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https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#1
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432594/microrna-transfer-between-bone-marrow-adipose-and-multiple-myeloma-cells
#2
REVIEW
Luna Soley, Carolyne Falank, Michaela R Reagan
PURPOSE OF REVIEW: Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. RECENT FINDINGS: MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28432289/simultaneous-detection-of-egfr-and-vegf-in-colorectal-cancer-using-fluorescence-raman-endoscopy
#3
Yong-Il Kim, Sinyoung Jeong, Kyung Oh Jung, Myung Geun Song, Chul-Hee Lee, Seock-Jin Chung, Ji Yong Park, Myeong Geun Cha, Sung Gun Lee, Bong-Hyun Jun, Yun-Sang Lee, Do Won Hwang, Hyewon Youn, Keon Wook Kang, Yoon-Sik Lee, Dae Hong Jeong, Dong Soo Lee
Fluorescence endomicroscopy provides quick access to molecular targets, while Raman spectroscopy allows the detection of multiple molecular targets. Using a simultaneous fluorescence-Raman endoscopic system (FRES), we herein demonstrate its potential in cancer diagnosis in an orthotopically induced colorectal cancer (CRC) xenograft model. In the model, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were targeted with antibody-conjugated fluorescence and surface-enhanced Raman scattering (F-SERS) dots...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432279/il-35-induces-n2-phenotype-of-neutrophils-to-promote-tumor-growth
#4
Jiu-Ming Zou, Jian Qin, Yong-Chao Li, Yu Wang, Dong Li, Yu Shu, Chao Luo, Shan-Shan Wang, Gang Chi, Fang Guo, Gui-Mei Zhang, Zuo-Hua Feng
IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431214/interferon-%C3%AE-released-by-activated-cd8-t-lymphocytes-impairs-the-calcium-resorption-potential-of-osteoclasts-in-calcified-human-aortic-valves
#5
Edit Nagy, Yang Lei, Eduardo Martínez-Martínez, Simon C Body, Florian Schlotter, Michael Creager, Alexander Assmann, Kamal Khabbaz, Peter Libby, Göran K Hansson, Elena Aikawa
Calcium content in patients with calcific aortic valve disease (CAVD) correlates with the severity of stenosis. In CAVD, activated T lymphocytes localize with osteoclast regions; however, the functional consequences of this association remain unknown. We hypothesized that CD8(+) T cells modulate calcification in CAVD. Explanted CAVD valves (n = 52) dissected into noncalcified and calcified portions were subjected to mRNA extraction, real-time quantitative PCR, enzyme-linked immunosorbent assay, and immunohistochemical analyses...
April 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430867/emerging-evidence-for-the-role-of-differential-tumor-microenvironment-in-breast-cancer-racial-disparity-a-closer-look-at-the-surroundings
#6
Sachin Kumar Deshmukh, Sanjeev K Srivastava, Nikhil Tyagi, Aamir Ahmad, Ajay P Singh, Ahmed Al Ghadhban, Donna L Dyess, James E Carter, Kari Dugger, Seema Singh
Although increased awareness leading to early detection and prevention, as well as advancements in treatment strategies, have resulted in superior clinical outcomes, African American women with breast cancer continue to have greater mortality rates, compared to Caucasian American counterparts. Moreover, African American women are more likely to have breast cancer at a younger age and be diagnosed with aggressive tumor sub-types. Such racial disparities can be attributed to socioeconomic differences, but it is increasingly being recognized that these disparities may indeed be due to certain genetic and other non-genetic biological differences...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430664/identification-of-a-novel-pd-l1-positive-solid-tumor-transplantable-in-hla-a-0201-drb1-0101-transgenic-mice
#7
Laurie Rangan, Jeanne Galaine, Romain Boidot, Mohamad Hamieh, Magalie Dosset, Julie Francoual, Laurent Beziaud, Jean-René Pallandre, Elodie Lauret Marie Joseph, Afag Asgarova, Christophe Borg, Talal Al Saati, Yann Godet, Jean Baptiste Latouche, Séverine Valmary-Degano, Olivier Adotévi
HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430635/unsuccessful-mitosis-in-multicellular-tumour-spheroids
#8
Annie Molla, Morgane Couvet, Jean-Luc Coll
Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429794/bone-in-culture-array-as-a-platform-to-model-early-stage-bone-metastases-and-discover-anti-metastasis-therapies
#9
Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T C Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A Mancini, Xiang H-F Zhang
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429770/neurons-secrete-mir-132-containing-exosomes-to-regulate-brain-vascular-integrity
#10
Bing Xu, Yu Zhang, Xu-Fei Du, Jia Li, Hua-Xing Zi, Ji-Wen Bu, Yong Yan, Hua Han, Jiu-Lin Du
Vascular integrity helps maintain brain microenvironment homeostasis, which is critical for the normal development and function of the central nervous system. It is known that neural cells can regulate brain vascular integrity. However, due to the high complexity of neurovascular interactions involved, understanding of the neural regulation of brain vascular integrity is still rudimentary. Using intact zebrafish larvae and cultured rodent brain cells, we find that neurons transfer miR-132, a highly conserved and neuron-enriched microRNA, via secreting exosomes to endothelial cells (ECs) to maintain brain vascular integrity...
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429725/estrogen-reprograms-the-activity-of-neutrophils-to-foster-protumoral-microenvironment-during-mammary-involution
#11
Hwa Hwa Chung, Yu Zuan Or, Smeeta Shrestha, Jia Tong Loh, Chew Leng Lim, Zoe Ong, Amanda Rui En Woo, I-Hsin Su, Valerie C L Lin
Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429464/inflammatory-features-of-frontal-fibrosing-alopecia
#12
Sophia A Ma, Sotonye Imadojemu, Kenneth Beer, John T Seykora
INTRODUCTION: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia typically occurring in post-menopausal women. The etiology and pathophysiology of FFA is poorly understood but thought to be immune mediated. This study aims to further explore the extent of fibrosis and the inflammatory microenvironment by characterizing Langerhans cells (LCs), helper T cells, cytotoxic T cells, and B cells near hair follicles in FFA. METHODS: 11 paraffin-embedded tissues from patients with a clinical and histopathologic diagnosis of FFA were selected for immunohistochemical studies using CD3, CD4, CD8, CD1a, and CD20...
April 21, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28429161/on-the-in-vivo-function-of-the-mitral-heart-valve-leaflet-insights-into-tissue-interstitial-cell-biomechanical-coupling
#13
Chung-Hao Lee, Will Zhang, Kristen Feaver, Robert C Gorman, Joseph H Gorman, Michael S Sacks
There continues to be a critical need for developing data-informed computational modeling techniques that enable systematic evaluations of mitral valve (MV) function. This is important for a better understanding of MV organ-level biomechanical performance, in vivo functional tissue stresses, and the biosynthetic responses of MV interstitial cells (MVICs) in the normal, pathophysiological, and surgically repaired states. In the present study, we utilized extant ovine MV population-averaged 3D fiducial marker data to quantify the MV anterior leaflet (MVAL) deformations in various kinematic states...
April 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28428965/natural-killer-cells-in-the-orchestration-of-chronic-inflammatory-diseases
#14
REVIEW
Luca Parisi, Barbara Bassani, Marco Tremolati, Elisabetta Gini, Giampietro Farronato, Antonino Bruno
Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#15
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428279/interaction-between-tumor-cell-surface-receptor-rage-and-proteinase-3-mediates-prostate-cancer-metastasis-to-bone
#16
Mikhail G Kolonin, Anna Sergeeva, Daniela I Staquicini, Tracey L Smith, Christy A Tarleton, Jeffrey J Molldrem, Richard L Sidman, Serena Marchiò, Renata Pasqualini, Wadih Arap
Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428267/association-of-nf%C3%AE%C2%BAb-polymorphisms-with-clinical-outcome-of-non-medullary-thyroid-carcinoma
#17
Theo S Plantinga, Mirela Petrulea, Marije Oosting, Leo Joosten, Doina Piciu, Jan Wa Smit, Romana T Netea-Maier, Carmen Georgescu
The NF-κB inflammatory pathway plays a major role in cancer development and clinical progression. Activation of NF-κB signaling is promoted by NFKB1 and inhibited by NFKBIA. The present study aimed to determine the relevance of NFKB1 rs4648068 and NFKBIA rs2233406 genetic variants for non-medullary thyroid cancer (NMTC) susceptibility, progression and clinical outcome. This case-control and cohort study consists of a Romanian discovery cohort (157 patients, 258 controls) and a Dutch validation cohort (138 patients, 188 controls)...
April 20, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28428193/pd-l1-expression-in-melanoma-a-quantitative-immunohistochemical-antibody-comparison
#18
Joel C Sunshine, Peter Nguyen, Genevieve Kaunitz, Tricia Cottrell, Sneha Berry, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Karen R Bleich, Toby C Cornish, Evan J Lipson, Robert A Anders, Janis Taube
PD-L1 expression in the pre-treatment tumor microenvironment enriches for response to anti-PD-1/PD-L1 therapies. The purpose of this study was to quantitatively compare the performance of five monoclonal anti-PD-L1 antibodies used in recent landmark publications.  <br /><br />Experimental Design: PD-L1 immunohistochemistry (IHC) was performed on thirty-four formalin-fixed paraffin-embedded archival melanoma samples using the 5H1, SP142, 28-8, 22C3 and SP263 clones.  The percentage of total cells (including melanocytes and immune cells) demonstrating cell surface PD-L1 staining, as well as intensity measurements/H-scores, were assessed for each melanoma specimen using a computer-assisted platform...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28428043/effects-of-bone-marrow-on-the-microenvironment-of-the-human-pancreatic-islet-a-protein-profile-approach
#19
Joseph William Kim, Souriya Vang, John Luo, William Newton, Luguang Luo
Stem cells are a new therapeutic modality that may support the viability and function of human organs and tissue. Our previous studies have revealed that human allogeneic bone marrow (BM) sustains pancreatic β cell function and survival. This paper examines whether BM creates a microenvironment that supports human pancreatic islets in vitro by evaluating 107 proteins in culture media from BM, islet, and islet/bone marrow (IB) with mass spectrometry. Proteins were considered up- or down-regulated if p-values < 0...
April 17, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28427634/enhanced-porosity-and-permeability-of-three-dimensional-alginate-scaffolds-via-acoustic-microstreaming-induced-by-low-intensity-pulsed-ultrasound
#20
Gepu Guo, Yong Ma, Yang Guo, Chunbing Zhang, Xiasheng Guo, Juan Tu, Alfred C H Yu, Junru Wu, Dong Zhang
The shear stress resulting from the microstreaming induced by low-intensity pulsed ultrasound (LIPUS) has been often used to improve the permeability of cell membrane or porous engineering scaffolds. In the present study, three-dimensional (3-D) scaffold culture systems were constituted to simulate the in vivo microenvironment, providing benefits for cell growth. In order to investigate the mechanism underlying the enhanced porosity and permeability of the 3-D alginate scaffolds by using LIPUS with varied acoustic intensities, two quantitative imaging techniques (i...
July 2017: Ultrasonics Sonochemistry
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