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https://www.readbyqxmd.com/read/29428948/ratio-of-immune-response-to-tumor-burden-predicts-survival-via-regulating-functions-of-lymphocytes-and-monocytes-in-diffuse-large-b-cell-lymphoma
#1
Hongfei Ji, Xingjian Niu, Lei Yin, Yiran Wang, Lan Huang, Qijia Xuan, Liru Li, Han Zhang, Jingtong Li, Yue Yang, Weiwei An, Qingyuan Zhang
BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival...
February 2, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29386574/development-of-an-immune-pathology-informed-radiomics-model-for-non-small-cell-lung-cancer
#2
Chad Tang, Brian Hobbs, Ahmed Amer, Xiao Li, Carmen Behrens, Jaime Rodriguez Canales, Edwin Parra Cuentas, Pamela Villalobos, David Fried, Joe Y Chang, David S Hong, James W Welsh, Boris Sepesi, Laurence Court, Ignacio I Wistuba, Eugene J Koay
With increasing use of immunotherapy agents, pretreatment strategies for identifying responders and non-responders is useful for appropriate treatment assignment. We hypothesize that the local immune micro-environment of NSCLC is associated with patient outcomes and that these local immune features exhibit distinct radiologic characteristics discernible by quantitative imaging metrics. We assembled two cohorts of NSCLC patients treated with definitive surgical resection and extracted quantitative parameters from pretreatment CT imaging...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29377887/identification-of-allosteric-inhibitors-of-the-ecto-5-nucleotidase-cd73-targeting-the-dimer-interface
#3
Rahila Rahimova, Simon Fontanel, Corinne Lionne, Lars Peter Jordheim, Suzanne Peyrottes, Laurent Chaloin
The ecto-5'-nucleotidase CD73 plays an important role in the production of immune-suppressive adenosine in tumor micro-environment, and has become a validated drug target in oncology. Indeed, the anticancer immune response involves extracellular ATP to block cell proliferation through T-cell activation. However, in the tumor micro-environment, two extracellular membrane-bound enzymes (CD39 and CD73) are overexpressed and hydrolyze efficiently ATP into AMP then further into immune-suppressive adenosine. To circumvent the impact of CD73-generated adenosine, we applied an original bioinformatics approach to identify new allosteric inhibitors targeting the dimerization interface of CD73, which should impair the large dynamic motions required for its enzymatic function...
January 29, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29344744/interleukin-1-receptor-antagonist-inhibits-angiogenesis-in-gastric-cancer
#4
Zhenqiang Gong, Jiachi Ma, He Su, Tiankang Guo, Hui Cai, Quan Chen, Xiaodan Zhao, Jianbo Qi, Jianbo Du
BACKGROUND: Interleukin-1 alpha (IL-1α) plays an important role in tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the interactions of tumor cells and their micro-environment is poorly understood. We have evaluated the role of IL-1RA in the metastatic process as well as the mutual or reciprocal actions between gastric cancer cells and stromal cells...
January 17, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29344312/an-endogenous-vaccine-based-on-fluorophores-and-multivalent-immunoadjuvants-regulates-tumor-micro-environment-for-synergistic-photothermal-and-immunotherapy
#5
Ling Li, Suleixin Yang, Linjiang Song, Yan Zeng, Tao He, Ning Wang, Chuan Yu, Tao Yin, Li Liu, Xiawei Wei, Qinjie Wu, Yuquan Wei, Li Yang, Changyang Gong
Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been widely applied in cancer treatment. However, in most cases, the tissue penetration depth of NIR light is not sufficient and thus photothermal therapy is unable to completely eradicate deep, seated tumors inevitably leading to recurrence of the tumor. Due to this significant limitation of NIR, improved therapeutic strategies are urgently needed. Methods: We developed an endogenous vaccine based on a novel nanoparticle platform for combinatorial photothermal ablation and immunotherapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29338562/targeted-microbubbles-with-ultrasound-irradiation-and-pd-1-inhibitor-to-increase-antitumor-activity-in-b-cell-lymphoma
#6
Shiya Zheng, Dan Song, Xiaoxiao Jin, Haijun Zhang, Mohanad Aldarouish, Yan Chen, Cailian Wang
AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells...
January 17, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29337282/comparative-proteome-analysis-of-monolayer-and-spheroid-culture-of-canine-osteosarcoma-cells
#7
Christiane Gebhard, Ingrid Miller, Karin Hummel, Martina Neschi Née Ondrovics, Sarah Schlosser, Ingrid Walter
Osteosarcoma is an aggressive bone tumor with high metastasis rate in the lungs and affects both humans and dogs in a similar way. Three-dimensional tumor cell cultures mimic the in vivo situation of micro-tumors and metastases and are therefore better experimental in vitro models than the often applied two-dimensional monolayer cultures. The aim of the present study was to perform comparative proteomics of standard monolayer cultures of canine osteosarcoma cells (D17) and three-dimensional spheroid cultures, to better characterize the 3D model before starting with experiments like migration assays...
January 11, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29327370/role-of-immune-system-in-tumor-progression-and-carcinogenesis
#8
Shishir Upadhyay, Nidhi Sharma, Kunj Bihari Gupta, Monisha Dhiman
Tumor micro-environment has potential to customize the behavior of the immune cell according to their need. In immune-eliminating phase, immune cells eliminate transformed cells but after tumor establishment innate and adaptive immune cells synergistically provide shelter as well as fulfill their requirement that helps in progression. In between eliminating and establishment phase, equilibrium and escaping phase regulate the immune cells response. During immune-escaping, i) the antigenic response generated is either inadequate, or focused entirely on tolerance, and (ii) immune response generated is specific and effective, but the tumor skips immune recognition...
January 12, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29319160/macrophage-plasticity-polarization-and-function-in-health-and-disease
#9
REVIEW
Abbas Shapouri Moghaddam, Saeed Mohammadian, Hossein Vazini, Mahdi Taghadosi, Seyed-Alireza Esmaeili, Fatemeh Mardani, Bita Seifi, Asadollah Mohammadi, Jalil Tavakol Afshari, Amirhossein Sahebkar
Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23 and TNF-α, and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29305422/tumor-stressors-induce-two-mechanisms-of-intracellular-p-glycoprotein-mediated-resistance-that-are-overcome-by-lysosomal-targeted-thiosemicarbazones
#10
Lina Al-Akra, Dong-Hun Bae, Sumit Sahni, Michael L H Huang, Kyung Chan Park, Darius J R Lane, Patric J Jansson, Des R Richardson
Multi-drug resistance (MDR) is a major obstacle in cancer treatment due to the ability of tumor cells to efflux chemotherapeutics via drug transporters e.g., P-glycoprotein (Pgp; ABCB1). While the mechanism of Pgp-mediated drug efflux is known at the plasma membrane, the functional role of intracellular Pgp is unclear. Moreover, there has been intense focus on the tumor micro-environment as a target for cancer treatment. This investigation aimed to dissect the effects of tumor micro-environmental stress on sub-cellular Pgp expression, localization and its role in MDR...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29304403/targeting-death-receptors-for-drug-resistant-cancer-therapy-codelivery-of-ptrail-and-monensin-using-dual-targeting-and-stimuli-responsive-self-assembling-nanocomposites
#11
Fan Xu, Huihai Zhong, Ya Chang, Dongdong Li, Hongyue Jin, Meng Zhang, Huiyuan Wang, Chen Jiang, Youqing Shen, Yongzhuo Huang
Chemoresistance remains a formidable hurdle against cancer therapy. Seeking for novel therapy strategies is an urgent need for those who no longer benefit from chemotherapy. Chemoresistance is usually associated with the dysfunction of intrinsic apoptosis. Targeting extrinsic apoptosis via TRAIL signaling and the death receptors could be a potential solution to treat chemoresistant cancer. A highly biocompatible nano system for codelivery of the TRAIL DNA and the death receptor sensitizer monensin was developed, in which low-molecular-weight PEI (LMW-PEI) was crosslinked by the sulfhydryl cyclodextrin via disulfide bonds, and then bound with DNA, thus forming the bioreducible polyplex cores...
December 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/29276835/a-sensitive-high-throughput-and-robust-trapping-micro-lc-ms-strategy-for-quantification-of-biomarkers-and-antibody-biotherapeutics
#12
Ming Zhang, Bo An, Yang Qu, Shichen Shen, Wei Fu, Yuan-Ju Chen, Xue Wang, Rebeccah Young, John M Canty, Joseph P Balthasar, Keeley Murphy, Debadeep Bhattacharyya, Jonathan L Josephs, Luca Ferrari, Shaolian Zhou, Surendra Bansal, Faye Vazvaei, Jun Qu
For LC-MS-based targeted quantification of biotherapeutics/biomarkers in clinical and pharmaceutical environments, high sensitivity, high throughput, and excellent robustness are all essential, but remain challenging. For example, though nano-LC-MS has been employed to enhance analytical sensitivity, it falls short due to its low loading capacity, poor throughput and low operational robustness. Furthermore, high chemical noise in protein bioanalysis typically limits the sensitivity. Here we describe a novel Trapping-micro-LC-MS (T-µLC-MS) strategy for targeted protein bioanalysis, achieving high sensitivity with exceptional robustness and high throughput...
December 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29273547/-molecular-characterisation-defines-several-subtypes-of-pancreatic-ductal-adenocarcinoma
#13
REVIEW
Jérôme Raffenne, Jérôme Cros
Multi-omics high throughput analyses lead to the description of multiple molecular subtypes of pancreatic adenocarcinoma with major prognostic impact for most of them. There is no consensual multilevel integrative classification yet like in colon or breast cancers. Genomic classifications have identified a tumor subtype (15% of the patients) with deficient homologous DNA repair-system leading to increase sensitivity to platinum-based therapies and possibly to PARP inhibitors and immunotherapies. Transcriptomic classifications are still debated but all have identified an aggressive subtype with a very poor prognosis, presumably unfit for a surgical approach...
December 19, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29230182/a-network-model-to-explore-the-effect-of-the-micro-environment-on-endothelial-cell-behavior-during-angiogenesis
#14
Nathan Weinstein, Luis Mendoza, Isidoro Gitler, Jaime Klapp
Angiogenesis is an important adaptation mechanism of the blood vessels to the changing requirements of the body during development, aging, and wound healing. Angiogenesis allows existing blood vessels to form new connections or to reabsorb existing ones. Blood vessels are composed of a layer of endothelial cells (ECs) covered by one or more layers of mural cells (smooth muscle cells or pericytes). We constructed a computational Boolean model of the molecular regulatory network involved in the control of angiogenesis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29221162/caveolin-1-mediated-stat3-activation-determines-electrotaxis-of-human-lung-cancer-cells
#15
Li Li, Kejun Zhang, Conghua Lu, Qin Sun, Sanjun Zhao, Lin Jiao, Rui Han, Caiyu Lin, Jianxin Jiang, Min Zhao, Yong He
Migration of cancer cells leads to the invasion of distant organs by primary tumors. Further, endogenous electric fields (EFs) in the tumor microenvironment direct the migration of lung cancer cells by a process referred to as electrotaxis - although the precise mechanism remains unclear. Caveolin-1 (Cav-1) is a multifunctional scaffolding protein that is associated with directional cell migration and lung cancer invasion; however, its precise role in lung cancer electrotaxis is unknown. In the present study, we first detected outward electric currents on the tumor body surface in lung cancer xenografts using a highly-sensitive vibrating probe...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29189936/p2y14-receptor-activation-decreases-interleukin-6-production-and-glioma-gl261-cell-proliferation-in-microglial-transwell-cultures
#16
Marjorie A Curet, Jyoti J Watters
Gliomas are rich in extracellular nucleotides that modulate glioma cell production of multiple cytokines including interleukin (IL)-6, which strongly contributes to glioma cell proliferation. However, little is known about how nucleotide signaling modulates microglial/macrophage (MG/MP) cytokine production in the context of gliomas, nor how MG/MP purinergic P2 receptor expression changes in the tumor micro-environment. We hypothesized that: (1) expression of key P2Y receptors will be augmented in glioma-derived MG/MP, and (2) selective activation of these receptors in vitro will regulate microglial production of IL-6 and glioma cell proliferation...
November 30, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29187427/the-role-of-the-androgen-receptor-signaling-in-breast-malignancies
#17
REVIEW
Panagiotis F Christopoulos, Nikolaos I Vlachogiannis, Christiana T Vogkou, Michael Koutsilieris
Breast cancer (BrCa) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. Despite the development of novel therapeutic modalities, triple-negative breast cancer (TNBC) remains an incurable disease. Androgen receptor (AR) is widely expressed in BrCa and its role in the disease may differ depending on the molecular subtype and the stage. Interestingly, AR has been suggested as a potential target candidate in TNBC, while sex hormone levels may regulate the role of AR in BrCa subtypes...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29117251/the-cxcl12-cxcr7-signaling-axis-isoforms-circadian-rhythms-and-tumor-cellular-composition-dictate-gradients-in-tissue
#18
Phillip C Spinosa, Kathryn E Luker, Gary D Luker, Jennifer J Linderman
Chemokine CXCL12 gradients drive chemotaxis in a CXCR4-dependent mechanism and have been implicated in cancer metastasis. While CXCL12 gradients are typically studied in organized, defined environments, the tumor microenvironment is disorganized. In vivo, CXCL12 gradients depend on many factors: the number and arrangement of cells secreting and degrading CXCL12, isoform-dependent binding to the extracellular matrix, diffusion, and circadian fluctuations. We developed a computational model of the tumor microenvironment to simulate CXCL12 gradient dynamics in disorganized tissue...
2017: PloS One
https://www.readbyqxmd.com/read/29105484/fast-high-resolution-laser-ablation-inductively-coupled-plasma-mass-spectrometry-imaging-of-the-distribution-of-platinum-based-anticancer-compounds-in-multicellular-tumor-spheroids
#19
Sarah Theiner, Stijn J M Van Malderen, Thibaut Van Acker, Anton Legin, Bernhard K Keppler, Frank Vanhaecke, Gunda Koellensperger
Multicellular tumor spheroid models serve as an important three-dimensional in vitro cell model system as they mimic the complex tumor microenvironment and thus have contributed to valuable assays in drug discovery studies. In this study, we present a state-of-the-art laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) setup for high spatial resolution elemental imaging of multicellular tumor spheroids and an approach to account for variations in cell density. A low dispersion LA-ICPMS setup was employed, providing accelerated throughput and high sensitivity and permitting a lateral image resolution down to ∼2...
November 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29103184/in-silico-evaluation-of-variable-ph-on-the-binding-of-epidermal-growth-factor-receptor-ectodomain-to-its-ligand-through-molecular-dynamics-simulation-in-tumors
#20
Inderpal Singh, Gurvinder Singh, Vijeshwar Verma, Shashank Singh, Ratna Chandra
Many aggressive and metastatic cancer cell types show Warburg Effect; therefore, it is a possible adaptation helping cancer cells to rapidly divide and utilize the glycolytic intermediates for biosynthesis of ribose sugars (for nucleotide biosynthesis), fatty acid synthesis (lipids for membrane synthesis), NADPH (cellular currency for reductive biosynthesis) and lactate. This in due course results in decrease of extracellular pH, leading to acidic tumor micro-environment. EGFR is a crucial cell surface signaling receptor implicated in cancer cell survival and progression...
November 4, 2017: Interdisciplinary Sciences, Computational Life Sciences
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