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https://www.readbyqxmd.com/read/28303764/recent-progress-in-gm-csf-based-cancer-immunotherapy
#1
Wan-Lun Yan, Kuan-Yin Shen, Chun-Yuan Tien, Yu-An Chen, Shih-Jen Liu
Cancer immunotherapy is a growing field. GM-CSF, a potent cytokine promoting the differentiation of myeloid cells, can also be used as an immunostimulatory adjuvant to elicit antitumor immunity. Additionally, GM-CSF is essential for the differentiation of dendritic cells, which are responsible for processing and presenting tumor antigens for the priming of antitumor cytotoxic T lymphocytes. Some strategies have been developed for GM-CSF-based cancer immunotherapy in clinical practice: GM-CSF monotherapy, GM-CSF-secreting cancer cell vaccines, GM-CSF-fused tumor-associated antigen protein-based vaccines, GM-CSF-based DNA vaccines and GM-CSF combination therapy...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#2
Haas Tobias, Heidegger Simon, Wintges Alexander, Bscheider Michael, Bek Sarah, Fischer Julius C, Eisenkolb Gabriel, Schmickl Martina, Spoerl Silvia, Peschel Christian, Poeck Hendrik, Ruland Jürgen
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within dendritic cells (DCs) that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#3
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Fiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28290959/benefit-type-and-care-source-in-relation-to-mammography-screening-and-breast-cancer-stage-at-diagnosis-among-dod-beneficiaries
#4
Janna Manjelievskaia, Derek Brown, Stephanie Shao, Keith Hofmann, Craig D Shriver, Kangmin Zhu
BACKGROUND: Type of insurance and out-of-pocket costs influence the use of medical care. Specifically, type of insurance can impact an individual's likelihood of receiving a screening mammogram. Additionally, variation in tumor stage at diagnosis exists for patients with different types of insurance. It is not clear whether different benefit types and care sources differ in breast cancer care and outcomes among Department of Defense (DoD) beneficiaries. METHODS: The objective of this study was to examine differences in screening mammography and tumor stage at diagnosis between different benefit types (TRICARE Prime vs...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28280038/pancreatic-cancer-progression-relies-upon-mutant-p53-induced-oncogenic-signaling-mediated-by-nop14
#5
Yongxing Du, Ziwen Liu, Lei You, Pengjiao Hou, Xiaoxia Ren, Tao Jiao, Wenjing Zhao, Zongze Li, Hong Shu, Changzheng Liu, Yu-Pei Zhao
Mutant p53 (mutp53) proteins promote tumor invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). However, the mechanism underlying sustained activation of mutp53 oncogenic signaling is currently unclear. In this study, we report that NOP14 nucleolar protein (NOP14) expression is upregulated in PDAC tumors and metastatic tissue specimens. NOP14 overexpression promoted cell motility, whereas NOP14 inhibition decreased invasive capacity of PDAC cells. In vivo invasion assays conducted on established subcutaneously, orthotopically, and intravenously injected tumor mouse models also indicated NOP14 as a promoter of PDAC metastasis...
March 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28276734/in-vitro-and-in-vivo-inhibitory-effects-of-6-hydroxyrubiadin-on-lipopolysaccharide-induced-inflammation
#6
Yanting Wu, Fujun Jin, Yiliang Wang, Feng Li, Zhe Ren, Yifei Wang
Inflammation is a defensive response against a multitude of harmful stimuli and stress conditions such as tissue injury, and is one of the most common pathological processes of human diseases. 6-Hydroxyrubiadin, an anthraquinone isolated from Rubia cordifolia L., exhibits several bioactive properties. The aim of this study was to evaluate whether 6-hydroxyrubiadin can reduce the production of pro-inflammatory cytokines and ameliorate acute lung injury (ALI) in a mouse model. In this study, we demonstrated that 6-hydroxyrubiadin suppressed lipopolysaccharide (LPS)-induced nuclear factor-kappa B activation as well as the phosphorylation of c-Jun N-terminal kinase in RAW 264...
March 3, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28275007/gene-expression-profiling-of-patient-derived-pancreatic-cancer-xenografts-predicts-sensitivity-to-the-bet-bromodomain-inhibitor-jq1-implications-for-individualized-medicine-efforts
#7
Benjamin Bian, Martin Bigonnet, Odile Gayet, Celine Loncle, Aurélie Maignan, Marine Gilabert, Vincent Moutardier, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Mehdi Ouaissi, Veronique Secq, Flora Poizat, Rémy Nicolle, Yuna Blum, Laetitia Marisa, Marion Rubis, Jean-Luc Raoul, James E Bradner, Jun Qi, Gwen Lomberk, Raul Urrutia, Andres Saul, Nelson Dusetti, Juan Iovanna
c-MYC controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient-derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC-high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state, and a shorter survival time compared to the MYC-low subgroup...
March 8, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28265230/electrotransfer-of-plasmid-dna-radiosensitizes-b16f10-tumors-through-activation-of-immune-response
#8
Monika Savarin, Urska Kamensek, Maja Cemazar, Richard Heller, Gregor Sersa
BACKGROUND: Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors. MATERIALS AND METHODS: The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation...
March 1, 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28259044/neuroimmune-mechanisms-of-behavioral-alterations-in-a-syngeneic-murine-model-of-human-papilloma-virus-related-head-and-neck-cancer
#9
Elisabeth G Vichaya, Daniel W Vermeer, Diana L Christian, Jessica M Molkentine, Kathy A Mason, John H Lee, Robert Dantzer
Patients with cancer often experience a high symptom burden prior to the start of treatment. As disease- and treatment-related neurotoxicities appear to be additive, targeting disease-related symptoms may attenuate overall symptom burden for cancer patients and improve the tolerability of treatment. It has been hypothesized that disease-related symptoms are a consequence of tumor-induced inflammation. We tested this hypothesis using a syngeneic heterotopic murine model of human papilloma virus (HPV)-related head and neck cancer...
February 11, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28257996/linking-of-mpges-1-and-inos-activates-stem-like-phenotype-in-egfr-driven-epithelial-tumor-cells
#10
Erika Terzuoli, Federica Finetti, Filomena Costanza, Antonio Giachetti, Marina Ziche, Sandra Donnini
Inflammatory prostaglandin E-2 (PGE-2) favors cancer progression in epithelial tumors characterized by persistent oncogene input. However, its effects on tumor cell stemness are poorly understood at molecular level. Here we describe two epithelial tumor cells A431 and A459, originating from human lung and skin tumors, in which epithelial growth factor (EGF) induces sequential up-regulation of mPGES-1 and iNOS enzymes, producing an inflammatory intracellular milieu. We demonstrated that concerted action of EGF, mPGES-1 and iNOS causes sharp changes in cell phenotype demonstrated by acquisition of stem-cell features and activation of the epithelial-mesenchymal transition (EMT)...
March 1, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28250801/press-pulse-a-novel-therapeutic-strategy-for-the-metabolic-management-of-cancer
#11
Thomas N Seyfried, George Yu, Joseph C Maroon, Dominic P D'Agostino
BACKGROUND: A shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of "Press-Pulse" disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28242071/recombinant-bcg-expressing-a-pspa-pdt-fusion-protein-protects-mice-against-pneumococcal-lethal-challenge-in-a-prime-boost-strategy
#12
Cibelly Goulart, Dunia Rodriguez, Alex I Kanno, Ying-Jie Lu, Richard Malley, Luciana C C Leite
Pneumococcal proteins have been evaluated as genetically-conserved potential vaccine candidates. We have previously demonstrated that a fragment of PspA in fusion with PdT (rPspA-PdT) induced protective immune responses in mice. However, purified proteins have shown poor immunogenicity and often require the combination with strong adjuvants and booster doses. Here, we investigated the use of a Bacillus Calmette-Guérin (BCG) strain, a well-established prophylactic vaccine for tuberculosis with known adjuvant properties, for delivery of the PspA-PdT fusion protein...
February 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28238951/oral-administration-of-the-nitroxide-radical-tempol-exhibits-immunomodulatory-and-therapeutic-properties-in-multiple-sclerosis-models
#13
Sarah Neil, Jaebong Huh, Victoria Baronas, Xinhui Li, Henry F McFarland, Murali Cherukuri, James B Mitchell, Jacqueline A Quandt
Therapies with both immunomodulatory and neuroprotective properties are thought to have the greatest promise in reducing the severity and progression of multiple sclerosis (MS). Several reactive oxygen (ROS) and reactive nitrogen species (RNS) are implicated in inflammatory-mediated damage to the central nervous system (CNS) in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a stable nitroxide radical with potent antioxidant activity...
February 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28235765/soluble-il-6r-expressed-by-myeloid-cells-reduces-tumor-specific-th1-differentation-and-drives-tumor-progression
#14
Hirotake Tsukamoto, Koji Fujieda, Masatoshi Hirayama, Tokunori Ikeda, Akira Yuno, Keiko Matsumura, Daiki Fukuma, Kimi Araki, Hiroshi Mizuta, Hideki Nakayama, Satoru Senju, Yasuharu Nishimura
IL-6 produced by tumor cells promotes their survival, conferring a poor prognosis in cancer patients. IL-6 also contributes to immunosuppression of CD4+ T cell-mediated antitumor effects. In this study, we focused on the impact of IL-6 trans-signaling mediated by soluble IL-6 receptors (sIL-6R) expressed in tumor-bearing hosts. Higher levels of sIL-6R circulating in blood was observed in tumor-bearing mice, whereas the systemic increase of sIL-6R was not prominent in tumor-bearing mice with myeloid cell-specific conditional deletion of IL-6R even when tumor cells produced sIL-6R...
February 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28208020/graphene-oxide-induced-perturbation-to-plasma-membrane-and-cytoskeletal-meshwork-sensitize-cancer-cells-to-chemotherapeutic-agents
#15
Jianqiang Zhu, Ming Xu, Ming Gao, Zhihong Zhang, Yong Xu, Tian Xia, Sijin Liu
The outstanding physicochemical properties endow graphene materials (e.g., graphene oxide, GO) with beneficial potentials in diverse biomedical fields such as bioimaging, drug delivery, and biomolecular detection. GO recently emerged as a chemosensitizer; however, the detailed molecular basis underlying GO-conducted sensitization and corresponding biological effects are still elusive. Based on our recent findings that GO treatment at sublethal concentrations could impair the general cellular priming state, including disorders of plasma membrane and cytoskeleton construction, we aimed here to explore the mechanism of GO as a sensitizer to make cancer cells more susceptible to chemotherapeutic agents...
February 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#16
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197387/ciita-driven-mhc-class-ii-expressing-tumor-cells-can-efficiently-prime-naive-cd4-th-cells-in-vivo-and-vaccinate-the-host-against-parental-mhc-ii-negative-tumor-cells
#17
Farah Bou Nasser Eddine, Greta Forlani, Letizia Lombardo, Alessandra Tedeschi, Giovanna Tosi, Roberto S Accolla
Our previous studies showed that non-immunogenic H-2(d) tumor cells of distinct epithelial histotypes can become highly immunogenic, induce a protective CD4(+) T cell response and vaccinate the animals against parental MHC-II-negative cells if they are rendered MHC class II-positive by stable transfection with the Air-1-encoded MHC-II transcriptional activator CIITA. These studies did not establish, however, whether tumor immunity was the consequence of a direct priming of naive CD4(+) T lymphocytes by CIITA-driven MHC-II-expressing tumor cells or by MHC-II-tumor antigen complexes engulfed by dendritic cells (DC) and exposed on the surface of these professional antigen presenting cells (APC)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197368/immunosuppressive-cd14-hla-dr-lo-neg-monocytes-are-elevated-in-pancreatic-cancer-and-primed-by-tumor-derived-exosomes
#18
Naureen Javeed, Michael P Gustafson, Shamit K Dutta, Yi Lin, William R Bamlet, Ann L Oberg, Gloria M Petersen, Suresh T Chari, Allan B Dietz, Debabrata Mukhopadhyay
Immunological strategies to treat pancreatic cancer offer new therapeutic approaches to improve patient outcomes. Understanding alterations in the immune systems of pancreatic cancer patients will likely lead to advances in immunotherapy for the disease. We profiled peripheral blood leukocytes from pancreatic cancer patients (n = 22) and age-matched controls (n = 20) using flow cytometry. Immune profiling of pancreatic cancer patients identified phenotypic changes in various immune cell populations, including a population of immunosuppressive monocytes (CD14(+)HLA-DR(lo/neg)), which were shown to be increased in these patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28187434/interface-between-breast-cancer-cells-and-the-tumor-microenvironment-using-platelet-rich-plasma-to-promote-tumor-angiogenesis-influence-of-platelets-and-fibrin-bundles-on-the-behavior-of-breast-tumor-cells
#19
Sheila Siqueira Andrade, Joana Tomomi Sumikawa, Eloísa Dognani Castro, Fabricio Pereira Batista, Edgar Paredes-Gamero, Lilian Carolina Oliveira, Izabel Monastério Guerra, Giovani Bravin Peres, Renan Pelluzzi Cavalheiro, Luiz Juliano, Afonso Pinto Nazário, Gil Facina, Siu Mui Tsai, Maria Luiza Vilela Oliva, Manoel João Batista Castello Girão
Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187046/effect-of-hydroxyethyl-starch-priming-on-the-systemic-inflammatory-response-and-lung-edema-following-cardiopulmonary-bypass-in-a-rat-model
#20
Yutaka Fujii, Takayuki Tanabe, Tsubasa Yamashiro, Mikiyasu Shirai, Yoshiaki Takewa, Eisuke Tatsumi
Cardiopulmonary bypass (CPB) preserves patients' lives during open heart surgery by providing sufficient oxygen delivery and blood supply to vital organs. However, previous studies have suggested that the interaction of hemodilution and vascular hyperpermeability induces tissue edema and an inflammatory response during CPB. In this study, we hypothesized that suppression of the systemic inflammatory response and tissue edema during CPB by a plasma substitute (hydroxyethyl starch: HES).Rats (450-500 g) were divided into a SHAM group (n=5), a Ringer's acetate CPB group (n=7), and an HES CPB group (n=7)...
February 7, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
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