Abstract：
:Cancer radiotherapy may be immunogenic, but it is unclear why its immunogenic effects are rarely sufficient to prevent tumor recurrence. Here, we report a novel Toll-like receptor 9 (TLR9)-dependent mechanism that initiates tumor regrowth after local radiotherapy. Systemic inhibition of TLR9, but not TLR4, delayed tumor recurrence in mouse models of B16 melanoma, MB49 bladder cancer, and CT26 colon cancer after localized high-dose tumor irradiation. Soluble factors in the microenvironment of regressing tumors triggered TLR9 signaling in freshly recruited myeloid cells appearing within four days of radiotherapy. The tumorigenic effects of TLR9 depended on MyD88/NF-κB-mediated upregulation of interleukin (IL)-6 expression, which in turn resulted in downstream activation of Jak/STAT3 signaling in myeloid cells. In comparing global gene expression in wild-type, TLR9-, or STAT3-deficient myeloid cells derived from irradiated tumors, we identified a unique set of TLR9/STAT3-regulated genes involved in tumor-promoting inflammation and revascularization. Blocking STAT3 function by two myeloid-specific genetic strategies corrected TLR9-mediated cancer recurrence after radiotherapy. Our results suggest that combining localized tumor irradiation with myeloid cell-specific inhibition of TLR9/STAT3 signaling may help eliminate radioresistant cancers.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gao C,Kozlowska A,Nechaev S,Li H,Zhang Q,Hossain DM,Kowolik CM,Chu P,Swiderski P,Diamond DJ,Pal SK,Raubitschek A,Kortylewski Mdoi
10.1158/0008-5472.CAN-13-1314subject
Has Abstractpub_date
2013-12-15 00:00:00pages
7211-21issue
24eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-13-1314journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Fes is a protein tyrosine kinase with cell autonomous oncogenic activities that are well established in cell culture and animal models, but its involvement in human cancer has been unclear. Abundant expression of Fes in vascular endothelial cells and myeloid cell lineages prompted us to explore roles for Fes in the tu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-3757
更新日期：2011-02-15 00:00:00
abstract：:Mutations in the human adenomatous polyposis (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. The APC gene is a tumor suppressor that has been termed the "gatekeeper gene" for colon ca...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:Monoclonal antibodies (MAbs) targeted to glioma-associated antigens may allow the selective delivery of imaging and therapeutic agents to brain tumors; the use of MAb fragments may be a strategy to further improve tumor uptake of such agents relative to normal tissues. In this study, we have examined the in vivo local...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-10-15 00:00:00
abstract：:The early cellular and molecular changes in the Solt-Farber model of hepatocarcinogenesis with and without initiation was studied by using histochemical, immunohistochemical, and in situ hybridization techniques. Increased cellularity was observed in the periductal space in both models 32 to 56 h after partial hepatec...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:Hypoxia drives malignant progression in part by promoting accumulation of the oncogenic transcription factor hypoxia inducible factor-1α (HIF-1α) in tumor cells. Tumor aggressiveness also relates to elevation of the cancer stem cell-associated membrane protein CD24, which has been causally implicated in tumor formatio...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-3666
更新日期：2012-11-01 00:00:00
abstract：:A human immunoglobulin that binds prostatic acid phosphatases (PAP) was isolated from the serum of normal individuals by affinity chromatography using a PAP-Sepharose solid adsorbent. The yield of isolated protein, termed PAP-binding globulin (PAPBG), ranged from 4.7 to 16.3 microgram/ml serum. As shown by immunoelect...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-08-01 00:00:00
abstract：:SOX9 is a transcription factor that plays a critical role in the development of multiple tissues. We previously reported that SOX9 in normal human adult prostate was restricted to basal epithelium. SOX9 was also expressed in a subset of prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa. ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5915
更新日期：2008-03-15 00:00:00
abstract：:Previous studies from our laboratory have shown that the activation of G(2)-M checkpoint after exposure of MCF-7 breast cancer cells to gamma-irradiation (IR) is dependent on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Studies presented in this report indicate that IR exposure of MC...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5818
更新日期：2008-07-01 00:00:00
abstract：:Enhancement of specific transplantation resistance to a syngeneic tumor (KMT-17) was observed in WKA rats by treatment with the antileukemia drug busulfan (BU) (15 mg/kg) 5 days before and 5 days after immunization with X-irradiated KMT-17 tumor cells. Rats immunized with X-irradiated KMT-17 cells and then treated wit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:Tumor-derived cell lines are used as in vitro cancer models, but their ability to accurately reflect the phenotype and genotype of the parental histology remains questionable, given the prevalence of documented cell line-specific cytogenetic changes. We have addressed the issue of whether copy number alterations seen ...
journal_title：Cancer research
pub_type： 杂志文章,meta分析
doi：10.1158/0008-5472.CAN-06-3674
更新日期：2007-04-15 00:00:00
abstract：:The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease e...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-2185
更新日期：2015-04-01 00:00:00
abstract：:The NY-ESO-1 gene product is expressed by a range of human tumors and is recognized by antibodies from sera of cancer patients with NY-ESO-1-expressing tumors. The NY-ESO-1 gene also encodes several MHC class I- and MHC class II-restricted tumor epitopes recognized by T lymphocytes. In particular, we previously report...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-01-01 00:00:00
abstract：:To investigate the influence of interleukin 6 (IL-6) production on malignancy of tumor cells we transfected cells of the high-metastatic, low-immunogenic D122 clone of the Lewis lung carcinoma with a mammalian expression vector containing the human IL-6 complementary DNA. In vitro, IL-6 positive transfectants showed g...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:In most patients with chronic myeloid leukemia (CML), the disease can be kept under control using the BCR/ABL kinase inhibitor imatinib. Nevertheless, resistance or intolerance to imatinib and other BCR/ABL inhibitors may occur during therapy. Therefore, CML research is focusing on novel targets and targeted drugs. Po...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-2181
更新日期：2010-02-15 00:00:00
abstract：:The expression of monomorphic determinants of the histocompatibility leukocyte antigens (HLA) class I antigens by human malignant tumor cells was studied in tissue specimens of 70 primary tumor lesions obtained from patients with carcinoma of the breast (41 patients), colon (8 patients), urinary bladder (8 patients), ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:The nucleoside analogue 1-beta-D-arabinofuranosylcytosine (ara-C) is incorporated into herpes simplex virus type 1 (HSV-1) DNA, and this correlates with inhibition of virus replication. The technique of Weigle-type reactivation (WR) was used to compare the ability of induced cellular DNA repair pathways to recognize o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Peroxisome proliferators (PPs) act as nongenotoxic tumor promoters in rodents. Their hepatocarcinogenicity requires the presence of the PP-activated receptor alpha (PPARalpha); however, the exact role played by this transcription factor in the liver, more precisely in liver cell growth and differentiation, is not know...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzym...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:Indomethacin, an inhibitor of prostaglandin (PG) synthesis, was investigated for its ability to increase radioresponse of two fibrosarcomas, FSA and NFSA, in C3Hf/Kam mice. In addition, the effect of indomethacin on radioresponse of hematopoietic tissue, jejunum, hair follicles, and tissues involved in the development...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:Verapamil has been shown to enhance immunotoxin activity but only at concentrations that are too high for in vivo use. Therefore, four structural analogues of verapamil (D792, D595, D528, and Sz45) were evaluated for their ability to enhance the in vitro activity of immunotoxins made with either ricin A chain or Pseud...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:We performed parallel array comparative genomic hybridization and array expression analysis of the 12p11-p12 amplicon in human testicular seminomas and an ovarian carcinoma cell line using an expressed sequence tags (ESTs) array spotted with 8254 ESTs. The data were normalized using a robust statistical modeling and t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-11-01 00:00:00
abstract：:One of the most promising new avenues for the development of more selective and efficacious cancer therapies relies on the antibody-mediated targeted delivery of bioactive agents (e.g., cytokines) to the tumor environment. The identification of quantitative differences in the expression of accessible vascular proteins...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-1436
更新日期：2007-11-15 00:00:00
abstract：:The photosensitization and survival recovery of cultured EJ human urinary bladder carcinoma cells containing nonexchangeable hematoporphyrin derivative (HPD) were studied. Cultures were incubated at 37 degrees C in growth medium supplemented with HPD (50 micrograms/ml) and 5% fetal bovine serum for 12 h followed by in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:A balanced lipid metabolism is crucial for all cells. Disturbance of this homeostasis by nonphysiological intracellular accumulation of fatty acids can result in apoptosis. This was proven in animal studies and was correlated to some human diseases, like lipotoxic cardiomyopathy. Some metabolic mechanisms of lipo-apop...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-03-3149
更新日期：2004-06-01 00:00:00
abstract：:The discovery of oncogenic driver mutations and the subsequent developments in targeted therapies have led to improved outcomes for subsets of lung cancer patients. The identification of additional oncogenic and drug-sensitive alterations may similarly lead to new therapeutic approaches for lung cancer. We identify an...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3771
更新日期：2015-08-01 00:00:00
abstract：:Heparanase is an enzyme that cleaves heparan sulfate chains of proteoglycans, and its expression has been associated with increased growth, metastasis, and angiogenesis of some tumors. Because myeloma tumor cells express high levels of the syndecan-1 heparan sulfate proteoglycan and because these tumors grow as highly...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-15 00:00:00
abstract：:Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adr...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-10-01 00:00:00
abstract：:The effect of basic fibroblast growth factor (b-FGF), one of the commonest angiogenic factors in various cancer types, on lymphocyte adhesion and transmigration across the endothelial cell monolayer was investigated using human umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty-eight h exp...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Copy number alterations are crucial for the development of colorectal cancer. Our whole-genome analysis identified tocopherol alpha transfer protein-like (TTPAL) as preferentially amplified in colorectal cancer. Here we demonstrate that frequent copy number gain of TTPAL leads to gene overexpression in colorectal canc...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-2986
更新日期：2019-07-01 00:00:00
