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https://www.readbyqxmd.com/read/28637024/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#1
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637021/dectin-1-signaling-inhibits-osteoclastogenesis-via-il-33-induced-inhibition-of-nfatc1
#2
Xiaoqing Zhu, Yinghua Zhao, Yuxue Jiang, Tianxue Qin, Jintong Chen, Xiao Chu, Qing Yi, Sujun Gao, Siqing Wang
Abnormal osteoclast activation contributes to osteolytic bone diseases (OBDs). It was reported that curdlan, an agonist of dectin-1, inhibits osteoclastogenesis. However, the underlying mechanisms are not fully elucidated. In this study, we found that curdlan potently inhibited RANKL-induced osteoclast differentiation and the resultant bone resorption. Curdlan inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcriptional factor for osteoclastogenesis. Notably, dectin-1 activation increased the expression of MafB, an inhibitor of NFATc1, and IL-33 in osteoclast precursors...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637010/local-application-of-bacteria-improves-safety-of-salmonella-mediated-tumor-therapy-and-retains-advantages-of-systemic-infection
#3
Dino Kocijancic, Sebastian Felgner, Tim Schauer, Michael Frahm, Ulrike Heise, Kurt Zimmermann, Marc Erhardt, Siegfried Weiss
Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#4
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#5
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
Background Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. Methods We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636433/immunogenicity-of-ags-004-dendritic-cell-therapy-in-patients-treated-during-acute-hiv-infection
#6
Cynthia L Gay, Mark A DeBenedette, Irina Y Tcherepanova, Alicia Gamble, Whitney E Lewis, Anna B Cope, JoAnn D Kuruc, Kara S McGee, Mary F Kearney, John M Coffin, Nancie M Archin, Charles B Hicks, Joseph J Eron, Charles A Nicolette, David M Margolis
AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4(+) T-cell infection (RCI) was measured by quantitative viral outgrowth assay...
June 21, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28635517/a-primer-for-oncoimmunology-immunooncology
#7
Brad Bolon, Famke Aeffner
Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28635368/efficacy-and-safety-of-autologous-cell-therapies-for-knee-cartilage-defects-autologous-stem-cells-chondrocytes-or-the-two-randomized-controlled-trial-design
#8
James B Richardson, Karina T Wright, Johanna Wales, Jan Herman Kuiper, Helen S McCarthy, Peter Gallacher, Paul E Harrison, Sally Roberts
AIM: The main aim of this trial is to test the safety and efficacy of autologous stromal/stem cells, chondrocytes or the two combined in the treatment of knee cartilage defects. PATIENTS & METHODS: Patients with symptomatic chondral/osteochondral defects will be randomized to cell therapy treatment with one of three cell populations (1:1:1). The primary efficacy outcome is a functional knee score (Lysholm) at 15 months post-treatment and the primary safety outcome is the incidence of adverse events...
June 21, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28634419/elevated-plasma-levels-of-sil-2r-in-complex-regional-pain-syndrome-a-pathogenic-role-for-t-lymphocytes
#9
Krishna D Bharwani, Maaike Dirckx, Dirk L Stronks, Willem A Dik, Marco W J Schreurs, Frank J P M Huygen
The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 - Q1 = 5731 pg/ml - 3546 pg/ml) versus 1907 pg/ml (Q3 - Q1: 2206 pg/ml - 1374 pg/ml), p < 0...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634212/prolonged-darkness-reduces-liver-fibrosis-in-a-mouse-model-of-primary-sclerosing-cholangitis-by-mir-200b-down-regulation
#10
Nan Wu, Fanyin Meng, Tianhao Zhou, Yuyan Han, Lindsey Kennedy, Julie Venter, Heather Francis, Sharon DeMorrow, Paolo Onori, Pietro Invernizzi, Francesca Bernuzzi, Romina Mancinelli, Eugenio Gaudio, Antonio Franchitto, Shannon Glaser, Gianfranco Alpini
Melatonin therapy or prolonged exposure to complete darkness reduces biliary hyperplasia and liver fibrosis in bile-duct-ligated (BDL) rats; however, no information exists in primary sclerosing cholangitis (PSC). Thus, we aimed to determine the therapeutic effects of prolonged dark therapy or melatonin administration on hepatic fibrosis in the Mdr2(-/-) mouse model of PSC. Melatonin levels, biliary mass, liver fibrosis, angiogenesis and miR-200b expression were evaluated in wild-type and Mdr2(-/-) mice exposed to darkness or melatonin treatment or in male PSC patient samples and healthy controls...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#11
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#12
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#13
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#14
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#15
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#16
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28632486/randomized-noncomparative-phase-ii-trial-of-early-switch-from-docetaxel-to-cabazitaxel-or-vice-versa-with-integrated-biomarker-analysis-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#17
Emmanuel S Antonarakis, Scott T Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B Lannin, Shalu Suri, Conor N Gruber, Erica D Pratt, Brian J Kirby, Mario A Eisenberger, David M Nanus, Fred Saad, Paraskevi Giannakakou
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327)...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28631712/-the-molecular-mechanisms-and-morphological-manifestations-of-leiomyoma-reduction-induced-by-selective-progesterone-receptor-modulators
#18
T A Demura, Z V Revazova, E A Kogan, L V Adamyan
AIM: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-β, and VEGF in tumor tissue. SUBJECTS AND METHODS: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28631608/one-year-in-review-2017-pathogenesis-of-rheumatoid-arthritis
#19
Francesca Angelotti, Alice Parma, Giacomo Cafaro, Riccardo Capecchi, Alessia Alunno, Ilaria Puxeddu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e...
May 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#20
Laetitia Laurent, Awena Lefur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic Lupus Erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
June 20, 2017: European Journal of Immunology
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