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Cancer microenvironment

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https://www.readbyqxmd.com/read/28110220/hypoxia-inducing-factor-hif-1%C3%AE-derived-peptide-capable-of-inducing-cancer-reactive-cytotoxic-t-lymphocytes-from-hla-a24-patients-with-renal-cell-carcinoma
#1
Takafumi Minami, Naoki Matsumura, Koichi Sugimoto, Nobutaka Shimizu, Marco De Velasco, Masahiro Nozawa, Kazuhiro Yoshimura, Nanae Harashima, Mamoru Harada, Hirotsugu Uemura
Hypoxic tumor microenvironment makes cancer cells to be therapy-resistant and hypoxia-inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel-Lindau (VHL) gene mutations, leading to up-regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti-cancer therapy. In this study, we searched for HIF-1α-derived peptides that are able to induce RCC-reactive cytotoxic T lymphocytes (CTLs) from HLA-A24(+) RCC patients...
January 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28110067/poly-glycerol-sebacate-elastomer-supports-bone-regeneration-by-its-mechanical-properties-being-closer-to-osteoid-tissue-rather-than-to-mature-bone
#2
S H Zaky, K W Lee, J Gao, A Jensen, K Verdelis, Y Wang, A J Almarza, C Sfeir
: Mechanical load influences bone structure and mass. Arguing the importance of load-transduction, we investigated the mechanisms inducing bone formation using an elastomeric substrate. We characterized Poly (glycerol sebacate) (PGS) in-vitro for its mechanical properties, compatibility with osteoprogenitor cells regarding adhesion, proliferation, differentiation under compression versus static cultures and in-vivo for the regeneration of a rabbit ulna critical size defect. The load-transducing properties of PGS were compared in-vitro to a stiffer poly lactic-co- glycolic-acid (PLA/PGA) scaffold of similar porosity and interconnectivity...
January 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28109792/bisacodyl-and-its-cytotoxic-activity-on-human-glioblastoma-stem-like-cells-implication-of-inositol-1-4-5-triphosphate-receptor-dependent-calcium-signaling
#3
Jihu Dong, Francisco Aulestia, Suzana Assad Kahn, Maria Zeniou, Luiz Gustavo Dubois, Elias A El-Habr, François Daubeuf, Nassera Tounsi, Samuel H Cheshier, Nelly Frossard, Marie-Pierre Junier, Hervé Chneiweiss, Isabelle Néant, Marc Moreau, Catherine Leclerc, Jacques Haiech, Marie-Claude Kilhoffer
Glioblastoma is the most common malignant brain tumor. The heterogeneity at the cellular level, metabolic specificities and plasticity of the cancer cells are a challenge for glioblastoma treatment. Identification of cancer cells endowed with stem properties and able to propagate the tumor in animal xenografts has opened a new paradigm in cancer therapy. Thus, to increase efficacy and avoid tumor recurrence, therapies need to target not only the differentiated cells of the tumor mass, but also the cancer stem-like cells...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28109751/cord-blood-natural-killer-cells-expressing-a-dominant-negative-tgf-%C3%AE-receptor-implications-for-adoptive-immunotherapy-for-glioblastoma
#4
Eric S Yvon, Rachel Burga, Allison Powell, Conrad R Cruz, Rohan Fernandes, Cecilia Barese, Tuongvan Nguyen, Mohamed S Abdel-Baki, Catherine M Bollard
Cord blood (CB) natural killer (NK) cells are promising effector cells for tumor immunotherapy but are currently limited by immune-suppressive cytokines in the tumor microenvironment, such as transforming growth factor (TGF-β). We observed that TGF-β inhibits expression of activating receptors such as NKG2D and DNAM1 and decreases killing activity against glioblastoma tumor cells through inhibition of perforin secretion. To overcome the detrimental effects of TGF-β, we engrafted a dominant negative TGF-β receptor II (DNRII) on CB-derived NK cells by retroviral transduction and evaluated their ability to kill glioblastoma cells in the presence of TGF-β...
January 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28109303/uptake-of-dna-by-cancer-cells-without-a-transfection-reagent
#5
Yanping Kong, Xianbo Zhang, Yongliang Zhao, Yanfang Xue, Ye Zhang
BACKGROUND: Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis...
January 21, 2017: Biological Research
https://www.readbyqxmd.com/read/28108950/t-cell-receptor-engineered-t-cells-for-cancer-treatment-current-status-and-future-directions
#6
REVIEW
Yu Ping, Chaojun Liu, Yi Zhang
T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1)...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108623/tumor-induced-stromal-stat1-accelerates-breast-cancer-via-deregulating-tissue-homeostasis
#7
Victoria R Zellmer, Patricia M Schnepp, Sarah L Fracci, Xuejuan Tan, Erin N Howe, Siyuan Zhang
: The tumor microenvironment (TME) is a dynamic tissue space in which the tumor exists, plays a significant role in tumor initiation, and is a key contributor in cancer progression; however, little is known about tumor-induced changes in the adjacent tissue stroma. Herein, tumor-induced changes in the TME were explored at the morphological and molecular level to further understand cancer progression. Tumor-adjacent mammary glands (TAGs) displayed altered branching morphology, expansion of myofibroblasts, and increased mammosphere formation, broadly suggesting a tumor-induced field effect...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108545/bombesin-antagonist-based-radiotherapy-of-prostate-cancer-combined-with-wst-11-vascular-targeted-photodynamic-therapy
#8
Kwanghee Kim, Hanwen Zhang, Stephen LaRosa, Sylvia Jebiwott, Pooja Desai, Simon Y Kimm, Avigdor J Scherz, Joseph A O'Donoghue, Wolfgang A Weber, Jonathan Coleman
PURPOSE: DOTA-AR, a bombesin-antagonist peptide, has potential clinical application for targeted imaging and therapy in Gastrin Releasing Peptide receptor (GRPr) positive malignancies when conjugated with a radioisotope such as 90Y. This therapeutic potential is limited by the fast washout of the conjugates from the target tumors. WST-11 (Weizmann STeba-11 drug; a negatively charged water-soluble palladium-bacteriochlorophyll derivative, Tookad® Soluble) Vascular targeted photodynamic therapy (VTP) is a local ablation approach recently approved for use in early stage prostate cancer...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108509/differential-pi3k%C3%AE-signaling-in-cd4-t-cell-subsets-enables-selective-targeting-of-t-regulatory-cells-to-enhance-cancer-immunotherapy
#9
Samir N Khleif, Shamim Ahmad, Rasha Abu Eid, Rajeev K Shrimali, Mason Webb, Vivek Verma, Atbin Doroodchi, Zuzana Berrong, Raed N Samara, Paulo C Rodriguez, Mikayel Mkrtichyan
To modulate T cell function for cancer therapy one challenge is to selectively attenuate regulatory but not conventional CD4+ T cell subsets (Treg and Tconv). In this study we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control TCR signaling, cell proliferation and survival...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107190/radiosynthesis-and-validation-of-%C3%A2-18f-3-fluoro-2-hydroxypropionate-18f-flac-as-a-pet-tracer-of-lactate-to-monitor-mct1-dependent-lactate-uptake-in-tumors
#10
Vincent F Van Hée, Daniel Labar, Gwenaël Dehon, Debora Grasso, Vincent Grégoire, Giulio G Muccioli, Raphaël Frédérick, Pierre Sonveaux
Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107186/the-combination-of-pd-l1-expression-and-decreased-tumor-infiltrating-lymphocytes-is-associated-with-a-poor-prognosis-in-triple-negative-breast-cancer
#11
Hitomi Mori, Makoto Kubo, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107044/quercetin-attenuates-cell-survival-inflammation-and-angiogenesis-via-modulation-of-akt-signaling-in-murine-t-cell-lymphoma
#12
Akhilendra Kumar Maurya, Manjula Vinayak
AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice...
January 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28106365/coordinatively-self-assembled-luminescent-gold-nanoparticles-fluorescence-turn-on-system-for-high-efficiency-passive-tumor-imaging
#13
Xuandi Lai, Lishan Tan, Xiulong Deng, Jinbin Liu, Aiqing Li, Jianyu Liu, Jianqiang Hu
A fluorescence turn-on system for highly efficient and prolonged tumor imaging has been established by Co2+-induced coordination self-assembly strategy, in which luminescent glutathione (GSH)-modified gold nanoparticles (LGAuNPs) are assembled into LGAuNPs assemblies (LGAuNPs-Co) through coordination bond between unoccupied orbit of Co2+ and lone pair electrons of GSH on the surface of LGAuNPs. The LGAuNPs-Co is sensitive to microenvironment pH and its quenched luminescence will be turned on in tumor tissues (acidic microenvironment), which behaves as a fluorescence turn-on system for passive tumor imaging...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28106295/macrophage-polarization-anti-cancer-strategies-to-target-tumor-associated-macrophage-in-breast-cancer
#14
Muhammad Tariq, Jieqiong Zhang, Guikai Liang, Ling Ding, Qiaojun He, Bo Yang
Tumor-associated macrophages (TAMs) are the most abundant inflammatory cells and orchestrate different stages of breast cancer development. TAMs participate in the tumor angiogenesis, matrix remodeling, invasion, immunosuppression, metastasis, and chemoresistance in breast cancer. Several clinical studies indicate the association between the high influx of TAMs in tumor with poor prognosis in hepatocellular, ovarian, cervical, and breast cancer. Previously developed hypotheses have proposed that TAMs participate in antitumor responses of the body, while recently many clinical and experimental studies have revealed that TAMs in tumor microenvironment predominantly resemble with M2-like polarized macrophages and produce a high amount of anti-inflammatory factors which are directly responsible for the development of tumor...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#15
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#16
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105368/clinical-and-immunologic-correlates-of-response-to-pd-1-blockade-in-a-patient-with-metastatic-renal-medullary-carcinoma
#17
Kathryn E Beckermann, Pradeep C Jolly, Ju Y Kim, Jennifer Bordeaux, Igor Puzanov, W Kimryn Rathmell, Douglas B Johnson
BACKGROUND: Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28104913/exosome-derived-micrornas-in-cancer-metabolism-possible-implications-in-cancer-diagnostics-and-therapy
#18
REVIEW
Marco Tomasetti, Wan Lee, Lory Santarelli, Jiri Neuzil
Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104684/broad-and-conserved-immune-regulation-by-genetically-heterogeneous-melanoma-cells
#19
Natalie J Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A Fuertes Marraco, Daniel E Speiser
While mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to cytotoxic T lymphocyte (CTL)-based immunotherapy. Here we studied the reactions of malignant and benign melanocyte lines to CTL using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations and similar in benign and malignant cells...
January 19, 2017: Cancer Research
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
#20
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
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