Abstract：
:CX3CR1+ macrophages in the intestinal lamina propria contribute to gut homeostasis through the immunomodulatory interleukin IL10, but there is little knowledge on how these cells or the CX3CR1 receptor may affect colorectal carcinogenesis. In this study, we show that CX3CR1-deficient mice fail to resolve gut inflammation despite high production of IL10 and have increased colitis and adenomatous polyps in chemical and genetic models of colon carcinogenesis. Mechanistically, CX3CL1-mediated engagement of the CX3CR1 receptor induced upregulation of heme-oxygenase-1 (HMOX-1), an antioxidant and anti-inflammatory enzyme. CX3CR1-deficient mice exhibited significantly lower expression of HMOX-1 in their adenomatous colon tissues. Combining LPS and CX3CL1 displayed a strong synergistic effect in vitro, but HMOX-1 levels were significantly lower in KO macrophages. Cohousing of wild-type and CX3CR1-/- mice during the AOM/DSS treatment attenuated disease severity in CX3CR1-/- mice, indicating the importance of the microbiome, but did not fully reinstate HMOX-1 levels and did not abolish polyp formation. In contrast, pharmacologic induction of HMOX-1 in vivo by cobalt protoporphyrin-IX treatment eradicated intestinal inflammation and fully protected KO mice from carcinogenesis. Taken together, our results establish an essential role for the receptor CX3CR1 in gut macrophages in resolving inflammation in the intestine, where it helps protects against colitis-associated cancer by regulating HMOX-1 expression. Cancer Res; 77(16); 4472-85. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Marelli G,Erreni M,Anselmo A,Taverniti V,Guglielmetti S,Mantovani A,Allavena Pdoi
10.1158/0008-5472.CAN-16-2501subject
Has Abstractpub_date
2017-08-15 00:00:00pages
4472-4485issue
16eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-2501journal_volume
77pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The operation of venereal factors in human cervical cancer is suggested by demographic and epidemiological data. Recent evidence supporting the genital herpesvirus hypothesis is consistent with this notion. A controlled epidemiological investigation has been undertaken on the role of the male coital partner in cervica...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1976-02-01 00:00:00
abstract：:Decreased BRCA1 expression in the absence of genetic mutation is observed frequently in sporadic cancers of the breast and other sites, although little is known regarding the mechanisms by which the expression of this gene can be repressed. Here, we show that activating and repressive E2Fs simultaneously bind the BRCA...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2119
更新日期：2005-12-15 00:00:00
abstract：:Male inbred F344 weanling rats were fed semipurified diets containing 20 or 5% beef fats. At 7 weeks of age, all animals except controls were given 1,2-dimethylhydrazine [DMH (150 mg/kg body weight s.c.; one dose)], methylazoxymethanol acetate [MAM acetate (35 mg/kg body weight i.p.; one dose)], or methylnitrosourea (...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:The induction of phase 2 detoxifying enzymes, such as UDP-glucuronosyltransferases (UGTs), in response to an array of naturally occurring and synthetic agents, such as oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione), provides an effective means of protection against a variety of carcinogens. Transcription fa...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1906
更新日期：2004-09-15 00:00:00
abstract：:Loss of DNA mismatch repair (MMR) increases the risk of spontaneous mutations. We sought to determine whether there was an interaction between hypoxia and MMR deficiency that might contribute to the phenomenon of tumor progression. Human colon carcinoma HCT116+ch2 (MMR-deficient) and HCT116+ch3 (MMR-proficient) sublin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-10-15 00:00:00
abstract：:The percentages of dark keratinocytes was quantitatively assessed in normal epidermis of Sencar mice before and after birth and in adult epidermis after topical application of several compounds of varying promoting efficiency. The percentage of dark keratinocytes reached a maximum at the 19th day of gestation (approxi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:This study was aimed to establish whether tamoxifen binds irreversibly to uterine DNA when given to women. Patients were given a single therapeutic dose of [(14)C]tamoxifen citrate orally (20 mg, 0.37 or 1.85 MBq) approximately 18 h prior to hysterectomy or breast surgery. Nonmalignant uterine tissue was separated int...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-01 00:00:00
abstract：:The cell cycle stimulation of individual species of the uracil DNA glycosylase was examined in WI-38 normal diploid fibroblasts. The nuclear uracil DNA glycosylase was induced as WI-38 cells traversed the cell cycle. In contrast, the specific activity of the mitochondrial glycosylase remained constant during cell prol...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:A monoclonal immunoglobulin M (IgM) antibody (38-13) which recognizes Burkitt's lymphoma (BL) cells, by reacting with the neutral glycolipid Gal alpha 1 leads to 4-Gal beta 1 leads to 4-Glc beta 1 leads to 1-ceramide, was recently characterized. This monoclonal IgM was coupled to either ricin A chain or gelonin. The t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:DNA damage inactivates cyclin-dependent kinases (CDKs) and arrests the cell cycle. Following DNA damage, the G1-S CDKs are inhibited by a mechanism involving p53-dependent induction of p21Cip1/Waf1; but how the Cdc2 is inhibited is less apparent. We found that the signal generated by the DNA damage checkpoint in G2 wa...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-11-15 00:00:00
abstract：:Rational therapeutic approaches based on synthetic lethality may improve cancer management. On the basis of a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL, and Mcl-1 is sufficient to elicit synthe...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-3424
更新日期：2017-07-01 00:00:00
abstract：:Molecular insights into how chronic stress affects lung tumorigenesis may offer new routes to chemoprevention. In this study, we show that chronic stress in mice chemically or genetically initiated for lung cancer leads to the release of norepinephrine and other catecholamines, thereby promoting lung tumorigenesis. Me...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-0990
更新日期：2016-11-15 00:00:00
abstract：:We compared L-phenylalanine mustard (L-PAM)-induced cytotoxicity and DNA cross-linking with and without a 42-h preincubation with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO, 1 mM) in a human lymphoma cell line. The combination showed increased toxicity with a Do ratio of 1.6. L-PAM-induc...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:The effects of the lipid-soluble dihydrofolate reductase inhibitor, trimetrexate, on the inhibition of thymidylate biosynthesis as a result of perturbation in cellular folate pools in H35 hepatoma cells in vitro has been investigated. Exposure of the cultures to increasing concentrations of trimetrexate between 2 and ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:MSN-1 is a monoclonal antibody, which was raised by immunizing mice with a human endometrial cancer cell line, SNG-II. The MSN-1 specifically recognizes a blood group carbohydrate antigen, Leb. We investigated the subcellular and suborganellar localization of the MSN-1-reactive carbohydrate antigens in the endometrial...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodessication. Although effective, surgery is costly and unsuitable for certain patients. Radiotherapy can leave a poor cosmetic effect, and current chemotherapy is limited by low cure rate...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-2837
更新日期：2004-04-15 00:00:00
abstract：:The renal handling of cis-diamminedichloroplatinum (CP) was investigated by measuring the renal clearance of creatinine, inulin, and free platinum in ten cancer patients. Free platinum clearances exceeded the glomerular filtration rate in all time periods. For example, at 1 to 2 hr, the mean clearance of free platinum...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:The expression of human leukocyte antigen (HLA) class I alleles was analyzed in 65 renal cell carcinomas using one-dimensional isoelectric focusing. Normal organ tissue and peripheral blood lymphocytes were used as controls. The patients were serologically typed using the standard microcytotoxicity test. Forty-two pat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-02-15 00:00:00
abstract：:We report here the use of viral fusogenic membrane glycoproteins (FMGs) as a new class of therapeutic genes for the control of tumor growth. FMGs kill cells by fusing them into large multinucleated syncytia, which die by sequestration of cell nuclei and subsequent nuclear fusion by a mechanism that is nonapoptotic, as...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-03-15 00:00:00
abstract：:All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isofor...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-2612
更新日期：2012-05-15 00:00:00
abstract：:The increase of interleukin-4 (IL-4) level in tumor environment and the up-regulation of IL-4 receptor (IL-4R) on tumor cells have been long observed. However, their significance for tumor development has not been investigated. Here, we found that endogenous IL-4 promotes tumor growth because neutralizing IL-4 by 11B1...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-0449
更新日期：2008-11-01 00:00:00
abstract：:A multilaminar alteration of endoplasmic reticulum (ER) has been observed in tumor cells of eight patients with Hodgkin's disease and a patient with histiocytic lymphoma. These multilaminar structures are more numerous in dividing cells and thus appear to arise primarily during mitosis. The stacked membranes in the mu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H) -one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L121...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Recombinant human gamma-interferon (IFN-gamma) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of gamma-interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Although chrysotile asbestos is a proven human carcinogen, several studies have concluded that these fibers are not mutagenic to cultured mammalian cells. We show here, on the other hand, that when tested using the AL cell system that detects both intragenic and multilocus mutations, chrysotile is indeed mutagenic and...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-11-15 00:00:00
abstract：:The Inflammation and Cancer Think Tank Meeting was organized by the National Cancer Institute with the purpose of identifying research advances, gaps, and opportunities for the study and clinical application of the role of inflammation on tumorigenesis. The format of this meeting consisted of brief presentations that ...
journal_title：Cancer research
pub_type：
doi：10.1158/0008-5472.CAN-05-1777
更新日期：2005-10-01 00:00:00
abstract：:Treatment of mice with the immunomodulator pyran copolymer inhibited leukemogenesis produced by Friend leukemia virus (FLV) complex, as evidenced by inhibition of the spleen focus-forming virus and lymphatic leukemia virus, as well as by a significant decrease in splenomegaly. In this report we present data suggesting...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:C19ORF5 is a sequence homologue of microtubule-associated proteins MAP1A/MAP1B of unknown function, except for its association with mitochondria-associated proteins and the paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Here, we show that when overexpressed in mammalian cells the recomb...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-3865
更新日期：2005-05-15 00:00:00
abstract：:Many N-nitroso compounds (NOC) are carcinogens. In this controlled study of 21 healthy male volunteers, levels of NOC on a high (420 grams) red meat diet were significantly greater (P = 0.001) than on a low (60 grams) meat diet but not significantly greater when an equivalent amount of vegetable protein was fed. An 8-...
journal_title：Cancer research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2003-05-15 00:00:00
