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https://www.readbyqxmd.com/read/28647611/autophagy-suppresses-isoprenaline-induced-m2-macrophage-polarization-via-the-ros-erk-and-mtor-signaling-pathway
#1
Meihua Shan, Junfang Qin, Fengjiao Jin, Xiao Han, Haitao Guan, Xiaoge Li, Jiahui Zhang, Hongyao Zhang, Yue Wang
The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant. Similarly, the polarization of RAW 264.7 to M2 macrophages was inhibited by the autophagy inducer rapamycin and increased by the autophagy inhibitor 3-MA or by siBeclin1...
June 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28647610/the-jak-stat3-axis-a-comprehensive-drug-target-for-solid-malignancies
#2
REVIEW
Jennifer Huynh, Nima Etemadi, Frédéric Hollande, Matthias Ernst, Michael Buchert
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families...
June 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28646444/engineering-3d-models-of-tumors-and-bone-to-understand-tumor-induced-bone-disease-and-improve-treatments
#3
REVIEW
Kristin A Kwakwa, Joseph P Vanderburgh, Scott A Guelcher, Julie A Sterling
PURPOSE OF REVIEW: Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. RECENT FINDINGS: 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment...
June 23, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28646022/nf1-hematopoietic-cells-accelerate-malignant-peripheral-nerve-sheath-tumor-development-without-altering-chemotherapy-response
#4
Rebecca D Dodd, Chang-Lung Lee, Tess Overton, Wesley Huang, William C Eward, Lixia Luo, Yan Ma, Davis R Ingram, Keila E Torres, Diana M Cardona, Alexander Lazar, David G Kirsch
Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of type 1 neurofibromatosis, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645939/combined-btk-and-pi3k%C3%AE-inhibition-with-acalabrutinib-and-acp-319-improves-survival-and-tumor-control-in-cll-mouse-model
#5
Carsten U Niemann, Helena I Mora-Jensen, Eman L Dadashian, Fanny Krantz, Todd Covey, Shih-Shih Chen, Nicholas- Chiorazzi, Raquel Izumi, Roger Ulrich, Brian J Lannutti, Adrian Wiestner, Sarah E M Herman
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645612/il-1%C3%AE-induced-methylation-of-the-estrogen-receptor-er%C3%AE-gene-correlates-with-emt-and-chemoresistance-in-breast-cancer-cells
#6
Aura M Jiménez-Garduño, Mónica G Mendoza-Rodríguez, Daniel Urrutia-Cabrera, María C Domínguez-Robles, Eloy A Pérez-Yépez, Jorge Tonatiuh Ayala-Sumuano, Isaura Meza
Inflammation has been recently acknowledged as a key participant in the physiopathology of oncogenesis and tumor progression. The inflammatory cytokine IL-1β has been reported to induce the expression of markers associated with malignancy in breast cancerous cells through Epithelial-Mesenchymal Transition (EMT). Aggressive breast cancer tumors classified as Triple Negative do not respond to hormonal treatment because they lack three crucial receptors, one of which is the estrogen receptor alpha (ERα). Expression of ERα is then considered a good prognostic marker for tamoxifen treatment of this type of cancer, as the binding of this drug to the receptor blocks the transcriptional activity of the latter...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645290/establishment-of-an-orthotopic-patient-derived-xenograft-mouse-model-using-uveal-melanoma-hepatic-metastasis
#7
Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Michael J Mastrangelo, Paolo Fortina, Andrew E Aplin, Takami Sato
BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment...
June 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28644558/current-understanding-of-cancer-stem-cells-review-of-their-radiobiology-and-role-in-head-and-neck-cancers
#8
REVIEW
Paul Ambrose Reid, Puthenparampil Wilson, Yanrui Li, Loredana Gabriela Marcu, Eva Bezak
Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose...
June 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#9
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28644032/receptor-and-microenvironment-dual-recognizable-nanogel-for-targeted-chemotherapy-of-highly-metastatic-malignancy
#10
Jinjin Chen, Jianxun Ding, Weiguo Xu, Tianmeng Sun, Haihua Xiao, Xiuli Zhuang, Xuesi Chen
Targeted delivery of chemotherapeutic drugs to the desired lesion sites is the main objective in malignancy treatment, especially in highly metastatic malignancies. However, extensive studies around the world on traditional targeting strategies of recognizing either over-expressed receptors or microenvironments in tumors show great limitations, owing to the off-target effect and tumor homogeneity. Integration of both receptor-mediated targeting (RMT) and environment-mediated targeting (EMT) enhances the tumor accumulation and subsequent cell uptake at the same time, which may avoid these limitations...
June 23, 2017: Nano Letters
https://www.readbyqxmd.com/read/28643902/modulation-of-antitumor-immunity-contributes-to-the-enhanced-therapeutic-efficacy-of-liposomal-oxaliplatin-in-mouse-model
#11
Taro Shimizu, Amr S Abu Lila, Miho Nishio, Yusuke Doi, Hidenori Ando, Masami Ukawa, Yu Ishima, Tatsuhiro Ishida
Immune modulation of the tumor microenvironment has been reported to participate to the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l-OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l-OHP in murine colorectal carcinoma-bearing mice via permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune-modulatory properties of liposomal l-OHP and/or free l-OHP to the overall antitumor efficacy was not elucidated...
June 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28643452/emerging-nanotechnology-and-advanced-materials-for-cancer-radiation-therapy
#12
REVIEW
Guosheng Song, Liang Cheng, Yu Chao, Kai Yang, Zhuang Liu
Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages...
June 23, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#13
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#14
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28642882/tumor-related-exosomes-contribute-to-tumor-promoting-microenvironment-an-immunological-perspective
#15
REVIEW
Wuzhen Chen, Jingxin Jiang, Wenjie Xia, Jian Huang
Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28642128/immunomodulation-of-parkinson-s-disease-using-mucuna-pruriens-mp
#16
REVIEW
Sachchida Nand Rai, Hareram Birla, Walia Zahra, Saumitra Sen Singh, Surya Pratap Singh
Immune control is associated with nigrostriatal neuroprotection for Parkinson's disease (PD); though its direct cause and effect relationships have not yet been realized and modulating the immune system for therapeutic gain has been openly discussed. While the pathobiology of PD remains in study, neuroinflammation is thought to speed nigrostriatal degeneration. The neuroinflammatory cascade associated with PD begins with aggregation of misfolded or post-translationally modified α-synuclein (α-syn). Such aggregation results in neuronal cell death and the presence of chronically activated glia (microglia and astroglia), leading to the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cyclooxygenase-2 (COX-2)...
June 19, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28642033/atg4b-inhibitors-with-a-benzotropolone-core-structure-block-autophagy-and-augment-efficiency-of-chemotherapy-in-mice
#17
Ammar Kurdi, Matthias Cleenewerck, Christel Vangestel, Sophie Lyssens, Wim Declercq, Jean-Pierre Timmermans, Sigrid Stroobants, Koen Augustyns, Guido R Y De Meyer, Pieter Van Der Veken, Wim Martinet
Autophagy is a cell survival mechanism hijacked by advanced tumors to endure a rough microenvironment. Late autophagy inhibitors such as (hydroxy)chloroquine have been used clinically to halt tumor progression with modest success. However, given the toxic nature of these compounds and their lack of specificity, novel targets should be considered. We recently identified a benzotropolone derivative that significantly inhibited the essential autophagy protein ATG4B. Therefore, we synthesized and tested additional benzotropolone compounds to identify a promising ATG4B inhibitor that impairs autophagy both in vitro and in vivo...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641473/co-targeting-intracellular-ph-and-essential-amino-acid-uptake-cooperates-to-induce-cell-death-of-t-all-ll-cells
#18
Véronique Imbert, Marielle Nebout, Didier Mary, Hitoshi Endou, Michael F Wempe, Claudiu T Supuran, Jean-Yves Winum, Jean-François Peyron
Cancer cells reprogram their metabolism to optimize their growth and proliferation in the host microenvironment. For this purpose, they enhance the uptake of extracellular nutrients and deal with the metabolic waste products through the overexpression of numerous membrane proteins including amino-acid transporters (LAT1) and acid-base regulating enzymes, such as carbonic anhydrases (CAs). Here we describe the anti-tumoral effects of a new class of CAXII inhibitors, the glycosyl coumarins on T-ALL/LL cells. These effects appeared to be mediated through inhibition of mTOR/Akt pathway and c-myc downregulation...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#19
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28640929/modulation-of-tumor-microenvironment-by-chemopreventive-natural-products
#20
REVIEW
Sin-Aye Park, Young-Joon Surh
The tumor microenvironment provides a niche in which cancer cells and their surrounding stromal cells reside and in which their interactions occur. The cross talk between cancer and stromal cells in the tumor microenvironment promotes many biological processes to support cancer cell growth, invasion, angiogenesis, and metastasis. Recently, not only cancer cells but also multiple types of surrounding stromal cells, including endothelial cells, immune cells, and fibroblasts in the tumor microenvironment, have been recognized to be attractive targets for reducing resistance to anticancer therapy and tumor recurrence...
June 22, 2017: Annals of the New York Academy of Sciences
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