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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#1
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28522598/immunotherapeutic-approaches-of-il-1-neutralization-in-the-tumor-microenvironment
#2
REVIEW
Ron N Apte, Elena Voronov
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515430/a-microfluidic-chip-for-screening-individual-cancer-cells-via-eavesdropping-on-autophagy-inducing-crosstalk-in-the-stroma-niche
#3
Hacer Ezgi Karakas, Junyoung Kim, Juhee Park, Jung Min Oh, Yongjun Choi, Devrim Gozuacik, Yoon-Kyoung Cho
Autophagy is a cellular homeostatic mechanism where proteins and organelles are digested and recycled to provide an alternative source of building blocks and energy to cells. The role of autophagy in cancer microenvironment is still poorly understood. Here, we present a microfluidic system allowing monitoring of the crosstalk between single cells. We used this system to study how tumor cells induced autophagy in the stromal niche. Firstly, we could confirm that transforming growth factor β1 (TGFβ1) secreted from breast tumor cells is a paracrine mediator of tumor-stroma interaction leading to the activation of autophagy in the stroma component fibroblasts...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#4
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511988/exploring-the-potential-of-nanotherapeutics-in-targeting-tumor-microenvironment-for-cancer-therapy
#5
REVIEW
Eameema Muntimadugu, Nagavendra Kommineni, Wahid Khan
Advanced research in the field of cancer biology clearly demonstrated the key role of tumor microenvironment (TME) in cancer development and metastasis particularly in solid tumors. Components of TME, being non-neoplastic in nature provide supportive and permissive conditions for the growth of cancer cells. Hence it is important to modify TME in cancer therapy and this would be achieved by better understanding of TME morphological features and functioning of stromal components. Nanotechnology based drug delivery offers various advantages such as prolonged circulation time, delivery of cargo at desired site, improved bioavailability, reduced toxicity etc...
May 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28507803/pd-l1-expression-on-malignant-cells-is-no-prerequisite-for-checkpoint-therapy
#6
Jan Willem Kleinovink, Koen A Marijt, Mark J A Schoonderwoerd, Thorbald van Hall, Ferry Ossendorp, Marieke F Fransen
Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for several tumor types, but the mechanism is not fully understood. PD-L1 expression on tumor biopsies is generally regarded as an inclusion criterion for this cancer therapy. Here, we describe the PD-L1-blocking therapeutic responses of preclinical tumors in which PD-L1 expression was removed from cancer cells, but not from immune infiltrate. Lack of PD-L1 expression on malignant cells delayed tumor outgrowth in a CD8(+) T cell-mediated fashion, showing the importance of this molecule in immune suppression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507793/composite-biomarkers-defined-by-multiparametric-immunofluorescence-analysis-identify-alk-positive-adenocarcinoma-as-a-potential-target-for-immunotherapy
#7
Hélène Roussel, Eléonore De Guillebon, Lucie Biard, Marion Mandavit, Laure Gibault, Elisabeth Fabre, Martine Antoine, Paul Hofman, Michèle Beau-Faller, Hélène Blons, Claire Danel, Françoise Le Pimpec Barthes, Alain Gey, Clémence Granier, Marie Wislez, Pierre Laurent-Puig, Stéphane Oudard, Patrick Bruneval, Cécile Badoual, Jacques Cadranel, Eric Tartour
Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8(+) T cells expressing PD-1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506312/pathomimetic-avatars-reveal-divergent-roles-of-microenvironment-in-invasive-transition-of-ductal-carcinoma-in-situ
#8
Mansoureh Sameni, Dora Cavallo-Medved, Omar E Franco, Anita Chalasani, Kyungmin Ji, Neha Aggarwal, Arulselvi Anbalagan, Xuequn Chen, Raymond R Mattingly, Simon W Hayward, Bonnie F Sloane
BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC. METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression...
May 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28501940/common-extracellular-matrix-regulation-of-myeloid-cell-activity-in-the-bone-marrow-and-tumor-microenvironments
#9
REVIEW
Sabina Sangaletti, Claudia Chiodoni, Claudio Tripodo, Mario P Colombo
The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28494747/new-diagnostic-and-therapeutic-aspects-of-pancreatic-ductal-adenocarcinoma
#10
Harald Mangge, Tobias Niedrist, Wilfried Renner, Stefan Lyer, Christoph Alexiou, Johannes Haybaeck
Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of its silent nature, the disease is often only diagnosed once it has reached an advanced, frequently inoperable stage. To date, we have no biomarkers that facilitate earlier diagnosis, leaving sufficient time for curative therapy that effectively lowers the very high mortality rate of this cancer entity. Because of this, the life expectancy of patients with PDAC is low (i.e. < 6% five-year survival rates). New data, including particular genetic signatures and features of the stromal architecture of PDAC tumors, may better explain their aggressiveness, their relatively long-lasting painless expansion, and why chemotherapy so frequently fails...
May 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28493304/cpam-type-2-derived-mesenchymal-stem-cells-malignancy-risk-study-in-a-14-month-old-boy
#11
Gloria Pelizzo, Maria A Avanzini, Marco Folini, Rossana Bussani, Melissa Mantelli, Stefania Croce, Gloria Acquafredda, Paola Travaglino, Graziella Cimino-Reale, Marina Boni, Irene Dambruoso, Valeria Calcaterra
INTRODUCTION: The association between congenital pulmonary airway malformations (CPAM) and malignancy is reported in the literature. Interactions between the tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. We characterized MSCs isolated from CPAM lesions in order to define potential malignancy risks. METHODS: CPAM II pulmonary tissue was used for MSC expansion; a "healthy" lung section from the same child was used as a comparator...
May 10, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28492519/theranostic-probes-for-targeting-tumor-microenvironment-an-overview
#12
REVIEW
Musafar Gani Sikkandhar, Anu Maashaa Nedumaran, Roopa Ravichandar, Satnam Singh, Induja Santhakumar, Zheng Cong Goh, Sachin Mishra, Govindaraju Archunan, Balázs Gulyás, Parasuraman Padmanabhan
Long gone is the time when tumors were thought to be insular masses of cells, residing independently at specific sites in an organ. Now, researchers gradually realize that tumors interact with the extracellular matrix (ECM), blood vessels, connective tissues, and immune cells in their environment, which is now known as the tumor microenvironment (TME). It has been found that the interactions between tumors and their surrounds promote tumor growth, invasion, and metastasis. The dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose a challenge for cancer diagnosis, drug design, and therapy...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28490538/cellular-constituents-of-the-prostate-stroma-key-contributors-to-prostate-cancer-progression-and-therapy-resistance
#13
Christine Levesque, Peter S Nelson
Reciprocal signaling between prostate stroma and its epithelium are fundamental to organ development and homeostasis. Similarly, interactions between tumor cells and stromal constituents are central to key aspects of carcinogenesis and malignancy growth involving tumor cell invasion, dissemination, and growth in distant sites. The prostate stroma is complex with several distinct resident cell types, infiltrating nonresident cell types and an amalgam of structural matrix factors, matricellular proteins, metabolites, growth factors, and cytokines...
May 10, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28486750/stromal-spock1-supports-invasive-pancreatic-cancer-growth
#14
Veronique L Veenstra, Helene Damhofer, Cynthia Waasdorp, Anne Steins, Hemant M Kocher, Jan Paul Medema, Hanneke W van Laarhoven, Maarten F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) is marked by an abundant stromal deposition. This stroma is suspected to harbor both tumor-promoting as well as -suppressing properties. This is underscored by the disappointing results of stroma targeting in clinical studies. Given the complexity of tumor-stroma interaction in PDAC, there is a need to identify the stromal proteins that are predominantly tumor-promoting. One possible candidate is SPOCK1 that we previously identified in a screening effort in PDAC. We extensively mined PDAC gene expression datasets, and used species-specific transcript analysis in mixed-species models for PDAC to study the patterns and driver mechanisms of SPOCK1 expression in PDAC...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28473858/stemness-in-cancer-stem-cells-cancer-stem-cells-and-their-microenvironment
#15
REVIEW
Pedro M Aponte, Andrés Caicedo
Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28471108/dna-methylation-in-the-tumor-microenvironment
#16
Meng-Wen Zhang, Kenji Fujiwara, Xu Che, Shu Zheng, Lei Zheng
The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth...
May 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28470572/tumor-associated-fibroblasts-and-microvessels-contribute-to-the-expression-of-immunosuppressive-factor-indoleamine-2-3-dioxygenase-in-human-esophageal-cancers
#17
Guanglin Cui, Can Li, Gang Xu, Zhenglu Sun, Li Zhu, Zhengfen Li, Wei Zheng, Junling Li, Aping Yuan
Recent studies have provided considerable evidence to support the hypothesis that tumor stroma plays a crucial role in the induction of immune tolerance to human cancers. Here, we investigated the contribution of reactive stromal tumor-associated fibroblasts (TAFs) and microvessels to the immunosuppressive factor indoleamine 2,3-dioxygenase (IDO) expression in the ESCC microenvironment. The immunohistochemical (IHC) analyses demonstrated a significant increased densities of TAFs and microvessels in the ESCC stroma, double IHCs showed that these increased TAFs and microvessels were with a high proliferation activity...
May 3, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28469183/coaxial-3d-bioprinting-of-self-assembled-multicellular-heterogeneous-tumor-fibers
#18
Xingliang Dai, Libiao Liu, Jia Ouyang, Xinda Li, Xinzhi Zhang, Qing Lan, Tao Xu
Three-dimensional (3D) bioprinting of living structures with cell-laden biomaterials has been achieved in vitro, however, some cell-cell interactions are limited by the existing hydrogel. To better mimic tumor microenvironment, self-assembled multicellular heterogeneous brain tumor fibers have been fabricated by a custom-made coaxial extrusion 3D bioprinting system, with high viability, proliferative activity and efficient tumor-stromal interactions. Therein, in order to further verify the sufficient interactions between tumor cells and stroma MSCs, CRE-LOXP switch gene system which contained GSCs transfected with "LOXP-STOP-LOXP-RFP" genes and MSCs transfected with "CRE recombinase" gene was used...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28462708/collaborative-and-defensive-fibroblasts-in-tumor-progression-and-therapy-resistance
#19
Barbara Chiavarina, Andrei Turtoi
Tumor microenvironment is a complex network of epithelial cancer cells and non-transformed stromal cells. Of the many stromal cell types, fibroblasts are the most numerous ones and are traditionally viewed as supportive elements of cancer progression. Many studies show that cancer cells engage in active crosstalk with associated fibroblasts in order to obtain key resources, such as growth factors and nutrients. The facets of fibroblast "complicity to murder" in cancer are multiple. However, recent therapeutic attempts aiming at depleting fibroblasts from tumors, perturbed our rather simplistic picture...
April 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28461568/novel-molecular-mechanism-of-regulation-of-cd40-ligand-by-the-transcription-factor-gli2
#20
Weiguo Han, David A Jackson, Stephan J Matissek, Jason A Misurelli, Matthew S Neil, Brandon Sklavanitis, Nansalmaa Amarsaikhan, Sherine F Elsawa
The interaction between tumor cells and their surrounding microenvironment is essential for the growth and persistence of cancer cells. This interaction is mediated, in part, by cytokines. Although the role of cytokines in normal and malignant cell biology is well established, many of the molecular mechanisms regulating their expression remain elusive. In this article, we provide evidence of a novel pathway controlling the transcriptional activation of CD40L in bone marrow-derived stromal cells. Using a PCR-based screening of cytokines known to play a role in the biology of bone marrow malignancies, we identified CD40L as a novel GLI2 target gene in stromal cells...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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