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tumor niche

Dorian Forte, Daria Sollazzo, Martina Barone, Marisole Allegri, Angela di Martella Orsi, Marco Romano, Barbara Sinigaglia, Giuseppe Auteri, Nicola Vianelli, Michele Cavo, Francesca Palandri, Lucia Catani
Inflammation may play a role in cancer. However, the contribution of cytokine-mediated crosstalk between normal hemopoietic stem/progenitor cells (HSPCs) and their (inflammatory) microenvironment is largely elusive. Here we compared survival, phenotype, and function of neonatal (umbilical cord blood (CB)) and adult (normal G-CSF-mobilized peripheral blood (mPB)) CD34+ cells after in vitro exposure to combined crucial inflammatory factors such as interleukin- (IL-) 1 β , IL-6, tumor necrosis factor- (TNF-) α , or tissue inhibitor of metalloproteinases-1 (TIMP-1)...
2018: Mediators of Inflammation
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Dariusz Łaski, Zbigniew Śledziński, Zbigniew Kmieć
The therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines...
August 13, 2018: Scientific Reports
Oluwaseun Adebayo Bamodu, Ching-Kuo Yang, Wei-Hong Cheng, David T W Tzeng, Kuang-Tai Kuo, Chun-Chih Huang, Li Deng, Michael Hsiao, Wei-Hwa Lee, Chi-Tai Yeh
BACKGROUND: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit the niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite the accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored...
August 10, 2018: Cancers
Guido Carpino, Vincenzo Cardinale, Trine Folseraas, Diletta Overi, Krzysztof Grzyb, Daniele Costantini, Pasquale Bartolomeo Berloco, Sabina Di Matteo, Tom Hemming Karlsen, Domenico Alvaro, Eugenio Gaudio
Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy frequently complicated by cholangiocarcinoma (CCA). Massive proliferation of biliary tree stem/progenitor cells (BTSCs), expansion of peribiliary glands (PBGs), and dysplasia were observed in PSC. The aims of the present study were to evaluate the involvement of PBGs and BTSCs in CCA which emerged in PSC patients. Specimens from normal liver (N=5), PSC (N=20), and PSC-associated CCA (N=20) were included. Samples were processed for histology, immunohistochemistry and immunofluorescence...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Danh Truong, Roberto Fiorelli, Eric S Barrientos, Ernesto Luna Melendez, Nader Sanai, Shwetal Mehta, Mehdi Nikkhah
Glioblastoma (GBM) is one of the deadliest forms of cancer. Despite many treatment options, prognosis of GBM remains dismal with a 5-year survival rate of 4.7%. Even then, tumors often recur after treatment. Tumor recurrence is hypothesized to be driven by glioma stem cell (GSC) populations which are highly tumorigenic, invasive, and resistant to several forms of therapy. GSCs are often concentrated around the tumor vasculature, referred to as the vascular niche, which are known to provide microenvironmental cues to maintain GSC stemness, promote invasion, and resistance to therapies...
July 30, 2018: Biomaterials
Karen A Cavassani, Rebecca J Meza, David M Habiel, Jie-Fu Chen, Alexander Montes, Manisha Tripathi, Gislâine A Martins, Timothy R Crother, Sungyong You, Cory M Hogaboam, Neil Bhowmick, Edwin M Posadas
BACKGROUND: Recruited myeloid cells are known to promote cancer initiation, malignant progression, metastasis, and resistance to therapy in the tumor niche. We tested the hypothesis that circulating blood monocytes from advanced prostate cancer (PCa) patients exhibit a protumor phenotype and directly influence the tumor microenvironment in response to tumor-derived signals. METHODS: Blood monocytes from advanced and stable PCa patients were cultured, and the conditioned media (CM) were collected and analyzed using standard invasion and wound closure assays to measure effects on invasion and motility of PCa tumor cells...
August 9, 2018: Cancer Medicine
Oshrat Attar-Schneider, Liat Drucker, Maya Gottfried
The fatality of non-small-cell lung cancer (NSCLC) and the role of the cancer microenvironment in its resistance to therapy are long recognized. Accumulating data allocate a significant role for mesenchymal stem cells (MSCs) in the malignant environment. Previously, we have demonstrated that MSCs from NSCLC metastatic bone marrow (BM) niche deleteriously affected NSCLC cells. Here, we have decided to examine the effect of MSCs from the primary niche of the lung (healthy or adjacent to tumor) on NSCLC phenotype...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Yue Zhao, Qiongzhu Dong, Jiahui Li, Kaili Zhang, Jie Qin, Jiangang Zhao, Qiye Sun, Zhefang Wang, Thomas Wartmann, Karl Walter Jauch, Peter J Nelson, LunXiu Qin, Christiane Bruns
A small subpopulation of cells within the bulk of tumors share features with somatic stem cells, in that, they are capable of self-renewal, they differentiate, and are highly resistant to conventional therapy. These cells have been referred to as cancer stem cells (CSCs). Recent reports support the central importance of a cancer stem cell-like niche that appears to help foster the generation and maintenance of CSCs. In response to signals provided by this microenvironment, CSCs express the tumorigenic characteristics that can drive tumor metastasis by the induction of epithelial-mesenchymal-transition (EMT) that in turn fosters the migration and recolonization of the cells as secondary tumors within metastatic niches...
August 3, 2018: Seminars in Cancer Biology
Balbina J Plotkin, Ira M Sigar, Julie A Swartzendruber, Amber Kaminski
Most mucosal surfaces along with the midpoints in tumors and stem cell niches are geographic areas of the body that are anoxic. Previous studies show that the incubation in normoxic (5% CO2 in air) or hypoxic (low oxygen levels) conditions followed by an anoxic incubation (an absence of free oxygen) results in limited viability (2-3 days). A novel methodology was developed that enables an anoxic cell cultivation (for at least 17 days; the maximum time tested). The most critical aspect of this methodology is to ensure that no oxygen is introduced into the system...
July 21, 2018: Journal of Visualized Experiments: JoVE
Ju Hun Yeon, Hyo Eun Jeong, Hyemin Seo, Siwoo Cho, Kimin Kim, Dokyun Na, Seok Chung, Jaesung Park, Nakwon Choi, Ji Yoon Kang
Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth, but very little has been known about its characteristics and origin. Recently, cancer-derived exosome has been suggested to transdifferentiate CAFs, by a new mechanism of endothelial to mesenchymal transition (EndMT), initiating angiogenic processes and triggering metastatic evolution. However, an enabling tool in vitro is yet to be developed to investigate complicated procedures of the EndMT and the transdifferentiation under reconstituted tumor microenvironment...
August 2018: Acta Biomaterialia
Tzuhua Lin, Jukka Pajarinen, Yusuke Kohno, Masahiro Maruyama, Monica Romero-Lopez, Jhih-Fong Huang, Karthik Nathan, Tahsin N Khan, Zhenyu Yao, Stuart B Goodman
BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation. METHODS: Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activation...
August 1, 2018: Cytotherapy
Mahnaz Janghorban, Li Xin, Jeffrey M Rosen, Xiang H-F Zhang
The Notch signaling pathway regulates important cellular processes involved in stem cell maintenance, proliferation, development, survival, and inflammation. These responses to Notch signaling involving both canonical and non-canonical pathways can be spatially and temporally variable and are highly cell-type dependent. Notch signaling can elicit opposite effects in regulating tumorigenicity (tumor-promoting versus tumor-suppressing function) as well as controlling immune cell responses. In various cancer types, Notch signaling elicits a "cancer stem cell (CSC)" phenotype that results in decreased proliferation, but resistance to various therapies, hence potentially contributing to cell dormancy and relapse...
2018: Frontiers in Immunology
Dawn M Kochanek, Shanawaz M Ghouse, Magdalena M Karbowniczek, Maciej M Markiewski
Complement is an effector of innate immunity and a bridge connecting innate immunity and subsequent adaptive immune responses. It is essential for protection against infections and for orchestrating inflammatory responses. Recent studies have also demonstrated contribution of the complement system to several homeostatic processes that are traditionally not considered to be involved in immunity. Thus, complement regulates homeostasis and immunity. However, dysregulation of this system contributes to several pathologies including inflammatory and autoimmune diseases...
2018: Frontiers in Immunology
Miki Nakamura, Atsushi Suetsugu, Kosuke Hasegawa, Tomoyuki Satake, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
BACKGROUND/AIM: Our laboratory pioneered color-coded imaging of the tumor microenvironment (TME). We observed recruitment of cancer and stromal cells to the TME and recombination between cancer and stromal cells. The aim of the present study was to observe the dynamics of the TME by color-coded imaging during metastasis and in the formation of a pre-metastatic niche. MATERIALS AND METHODS: Red-fluorescent protein (RFP-expressing) mouse colon-cancer 26 cells were initially injected subcutaneously in green-fluorescent protein (GFP) nude mice...
August 2018: Anticancer Research
Bo Ren, Ming Cui, Gang Yang, Huanyu Wang, Mengyu Feng, Lei You, Yupei Zhao
Pancreatic cancer is a deadly disease with high mortality due to difficulties in its early diagnosis and metastasis. The tumor microenvironment induced by interactions between pancreatic epithelial/cancer cells and stromal cells is critical for pancreatic cancer progression and has been implicated in the failure of chemotherapy, radiation therapy and immunotherapy. Microenvironment formation requires interactions between pancreatic cancer cells and stromal cells. Components of the pancreatic cancer microenvironment that contribute to desmoplasia and immunosuppression are associated with poor patient prognosis...
July 30, 2018: Molecular Cancer
Go J Yoshida
The pathophysiological roles and the therapeutic potentials of Myc family are reviewed in this article. The physiological functions and molecular machineries in stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, are clearly described. The c-Myc/Max complex inhibits the ectopic differentiation of both types of artificial stem cells. Whereas c-Myc plays a fundamental role as a "double-edged sword" promoting both iPS cells generation and malignant transformation, L-Myc contributes to the nuclear reprogramming with the significant down-regulation of differentiation-associated genetic expression...
July 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Barbara Breznik, Clara Limbaeck Stokin, Janko Kos, Mohammed Khurshed, Vashendriya V V Hira, Roman Bošnjak, Tamara T Lah, Cornelis J F Van Noorden
Glioblastoma (GBM) is the most lethal brain tumor also due to malignant and therapy-resistant GBM stem cells (GSCs) that are localized in protecting hypoxic GSC niches. Some members of the cysteine cathepsin family of proteases have been found to be upregulated in GBM. Cathepsin K gene expression is highly elevated in GBM tissue versus normal brain and it has been suggested to regulate GSC migration out of the niches. Here, we investigated the cellular distribution of cathepsins B, X and K in GBM tissue and whether these cathepsins are co-localized in GSC niches...
July 25, 2018: Journal of Molecular Histology
Elizabeth A Wellberg, Peter Kabos, Austin E Gillen, Britta M Jacobsen, Heather M Brechbuhl, Stevi J Johnson, Michael C Rudolph, Susan M Edgerton, Ann D Thor, Steven M Anderson, Anthony Elias, Xi Kathy Zhou, Neil M Iyengar, Monica Morrow, Domenick J Falcone, Omar El-Hely, Andrew J Dannenberg, Carol A Sartorius, Paul S MacLean
Obesity increases breast cancer mortality by promoting resistance to therapy. Here, we identified regulatory pathways in estrogen receptor-positive (ER-positive) tumors that were shared between patients with obesity and those with resistance to neoadjuvant aromatase inhibition. Among these was fibroblast growth factor receptor 1 (FGFR1), a known mediator of endocrine therapy resistance. In a preclinical model with patient-derived ER-positive tumors, diet-induced obesity promoted a similar gene expression signature and sustained the growth of FGFR1-overexpressing tumors after estrogen deprivation...
July 25, 2018: JCI Insight
Aurélie S Cazet, Mun N Hui, Benjamin L Elsworth, Sunny Z Wu, Daniel Roden, Chia-Ling Chan, Joanna N Skhinas, Raphaël Collot, Jessica Yang, Kate Harvey, M Zahied Johan, Caroline Cooper, Radhika Nair, David Herrmann, Andrea McFarland, Niantao Deng, Manuel Ruiz-Borrego, Federico Rojo, José M Trigo, Susana Bezares, Rosalía Caballero, Elgene Lim, Paul Timpson, Sandra O'Toole, D Neil Watkins, Thomas R Cox, Michael S Samuel, Miguel Martín, Alexander Swarbrick
The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibroblasts (CAFs) to provide a supportive niche for the acquisition of a chemo-resistant, cancer stem cell (CSC) phenotype via FGF5 expression and production of fibrillar collagen. Stromal treatment of patient-derived xenografts with smoothened inhibitors (SMOi) downregulates CSC markers expression and sensitizes tumors to docetaxel, leading to markedly improved survival and reduced metastatic burden...
July 24, 2018: Nature Communications
Gábor Valcz, Edit Irén Buzás, Zoltán Szállási, Alexandra Kalmár, Tibor Krenács, Zsolt Tulassay, Péter Igaz, Béla Molnár
Carcinomas are complex structures composed of hierarchically organized distinct cell populations such as cancer stem cells and non-stem (bulk) cancer cells. Their genetic/epigenetic makeup and the dynamic interplay between the malignant cell populations and their stromal fibroblasts are important determinants of metastatic tumor invasion. Important mediators of these interactions are the small, membrane-enclosed extracellular vesicles, in particular exosomes. Both cancer cell and fibroblast-derived exosomes carry a set of regulatory molecules, including proteins and different species of RNA, which cooperatively support metastatic tumor spread...
2018: NPJ Breast Cancer
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