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https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#1
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28912777/class-a-cpg-oligonucleotide-priming-rescues-mice-from-septic-shock-via-activation-of-platelet-activating-factor-acetylhydrolase
#2
Yoshinari Yamamoto, Ryu Sugimura, Takafumi Watanabe, Suguru Shigemori, Takuma Okajima, Shireen Nigar, Fu Namai, Takashi Sato, Tasuku Ogita, Takeshi Shimosato
Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF) induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585) strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#3
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28906259/radiation-and-immunotherapy-in-high-grade-gliomas-where-do-we-stand
#4
Elizabeth Reznik, Andrew W Smith, Shoshana Taube, Justin Mann, Menachem Z Yondorf, Bhupesh Parashar, A Gabriella Wernicke
High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease...
September 12, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28904888/routine-clinical-use-of-circulating-tumor-cells-for-diagnosis-of-mutations-and-chromosomal-rearrangements-in-non-small-cell-lung-cancer-ready-for-prime-time
#5
REVIEW
Emma Pailler, Vincent Faugeroux, Marianne Oulhen, Cyril Catelain, Françoise Farace
In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28898188/contrast-enhanced-us-approach-to-the-diagnosis-of-focal-liver-masses
#6
David P Burrowes, Alexandra Medellin, Allison C Harris, Laurent Milot, Stephanie R Wilson
Focal liver lesions are commonly encountered and often demonstrate nonspecific findings at initial imaging. Although most incidentally discovered liver lesions are benign, their noninvasive diagnosis is necessary, especially if they are large or atypical. Imaging characterization of focal liver lesions and exclusion of malignancy are of prime importance, particularly in high-risk populations. Contrast agent-enhanced ultrasonography of liver lesions is both accurate and reproducible for evaluation of benign and malignant liver tumors...
September 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#7
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28889919/emerging-immunotherapy-in-advanced-renal-cell-carcinoma
#8
REVIEW
Prateek Mendiratta, Brian I Rini, Moshe C Ornstein
Immunotherapy has recently catapulted to the forefront of treatments for patients with solid tumors. Given its inherent immunogenic properties, renal cell carcinoma (RCC) has historically responded to immunotherapy and remains primed for further development. Although immunotherapy with high-dose interleukin 2 was a primary treatment for advanced RCC (aRCC), recent discoveries of key molecular and immunological alterations have led to the FDA-approval of nivolumab, an antiprogrammed cell death inhibitor, which has demonstrated an overall survival in patients with previously treated aRCC...
September 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28884480/blood-monocytes-sample-melana-mart1-antigen-for-long-lasting-cross-presentation-to-cd8-t-cells-after-differentiation-into-dendritic-cells
#9
Florence Faure, Mabel Jouve, Isabelle Lebhar-Peguillet, Charlotte Sadaka, Fernando Sepulveda, Olivier Lantz, Stefano Berre, Raphael Gaudin, Silvia Sánchez-Ramón, Sebastian Amigorena
Human blood monocytes are very potent to take up antigens. Like macrophages in tissue, they efficiently degrade exogenous protein and are less efficient than dendritic cells at cross-presenting antigens to CD8(+) T cells. Although it is generally accepted that dendritic cells take up tissue antigens and then migrate to lymph nodes to prime T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented so far. In the present work, we show that monocytes loaded in vitro with MelanA long peptides retain the capacity to stimulate antigen-specific CD8(+) T cell clones after 5 days of differentiation into monocytes-derived dendritic cells (MoDC)...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28884337/the-multifaceted-role-of-periostin-in-priming-the-tumor-microenvironments-for-tumor-progression
#10
REVIEW
Dan Cui, Zhengjie Huang, Yingfu Liu, Gaoliang Ouyang
Tumor microenvironment consists of tumor cells, stromal cells, extracellular matrix and a plethora of soluble components. The complex array of interactions between tumor cells and their surrounding tumor microenvironments contribute to the determination of the fate of tumor cells during tumorigenesis and metastasis. Matricellular protein periostin is generally absent in most adult tissues but is highly expressed in tumor microenvironments. Current evidence reveals that periostin plays a critical role in establishing and remodeling tumor microenvironments such as the metastatic niche, cancer stem cell niche, perivascular niche, pre-metastatic niche, fibrotic microenvironment and bone marrow microenvironment...
September 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28881739/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#11
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, Randy C Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880687/tnf-%C3%AE-potentiates-uric-acid-induced-interleukin-1%C3%AE-il-1%C3%AE-secretion-in-human-neutrophils
#12
Kohei Yokose, Shuzo Sato, Tomoyuki Asano, Makiko Yashiro, Hiroko Kobayashi, Hiroshi Watanabe, Eiji Suzuki, Chikako Sato, Hideko Kozuru, Hiroshi Yatsuhashi, Kiyoshi Migita
OBJECTIVE: Monosodium urate (MSU) has been shown to promote interleukin-1β (IL-1β) secretion in human monocytes, but the priming signals for NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway remains elusive. In this study, we investigated the role of Tumor necrosis factor-alpha (TNF-α) on MSU-mediated IL-1β induction in human neutrophils. METHODS: Human neutrophils were stimulated with MSU, in the presence or absence of TNF-α priming...
September 7, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28880262/acceleration-of-pancreatic-tumorigenesis-under-immunosuppressive-microenvironment-induced-by-reg3g-overexpression
#13
Xiulan Liu, Zhongshi Zhou, Qi Cheng, Hongjie Wang, Hui Cao, Qianqian Xu, Yali Tuo, Li Jiang, You Zou, Hongyu Ren, Ming Xiang
Reg3g is a potential risk for pancreatic ductal adenocarcinoma (PDAC). We previously demonstrated that Reg3g promoted pancreatic carcinogenesis via a STAT3 signaling pathway in a murine model of chronic pancreatitis. Whether the immune response is involved in tumorigenesis induced by Reg3g remains unknown. In this study, Reg3g-regulated tumor immunity was evaluated in tumor-implanted murine models, immune cells, and tumor microenvironment. In mice that had been orthotopically or ectopically implanted with Panc02 cells, Reg3g overexpression increased EGFR and Ki67, diminished MHC-I and caspase-3 expression, and accelerated growth of tumors...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28877735/priming-astrocytes-with-tnf-enhances-their-susceptibility-to-trypanosoma-cruzi-infection-and-creates-a-self-sustaining-inflammatory-milieu
#14
Andrea Alice Silva, Rafael Rodrigues Silva, Daniel Gibaldi, Rafael Meyer Mariante, Jessica Brandão Dos Santos, Isabela Resende Pereira, Otacílio Cruz Moreira, Joseli Lannes-Vieira
BACKGROUND: In conditions of immunosuppression, the central nervous sty 5ystem (CNS) is the main target tissue for the reactivation of infection by Trypanosoma cruzi, the causative agent of Chagas disease. In experimental T. cruzi infection, interferon gamma (IFNγ)(+) microglial cells surround astrocytes harboring amastigote parasites. In vitro, IFNγ fuels astrocyte infection by T. cruzi, and IFNγ-stimulated infected astrocytes are implicated as potential sources of tumor necrosis factor (TNF)...
September 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28871357/-immunotherapy-as-modern-tumor-treatment
#15
REVIEW
C Grüllich
BACKGROUND: The specific immune system is capable of preventing the development of tumor diseases and stimulation of cytotoxic T‑lymphocytes can repress existing tumors. The activation of T‑lymphocytes is influenced by a new class of antibody-based medication, the immune checkpoint inhibitors. METHODS: Review of the scientific background and the published clinical trials on the activity and approval of immune checkpoint inhibitors for various tumor diseases...
September 4, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28866803/personalized-ex-vivo-multiple-peptide%C3%A2-enrichment-and-detection-of-t-cells-reactive-to-multiple-tumor-associated-antigens-in-prostate-cancer-patients
#16
Pavla Taborska, Dmitry Stakheev, Zuzana Strizova, Katerina Vavrova, Michal Podrazil, Jirina Bartunkova, Daniel Smrz
Personalized peptide vaccination is a promising immunotherapeutic approach in prostate cancer (PCa). We therefore examined whether an approach, utilizing personalized multiple peptide-mediated ex vivo enrichment with effector T cells reactive to multiple tumor-associated antigens (TAAs), could be employed as a basis for the development of T cell immunotherapy of PCa. In this study, we used the non-adherent fraction (lymphocytes) of cryopreserved peripheral blood mononuclear cells from a leukapheretic product of biochemically recurrent (BR, n = 14) and metastatic hormone-refractory (HR, n = 12) PCa patients...
September 2, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28861931/the-ubiquitin-ligase-trim25-inhibits-hepatocellular-carcinoma-progression-by-targeting-metastasis-associated-1-protein
#17
Hong-Liang Zang, Sheng-Nan Ren, Hong Cao, Xiao-Feng Tian
Metastasis associated 1 protein (MTA1) is one of the prime facilitators of metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanism of MTA1 expression in HCC is not clear. In this study, we evaluated MTA1 transcript and protein expression in HCC and normal hepatic cell lines. The results revealed that MTA1 protein expression had a significantly increase in HCC cell line, HuH6, compared with that in normal hepatic cell line, THLE-2. Determination of protein half-life using cycloheximide (CHX) treatment did not reveal any statistically significant difference in protein turn-over rates between THLE-2 (3...
August 31, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28859307/arthritis-is-inhibited-in-borrelia-primed-and-infected-interleukin-17a-deficient-mice-after-administration-of-anti-gamma-interferon-anti-tumor-necrosis-factor-alpha-and-anti-interleukin-6-antibodies
#18
Joseph Kuo, Thomas F Warner, Ronald F Schell
The role that cytokines play in the induction of Lyme arthritis is gradually being delineated. We showed previously that severe arthritis developed in a T-cell-driven murine model, even in mice lacking interleukin-17A (IL-17A) and administered anti-gamma-interferon (IFN-γ) antibody. Increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), two pro-inflammatory cytokines, were detected in cultures of popliteal lymph node cells obtained from these mice. We hypothesized that concomitantly administered anti-IL-6, anti-TNF-α and anti-IFN-γ antibodies would inhibit the development of arthritis in IL-17A-deficient mice...
August 31, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28855352/low-dose-cyclophosphamide-induces-anti-tumor-t-cell-responses-which-associate-with-survival-in-metastatic-colorectal-cancer
#19
Martin J Scurr, Tom Pembroke, Anja Bloom, David J Roberts, Amanda Thomson, Kathryn Smart, Hayley Bridgeman, Richard A Adams, Alison E Brewster, Robert Jones, Sarah Gwynne, Daniel Blount, Richard Harrop, Robert Hills, Awen Gallimore, Andrew Godkin
PURPOSE: Anti-cancer T-cell responses can control tumors, but immune-suppressive mechanisms in vivo prevent their function. The role of regulatory T-cells (Tregs) in metastatic colorectal cancer (mCRC) is unclear. We have previously shown depletion of Tregs enhances CRC-specific effector T-cell responses. Low dose cyclophosphamide (CPM) targets Tregs in animal models and some human studies, however the effect of CPM in mCRC is unknown. EXPERIMENTAL DESIGN: Fifty-five mCRC patients were enrolled onto a phase I/II trial and randomized to receive two week-long courses of low-dose (50mg twice-a-day) CPM or not...
August 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28854279/transfer-of-in-vitro-expanded-na%C3%A3-ve-t-cells-after-lymphodepletion-enhances-antitumor-immunity-through-the-induction-of-polyclonal-antitumor-effector-t-cells
#20
Tomohiro Tanaka, Satoshi Watanabe, Miho Takahashi, Ko Sato, Yu Saida, Junko Baba, Masashi Arita, Miyuki Sato, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Nobumasa Aoki, Yasuyoshi Ohshima, Takuro Sakagami, Tetsuya Abe, Hiroshi Moro, Toshiyuki Koya, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Toshiaki Kikuchi
The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult...
2017: PloS One
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