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Tumor priming

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https://www.readbyqxmd.com/read/28528219/the-ongoing-saga-of-the-mechanism-s-of-mhc-class-i-restricted-cross-presentation
#1
Jeff E Grotzke, Debrup Sengupta, Qiao Lu, Peter Cresswell
Cross-presentation is an MHC-I antigen processing pathway that results in the presentation of peptides from exogenous viral, bacterial, parasitic, and tumor antigens and ultimately leads to priming of naïve CD8(+) T cells. This process involves several cellular compartments and multiple components. Successful generation of MHC-I-peptide complexes requires that these components act together in a coordinated fashion. We discuss recent findings on the source of MHC-I, the role of the TAP transporter, the importance of intracellular trafficking events, mechanisms of antigen access the cytosol, and how innate immune signals can affect presentation, with an emphasis on how these pathways compare to conventional antigen presentation and how they correlate with existing data...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28523512/reduced-adipogenesis-after-lung-tumor-exosomes-priming-in-human-mesenchymal-stem-cells-via-tgf%C3%AE-signaling-pathway
#2
Shihua Wang, Xiaoxia Li, Meiqian Xu, Jing Wang, Robert Chunhua Zhao
A key feature of cancer cachexia is the loss of adipose tissue, mainly due to increased lipolysis and an impairment of adipogenesis. Recent findings have shown that cancer exosomes promoted lipolysis in adipose tissue. However, effects of cancer exosomes on adipogenesis were not reported. In this study, we found that lung cancer exosomes could be internalized by human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and significantly inhibited hAD-MSC adipogenesis as demonstrated by Oil Red O staining and decreased expression of adipogenic-specific genes...
May 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28512410/rrx-001-priming-of-pd-1-inhibition-in-the-treatment-of-small-cell-carcinoma-of-the-vagina-a-rare-gynecological-tumor
#3
Christina Brzezniak, Bryan Oronsky, Jane Trepel, Thomas A Summers, Pedro Cabrales, Min-Jung Lee, Regina Day, Saheli Jha, Scott Caroen, Karen Zeman, Lindsey Ferry, Cindy Harmer, Neil Oronsky, Michelle Lybeck, Harry E Lybeck, James F Brown, Tony R Reid, Corey A Carter
Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28512243/plk1-phosphorylation-of-mre11-antagonizes-the-dna-damage-response
#4
Zhiguo Li, Jie Li, Yifan Kong, Shan Yan, Nihal Ahmad, Xiaoqi Liu
The mitotic kinase Plk1 contributes to the DNA damage response (DDR) by targeting multiple factors downstream of the core responder kinase ATM/ATR. In this study, we show that Plk1 also phosphorylates key factors upstream of ATM/ATR and regulates their DDR-related functions. Plk1 phosphorylated Mre11, a component of the Mre11/Rad50/Nbs1 (MRN) complex, at serine 649 (S649) during DDR. Phosphorylation of Mre11-S649 by Plk1 primed subsequent CK2-mediated phosphorylation at Mre11-serine 688 (S688). Phosphorylation of Mre11 at S649/S688 inhibited loading of the MRN complex to damaged DNA, leading to both premature DNA damage checkpoint termination and inhibition of DNA repair...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507029/cd63-mediated-antigen-delivery-into-extracellular-vesicles-via-dna-vaccination-results-in-robust-cd8-t-cell-responses
#5
Tomohiro Kanuma, Takuya Yamamoto, Kouji Kobiyama, Eiko Moriishi, Yuji Masuta, Takato Kusakabe, Koji Ozasa, Etsushi Kuroda, Nao Jounai, Ken J Ishii
DNA vaccines are attractive immunogens for priming humoral and cellular immune responses to the encoded Ag. However, their ability to induce Ag-specific CD8(+) T cell responses requires improvement. Among the strategies for improving DNA vaccine immunogenicity are booster vaccinations, alternate vaccine formulations, electroporation, and genetic adjuvants, but few, such as extracellular vesicles (EVs), target natural Ag delivery systems. By focusing on CD63, a tetraspanin protein expressed on various cellular membranes, including EVs, we examined whether a DNA vaccine encoding an Ag fused to CD63 delivered into EVs would improve vaccine immunogenicity...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28504320/photosensitization-priming-of-tumor-microenvironments-improves-delivery-of-nanotherapeutics-via-neutrophil-infiltration
#6
Dafeng Chu, Xinyue Dong, Qi Zhao, Jingkai Gu, Zhenjia Wang
Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is comprised of NPs coated with anti-CD11b antibodies (Abs) that target activated neutrophils. Intravital microscopy demonstrates that the movement of anti-CD11b Abs-decorated NPs (NPs-CD11b) into the tumor is mediated by neutrophil infiltration induced by photosensitization (PS) because the systemic depletion of neutrophils completely abolishes the nanoparticle tumor deposition...
May 15, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28504304/exploiting-scavenger-receptors-in-cancer-immunotherapy-lessons-from-cd5-and-sr-b1
#7
REVIEW
Marcos Vasquez, Inês Simões, Marta Consuegra-Fernández, Fernando Aranda, Francisco Lozano, Pedro Berraondo
Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28503645/immune-checkpoint-inhibitors-an-innovation-in-immunotherapy-for-the-treatment-and-management-of-patients-with-cancer
#8
REVIEW
Jennifer Dine, RuthAnn Gordon, Yelena Shames, Mary Kate Kasler, Margaret Barton-Burke
Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mechanisms. The second half of the review discusses in greater depth immune checkpoint inhibitors that have recently demonstrated tremendous promise for the treatment of diverse solid tumor types, including melanoma, non-small cell lung cancer, and others...
April 2017: Asia-Pacific Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#9
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28494200/a-new-therapeutic-potential-for-cancers-one-car-with-2-different-engines
#10
Abdolkarim Sheikhi, Abdollah Jafarzadeh
Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain...
May 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28491264/priming-radioimmunotherapy-with-external-beam-radiation-in-patients-with-relapsed-low-grade-non-hodgkin-lymphoma
#11
Yazan Abuodeh, Kamran Ahmed, Michelle Echevarria, Arash Naghavi, G Daniel Grass, Timothy J Robinson, Michael Tomblyn, Bijal Shah, Julio Chavez, Celeste Bello, Ghassan El-Haddad, Louis Harrison, Sungjune Kim
BACKGROUND: The aim of this study was to evaluate the outcomes of priming salvage radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). METHODS: Patients who received salvage RIT with or without 2 × 2 Gy EBRT between March 2009 and February 2013 were retrospectively reviewed at a single institution. Planning target volume (PTV) for EBRT was created by adding a 1-2 cm expansion to the gross tumor volume depending on the anatomical location...
April 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28491060/shaping-of-natural-killer-cell-antitumor-activity-by-ex-vivo-cultivation
#12
REVIEW
Markus Granzin, Juliane Wagner, Ulrike Köhl, Adelheid Cerwenka, Volker Huppert, Evelyn Ullrich
Natural killer (NK) cells are a promising tool for the use in adoptive immunotherapy, since they efficiently recognize and kill tumor cells. In this context, ex vivo cultivation is an attractive option to increase NK cells in numbers and to improve their antitumor potential prior to clinical applications. Consequently, various strategies to generate NK cells for adoptive immunotherapy have been developed. Here, we give an overview of different NK cell cultivation approaches and their impact on shaping the NK cell antitumor activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28489600/oleate-induced-ptx3-promotes-head-and-neck-squamous-cell-carcinoma-metastasis-through-the-up-regulation-of-vimentin
#13
Shih-Hung Chan, Jhih-Peng Tsai, Chih-Jie Shen, Yu-Han Liao, Ben-Kuen Chen
The association between metabolic diseases and the risk of developing cancer is emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia-associated tumor metastasis remains unknown. In this study, we found that oleate induced PTX3 expression and secretion through the activation of Akt/NF-κB pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF-κB was essential for the oleate-induced stabilization of PTX3 mRNA. In addition, both the depletion of PTX3 and the inhibition of NF-κB significantly inhibited oleate-induced tumor cell migration and invasion...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486109/tumor-residing-batf3-dendritic-cells-are-required-for-effector-t-cell-trafficking-and-adoptive-t-cell-therapy
#14
Stefani Spranger, Daisy Dai, Brendan Horton, Thomas F Gajewski
Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103(+) dendritic cells (DCs) in T cell-inflamed tumors...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28483787/a-sting-agonist-given-with-ox40-receptor-and-pd-l1-modulators-primes-immunity-and-reduces-tumor-growth-in-tolerized-mice
#15
Jeremy B Foote, Marleen Kok, James M Leatherman, Todd D Armstrong, Bridget C Marcinkowski, Laureen S Ojalvo, David B Kanne, Elizabeth M Jaffee, Thomas W Dubensky, Leisha A Emens
STING signaling induces interferon-β (IFNβ) production by intratumoral dendritic cells (DCs), driving T-cell priming and recruitment into the tumor microenvironment (TME). We examined to what extent pre-existing antigen tolerance influenced the efficacy of in situ delivery of a potent STING-activating cyclic dinucleotide (CDN), ADU S-100, against established HER-2(+) breast tumors. ADU S-100 induced HER-2-specific CD8(+) T-cell priming and durable tumor clearance in 100% of nontolerant parental FVB/N mice...
May 8, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468776/vulnerability-of-small-cell-lung-cancer-to-apoptosis-induced-by-the-combination-of-bet-bromodomain-proteins-and-bcl2-inhibitors
#16
Lloyd T Lam, Xiaoyu Lin, Emily J Faivre, Ziping Yang, Xiaoli Huang, Denise M Wilcox, Richard J Bellin, Sha Jin, Stephen K Tahir, Michael Mitten, Terry Magoc, Anahita Bhathena, Warren M Kati, Daniel H Albert, Yu Shen, Tamar Uziel
10% to 15% of all lung cancers are small cell lung cancer (SCLC). SCLC usually grows and metastasizes before it is diagnosed and relapses rapidly upon treatment. Unfortunately, no new targeted agent has been approved in the past 30 years for patients with SCLC. The BET (bromodomain and extra-terminal) proteins bind acetylated histones and recruit protein complexes to promote transcription initiation and elongation. BET proteins have been shown to regulate expression of key genes in oncogenesis such as MYC, CCND2, and BCL2L1 Here, we demonstrate that ~50% of SCLC cell lines are exquisitely sensitive to growth inhibition by the BET inhibitor, ABBV-075...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28468610/a-case-report-of-novel-mutation-in-prf1-gene-which-causes-familial-autosomal-recessive-hemophagocytic-lymphohistiocytosis
#17
Mohammad Reza Bordbar, Farzaneh Modarresi, Mohammad Ali Farazi Fard, Hassan Dastsooz, Nader Shakib Azad, Mohammad Ali Faghihi
BACKGROUND: Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis...
May 3, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28465481/genome-wide-screening-of-dna-methylation-associated-with-lymph-node-metastasis-in-esophageal-squamous-cell-carcinoma
#18
Hiroaki Nagata, Ken-Ichi Kozaki, Tomoki Muramatsu, Hidekazu Hiramoto, Kousuke Tanimoto, Naoto Fujiwara, Seiya Imoto, Daisuke Ichikawa, Eigo Otsuji, Satoru Miyano, Tatsuyuki Kawano, Johji Inazawa
Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28457810/chronic-stress-suppresses-anti-tumor-tcd8-responses-and-tumor-regression-following-cancer-immunotherapy-in-a-mouse-model-of-melanoma
#19
Annette Sommershof, Lisa Scheuermann, Julia Koerner, Marcus Groettrup
Animal tumor models and human cancer studies have provided convergent evidence that chronic psychological stress plays a decisive role in modulating anti-tumor T cell immunity. However, whether chronic stress also affects anti-cancer vaccine strategies that rely on the induction of functional tumor-specific TCD8+ cells has not been investigated yet. In this study we provide direct evidence that chronic stress suppresses the therapeutic efficacy of a biodegradable poly(d,l-lactide-co-glycolide) microsphere (PLGA-MS) based cancer vaccine in a murine melanoma model...
April 27, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28454374/arsenic-trioxide-inhibits-tumor-induced-myeloid-derived-suppressor-cells-and-enhances-t-cell-activity
#20
Qingmin Gao, Jingwei Jiang, Zhaohui Chu, Hao Lin, Xinli Zhou, Xiaohua Liang
Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor...
April 2017: Oncology Letters
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