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https://www.readbyqxmd.com/read/28647464/data-against-a-common-assumption-xenogeneic-mouse-models-can-be-used-to-assay-suppression-of-immunity-by-human-mscs
#1
REVIEW
Darwin J Prockop, Joo Youn Oh, Ryang Hwa Lee
Much of what we know about immunology suggests that little is to be gained from experiments in which human cells are administered to immunocompetent mice. Multiple reports have demonstrated that this common assumption does not hold for experiments with human mesenchymal stem/stromal cells (hMSCs). The data demonstrate that hMSCs can suppress immune responses to a variety of stimuli in immunocompetent mice by a range of different mechanisms that are similar to those employed by mouse MSCs. Therefore, further experiments with hMSCs in mice will make it possible to generate preclinical data that will improve both the efficacy and safety of the clinical trials with the cells that are now in progress...
June 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28646903/human-adipose-tissue-mesenchymal-stromal-cells-and-their-extracellular-vesicles-act-differentially-on-lung-mechanics-and-inflammation-in-experimental-allergic-asthma
#2
Ligia Lins de Castro, Debora Gonçalves Xisto, Jamil Zola Kitoko, Fernanda Ferreira Cruz, Priscilla Christina Olsen, Patricia Albuquerque Garcia Redondo, Tatiana Paula Teixeira Ferreira, Daniel Jay Weiss, Marco Aurélio Martins, Marcelo Marcos Morales, Patricia Rieken Macedo Rocco
BACKGROUND: Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma...
June 24, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28646606/vismodegib-for-recurrent-locally-destructive-basal-cell-carcinoma-in-a-renal-transplant-patient
#3
P Koelblinger, R Dummer, M Laimer, S Hecht, J W Bauer, A Gaggl, A Kugler
Solid organ transplant patients are at an increased risk of developing cutaneous malignancies owing to long-lasting immunosuppression. The strongest increase in incidence (35-fold) has been reported for cutaneous squamous cell carcinoma [1]. Basal cell carcinoma (BCC) may occur even more frequently, especially during the first years after transplantation [2]. The hedgehog-inhibitor vismodegib has been safely used for the treatment of locally advanced or metastatic BCC in immunocompetent patients since 2012 [3]...
June 24, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28643902/modulation-of-antitumor-immunity-contributes-to-the-enhanced-therapeutic-efficacy-of-liposomal-oxaliplatin-in-mouse-model
#4
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/28638724/calcium-electroporation-induces-tumor-eradication-long-lasting-immunity-and-cytokine-responses-in-the-ct26-colon-cancer-mouse-model
#5
Hanne Falk, Patrick F Forde, Marie Lund Bay, Uma Maheswari Mangalanathan, Pernille Hojman, Declan M Soden, Julie Gehl
Electroporation is used in cancer treatment because of its ability to increase local cytotoxicity of e.g. bleomycin (electrochemotherapy) and calcium (calcium electroporation). Calcium electroporation is a novel anticancer treatment that selectively kills cancer cells by necrosis, a cell death pathway that stimulates the immune system due to high release of antigens and "danger signals." In this exploratory study, we aimed to investigate whether calcium electroporation could initiate an anticancer immune response similar to electrochemotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638039/-headache-immunology
#6
A V Prishchepa, A B Danilov
The overview is dedicated to the neuroimmunological mechanisms of headache development and chronification. Based on the analyzed data, the authors determined the relationship between immunological parameters and duration, intensity and other characteristics of this disease. These findings confirm that immunocompetent cells can be used as headache biomarkers and predictors of treatment efficacy. Questions about the role of separate parts of the immune system in the development and maintenance of a headache require further research...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28630178/efficacy-of-cefiderocol-against-carbapenem-resistant-gram-negative-bacilli-in-immunocompetent-rat-respiratory-tract-infection-models-recreating-human-plasma-pharmacokinetics
#7
Shuhei Matsumoto, Christine M Singley, Jennifer Hoover, Rio Nakamura, Roger Echols, Stephen Rittenhouse, Masakatsu Tsuji, Yoshinori Yamano
Cefiderocol (S-649266), a novel siderophore cephalosporin, shows potent activity against carbapenem-resistant Gram-negative bacilli. In this study, we evaluated the efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli (Pseudomonas aeruginosa,Acinetobacter baumannii and Klebsiella pneumoniae) in immunocompetent rat respiratory tract infection models recreating plasma pharmacokinetics (PK) profiles in healthy human subjects. A total of 6 clinical isolates (1 cephalosporin-susceptible P. aeruginosa, 1 multidrug-resistant P...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#8
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28622397/looking-for-the-most-suitable-orthotopic-retinoblastoma-mouse-model-in-order-to-characterize-the-tumoral-development
#9
Stéphanie Lemaitre, Florent Poyer, Sergio Marco, Paul Fréneaux, François Doz, Isabelle Aerts, Laurence Desjardins, Nathalie Cassoux, Carole D Thomas
Purpose: Because retinoblastoma therapies have many adverse effects, new approaches must be developed and evaluated on animal models. We describe orthotopic xenograft models of retinoblastoma using different strains of mice, suitable for this purpose. Methods: Human retinoblastoma tumors were established on immunodeficient mice by subcutaneous engraftment of tumors from enucleated eyes. The orthotopic model was obtained by subretinal injections of suspension cells into the right eye of immunodeficient (Swiss-nude, severe combined immunodeficiency [SCID]) and immunocompetent mice (C57BL/6N, B6Albino)...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#10
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28614360/comparative-genomics-of-cryptococcus-neoformans-var-grubii-associated-with-meningitis-in-hiv-infected-and-uninfected-patients-in-vietnam
#11
Jeremy N Day, Seet Qihui, Lam Tuan Thanh, Phan Hai Trieu, Anh Duong Van, Nha Hoang Thu, Tran Thi Hong Chau, Nguyen P H Lan, Nguyen Van Vinh Chau, Philip M Ashton, Guy E Thwaites, Maciej F Boni, Marcel Wolbers, Niranjan Nagarajan, Patrick B O Tan, Stephen Baker
The vast burden of cryptococcal meningitis occurs in immunosuppressed patients, driven by HIV, and is caused by Cryptococcus neoformans var. grubii. We previously reported cryptococcal meningitis in Vietnam arising atypically in HIV uninfected, apparently immunocompetent patients, caused by a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans var. grubii (VNIγ). This variant was less common in HIV infected individuals; it remains unclear why this lineage is associated with apparently immunocompetent patients...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28613147/frequent-detection-of-merkel-cell-polyomavirus-dna-in-tissues-from-10-consecutive-autopsies
#12
Giuseppe Mancuso, Jlenia Antona, Camilla Sirini, Michela Salvo, Lorenzo Giacometti, Carlotta Olivero, Elena Trisolini, Rossella Indellicato, Renzo Boldorini
Merkel cell polyomavirus (MCPyV) has been identified in samples of Merkel cell carcinoma (MCC), an aggressive skin cancer. Seroepidemiologic studies indicated a high frequency of MCPyV infection in humans, suggesting respiratory and faecal-oral routes, or transmission by skin contact. Since MCC is more frequent in immunocompromised patients, a reactivation of MCPyV latently infecting target cells has been proposed. However, neither definite ways of transmission nor specific target organs have been identified with certainty...
June 14, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28607757/lymphocyte-subtypes-in-relapsing-remitting-multiple-sclerosis-patients-treated-with-dimethyl-fumarate
#13
C Chaves, R Ganguly, C Ceresia, A Camac
BACKGROUND: Recent data suggest that lymphopenia is more prevalent than reported in relapsing-remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF). OBJECTIVE: The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia. METHOD: A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1, n = 35) and normal lymphocyte counts (G2, n = 24)...
April 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28607587/impact-of-cd44-expression-on-radiation-response-for-bladder-cancer
#14
Chun-Te Wu, Wei-Yu Lin, Ying-Hsu Chang, Wen-Cheng Chen, Miao-Fen Chen
Background Identification of potential factors that can stratify tumors' response to specific therapies will aid in the selection of cancer therapy. Radioresistance is the major obstacles to positive outcomes in bladder cancer patients after definite chemotherapy. CD44, a cancer stem cell surface marker, is relevant in treatment resistance. In the present study, we examined the role of CD44 in bladder cancer. Methods We retrospectively analyzed the clinical outcomes of 85 bladder cancer patients treated with definite chemoradiotherapy, and correlated the expressions of CD44 with IL-6 and treatment response...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28605939/real-world-treatment-outcomes-in-patients-with-metastatic-merkel-cell-carcinoma-treated-with-chemotherapy-in-the-usa
#15
C Lance Cowey, Lisa Mahnke, Janet Espirito, Christoph Helwig, Dina Oksen, Murtuza Bharmal
AIM: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy. PATIENTS & METHODS: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients. RESULTS: In the 2L+ primary analysis population, objective response rate (ORR) was 28...
June 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/28603578/restraint-and-social-isolation-stressors-differentially-regulate-adaptive-immunity-and-tumor-angiogenesis-in-a-breast-cancer-mouse-model
#16
Raluca A Budiu, Anda M Vlad, Linda Nazario, Chandra Bathula, Kristine L Cooper, Jessica Edmed, Premal H Thaker, Julie Urban, Pawel Kalinski, Adrian V Lee, Esther L Elishaev, Thomas P Conrads, Melanie S Flint
The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system in vivo, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS)...
May 2017: Cancer and Clinical Oncology
https://www.readbyqxmd.com/read/28598999/lymphatic-endothelial-progenitors-originate-from-plastic-myeloid-cells-activated-by-toll-like-receptor-4
#17
Lisa D Volk-Draper, Kelly L Hall, Andrew C Wilber, Sophia Ran
BACKGROUND: Myeloid-derived lymphatic endothelial cells (M-LECP) are induced by inflammation and play an important role in adult lymphangiogenesis. However, the mechanisms driving M-LECP differentiation are currently unclear. We previously showed that activation of Toll-like receptor-4 (TLR4) induces myeloid-lymphatic transition (MLT) of immortalized mouse myeloid cells. Here the goals were to assess the potential of different TLR4 ligands to induce pro-lymphatic reprogramming in human and mouse primary myeloid cells and to identify transcriptional changes regulating this process...
2017: PloS One
https://www.readbyqxmd.com/read/28596486/experimental-african-trypanosome-infection-suppresses-the-development-of-multiple-myeloma-in-mice-by-inducing-intrinsic-apoptosis-of-malignant-plasma-cells
#18
Nathan De Beule, Eline Menu, Mathieu Jm Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, Magdalena Radwanska, Afshin Samali, Stefan Magez, Karin Vanderkerken, Carl De Trez
Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28594271/treatment-of-cyclosporin-a-retains-host-defense-against-invasive-pulmonary-aspergillosis-in-a-non-immunosuppressive-murine-model-by-preserving-the-myeloid-cell-population
#19
Sarah Sze Wah Wong, Orhan Rasid, Paris Laskaris, Arnaud Fekkar, Jean-Marc Cavaillon, William J Steinbach, Oumaima Ibrahim-Granet
Cyclosporin A (CsA) is widely used as an immunosuppressive agent for organ transplant recipients. CsA inhibits calcineurin, which is highly conserved in mammals and fungi, and thus affects both types of organism. In mammals, the immunosuppressive effect of CsA is via hampering T cell activation. In fungi, the growth inhibitory effect of CsA is via interference with hyphal growth. The aim of this study was to determine whether CsA renders mice susceptible to invasive pulmonary aspergillosis (IPA) and whether it can protect immunosuppressed mice from infection...
June 8, 2017: Virulence
https://www.readbyqxmd.com/read/28592757/hiv-negative-plasmablastic-lymphoma-attaining-sustained-remission-with-bortezomib-combined-dose-adjusted-epoch-therapy
#20
Hiroyuki Kobayashi, Norito Miyagi
A 61-year-old, HIV-negative, immunocompetent woman was admitted to our hospital for significant weight loss, painful swelling of her right cheek, and rapid growth of a tumor in the right hard palate. A CT scan revealed a neoplastic lesion in the right maxillary sinus, extending to the surrounding soft bone tissue and oral cavity, as well as multiple osteolytic lesions in the skull. A pathologic examination revealed that the neoplastic cells in the oral cavity were plasmablasts tending to appear as differentiated plasma cells...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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