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Cancer microenvironment

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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323572/bilateral-changes-in-deep-tissue-environment-after-manual-lymphatic-drainage-in-patients-with-breast-cancer-treatment-related-lymphedema
#2
Paula M C Donahue, Rachelle Crescenzi, Allison O Scott, Vaughn Braxton, Aditi Desai, Seth A Smith, John Jordi, Ingrid M Meszoely, Ana M Grau, Rondi M Kauffmann, Raeshell S Sweeting, Kandace Spotanski, Sheila H Ridner, Manus J Donahue
BACKGROUND: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD)...
March 2017: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/28323500/strategies-to-target-glucose-metabolism-in-tumor-microenvironment-on-cancer-by-flavonoids
#3
Gang Wang, Jun-Jie Wang, Rui Guan, Li Du, Jing Gao, Xing-Li Fu
The imbalance between glucose metabolism and cancer cell growth in tumor microenvironment (TME), which are closely related with the occurrence and progression of cancer. Accumulating evidence has demonstrated that flavonoids exert many biological properties, including antioxidant and anticarcinogenic activities. Recently, the roles and applications of flavonoids, particularly in relation to glucose metabolism in cancers, have been highlighted. Thus, the identification of flavonoids targeting alternative glucose metabolism pathways in TME may represent an attractive approach to the more effective therapeutic strategies for cancer...
March 21, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28319647/cancer-specific-intracellular-reductive-activation-of-anticancer-pt-iv-prodrugs
#4
Andriy Mokhir, Viktor Reshetnikov, Steffen Daum
Since cellular uptake of anticancer Pt(II)- and Pt(IV)-drugs occurs via different mechanisms, the latter ones can exhibit substantial activity towards cells, which have either intrinsic or acquired resistance towards Pt(II)-drugs. However, this positive effect is diminished due to reductive activation of Pt(IV)-drugs in extracellular space that can be one of the reasons why they were not yet approved for clinical use despite over 60 clinical trials conducted worldwide. Herein we suggest a solution to this problem by achieving highly specific intracellular versus extracellular prodrug reduction...
March 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28319088/reference-component-analysis-of-single-cell-transcriptomes-elucidates-cellular-heterogeneity-in-human-colorectal-tumors
#5
Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs)...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28318896/role-of-ahr-and-hif-1%C3%AE-in-glioblastoma-metabolism
#6
REVIEW
Galina Gabriely, Michael A Wheeler, Maisa C Takenaka, Francisco J Quintana
Glioblastoma (GBM) progression is associated with metabolic remodeling in both glioma and immune cells, resulting in the use of aerobic glycolysis as the main source of energy and biosynthetic molecules. The transcription factor hypoxia-inducible factor (HIF)-1α drives this metabolic reorganization. Oxygen levels, as well as other factors, control the activity of HIF-1α. In addition, the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) modulates tumor-specific immunity and can also participate in metabolic remodeling...
March 16, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#7
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28317401/biological-implications-and-clinical-value-of-mir-210-in-gastrointestinal-cancer
#8
Wanli Yang, Jiaojiao Ma, Wei Zhou, Xin Zhou, Bo Cao, Daiming Fan, Liu Hong
Introduction Hypoxia, a common feature of tumor microenvironment, is known to accelerate tumor development and growth by promoting the formation of a neoplastic environment. Recent studies have provided a wealth of evidence that miRNAs are significant members of the adaptive response to low oxygen in tumors. miR-210 is one of the hypoxia-induced miRNAs, which has been reported extensively in cancer researches. However, there is no systematic discussion about the role of miR-210 in gastrointestinal cancer. We conducted a literature research in database including PubMed, Elsevier Science Direct and Medline before September 16, 2016, in order to collect articles of miR-210 in gastrointestinal cancer...
March 18, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28317128/comparison-of-dce-mri-kinetic-parameters-and-fmiso-pet-uptake-parameters-in-head-and-neck-cancer-patients
#9
Urban Simoncic, Sara Leibfarth, Stefan Welz, Nina Schwenzer, Holger Schmidt, Gerald Reischl, Christina Pfannenberg, Christian la Fougère, Konstantin Nikolaou, Daniel Zips, Daniela Thorwarth
PURPOSE: Tumour hypoxia is a major cause of radiation resistance, often present in various solid tumours. Dynamic [(18) F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumour hypoxia. Comprehensive characterization of tumour microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters...
March 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#10
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28315938/the-relationship-between-breast-cancer-molecular-subtypes-and-mast-cell-populations-in-tumor-microenvironment
#11
Anna Glajcar, Joanna Szpor, Agnieszka Pacek, Katarzyna Ewa Tyrak, Florence Chan, Joanna Streb, Diana Hodorowicz-Zaniewska, Krzysztof Okoń
Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples...
March 18, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28315495/legumain-cleavable-4-arm-poly-ethylene-glycol-doxorubicin-conjugate-for-tumor-specific-delivery-and-release
#12
Huicong Zhou, Huanjiao Sun, Shixian Lv, Dawei Zhang, Xuefei Zhang, Zhaohui Tang, Xuesi Chen
Traditional chemotherapy strategy exists undesirable toxic side-effects to normal tissues due to the low selectively to cancer cells of micromolecule cytotoxic drugs. One considered method to realizing the targeted delivery and increasing the specificity to tumor tissues of the cytotoxic drug is to transporting and discharging it through an environment-sensitive mechanism. In this study, a novel enzyme-sensitive polymer-doxorubicin conjugate was designed to delivery chemotherapeutic drug in a tumor-specific behavior and selectively activated in tumor tissue...
March 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28315265/sigma-1-receptor-and-ion-channel-dynamics-in-cancer
#13
Olivier Soriani, Raphaël Rapetti-Mauss
SigmaR1 is a multitasking chaperone protein which has mainly been studied in CNS physiological and pathophysiological processes such as pain, memory, neurodegenerative diseases (amyotrophic lateral sclerosis , Parkinson's and Alzheimer's diseases, retinal neurodegeneration ), stroke and addiction . Strikingly, G-protein and ion channels are the main client protein fami lies of this atypical chaperone and the recent advances that have been performed for the last 10 years demonstrate that SigmaR1 is principally activated following tissue injury and disease development to promote cell survival...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315254/live-cell-imaging-of-protease-activity-assays-to-screen-therapeutic-approaches
#14
Anita Chalasani, Kyungmin Ji, Mansoureh Sameni, Samia H Mazumder, Yong Xu, Kamiar Moin, Bonnie F Sloane
Methodologies to image and quantify the activity of proteolytic enzymes have been developed in an effort to identify protease-related druggable pathways that are involved in malignant progression of cancer. Our laboratory has pioneered techniques for functional live-cell imaging of protease activity in pathomimetic avatars for breast cancer. We analyze proteolysis in the context of proliferation and formation of structures by tumor cells in 3-D cultures over time (4D). In order to recapitulate the cellular composition and architecture of tumors in the pathomimetic avatars, we include other tumor-associated cells (e...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315070/mechanisms-of-resistance-in-multiple-myeloma
#15
Athanasios Papadas, Fotis Asimakopoulos
Multiple myeloma (MM) is an incurable hematopoietic cancer that is characterized by malignant plasma cell infiltration of the bone marrow and/or extramedullary sites. Multi-modality approaches including "novel agents," traditional chemotherapy, and/or stem cell transplantation are used in MM therapy. Drug resistance, however, ultimately develops and the disease remains incurable for the vast majority of patients. In this chapter, we review both tumor cell-autonomous and non-autonomous (microenvironment-dependent) mechanisms of drug resistance...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28314844/abituzumab-targeting-of-alphav-class-integrins-inhibits-prostate-cancer-progression
#16
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt and ERK were determined...
March 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28314212/gene-delivery-of-tipe2-inhibits-breast-cancer-development-and-metastasis-via-cd8-t-and-nk-cell-mediated-antitumor-responses
#17
Zhenhua Zhang, Li Liu, Shousong Cao, Yizhun Zhu, Qibing Mei
Breast cancer is the second leading cause of cancer-related deaths in the female patients which was mainly caused by metastasis. Development of target gene therapy for breast cancer to suppress tumor progress and metastasis will improve the therapeutic options and be of great benefit to the patients. Tumor necrosis factor-alpha-induced protein 8-like 2 is a novel molecule for maintaining immune homeostasis and is involved in cancer development. In the present study, we overexpressed TIPE2 in breast cancer cells to investigate the role of TIPE2 in the development of breast cancer...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28306507/structural-and-molecular-mechanisms-of-cytokine-mediated-endocrine-resistance-in-human-breast-cancer-cells
#18
Joshua D Stender, Jerome C Nwachukwu, Irida Kastrati, Yohan Kim, Tobias Strid, Maayan Yakir, Sathish Srinivasan, Jason Nowak, Tina Izard, Erumbi S Rangarajan, Kathryn E Carlson, John A Katzenellenbogen, Xin-Qiu Yao, Barry J Grant, Hon S Leong, Chin-Yo Lin, Jonna Frasor, Kendall W Nettles, Christopher K Glass
Human breast cancers that exhibit high proportions of immune cells and elevated levels of pro-inflammatory cytokines predict poor prognosis. Here, we demonstrate that treatment of human MCF-7 breast cancer cells with pro-inflammatory cytokines results in ERα-dependent activation of gene expression and proliferation, in the absence of ligand or presence of 4OH-tamoxifen (TOT). Cytokine activation of ERα and endocrine resistance is dependent on phosphorylation of ERα at S305 in the hinge domain. Phosphorylation of S305 by IKKβ establishes an ERα cistrome that substantially overlaps with the estradiol (E2)-dependent ERα cistrome...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28304339/the-five-immune-forces-impacting-dna-based-cancer-immunotherapeutic-strategy
#19
REVIEW
Suneetha Amara, Venkataswarup Tiriveedhi
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28303973/e6-e7-p53-pou2f1-cthrc1-axis-promotes-cervical-cancer-metastasis-and-activates-wnt-pcp-pathway
#20
Rong Zhang, Huan Lu, Yuan-Yuan Lyu, Xiao-Mei Yang, Lin-Yan Zhu, Guang-Dong Yang, Peng-Cheng Jiang, Yuan Re, Wei-Wei Song, Jin-Hao Wang, Can-Can Zhang, Fei Gu, Tian-Jiao Luo, Zhi-Yong Wu, Cong-Jian Xu
Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters...
March 17, 2017: Scientific Reports
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