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Cancer microenvironment

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https://www.readbyqxmd.com/read/28231588/checkpoint-inhibition-in-head-and-neck-cancer-immune-therapeutic-options-limitations-and-beyond
#1
Bastian Höchst, Percy A Knolle
The immune system functions to defend the organism against infectious microorganisms but also against transformed cells. This key role of the immune system, in particular cancer-specific T cells, in eliminating cancer cells is compromised by various immune escape strategies employed by cancer cells and the cancer microenvironment. Here, we review the current knowledge about the immune escape mechanisms of cancer and the attempts to reconstitute cancer-specific immunity by using checkpoint inhibitors in head and neck squamous cell carcinoma...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28231431/enhancing-adoptive-cell-therapy-of-cancer-through-targeted-delivery-of-small-molecule-immunomodulators-to-internalizing-or-non-internalizing-receptors
#2
Yiran Zheng, Li Tang, Llian Mabardi, Sudha Kumari, Darrell J Irvine
Adoptive cell therapy (ACT) has achieved striking efficacy in B-cell leukemias, but less success treating other cancers, in part due to the rapid loss of ACT T-cell effector function in vivo due to immunosuppression in solid tumors. Transforming growth factor-β (TGF-β) signaling is an important mechanism of immune suppression in the tumor microenvironment, but systemic inhibition of TGF-β is toxic. Here we evaluated the potential of targeting a small molecule inhibitor of TGF-β to ACT T-cells using PEGylated immunoliposomes...
February 23, 2017: ACS Nano
https://www.readbyqxmd.com/read/28229976/immune-modulation-by-dendritic-cell-based-cancer-vaccines
#3
Chaitanya Kumar, Sakshi Kohli, Poonamalle Parthasarathy Bapsy, Ashok Kumar Vaid, Minish Jain, Venkata Sathya Suresh Attili, Bandana Sharan
The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells by modulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing the recombinant human immune system components to target the pro-tumour microenvironment or by revitalizing the immune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review, current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines are discussed...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229276/effects-of-chlorella-vulgaris-on-tumor-growth-in-mammary-tumor-bearing-balb-c-mice-discussing-association-of-an-immune-suppressed-protumor-microenvironment-with-serum-ifn%C3%AE-and-igg-decrease-and-spleen-igg-potentiation
#4
Ahad Khalilnezhad, Elham Mahmoudian, Nariman Mosaffa, Ali Anissian, Mohsen Rashidi, Davar Amani
PURPOSE: Chlorella vulgaris (CV) has exhibited immune-enhancing and protective activities against cancer and infections. However, there is an increasing concern about the use of Chlorella species in human, regarding its various molecules with antigenic features found in infectious microorganisms. Our goal was to investigate the impact of higher concentrations of CV on tumor growth in spontaneous mouse mammary tumor (SMMT) models. METHODS: Balb/c mice were daily given CV powder at doses of 0, 200, or 300 mg/kg for 42 days (CONTROL, CV200, and CV300 groups, respectively; n = 6/group)...
February 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28229217/foxo3-estrogen-receptor-alpha-and-androgen-receptor-impact-tumor-growth-rate-and-infiltration-of-dendritic-cell-subsets-differentially-between-male-and-female-mice
#5
Matthew G Thompson, Daniel S Peiffer, Michelle Larson, Flor Navarro, Stephanie K Watkins
Tumors evade immune recognition and destruction in many ways including the creation of an immune-suppressive tumor microenvironment (TME). Dendritic cells (DC) that infiltrate the TME are tolerogenic, and suppress effector T cells and anti-tumor activity. Previous reports demonstrated that a key regulator of tolerance in DC is the transcription factor FOXO3. Gender disparity has been studied in cancer in relation to incidence, aggressiveness, and prognosis. Few studies have touched on the importance in relation to impact on the immune system...
February 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28228541/cell-dynamics-in-tumour-environment-after-treatments
#6
Leili Shahriyari
Most cancer treatments cause necrotic cell deaths in the tumour microenvironment. Necrotic cells send signals to immune cells to start the wound healing process in the tissue. Therefore, we assume after stopping treatments there is a wound that needs to be healed. We develop a simple computational model to investigate cell dynamics during the wound healing process after treatments. The model predicts that the involvement of high-fitness cancer cells in the wound healing leads to fast relapse, and cancer cells outside of the wound can cause a slow recurrence of the tumour...
February 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28227912/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#7
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giannis Zacharakis, Vangelis Sakkalis, Evangelos Liapis, Giorgos Tzedakis, Eleftheria Tzamali
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227910/development-of-a-three-dimensional-lattice-free-multiscale-model-of-the-mammary-terminal-end-bud
#8
Joseph D Butner, Vittorio Cristini, Zhihui Wang, Joseph D Butner, Vittorio Cristini, Zhihui Wang, Vittorio Cristini, Joseph D Butner, Zhihui Wang
The terminal end bud (TEB) is a bulbous structure composed of highly proliferative cells that is responsible for mammary gland development during the pubertal stage. This is a highly organized process, involving cellular differentiation hierarchies regulated by endocrine and paracrine signaling. Here, we present development of a lattice-free, three dimensional multiscale agent based model of the TEB to study the effects of cellular phenotypic hierarchies, endocrine and paracrine signaling, and proliferation demographics on pubertal mammary gland development...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226244/molecularly-organic-inorganic-hybrid-hollow-mesoporous-organosilica-nanocapsules-with-tumor-specific-biodegradability-and-enhanced-chemotherapeutic-functionality
#9
Ping Huang, Yu Chen, Han Lin, Luodan Yu, Linlin Zhang, Liying Wang, Yufang Zhu, Jianlin Shi
Based on the intrinsic features of high stability and unique multifunctionality, inorganic nanoparticles have shown remarkable potentials in combating cancer, but their biodegradability and biocompatibility are still under debate. As a paradigm, this work successfully demonstrates that framework organic-inorganic hybridization can endow the inorganic mesoporous silica nanocarriers with unique tumor-sensitive biodegradability and high biocompatibility. Based on a "chemical homology" mechanism, molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules (HMONs) with high dispersity and sub-50 nm particle dimension were constructed in mass production...
February 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28225579/intravoxel-incoherent-motion-mri-assessment-of-chemoradiation-induced-pelvic-bone-marrow-changes-in-cervical-cancer-and-correlation-with-hematological-toxicity
#10
Elaine Yuen Phin Lee, Jose Angelo Udal Perucho, Vince Vardhanabhuti, Jian He, Steven Wai Kwan Siu, Siew Fei Ngu, Nina A Mayr, William T C Yuh, Queenie Chan, Pek-Lan Khong
PURPOSE: To investigate bone marrow changes after chemoradiation (CRT) using intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) and correlate imaging changes with hematological toxicity (HT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: Thirty-nine patients with newly diagnosed cervical cancer were prospectively recruited for two sequential 3.0T IVIM-MRI studies: before treatment (MRI-1) and 3-4 weeks after standardized CRT (MRI-2)...
February 22, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28224212/upregulation-of-thioredoxin-1-in-activated-human-nk-cells-confers-increased-tolerance-to-oxidative-stress
#11
Kousaku Mimura, Ley-Fang Kua, Noriko Shimasaki, Kensuke Shiraishi, Shotaro Nakajima, Lim Kee Siang, Asim Shabbir, Jimmy So, Wei-Peng Yong, Koji Kono
Adoptive transfer of immune cells, such as T lymphocytes and NK cells, has potential to control cancer growth. However, this can be counteracted by immune escape mechanisms within the tumor microenvironment, including those mediated by reactive oxygen species (ROS). Here, we determined the levels of anti-oxidant molecules in NK cells and their capacity to overcome ROS-induced immune suppression. We investigated the effect of H2O2 on resting NK cells, IL-2-activated NK cells and NK cells expanded by coculture with the K562 leukemia cell line genetically modified to express membrane-bound IL-15 and 4-1BB ligand (K562-mb15-41BBL)...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28224125/how-do-mesenchymal-stem-cells-influence-or-are-influenced-by-microenvironment-through-extracellular-vesicles-communication
#12
REVIEW
Gabriel Dostert, Benjamin Mesure, Patrick Menu, Émilie Velot
Mesenchymal stem cells (MSCs) are widely used in cell therapy and tissue engineering thanks to their self-renewal, their multipotency, and their immunomodulatory properties that make them an attractive tool for regenerative medicine. A large part of MSCs positive effects is due to their secretion products which participate in creating a favorable microenvironment and closely relate these cells to other cell types. Extracellular vesicles (EVs) belong to cellular secretions. They are produced by cells continuously or after stimulation (e...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28223815/antitumor-effects-of-oncolytic-herpes-simplex-virus-type-2-against-colorectal-cancer-in-vitro-and-in-vivo
#13
Lei Yin, Chunhong Zhao, Jixia Han, Zengjun Li, Yanan Zhen, Ruixue Xiao, Zhongfa Xu, Yanlai Sun
BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28223547/cabozantinib-targets-bone-microenvironment-modulating-human-osteoclast-and-osteoblast-functions
#14
Marco Fioramonti, Daniele Santini, Michele Iuliani, Giulia Ribelli, Paolo Manca, Nicola Papapietro, Filippo Spiezia, Bruno Vincenzi, Vincenzo Denaro, Antonio Russo, Giuseppe Tonini, Francesco Pantano
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#15
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223185/nanomedicine-as-a-potent-strategy-in-melanoma-tumor-microenvironment
#16
REVIEW
Vincent Pautu, Daniela Leonetti, Elise Lepeltier, Nicolas Clere, Catherine Passirani
Melanoma originated from melanocytes is the most aggressive type of skin cancer. Despite considerable progresses in clinical treatment with the discovery of BRAF or MEK inhibitors and monoclonal antibodies, the durability of response to treatment is often limited to the development of acquired resistance and systemic toxicity. The limited success of conventional treatment highlights the importance of understanding the role of melanoma tumor microenvironment in tumor developement and drug resistance. Nanoparticles represent a promising strategy for the development of new cancer treatments able to improve the bioavailability of drugs and increase their penetration by targeting specifically tumours cells and/or tumour environment...
February 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28223148/stat3-activation-in-infection-and-infection-associated-cancer
#17
Rong Lu, Yong-Guo Zhang, Jun Sun
The Janus kinase/signal transducers and activators for transcription (JAK/STAT) pathway plays crucial roles in regulating apoptosis, proliferation, differentiation, and the inflammatory response. The JAK/STAT families are composed of four JAK family members and seven STAT family members. STAT3 plays a key role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment. Recent evidence suggests that STAT3 regulates diverse biological functions in pathogenesis of diseases, such as infection and cancer...
February 18, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28223127/multidrug-resistance-in-glioblastoma-stem-like-cells-role-of-the-hypoxic-microenvironment-and-adenosine-signaling
#18
REVIEW
Daniel Uribe, Ángelo Torres, José Dellis Rocha, Ignacio Niechi, Carlos Oyarzún, Luis Sobrevia, Rody San Martín, Claudia Quezada
Glioblastoma multiforme (GBM) is considered the most common and aggressive tumour of the central nervous system and is characterized for being highly chemoresistant. This property is mainly due to the activation of Multiple Drug Resistance (MDR) mechanisms that protect cancer cells from structurally and morphologically different drugs. Overexpression and increased ABC transporters activity is one of the most important MDR mechanisms at the clinical level, and both its expression and activity are elevated in GBM cells...
February 18, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28221800/self-associating-poly-ethylene-oxide-block-poly-%C3%AE%C2%B5-caprolactone-peo-b-pcl-drug-conjugates-for-the-delivery-of-stat3-inhibitor-jsi-124-potential-application-in-cancer-immunotherapy
#19
Shyam M Garg, Mohammad Reza Vakili, Ommoleila Molavi, Afsaneh Lavasanifar
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) in tumor cells and tumor associated dendritic cells (DCs) plays a major role in the progression of cancer. JSI-124 (Cucurbitacin I) is a potent inhibitor of STAT3, however, its poor solubility and non-specificity limits its effectiveness in cancer immunotherapy. In order to achieve a nano-carrier for solubilisation and passive targeting of JSI-124 to tumor cells and tumor associated DCs, the drug was chemically conjugated to pendent COOH groups of self-associating poly(ethylene oxide)-block-poly(-carboxylate-ε-caprolactone) (PEO-b-PCCL)...
February 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28220772/tumour-and-host-cell-pd-l1-is-required-to-mediate-suppression-of-anti-tumour-immunity-in-mice
#20
Janet Lau, Jeanne Cheung, Armando Navarro, Steve Lianoglou, Benjamin Haley, Klara Totpal, Laura Sanders, Hartmut Koeppen, Patrick Caplazi, Jacqueline McBride, Henry Chiu, Rebecca Hong, Jane Grogan, Vincent Javinal, Robert Yauch, Bryan Irving, Marcia Belvin, Ira Mellman, Jeong M Kim, Maike Schmidt
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics...
February 21, 2017: Nature Communications
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