Abstract:
:Dendritic cells (DCs) are antigen presenting cells that play a role in T-cell activation. Liver-associated natural killer T lymphocytes (NKTs) are a unique subset of lymphocytes that may be important in antitumor immunity. Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) expresses hepatitis B virus surface antigen (HBsAg) on its cell surface and may serve as a tumor-associated antigen. The aim of the study was to evaluate the antitumor effect of DC pulsed with tumor or viral-associated antigens in HBV-expressing HCC in mice and to determine the role of NKT lymphocytes in this process. Balb/c mice were sublethally irradiated and transplanted with Hep3b HCC cell line, followed by transplantation of naive splenocytes. DCs were separated using CD11c beads and pulsed with HBV-enveloped proteins (group A), HCC cell lysate (group B), or BSA (control group C). Mice were followed for survival and tumor size. To determine the mechanism of the antitumor effect, intrasplenic and intrahepatic lymphocyte subpopulations were analyzed by FACS for NKT, CD4 and CD8 markers. Tumor-associated antigens-specific IFNgamma ELISPOT, T-cell proliferation assays and serum cytokine analysis were performed. Treatment with tumor-associated antigen-pulsed DC significantly improved survival (40% and 50% as compared with 0% in groups A, B, and control group C, respectively; p < 0.005). Tumor size decreased to 12.8 +/- 0.4 and 0 from 60.4 +/- 0.9 mm(3) in groups A, B, and control group C, respectively (p < 0.005). Adoptive transfer of HBV or Hep3b-associated antigens-pulsed DC induced a 6-fold increase in peripheral CD8(+) lymphocytes (from 1% in control mice to 6% and 5.5% in groups A and B, respectively), along with a decrease in CD4(+) lymphocytes (from 3.5% in controls to 1.4% and 2.3% in A and B, respectively; p < 0.005). The CD8(+)/CD4(+) ratio increased from 0.28 in controls to 4.28 and 2.39 in groups A and B, respectively (p < 0.005). Intrasplenic NKT cells increased from 7% in control mice to 7.98% and 14.6% in groups A and B, respectively. In contrast, an opposite shift was observed inside the liver. Intrahepatic lymphocyte analysis showed a marked increase in CD4(+) and a decrease in CD8(+) lymphocytes in treated groups. The intrahepatic CD4(+) number increased from 0.5% in controls to 2.15% and 25.8% in groups A and B, respectively (p < 0.005). In contrast, a significant decrease in the intrahepatic CD8(+) numbers was observed (from 7% in controls to 1.0% and 2.4% in groups A and B, respectively; p < 0.005). A significant increase was noted in HBV-specific IFNgamma spot-forming T-cell colonies from 0.0 to 8.8 +/- 1.7 and 1.8 +/- 2.9 in groups C, A, and B, respectively (p < 0.005). Similarly, a significant increase in the HBV-specific T-cell stimulation index, from 0.8 +/- 0.2 to 7.2 +/- 0.4, in groups C and B, respectively, was noted (p < 0.002). IFNgamma and IL12 serum levels increased significantly in treated groups. IFNgamma and IL12 serum levels increased to 380 +/- 30 and 400 +/- 20, and 960 +/- 40 and 760 +/- 60 in groups A and B, compared with 150 +/- 16 and 490 +/- 40 pg/ml in control mice (p < 0.005). Tumor antigen-pulsed DCs effectively suppressed the growth of hepatocellular carcinoma in mice. This effect was associated with enhanced NKT and CD8(+) lymphocyte function and augmentation of the antitumor/antiviral-specific IFNgamma production.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Shibolet O,Alper R,Zlotogarov L,Thalenfeld B,Engelhardt D,Rabbani E,Ilan Ydoi
10.1002/ijc.11201keywords:
subject
Has Abstractpub_date
2003-08-20 00:00:00pages
236-43issue
2eissn
0020-7136issn
1097-0215journal_volume
106pub_type
杂志文章abstract::Endometrial cancer (EC) shares some environmental or genetic risk factors with colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis colorectal cancer) and, in this syndrome, it has the same inheritance pattern as CRC....
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980703)77:1<29::aid-ijc6
更新日期:1998-07-03 00:00:00
abstract::Multiple myeloma, a neoplasm of plasma cells, accounts for approximately approximately 15% of lymphatohematopoietic cancers (LHC) and 2% of all cancers in the US. Incidence rates increase with age, particularly after age 40, and are higher in men, particularly African American men. The etiology is unknown with no esta...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.22718
更新日期:2007-01-01 00:00:00
abstract::IL-15 is an immunostimulatory cytokine with IL-2-like activities. To exploit the potential role of IL-15 in cancer immuno-/gene therapy, we engineered murine TS/A cells with different IL-15 cDNA constructs. Significant IL-15 secretion was achieved only by the use of a modified cDNA encoding for an IL-15 pre-protein be...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::The results of a survey of a population with a high incidence of oral and oesophageal cancer are presented. The population under study appears to have several epidemiologic characteristics, some of which may be associated with a high incidence of oral and oesophageal cancer. A remarkably high proportion (41%) of the m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360205
更新日期:1985-08-15 00:00:00
abstract::Breast cancer is a common malignancy with current biological therapies tailored to steroid hormone (ER, PR) and HER2 receptor status. Understanding the biological basis of resistance to current targeted therapies and the identification of new potential therapeutic targets is an ongoing challenge. The PI3K pathway is a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24831
更新日期:2010-03-01 00:00:00
abstract::Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) w...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31339
更新日期:2018-08-01 00:00:00
abstract::Loss of heterozygosity (LOH) on 10q is associated with late-stage events in urothelial neoplastic progression. The tumor suppressor gene PTEN, which is mutated or homozygously deleted in numerous cancers, maps to a region of 10q within the reported region of minimal loss in bladder tumors. In two recent studies altera...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(20001115)88:4<620::aid-ijc16>3.0
更新日期:2000-11-15 00:00:00
abstract::ErbB-2 and EGF receptors are often co-expressed in human tumors and have been shown to synergize in the transformation of cells in experimental model systems. Transactivation of ErbB-2 can occur via ligand-induced heterodimerization with EGF receptor or other members of the ErbB family of receptor tyrosine kinases. We...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960208)65:4<538::AID-IJC
更新日期:1996-02-08 00:00:00
abstract::Risk factors for pancreatic cancer, other than smoking and diabetes, are not well-established, especially for women. In a cohort of 1.3 million middle-aged women, followed for 9.2 million person-years for cancer incidence and 11.5 million person-years for mortality, there were 1,338 incident pancreatic cancer cases an...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24196
更新日期:2009-05-15 00:00:00
abstract::The relative expression of estrogen receptor (ER) and progesterone receptor (PR) mRNA transcripts was measured in 71 primary breast-cancer biopsies. ER and PR binding activity were estimated in parallel by the dextran-coated-charcoal method. There was a close correlation between the amount of ER mRNA and estradiol bin...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910590310
更新日期:1994-11-01 00:00:00
abstract::Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32920
更新日期:2020-06-01 00:00:00
abstract::The transcription factor PAX3 is expressed during early embryogenesis and in multiple cancer types, including embryonal rhabdomyosarcoma (ERMS), Ewing sarcoma (ES) and malignant melanoma (MEL), suggesting that it could function as a general tumor associated antigen. Major histocompatibility complex (MHC) peptide bindi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21817
更新日期:2006-07-01 00:00:00
abstract::Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10471
更新日期:2002-07-10 00:00:00
abstract::The Japanese have a much lower incidence of nonmelanoma skin cancers (NMSCs) than Caucasians, presumably due in part to their skin type conferring relative protection from ultraviolet light radiation (UVR). To examine the contribution of environmental or endogenous mutagens other than UVR, which are expected to be rel...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970502)71:3<370::aid-ijc
更新日期:1997-05-02 00:00:00
abstract::We evaluated the efficacy of a candidate melanoma vaccine approach in mice genetically prone to develop melanoma due to the introduction of an oncogenic mutation (R24C) in the germline sequence of the cyclin-dependent kinase 4 (cdk4), a protein critically involved in cell cycle regulation. Melanomas were induced in cd...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21349
更新日期:2006-01-15 00:00:00
abstract::Lymphatic leukemia developed in C57BL/6 mice following inoculation of normal thymocytes that and been co-cultured on leukemic thymus epithelial reticulum monolayer cells. Using thymocytes genetically marked in Ly membrane antigens, we showed that the thymomas which developed were produced by the co-cultured thymocytes...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910210119
更新日期:1978-01-15 00:00:00
abstract::Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910170102
更新日期:1976-01-15 00:00:00
abstract::Erythropoietin (Epo) regulates erythropoiesis by binding to its receptor (EpoR) and promoting cell proliferation, differentiation and inhibition of apoptosis. Epo is widely used to treat cervical cancer-related anaemia. However, there are data suggesting that administration of Epo is associated with an increment in re...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25935
更新日期:2011-12-01 00:00:00
abstract::Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage infiltrate surrounding the tumour, but the cellular/molecular interactions leading to TNF gene expression in macrophages are unknown. The in vitro system in which human blood monocytes are stimulated with human cancer cells for TNF release was used ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910560221
更新日期:1994-01-15 00:00:00
abstract::Receptors for the third component of complement (C3) were demonstrated on the surface of established human lymphoid cell lines by a membrane fluorescence test with FITC- or TRITC-conjugated antibodies against human C3. Two-color fluorescence staining of EBV receptors and C3 receptors showed complete overlapping of gre...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910170602
更新日期:1976-06-15 00:00:00
abstract::Although human NK cells lyse a wide spectrum of target cells, the precise target structure recognized by NK cells has not yet been elucidated. In order to define a possible relationship between gangliosides on human target cells and susceptibility to NK lysis, 14 human leukemia and lymphoma cell lines were studied. A ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910400104
更新日期:1987-07-15 00:00:00
abstract::Human oocytes in different stages of maturation were obtained by follicular aspiration from women given Clomovid and Gonadex. Particles similar to type-C virus were observed in three out of 16 oocytes. The particles were irregularly distributed along the oocyte membrane. They were seen both in a state of budding and l...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910280504
更新日期:1981-11-15 00:00:00
abstract::Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX is a promising tool in bladder-cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumo...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(20010601)92:5<671::aid-ijc1240>3
更新日期:2001-06-01 00:00:00
abstract::We have examined the effects of the synthetic matrix metalloproteinase inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme inhibitor, captopril, on metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990531)81:5<761::aid-ijc
更新日期:1999-05-31 00:00:00
abstract::Abnormal cell adhesion is an important contributing factor in invasion and metastasis. Here, we show that morphologically 'normal' cell-cell and cell-substratum adhesion can be restored to a poorly differentiated carcinoma cell line by activation of protein kinase C (PKC). This cell line, VACO 10MS, grows as multicell...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990129)80:3<455::aid-ijc
更新日期:1999-01-29 00:00:00
abstract::Although viral sequences closely related to feline leukaemia virus are represented in multiple copies in cellular DNA of all domestic cats, a specific fraction was present only in the virus-infected cells. This fraction was detected by viral cDNA enriched by a prior absorption of a total complementary DNA (cDNA) trans...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910220114
更新日期:1978-07-15 00:00:00
abstract::A pilot case-control study on bladder cancer, with population-based controls matched for each of 74 cases, has been conducted in two industrial areas of Southern Belgium in order to analyze the influence of tobacco use and occupation. Observed bladder cancer risk for smokers is more than 5 times higher than that for n...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910390304
更新日期:1987-03-15 00:00:00
abstract::Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25255
更新日期:2010-11-15 00:00:00
abstract::Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly in...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21192
更新日期:2005-11-10 00:00:00
abstract::Polyamines are essential for cell growth and differentiation. Their specific uptake contributes to the regulation of intracellular polyamine levels. In this study, we describe the modulation of this transport mechanism in a rat tumoral pancreatic acinar cell line (AR4-2J) and analyze the transport system characteristi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910490418
更新日期:1991-10-21 00:00:00