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https://www.readbyqxmd.com/read/28425064/a-pathway-to-personalizing-therapy-for-metastases-using-liver-on-a-chip-platforms
#1
A S Khazali, A M Clark, A Wells
Metastasis accounts for most cancer-related deaths. The majority of solid cancers, including those of the breast, colorectum, prostate and skin, metastasize at significant levels to the liver due to its hemodynamic as well as tumor permissive microenvironmental properties. As this occurs prior to detection and treatment of the primary tumor, we need to target liver metastases to improve patients' outcomes. Animal models, while proven to be useful in mechanistic studies, do not represent the heterogeneity of human population especially in drug metabolism lack proper human cell-cell interactions, and this gap between animals and humans results in costly and inefficient drug discovery...
April 19, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28419818/local-group-2-innate-lymphoid-cells-promote-corneal-regeneration-after-epithelial-abrasion
#2
Jun Liu, Chengju Xiao, Hanqing Wang, Yunxia Xue, Dong Dong, Cuipei Lin, Fang Song, Ting Fu, Zhaorui Wang, Jiansu Chen, Hongwei Pan, Yangqiu Li, Dongqing Cai, Zhijie Li
Corneal injuries and infections are the leading cause of blindness worldwide. Thus, understanding the mechanisms that control healing of the damaged cornea is critical for the development of new therapies to promptly restore vision. Innate lymphoid cells (ILCs) are a recently identified heterogeneous cell population that has been reported to orchestrate immunity and promote tissue repair in the lungs and skin after injury. However, whether ILCs can modulate the repair process in the cornea remains poorly understood...
April 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28419151/skin-resident-cd4-t-cells-protect-against-leishmania-major-by-recruiting-and-activating-inflammatory-monocytes
#3
Nelson D Glennie, Susan W Volk, Phillip Scott
Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells...
April 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28416697/small-molecule-mediated-inhibition-of-myofibroblast-transdifferentiation-for-the-treatment-of-fibrosis
#4
Michael J Bollong, Baiyuan Yang, Naja Vergani, Brittney A Beyer, Emily N Chin, Claudio Zambaldo, Danling Wang, Arnab K Chatterjee, Luke L Lairson, Peter G Schultz
Fibrosis, a disease in which excessive amounts of connective tissue accumulate in response to physical damage and/or inflammatory insult, affects nearly every tissue in the body and can progress to a state of organ malfunction and death. A hallmark of fibrotic disease is the excessive accumulation of extracellular matrix-secreting activated myofibroblasts (MFBs) in place of functional parenchymal cells. As such, the identification of agents that selectively inhibit the transdifferentiation process leading to the formation of MFBs represents an attractive approach for the treatment of diverse fibrosis-related diseases...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28349520/a-retrospective-review-of-the-dermatologic-manifestations-of-chronic-arsenic-poisoning-in-the-philippines
#5
Sheena Maureen T Sy, Charissa M Salud-Gnilo, Claudine Yap-Silva, Erin Jane L Tababa
BACKGROUND: The Section of Dermatology of the University of the Philippines, Philippine General Hospital, reported a case of chronic arsenic poisoning from a community in Luzon island to the Department of Health resulting in the conduct of two health and environmental assessment missions in December 2014. OBJECTIVE: To describe the demographic profile and cutaneous manifestations of chronic arsenic poisoning among affected residents in Luzon, Philippines. METHODS: A review of the medical records of 116 residents screened during the health assessment missions in December 2014 was conducted...
March 28, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28346486/grem1-is-expressed-in-the-cancer-associated-myofibroblasts-of-basal-cell-carcinomas
#6
Hye Sung Kim, Myung Soo Shin, Min Seok Cheon, Jae Wang Kim, Cheol Lee, Woo Ho Kim, Young Sill Kim, Bo Gun Jang
Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1...
2017: PloS One
https://www.readbyqxmd.com/read/28345628/tissue-resident-memory-t-cells-in-the-human-conjunctiva-and-immune-signatures-in-human-dry-eye-disease
#7
Tanima Bose, Ryan Lee, Aihua Hou, Louis Tong, K George Chandy
Non-recirculating resident memory (TRM) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract. Using impression cytology followed by flow cytometry we identified two TRM subsets and four recirculating T-subsets in the healthy human ocular surface. In dry eye disease, principal component analysis (PCA) revealed two clusters of patients with distinct T-cell signatures. Increased conjunctival central memory and naïve T cells characterized Cluster-1 patients, and increased CD8(+) TRMs and CD4(+) recirculating memory T cells characterized Cluster-2 patients...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344860/il-32-induces-indoleamine-2-3-dioxygenase-cd1c-dendritic-cells-and-indoleamine-2-3-dioxygenase-cd163-macrophages-relevance-to-mycosis-fungoides-progression
#8
Hanako Ohmatsu, Daniel Humme, Juana Gonzalez, Nicholas Gulati, Markus Möbs, Wolfram Sterry, James G Krueger
Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c(+) myeloid dendritic cells (mDC) and/or CD163(+) macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28330499/a-novel-multi-network-approach-reveals-tissue-specific-cellular-modulators-of-fibrosis-in-systemic-sclerosis
#9
Jaclyn N Taroni, Casey S Greene, Viktor Martyanov, Tammara A Wood, Romy B Christmann, Harrison W Farber, Robert A Lafyatis, Christopher P Denton, Monique E Hinchcliff, Patricia A Pioli, J Matthew Mahoney, Michael L Whitfield
BACKGROUND: Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. METHODS: We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues...
March 23, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28329631/the-burden-of-keratinocyte-cancer-occurrence-multiplicity-and-predicting-risk
#10
David C Whiteman, Nirmala Pandeya, Bridie Thompson, Padmini Subramaniam, Jean Claude Dusingize, Rachel E Neale, Adele C Green, Catherine M Olsen
The costs of diagnosing and treating basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the highest of all cancers in Australia. However, information regarding incidence, multiplicity and risk are scarce as keratinocyte cancers (KCs) are not captured by most registries. To address these gaps, we initiated the QSKIN Study in 2010 recruiting 43,794 Queensland residents from a population register (participation 24%). Participants self-completed a baseline survey recording information on residential history, sun exposure, phenotype and medical and family history...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28287855/association-between-cataract-and-keratinocytic-skin-cancers-or-melanoma-speculating-on-the-common-role-of-sun-and-ultraviolet-radiation-exposures
#11
David Varssano, Mira Friedman, Michaella Goldstein, Shai Bar-Sela, Tal Sella, Varda Shalev, Gabriel Chodick
PURPOSE: Cataract and sun-related skin conditions are proxies to lifetime UV exposure. We examined the association between them using real-world data from an unselected Israeli population. METHODS: Computerized data was obtained from an Israeli health maintenance organization regarding cases of sun-related skin pathologies and cataract diagnosed between 2006 and 2011 in 686,260 members aged 40 or above. RESULTS: Sun-related skin disorders were found in 9...
March 13, 2017: Ophthalmic Epidemiology
https://www.readbyqxmd.com/read/28286864/in-vivo-expansion-of-melanoma-specific-t-cells-using-microneedle-arrays-coated-with-immune-polyelectrolyte-multilayers
#12
Qin Zeng, Joshua M Gammon, Lisa H Tostanoski, Yu-Chieh Chiu, Christopher M Jewell
Microneedles (MNs) are micron-scale polymeric or metallic structures that offer distinct advantages for vaccines by efficiently targeting skin-resident immune cells, eliminating injection-associated pain, and improving patient compliance. These advantages, along with recent studies showing therapeutic benefits achieved using traditional intradermal injections in human cancer patients, suggest MN delivery might enhance cancer vaccines and immunotherapies. We recently developed a new class of polyelectrolyte multilayers based on the self-assembly of model peptide antigens and molecular toll-like receptor agonists (TLRa) into ultrathin, conformal coatings...
February 13, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28271445/establishment-and-function-of-tissue-resident-innate-lymphoid-cells-in-the-skin
#13
REVIEW
Jie Yang, Luming Zhao, Ming Xu, Na Xiong
Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood...
March 7, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28261938/mast-cell-disorders-in-ehlers-danlos-syndrome
#14
REVIEW
Suranjith L Seneviratne, Anne Maitland, Lawrence Afrin
Well known for their role in allergic disorders, mast cells (MCs) play a key role in homeostatic mechanisms and surveillance, recognizing and responding to different pathogens, and tissue injury, with an array of chemical mediators. After being recruited to connective tissues, resident MCs progenitors undergo further differentiation, under the influence of signals from surrounding microenvironment. It is the differential tissue homing and local maturation factors which result in a diverse population of resident MC phenotypes...
March 6, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28223745/intense-pulsed-light-alone-and-in-combination-with-erbium-yttrium-aluminum-garnet-laser-on-small-to-medium-sized-congenital-melanocytic-nevi-single-center-experience-based-on-retrospective-chart-review
#15
Mi So Lee, Hee Jin Jun, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim
BACKGROUND: Treatment of congenital melanocytic nevi (CMN) with intense pulsed light (IPL) has recently produced promising results. OBJECTIVE: To evaluate the clinical and histological outcomes of small-to-medium sized CMN treated with IPL alone and in combination with erbium: yttrium-aluminum-garnet (Er: YAG) laser. METHODS: We performed a retrospective chart review of 26 small-to-medium sized CMN treated as described above. The reduction in visible pigmentation, signs of recurrence and any adverse skin changes were evaluated by two independent clinicians...
February 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28219704/%C3%AE-lactam-hypersensitivity-involves-expansion-of-circulating-and-skin-resident-th22%C3%A2-cells
#16
Andrew Sullivan, Eryi Wang, John Farrell, Paul Whitaker, Lee Faulkner, Daniel Peckham, B Kevin Park, Dean J Naisbitt
BACKGROUND: β-Lactam hypersensitivity has been classified according to the phenotype and function of drug-specific T cells. However, new T-cell subsets have not been considered. OBJECTIVE: The objective of this study was to use piperacillin as a model of β-lactam hypersensitivity to study the nature of the drug-specific T-cell response induced in the blood and skin of hypersensitive patients and healthy volunteers. METHODS: Drug-specific T cells were cloned from blood and inflamed skin, and cellular phenotype and function were explored...
February 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28219080/survival-of-tissue-resident-memory-t-cells-requires-exogenous-lipid-uptake-and-metabolism
#17
Youdong Pan, Tian Tian, Chang Ook Park, Serena Y Lofftus, Shenglin Mei, Xing Liu, Chi Luo, John T O'Malley, Ahmed Gehad, Jessica E Teague, Sherrie J Divito, Robert Fuhlbrigge, Pere Puigserver, James G Krueger, Gökhan S Hotamisligil, Rachael A Clark, Thomas S Kupper
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8(+) TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#18
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28205312/essential-roles-of-tbx3-in-embryonic-skin-development-during-epidermal-stratification
#19
Ryo Ichijo, Yui Iizuka, Hirokazu Kubo, Fumiko Toyoshima
Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function...
March 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28199847/neuropilin-1-is-expressed-on-lymphoid-tissue-residing-lti-like-group-3-innate-lymphoid-cells-and-associated-with-ectopic-lymphoid-aggregates
#20
Medya Mara Shikhagaie, Åsa K Björklund, Jenny Mjösberg, Jonas S Erjefält, Anne S Cornelissen, Xavier Romero Ros, Suzanne M Bal, Jasper J Koning, Reina E Mebius, Michiko Mori, Melanie Bruchard, Bianca Blom, Hergen Spits
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1(+) group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1(+) ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells...
February 14, 2017: Cell Reports
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