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https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#1
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28624842/increased-levels-of-pro-inflammatory-and-anti-inflammatory-cellular-responses-in-parkinson-s-disease-patients-search-for-a-disease-indicator
#2
Likun Yang, Changfeng Guo, Jie Zhu, Yi Feng, Weiliang Chen, Zhizhong Feng, Dan Wang, Shibai Sun, Wei Lin, Yuhai Wang
BACKGROUND Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and it arises when most of the dopaminergic neurons of substantia nigra region die. Several mechanisms have been postulated as the causative event in PD pathology, and neuroinflammation is most crucial among them. MATERIAL AND METHODS We analyzed T-helper 17 (Th17) cells and myeloid-derived suppressor cells (MDSCs) from 80 PD patients to assess inflammatory processes and to find a cost-effective means to evaluate PD prognosis...
June 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28623127/the-inhibition-of-nlrp3-signaling-attenuates-liver-injury-in-an-%C3%AE-galactosylceramide-induced-hepatitis-model
#3
Ayumu Kanbe, Hiroyasu Ito, Yukari Omori, Akira Hara, Mitsuru Seishima
Inflammasomes are involved in innate immune responses. Several NOD-Like receptors (NLRs) participate in the formation of inflammasomes. NACHT, LRR and PYD domains-containing protein 3 (NALP3) belongs to the NLR family and recognizes adenosine triphosphate (ATP), crystals, and Reactive Oxygen Species (ROS). This study examined the effect of inflammasomes on alpha-galactosylceramide (GalCer)-induced liver injury using NALP3-knockout (KO) mice. GalCer administration induced inflammasome activation and IL-1β-maturation...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621200/muscle-derived-stem-cells-in-peripheral-nerve-regeneration-reality-or-illusion
#4
Jing Zhou, Haiyan Cui, Haibin Lu, Zhuqiu Xu, Weifeng Feng, Lulu Chen, Xiaolei Jin, Xiaonan Yang, Zuoliang Qi
Owing to the complicated and time-consuming regenerative process, the repair of injured peripheral nerves depends largely on ongoing stem-cell therapy. Decades ago, researchers successfully isolated and identified muscle-derived stem cells (MDSCs) and discovered their potential for multidifferentiation. MDSCs play an important role in trauma repair associated with neuromuscular and vascular injury by simultaneously promoting tissue regrowth via direct differentiation and systematic secretion under physiological conditions...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28619949/expansion-and-activation-of-granulocytic-myeloid-derived-suppressor-cells-in-childhood-precursor-b-cell-acute-lymphoblastic-leukemia
#5
Yu-Feng Liu, Ying-Ying Chen, Ying-Yi He, Jia-Yi Wang, Jian-Ping Yang, Shu-Ling Zhong, Nan Jiang, Pan Zhou, Hua Jiang, Jie Zhou
Precursor B cell acute lymphoblastic leukemia (B-ALL) is a B cell-derived, malignant disorder with the highest incidence among children. In addition to the genetic abnormality, a dysregulated immune system also has an important role in the pathogenesis of B-ALL. Myeloid-derived suppressor cells (MDSCs) represent one of the key drivers in immune tolerance against tumor cells, including various solid tumors and hematologic malignancies. The role of MDSCs in B-ALL remains poorly understood. Here, we showed that the granulocytic (G)-MDSC population was significantly elevated in both the peripheral blood and BM of patients with B-ALL, when compared with age-matched healthy controls...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28611302/the-peripheral-immune-status-of-granulocytic-myeloid-derived-suppressor-cells-correlates-the-survival-in-advanced-gastric-cancer-patients-receiving-cisplatin-based-chemotherapy
#6
Hirokazu Shoji, Kohei Tada, Shigehisa Kitano, Takashi Nishimura, Yasuhiro Shimada, Kengo Nagashima, Kazunori Aoki, Nobuyoshi Hiraoka, Yoshitaka Honma, Satoru Iwasa, Atsuo Takashima, Ken Kato, Narikazu Boku, Kazufumi Honda, Tesshi Yamada, Yuji Heike, Tetsuya Hamaguchi
BACKGROUND: The prognostic significance of peripheral immune status in patients with advanced gastric cancer (AGC) remains unclear. RESULTS: From July 2013 through December 2014, 37 patients were enrolled. Among patients with 25 subsets of immune cells, patients in the high group of granulocytic myeloid-derived suppressor cells (Gr-MDSCs) showed significantly shorter progression-free survival (PFS) than those in the low group (3.98 vs. 8.78 months; hazards ratio (HR), 2...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609459/het0016-decreases-lung-metastasis-from-breast-cancer-in-immune-competent-mouse-model
#7
Thaiz F Borin, Adarsh Shankar, Kartik Angara, Mohammad H Rashid, Meenu Jain, Asm Iskander, Roxan Ara, Iryna Lebedyeva, Hasan Korkaya, Bhagelu R Achyut, Ali S Arbab
Distant metastasis is the primary cause of death in the majority of the cancer types. Recently, much importance has been given to tumor microenvironment (TME) in the development of invasive malignant tumors, as well as the metastasis potential. The ability of tumor cells to modulate TME and to escape immune-mediated attack by releasing immunosuppressive cytokines has become a hallmark of breast cancer. Our study shows the effect of IV formulation of HET0016 (HPßCD-HET0016) a selective inhibitor of 20-HETE synthesis, administered intravenously in immune-competent in vivo mouse model of murine breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28605567/mir-30a-increases-mdsc-differentiation-and-immunosuppressive-function-by-targeting-socs3-in-mice-with-b-cell-lymphoma
#8
Zhen Xu, Jianjian Ji, Jingjing Xu, Dan Li, Guoping Shi, Fei Liu, Liang Ding, Jing Ren, Huan Dou, Tingting Wang, Yayi Hou
Myeloid-derived suppressor cells (MDSCs), including granulocytic (G)-MDSCs and monocytic (M)-MDSCs, play a critical role in tumor-induced T cell tolerance. MDSCs immunosuppressive function and differentiation are significantly promoted in patients and B-cell lymphoma model mice. However, the mechanisms regulating these processes remain largely unclear. In this study, we observed increased microRNA (miR)-30a expression both in G-MDSCs and in M-MDSCs from B cell lymphoma model mice. After transfection with miR-30a mimics, the differentiation and suppressive capacities of MDSCs were significantly increased via up-regulation of arginase-1...
June 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28592438/cd14-cd15-hla-dr-myeloid-derived-suppressor-cells-impair-antimicrobial-responses-in-patients-with-acute-on-chronic-liver-failure
#9
Christine Bernsmeier, Evangelos Triantafyllou, Robert Brenig, Fanny J Lebosse, Arjuna Singanayagam, Vishal C Patel, Oltin T Pop, Wafa Khamri, Rooshi Nathwani, Robert Tidswell, Christopher J Weston, David H Adams, Mark R Thursz, Julia A Wendon, Charalambos Gustav Antoniades
OBJECTIVE: Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14(+)HLA-DR(-) myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses. DESIGN: Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30)...
June 7, 2017: Gut
https://www.readbyqxmd.com/read/28591224/low-dose-glucocorticoids-suppresses-ovarian-tumor-growth-and-metastasis-in-an-immunocompetent-syngeneic-mouse-model
#10
Kai-Ti Lin, Shu-Pin Sun, Jui-I Wu, Lu-Hai Wang
Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708. In this study, we used an immunocompetent syngeneic mouse model and further evaluated the effect and optimal dosages of GCs in treating metastatic ovarian cancer. The treatment of C57BL/6-derived ovarian cancer ID-8 cells with a synthetic GC, dexamethasone (DEX), induced the expression of microRNA-708, leading to decreased cell migration and invasion through targeting Rap1B...
2017: PloS One
https://www.readbyqxmd.com/read/28582845/elevated-lactate-dehydrogenase-ldh-can-be-a-marker-of-immune-suppression-in-cancer-interplay-between-hematologic-and-solid-neoplastic-clones-and-their-microenvironments
#11
Jennifer Ding, Judith E Karp, Ashkan Emadi
Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment...
May 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28570446/vascular-endothelial-growth-factor-induction-of-muscle-derived-stem-cells-enhances-vascular-phenotype-while-preserving-myogenic-potential
#12
Howard D Wang, Qiongyu Guo, Amy Quan, Joseph Lopez, Jose C Alonso-Escalante, Denver M Lough, W P Andrew Lee, Gerald Brandacher, Anand R Kumar
BACKGROUND: Previous work by our group and other laboratories have revealed that muscle-derived stem cells (MDSCs) may contain both myogenic and endothelial progenitors, making MDSCs a promising option for skeletal muscle regeneration. The purpose of this study was to investigate the impact of vascular endothelial growth factor (VEGF) induction on the vascular and myogenic potential of MDSCs. METHODS: Muscle-derived stem cells were isolated from 4- to 8-week-old C57BL/6J mice using a preplate technique and recombinant human VEGFa was used as the induction agent...
May 31, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28570288/myeloid-derived-suppressor-cells-associated-with-disease-progression-in-primary-hiv-infection-pd-l1-blockade-attenuates-inhibition
#13
Zi-Ning Zhang, Nan Yi, Tong-Wei Zhang, Le-Le Zhang, Xian Wu, Mei Liu, Ya-Jing Fu, Si-Jia He, Yong-Jun Jiang, Hai-Bo Ding, Zhen-Xing Chu, Hong Shang
OBJECTIVE: Events occurring during the initial phase of human immunodeficiency virus (HIV) infection are intriguing because of their dramatic impact on the subsequent course of the disease. In particular, the relationship between myeloid-derived suppressor cells (MDSCs) and HIV pathogenesis in primary infection remains unknown and the mechanism of MDSCs in HIV infection are incompletely defined. METHODS: The frequency of MDSC expression in patients with primary (PHI) and chronic HIV infection was measured, and the association with disease progression was studied...
May 31, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28546500/myeloid-derived-suppressor-cells-a-new-therapeutic-target-to-overcome-resistance-to-cancer-immunotherapy
#14
REVIEW
Jason A Chesney, Robert A Mitchell, Kavitha Yaddanapudi
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate during pathologic conditions, such as cancer. Patients diagnosed with advanced metastatic cancers have an average survival of 12-24 mo, a survival time that hasn't changed significantly in the past 30 yr. Despite some encouraging improvements in response rates and overall survival in patients receiving immunotherapies, such as immune checkpoint inhibitors, most patients will ultimately progress...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28543406/novel-murine-xenograft-model-for-the-evaluation-of-stem-cell-therapy-for-profound-dysphagia
#15
Maggie A Kuhn, Amanda B Black, M Tausif Siddiqui, Jan A Nolta, Peter C Belafsky
OBJECTIVES/HYPOTHESIS: Dysphagia is common and costly. Treatments are limited and innovative therapies are required. The tongue is essential for safe, effective swallowing and is a natural target for regenerative therapy. Muscle-derived stem cells (MDSCs) hold potential to restore dynamic function, and their application in the damaged tongue is appealing. We examined the safety and efficacy of human MDSC implantation into a novel mouse tongue model. STUDY DESIGN: Animal study...
May 23, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28534709/mdscs-are-involved-in-the-protumorigenic-potentials-of-gm-csf-in-colitis-associated-cancer
#16
Ning Ma, Qilin Liu, Lin Hou, Yalin Wang, Ziling Liu
Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation...
May 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28533357/tlr9-expression-and-secretion-of-lif-by-prostate-cancer-cells-stimulates-accumulation-and-activity-of-polymorphonuclear-mdscs
#17
Haejung Won, Dayson Moreira, Chan Gao, Priyanka Duttagupta, Xingli Zhao, Edwin Manuel, Don Diamond, Yate-Ching Yuan, Zheng Liu, Jeremy Jones, Massimo D'Apuzzo, Sumanta Pal, Marcin Kortylewski
Proinflammatory signals promote prostate tumorigenesis and progression, but their origins and downstream effects remain unclear. We recently demonstrated that the expression of an innate immune receptor, TLR9, by prostate cancer cells is critical for their tumor-propagating potential. We investigated whether cancer cell-intrinsic TLR9 signaling alters composition of the prostate tumor microenvironment. We generated Ras/Myc (RM9) and Myc-driven (Myc-CaP) prostate cancer cells expressing the tetracycline-inducible gene Tlr9 (Tlr9(ON) ) or the control LacZ (LacZ(ON) )...
May 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#18
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28512922/effect-of-chemical-immobilization-of-sdf-1%C3%AE-into-muscle-derived-scaffolds-on-angiogenesis-and-muscle-progenitor-recruitment
#19
Sareh Rajabi-Zeleti, Sasan Jalili-Firoozinezhad, Mohammad Kazemi Ashtiani, Gilles Le Carrou, Shahragim Tajbakhsh, Hossein Baharvand
The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix (ECM) promotes cellular behavior in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28512255/immune-consequences-of-penfluridol-treatment-associated-with-inhibition-of-glioblastoma-tumor-growth
#20
Alok Ranjan, Stephen Wright, Sanjay K Srivastava
Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics...
April 26, 2017: Oncotarget
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