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Tumor microenvironent

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https://www.readbyqxmd.com/read/28545187/enterolactone-suppresses-proliferation-migration-and-metastasis-of-mda-mb-231-breast-cancer-cells-through-inhibition-of-upa-induced-plasmin-activation-and-mmps-mediated-ecm-remodeling
#1
Aniket V Mali, Asavari A Joshi, Mahabaleshwar V Hegde, Shivajirao S Kadam
Background: To enhance their own survival, tumor cells can manipulate their microenvironment through remodeling of the extra cellular matrix (ECM). The urokinase-type plasminogen activator (uPA) system catalyzes plasmin production which further mediates activation of matrix metalloproteinases (MMPs) and plays an important role in breast cancer invasion and metastasis through ECM remodeling. This provides a potential target for therapeutic intervention of breast cancer treatment. Enterolactone (EL) is derived from dietary flax lignans in the human body and is known to have anti-breast cancer activity...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28544932/vascular-homing-peptides-for-cancer-therapy
#2
REVIEW
Lan Lu, Huan Qi, Jie Zhu, Wen Xia Sun, Bin Zhang, Chun Yan Tang, Qiang Cheng
In the past 30 years, a variety of phage libraries have been extensively utilized to identify and develop tumor homing peptides (THPs). THPs specifically bind to tumor cells or elements of the tumor microenvironment while no or low affinity to normal cells. In this regard, the efficacy of therapeutic agents in cancer therapy can be enhanced by targeting strategies based on coupling with THPs that recognize receptors expressed by tumor cells or tumor vasculature. Especially, vascular-homing peptides, targeting tumor vasculature, have their receptors expressed on or around the blood vessel including pro-angiogenic factors, metalloproteinase, integrins, fibrin-fibronectin complexes, etc...
May 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28544647/dual-cross-linked-biofunctional-and-self-healing-networks-to-generate-user-defined-modular-gradient-hydrogel-constructs
#3
Zhao Wei, Daniel M Lewis, Yu Xu, Sharon Gerecht
Gradient hydrogels have been developed to mimic the spatiotemporal differences of multiple gradient cues in tissues. Current approaches used to generate such hydrogels are restricted to a single gradient shape and distribution. Here, a hydrogel is designed that includes two chemical cross-linking networks, biofunctional, and self-healing networks, enabling the customizable formation of modular gradient hydrogel construct with various gradient distributions and flexible shapes. The biofunctional networks are formed via Michael addition between the acrylates of oxidized acrylated hyaluronic acid (OAHA) and the dithiol of matrix metalloproteinase (MMP)-sensitive cross-linker and RGD peptides...
May 23, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544639/biomimetic-model-of-tumor-microenvironment-on-microfluidic-platform
#4
Minhwan Chung, Jungho Ahn, Kyungmin Son, Sudong Kim, Noo Li Jeon
The "Tumor microenvironment" (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in-depth research into the TME. Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner...
May 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544324/albumin-templated-manganese-dioxide-nanoparticles-for-enhanced-radioisotope-therapy
#5
Longlong Tian, Qian Chen, Xuan Yi, Jiawen Chen, Chao Liang, Yu Chao, Kai Yang, Zhuang Liu
Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide (131) I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles ((131) I-HSA-MnO2 ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME)...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28543663/lncrna-malat1-promotes-angiogenesis-of-thyroid-cancer-by-modulating-tumor-associated-macrophage-fgf2-protein-secretion
#6
Jian-Kang Huang, Wen-Hua Song, Bang-Yu Lu, Yu-Bin Huang, Hui-Ming Dong, Xiao-Kai Ma, Zheng-Zhi Zhu, Rui Zhou, Ling Ma
OBJECTIVE: Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. METHODS: The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543514/angioimmunoblastic-t-cell-lymphoma-more-than-a-disease-of-t-follicular-helper-cells
#7
François Lemonnier, Tak W Mak
Angioimmunoblastic T cell lymphoma (AITL) is one of the most frequent entities of peripheral T cell lymphoma. An AITL has two components: the AITL tumor cells that have a T follicular helper (TFH) cell phenotype, and a surrounding and extensive tumor microenvironment that is populated with various reactive cell types, including B cells. Recurrent TET2 mutations have been described in 50-80% of AITLs, possibly occurring in a hematopoietic progenitor cell. An article published recently in The Journal of Pathology describes the use of microdissection to isolate PD1(+) AITL tumor cells and CD20(+) B cells from the AITL microenvironment and to show that TET2 mutations are actually more frequent in these diseases than previously thought...
May 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28543176/regional-immunotherapy-for-liver-and-peritoneal-metastases
#8
REVIEW
Jeffrey Reha, Steven C Katz
Pancreatic adenocarcinoma is a biologically aggressive disease, with liver and peritoneal metastases being a frequent cause of death. We examine how the pancreatic carcinoma microenvironment and immunosuppressive landscape favor tumor progression. Immunotherapy has shown promise in select solid tumors, yet challenges remain in applying these gains to stage IV pancreatic adenocarcinoma. We discuss how regional therapy strategies may be leveraged to open new avenues for treating pancreatic carcinoma metastases with immunotherapy...
May 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28542126/human-mscs-promotes-colorectal-cancer-epithelial-mesenchymal-transition-and-progression-via-ccl5-%C3%AE-catenin-slug-pathway
#9
Ke Chen, Qianqian Liu, Lai Ling Tsang, Qiao Ye, Hsiao Chang Chan, Yunwei Sun, Xiaohua Jiang
Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) progression and metastasis is controversial. This study was designed to identify the role of inflammation-activated-MSCs in CRC development. Our results show that tumor necrosis factor (TNF)-α-preactivated-hMSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial-mesenchymal transition, migration, and invasion...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541485/histologically-defined-intratumoral-sequencing-uncovers-evolutionary-cues-into-conserved-molecular-events-driving-gliomagenesis
#10
Antony Prabhu, Pravin Kesarwani, Shiva Kant, Stewart F Graham, Prakash Chinnaiyan
BACKGROUND: Glioblastoma represents an archetypal example of a heterogeneous malignancy. To understand the diverse molecular consequences of this complex tumor ecology, we analyzed RNA-seq data generated from commonly identified intra-tumoral structures in glioblastoma enriched using laser capture microdissection. METHODS: Raw gene-level fragments per kilobase of transcript per million reads mapped (FPKM) values and the associated clinical data were acquired from the publically available Ivy GAP database and analyzed using MetaboAnalyst (v...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28541444/blood-brain-barrier-pericyte-importance-in-malignant-gliomas-what-we-can-learn-from-stroke-and-alzheimer-s-disease
#11
Sadhana Jackson, Ayman ElAli, Daniela Virgintino, Mark R Gilbert
The pericyte, a constitutive component of the central nervous system, is a poorly understood cell type that envelops the endothelial cell with the intended purpose of regulating vascular flow and endothelial cell permeability. Previous studies of pericyte function have been limited to a small number of disease processes such as ischemic stroke and Alzheimer's disease. Recently, publications have postulated a link between glioma stem cell differentiation and pericyte function. These studies suggest that there may be an important interaction of pericytes with tumor cells and other components of the tumor microenvironment in malignant primary glial neoplasms, most notably glioblastoma...
May 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28540417/monitoring-early-response-to-chemoradiotherapy-with-18-f-fmiso-dynamic-pet-in-head-and-neck-cancer
#12
Milan Grkovski, Nancy Y Lee, Heiko Schöder, Sean D Carlin, Bradley J Beattie, Nadeem Riaz, Jonathan E Leeman, Joseph A O'Donoghue, John L Humm
PURPOSE: There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of (18)F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC. EXPERIMENTAL DESIGN: Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy...
May 24, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28539557/prospects-for-personalized-combination-immunotherapy-for-solid-tumors-based-on-adoptive-cell-therapies-and-immune-checkpoint-blockade-therapies
#13
Daiki Kato, Tomonori Yaguchi, Takashi Iwata, Kenji Morii, Takayuki Nakagawa, Ryohei Nishimura, Yutaka Kawakami
  Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539475/the-brain-microenvironment-mediates-resistance-in-luminal-breast-cancer-to-pi3k-inhibition-through-her3-activation
#14
David P Kodack, Vasileios Askoxylakis, Gino B Ferraro, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Z Alexander Cao, Rakesh R Ramjiawan, Divya Bezwada, Bhushankumar Patel, Yongchul Song, Carlotta Costa, Kamila Naxerova, Christina S F Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G Duda, C Ryan Miller, Marni B Siegel, Carey K Anders, Melinda Sanders, Monica V Estrada, Robert Schlegel, Carlos L Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A Engelman, Rakesh K Jain
Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539271/gene-expression-profiling-of-tumor-associated-macrophages-after-exposure-to-single-dose-irradiation
#15
Wei-Hsiang Kung, Ching-Fang Yu, Andy Chi-Lung Lee, Chi-Dung Yang, Yu-Chen Liu, Fang-Hsin Chen, Hsien-Da Huang
Radiotherapy (RT) is a common cancer treatment approach that accounts for nearly 50% of patient treatment; however, tumor relapse after radiotherapy is still a major issue. To study the crucial role of tumor-associated macrophages (TAMs) in the regulation of tumor progression post-RT, microarray experiments comparing TAM gene expression profiles between unirradiated and irradiated tumors were conducted to discover possible roles of TAMs in initiation or contribution to tumor recurrence following RT, taking into account the relationships among gene expression, tumor microenvironment, and immunology...
April 30, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28539161/single-cell-rna-seq-unveils-tumor-microenvironment
#16
Hae-Ock Lee, Woong-Yang Park
Single cell transcriptome analysis became an essential tool to define cell types or sub-populations within a heterogeneous bulk population. Tumor-associated microenvironment is a complex ecosystem with numerous cell types, supporting the tumor growth, angiogenesis, immune evasion, and metastasis. With the success of checkpoint inhibitors targeting the immune cell compartment, tumor microenvironment is an emerging anti-cancer target and its understanding becomes an imminent issue in the cancer biology.
May 25, 2017: BMB Reports
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#17
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#18
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#19
REVIEW
Nathalie Dehne, Javier Mora, Dmitry Namgaladze, Andreas Weigert, Bernhard Brüne
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming...
May 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28537908/increased-expression-of-irf8-in-tumor-cells-inhibits-the-generation-of-th17-cells-and-predicts-unfavorable-survival-of-diffuse-large-b-cell-lymphoma-patients
#20
Weijie Zhong, Xin Xu, Zhigang Zhu, Qinghua Du, Hong Du, Li Yang, Yanying Ling, Huabao Xiong, Qingshan Li
The immunological pathogenesis of diffuse large B cell lymphoma (DLBCL) remains elusive. Searching for new prognostic markers of DLBCL is a crucial focal point for clinical scientists. The aim of the present study was to examine the prognostic value of interferon regulatory factor 8 (IRF8) expression and its effect on the development of Th17 cells in the tumor microenvironment of DLBCL patients. Flow cytometry, immunohistochemistry, and quantitative real-time PCR were used to detect the distribution of Th17 cells and related cytokines and IRF8 in tumor tissues from DLBCL patients...
May 8, 2017: Oncotarget
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