-in-mediating-intratumour-phenotypic-heterogeneity
#12
Tommaso Lorenzi, Chandrasekhar Venkataraman, Alexander Lorz, Mark A J Chaplain
We present here a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of abiotic components of the tumour microenvironment in mediating phenotypic selection of cancer cells. Numerical simulations are performed both on the 3D geometry of an in silico multicellular tumour spheroid and on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography...
May 8, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29748898/cystatin-f-as-a-regulator-of-immune-cell-cytotoxicity
#13
REVIEW
Janko Kos, Milica Perišić Nanut, Mateja Prunk, Jerica Sabotič, Esmeralda Dautović, Anahid Jewett
Cysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors-cystatins. Whereas other cystatins are generally cytosolic or extracellular proteins, cystatin F is present in endosomes and lysosomes and is thus able to regulate the activity of its target directly...
May 10, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29748602/author-correction-inflammatory-breast-cancer-biology-the-tumour-microenvironment-is-key
#14
Bora Lim, Wendy A Woodward, Xiaoping Wang, James M Reuben, Naoto T Ueno
The originally published article contained an error in Table 1, in which two neoadjuvant clinical trials (NCT02876107 and NCT03101748) were not included. This omission has been corrected in the online and print versions of the manuscript through the addition of these two trials and their relevant details (agents, cohort details, targeted biology, main targeted pathway or characteristic and phase) to Table 1.
May 10, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29743717/integrating-oncolytic-viruses-in-combination-cancer-immunotherapy
#15
REVIEW
Praveen K Bommareddy, Megha Shettigar, Howard L Kaufman
Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments...
May 9, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29743167/characterising-the-adipose-inflammatory-microenvironment-in-male-breast-cancer
#16
Tom Lees, Angharad Cullinane, Alexandra Condon, Abeer M Shaaban, Matthew Humphries, Valerie Speirs
Male breast cancer (MBC) incidence seems to parallel global increases in obesity. The stromal microenvironment contributes to carcinogenesis, yet the role of adipocytes in this is understudied in MBC. We identified 4 cohorts of male breast tissues diagnosed when obesity was rare (archival cohort) and more common (contemporary cohort). We examined the microenvironment of archival and contemporary cohorts of MBC, diagnosed 1940 - 1970 and 1998 - 2006, respectively, with 2 cohorts of, archival and contemporary gynaecomastia, diagnosed 1940 - 1979 and 1996 - 2011, respectively serving as controls...
May 9, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29741547/microenvironmental-influence-on-microtumour-infiltration-patterns-3d-mathematical-modelling-supported-by-in-vitro-studies
#17
Emmanuel Luján, Daniela Soto, María S Rosito, Alejandro Soba, Liliana N Guerra, Juan C Calvo, Guillermo Marshall, Cecilia Suárez
Mathematical modelling approaches have become increasingly abundant in cancer research. Tumour infiltration extent and its spatial organization depend both on the tumour type and stage and on the bio-physicochemical characteristics of the microenvironment. This sets a complex scenario that often requires a multidisciplinary and individually adjusted approach. The ultimate goal of this work is to present an experimental/numerical combined method for the development of a three-dimensional mathematical model with the ability to reproduce the growth and infiltration patterns of a given avascular microtumour in response to different microenvironmental conditions...
May 9, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29740440/targeting-head-and-neck-cancer-by-vaccination
#18
REVIEW
Chuan Wang, James Dickie, Ruhcha V Sutavani, Catherine Pointer, Gareth J Thomas, Natalia Savelyeva
Head and neck cancer (HNC) is a heterogeneous group of squamous cell cancers that affect the oral cavity, pharynx, and larynx. Worldwide, it is the sixth most common cancer but in parts of Southern and South-East Asia, HNC is one of the most common cancers. A significant proportion of HNC is driven by human papillomavirus (HPV) infection, whereas HPV-independent HNC is associated with alcohol, smoking, and smokeless tobacco consumption. Here, we review the past and present experience of targeting HNC with vaccination focusing on HPV-derived antigens as well as non-viral antigens for HPV-negative HNC...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29737636/a-peroxiredoxin-based-proteinaceous-scaffold-for-the-growth-and-differentiation-of-neuronal-cells-and-tumour-stem-cells-in-the-absence-of-prodifferentiation-agents
#19
Annamaria Cimini, Matteo Ardini, Roberta Gentile, Francesco Giansanti, Elisabetta Benedetti, Loredana Cristiano, Alessia Fidoamore, Stefano Scotti, Gloria Panella, Francesco Angelucci, Rodolfo Ippoliti
The use of nanoscale materials in the design of scaffolds for CNS tissue is increasing, due to their ability to promote cell adhesion, to mimic an extracellular matrix microenvironment and to interact with neuronal membranes. In this framework, one of the major challenges when using undifferentiated neural cells is how to control the differentiation process. Here we report the characterization of a scaffold based on the self-assembled nanotubes of a mutant of the protein peroxiredoxin (from Schistosoma mansoni or Bos taurus), which allows the growth and differentiation of a model neuronal cell line (SHSY5Y)...
September 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29735363/host-dependent-variables-the-missing-link-to-personalized-medicine
#20
REVIEW
Regina Demlova, Lenka Zdrazilova-Dubska, Jaroslav Sterba, Giorgio Stanta, Dalibor Valik
Individualized medicine has the potential to tailor anticancer therapy with the best response and highest safety margin to provide better patient care. However, modern targeted therapies are still being tested through clinical trials comparing preselected patient cohorts and assessed upon behaviour of group averages. Clinically manifesting malignant disease requires identification of host- and tumour-dependent variables such as biological characteristics of the tumour and its microenvironment including immune response features, and overall capacity of the host to receive, tolerate and efficiently utilize treatment...
April 26, 2018: European Journal of Surgical Oncology
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