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Tumor priming

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https://www.readbyqxmd.com/read/27910826/enhancing-radiotherapy-for-lung-cancer-using-immunoadjuvants-delivered-in-situ-from-new-design-radiotherapy-biomaterials-a-preclinical-study
#1
Yao Hao, Sayeda Yasmin-Karim, Michele Moreau, Neeharika Sinha, Erno Sajo, Wilfred Ngwa
Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize the toxicities and prime a more potent immune response, Ngwa et al have proposed that inert radiotherapy biomaterials such as fiducials could be upgraded to multifunctional ones loaded with IA for in situ delivery directly into the tumor sub-volume at no additional inconvenience to patients...
December 21, 2016: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#2
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27903123/drug-priming-enhances-radiosensitivity-of-adamantinomatous-craniopharyngioma-via-downregulation-of-survivin
#3
Christina Stache, Christiane Bils, Rudolf Fahlbusch, Jörg Flitsch, Michael Buchfelder, Harald Stefanits, Thomas Czech, Udo Gaipl, Benjamin Frey, Rolf Buslei, Annett Hölsken
OBJECTIVE In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#4
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27899639/histone-demethylase-phf8-promotes-epithelial-to-mesenchymal-transition-and-breast-tumorigenesis
#5
Peng Shao, Qi Liu, Peterson Kariuki Maina, Jiayue Cui, Thomas B Bair, Tiandao Li, Shaikamjad Umesalma, Weizhou Zhang, Hank Heng Qi
Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27889319/cell-type-specific-chromatin-states-differentially-prime-squamous-cell-carcinoma-tumor-initiating-cells-for-epithelial-to-mesenchymal-transition
#6
Mathilde Latil, Dany Nassar, Benjamin Beck, Soufiane Boumahdi, Li Wang, Audrey Brisebarre, Christine Dubois, Erwin Nkusi, Sandrine Lenglez, Agnieszka Checinska, Alizée Vercauteren Drubbel, Michael Devos, Wim Declercq, Rui Yi, Cédric Blanpain
Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential...
November 16, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27876552/long-term-altered-immune-responses-following-fetal-priming-in-a-non-human-primate-model-of-maternal-immune-activation
#7
Destanie R Rose, Milo Careaga, Judy Van de Water, Kim McAllister, Melissa D Bauman, Paul Ashwood
Infection during pregnancy can lead to activation of the maternal immune system and has been associated with an increased risk of having an offspring later diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) or Schizophrenia (SZ). Most maternal immune activation (MIA) studies to date have been in rodents and usually involve the use of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However, since NDD are based on behavioral changes, a model of MIA in non-human primates could potentially provide data that helps illuminate complex behavioral and immune outputs in human NDD...
November 19, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27875297/glycogen-synthase-kinase-3-gsk-3-mediated-phosphorylation-of-uracil-n-glycosylase-2-ung2-facilitates-repair-of-floxuridine-induced-dna-lesions-and-promotes-cell-survival
#8
Carly A Baehr, Catherine J Huntoon, Song-My Hoang, Calvin R Jerde, Larry M Karnitz
Uracil N-glycosylase 2 (UNG2), the nuclear isoform of UNG, catalyzes the removal of uracil or 5-fluorouracil lesions that accumulate in DNA following treatment with the anti-cancer agents 5-fluorouracil and 5-fluorodeoxyuridine (floxuridine), a 5-fluorouracil metabolite. By repairing these DNA lesions before they can cause cell death, UNG2 promotes cancer cell survival and is therefore critically involved in tumor resistance to these agents. However, the mechanisms by which UNG2 is regulated remain unclear...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27874054/combinational-immunotherapy-with-allo-dribble-vaccines-and-anti-ox40-co-stimulation-leads-to-generation-of-cross-reactive-effector-t-cells-and-tumor-regression
#9
Guangjie Yu, Yuhuan Li, Zhihua Cui, Nicholas P Morris, Andrew D Weinberg, Bernard A Fox, Walter J Urba, Lixin Wang, Hong-Ming Hu
It is well-known that vaccines comprising of irradiated whole tumor cells or tumor-derived heat shock proteins can generate tumor-specific immune responses. In contrast, we showed recently that vaccines composed of autophagosomes (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell responses and cross-protection against the tumor. This unusual property of DRibbles was related to the selective recruitment of defective ribosomal products (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the autophagy gene product LC3...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871911/in-vitro-and-in-vivo-anti-inflammatory-effects-of-theaflavin-3-3-digallate-on-lipopolysaccharide-induced-inflammation
#10
Yanting Wu, Fujun Jin, Yiliang Wang, Feng Li, Lu Wang, Qiaoli Wang, Zhe Ren, Yifei Wang
Inflammation is a defensive response against various harmful stimuli and stress conditions, such as tissue injury and one of the most common pathological processes occurring in human diseases. Theaflavin-3,3'-digallate, one of the theaflavins present in black tea, exhibits several bioactive properties, including the ability to lower the incidence of coronary heart disease, a positive effect on the bone mineral density, and the ability to prevent cancer. The aim of this study was to evaluate whether theaflavin-3,3'-digallate could reduce the production of pro-inflammatory cytokines in vivo and in vitro and ameliorate acute lung injury (ALI) in a mouse model...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27869670/homologous-prime-boost-vaccination-with-ova-entrapped-in-self-adjuvanting-archaeosomes-induces-high-numbers-of-ova-specific-cd8%C3%A2-%C2%BA-t-cells-that-protect-against-subcutaneous-b16-ova-melanoma
#11
Felicity C Stark, Michael J McCluskie, Lakshmi Krishnan
Homologous prime-boost vaccinations with live vectors typically fail to induce repeated strong CD8⁺ T cell responses due to the induction of anti-vector immunity, highlighting the need for alternative delivery vehicles. The unique ether lipids of archaea may be constituted into liposomes, archaeosomes, which do not induce anti-carrier responses, making them an ideal candidate for use in repeat vaccination systems. Herein, we evaluated in mice the maximum threshold of antigen-specific CD8⁺ T cell responses that may be induced by multiple homologous immunizations with ovalbumin (OVA) entrapped in archaeosomes derived from the ether glycerolipids of the archaeon Methanobrevibacter smithii (MS-OVA)...
November 17, 2016: Vaccines
https://www.readbyqxmd.com/read/27865799/oleic-acid-induced-angptl4-enhances-head-and-neck-squamous-cell-carcinoma-anoikis-resistance-and-metastasis-via-up-regulation-of-fibronectin
#12
Chih-Jie Shen, Shih-Hung Chan, Chung-Ta Lee, Wan-Chen Huang, Jhih-Peng Tsai, Ben-Kuen Chen
Obese patients have higher levels of free fatty acids (FFAs) in their plasma and a higher risk of cancer than their non-obese counterparts. However, the mechanisms involved in the regulation of cancer metastasis by FFAs remain unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4 (ANGPTL4) protein expression and secretion and conferred anoikis resistance to head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA-induced ANGPTL4 further promoted HNSCC migration and invasion...
November 16, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27863558/development-of-an-autologous-canine-cancer-vaccine-system-for-resectable-malignant-tumors-in-dogs
#13
J R Yannelli, R Wouda, T J Masterson, M G Avdiushko, D A Cohen
While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27863199/mesothelin-immunotherapy-for-cancer-ready-for-prime-time
#14
Raffit Hassan, Anish Thomas, Christine Alewine, Dung T Le, Elizabeth M Jaffee, Ira Pastan
Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27859049/lps-primed-heterotolerant-dendritic-cells-suppress-experimental-autoimmune-uveoretintitis-by-multiple-mechanisms
#15
Izabela P Klaska, Elizabeth Muckersie, Cristina Martin-Granados, Maria Christofi, John V Forrester
Exposure of bone marrow derived dendritic cells (BMDC) to high dose ultrapure lipopolysaccharide for 24 hours (h) (LPS-primed BMDC) enhances their potency in preventing inter-photoreceptor retinoid binding protein (IRBP): complete Freund's adjuvant (CFA)-induced experimental autoimmune uveoretinitis (EAU). LPS-primed BMDC are refractory to further exposure to LPS (= endotoxin tolerance, ET), evidenced here by decreased phosphorylation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) as well as impaired nuclear translocation of nuclear factor κB (NF-κB) and IRF3, resulting in reduced tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-12 and interferon beta (IFN-β) secretion...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27854511/a-negative-feedback-loop-between-autophagy-and-immune-responses-in-mycobacterium-leprae-infection
#16
Yuelong Ma, Li Zhang, Jie Lu, Tiejun Shui, Jia Chen, Jun Yang, Joanna Yuan, Yeqiang Liu, Degang Yang
The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level...
November 17, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27852743/immunogenic-dendritic-cell-generation-from-pluripotent-stem-cells-by-ectopic-expression-of-runx3
#17
Erika Takacs, Pal Boto, Emilia Simo, Tamas I Csuth, Bianka M Toth, Hadas Raveh-Amit, Attila Pap, Elek G Kovács, Julianna Kobolak, Szilvia Benkö, Andras Dinnyes, Istvan Szatmari
Application of dendritic cells (DCs) to prime responses to tumor Ags provides a promising approach to immunotherapy. However, only a limited number of DCs can be manufactured from adult precursors. In contrast, pluripotent embryonic stem (ES) cells represent an inexhaustible source for DC production, although it remains a major challenge to steer directional differentiation because ES cell-derived cells are typically immature with impaired functional capacity. Consistent with this notion, we found that mouse ES cell-derived DCs (ES-DCs) represented less mature cells compared with bone marrow-derived DCs...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27852038/transcriptomic-metabolomic-reprogramming-in-egfr-mutant-nsclc-early-adaptive-drug-escape-linking-tgf%C3%AE-2-bioenergetics-mitochondrial-priming
#18
Praveena S Thiagarajan, Xiaoliang Wu, Wei Zhang, Ivy Shi, Rakesh Bagai, Patrick Leahy, Yan Feng, Martina Veigl, Daniel Lindner, David Danielpour, Lihong Yin, Rafael Rosell, Trever G Bivona, Zhenfeng Zhang, Patrick C Ma
The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846389/characteristics-and-significance-of-the-pre-metastatic-niche
#19
REVIEW
Yang Liu, Xuetao Cao
Primary tumors create a favorable microenvironment, namely, pre-metastatic niche, in secondary organs and tissue sites for subsequent metastases. The pre-metastatic niche can be primed and established through a complex interplay among primary tumor-derived factors, tumor-mobilized bone marrow-derived cells, and local stromal components. We review here our current understanding of the key components and underlying mechanisms for pre-metastatic niche formation. We propose six characteristics that define the pre-metastatic niche, which enable tumor cell colonization and promote metastasis, including immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, and reprogramming...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27843208/immunotherapy-in-metastatic-prostate-cancer
#20
REVIEW
Susan F Slovin
INTRODUCTION: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. METHODS: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. RESULTS: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
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