Abstract：
:HER-2/neu (neu-N) transgenic mice, which express the nontransforming rat proto-oncogene, develop spontaneous focal mammary adenocarcinomas beginning at 5-6 months of age. The development and histology of these tumors bears a striking resemblance to what is seen in patients with breast cancer. We have characterized the immunological responses to HER-2/neu (neu) in this animal model. neu-positive tumor lines, which were derived from spontaneous tumors that formed in neu-N animals, are highly immunogenic in parental, FVB/N mice. In contrast, a 100-fold lower tumor challenge is sufficient for growth in 100% of transgenic animals. Despite significant tolerance to the transgene, neu-specific immune responses similar to those observed in breast cancer patients can be demonstrated in neu-N mice prior to vaccination. Both cellular and humoral neu-specific responses in transgenic mice can be boosted with neu-specific vaccination, although to a significantly lesser degree than what is observed in FVB/N mice, indicating that the T cells involved are less responsive than in the nontoleragenic parental strain. Using irradiated whole-cell and recombinant vaccinia virus vaccinations we are able to protect neu-N mice from a neu-expressing tumor challenge. T-cell depletion experiments demonstrated that the observed protection is T cell dependent. The vaccine-dependent neu-specific immune response is also sufficient to delay the onset of spontaneous tumor formation in these mice. These data suggest that, despite tolerance to neu in this transgenic model, it is possible to immunize neu-specific T cells to achieve neu-specific tumor rejection in vivo. These transgenic mice provide a spontaneous tumor model for identifying vaccine approaches potent enough to overcome mechanisms of immune tolerance that are likely to exist in patients with cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Reilly RT,Gottlieb MB,Ercolini AM,Machiels JP,Kane CE,Okoye FI,Muller WJ,Dixon KH,Jaffee EMsubject
Has Abstractpub_date
2000-07-01 00:00:00pages
3569-76issue
13eissn
0008-5472issn
1538-7445journal_volume
60pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian,...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0061
更新日期：2014-11-15 00:00:00
abstract：:We have assessed the role of the p53 tumor suppressor gene in cell cycle arrest and cytotoxicity of ionizing radiation in 17 Burkitt's lymphoma and lymphoblastoid cell lines. Cell cycle arrest was assessed by flow cytometry of cells 16 h following irradiation. In addition to the usual G2 arrest, the cell lines exhibit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-10-15 00:00:00
abstract：:Metabolite profiling using (1)H nuclear magnetic resonance (NMR) spectroscopy was used to investigate the metabolic changes associated with deletion of the gene for the transcriptional coactivator p300 in the human colon carcinoma cell line HCT116. Multivariate statistical methods were used to distinguish between meta...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2999
更新日期：2006-08-01 00:00:00
abstract：:Here, we report the molecular regulation of interleukin (IL)-8 expression in human melanoma cells. The inflammatory cytokines IL-1beta and tumor necrosis factor-alpha (TNF-alpha) up-regulated IL-8 expression, in a time- and concentration-dependent manner, in three metastatic melanoma variants, SBC-2 (nonmetastatic), A...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:High levels of anti-phosphatidylinositol (PtdIns) autoantibodies (autoAb) have been previously described in sera of cancer patients and in plasma of dimethylbenzanthracene-treated female Sprague-Dawley rats. The presence of anti-PtdIns autoAb was tested in a model of highly malignant sarcomas induced by a single dose ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-05-15 00:00:00
abstract：:The expression of genes involved in p53-mediated apoptosis was studied using cDNA microarray after treating isogenic cell lines with either ionizing radiation or doxorubicin. Most of the known p53 transcriptional activation target genes clustered in a functional category defined by early and p53-dependent induction, r...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-09-15 00:00:00
abstract：:We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-01-15 00:00:00
abstract：:The population of California and the San Francisco Bay Area has a number of ethnic components that differ in the frequency with which certain cancers occur. Mortality rates of California Janpanese and incidence data from the cancer reporting system of the Bay Area are analyzed for the cancer sites considered related t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
abstract：:Four murine monoclonal antibodies against human lung carcinoma were generated using a novel immunization procedure. BALB/c mice were rendered neonatally tolerant to normal human lung tissues and subsequently immunized with human lung tumor tissues. The lower level of antibody-reactivity to the tolerogen was seen in th...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:Each tumor harbors unique repertoire of mutated antigenic peptides that are immunogenic and potentially can induce tumor-specific immune responses. Because heat shock proteins (HSPs) have the promiscuous ability to chaperone and present a broad repertoire of tumor antigens to antigen presenting cells, HSP tumor vaccin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-11-01 00:00:00
abstract：:The thiopurines 6-thioguanine (6TG) and 6-mercaptopurine (6MP) are cytotoxic to proliferating cells by a mechanism involving incorporation into DNA via the purine salvage pathway, and resistance to these agents can be conferred by lack of the salvage pathway enzyme hypoxanthine-guanine phosphoribosyltransferase. Howev...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-10-15 00:00:00
abstract：:The distribution and localization of a glioma-associated antigen defined by monoclonal antibody 81C6 has been examined using human cultured cell lines and tissues. Monoclonal antibody 81C6 was selected from a hybridoma fusion of spleen cells of mice immunized with the glial fibrillary acidic protein-positive human gli...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-06-01 00:00:00
abstract：:We investigated the prognostic value of p53 mutation type for 145 soft tissue sarcoma patients. In a PCR-SSCP-sequencing analysis, 15 mutations were identified: 10 non-frameshift (non-fs) and 5 frameshift (fs) mutations. Patients possessing non-fs mutations had a significantly poorer prognosis than patients without p5...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-09-15 00:00:00
abstract：:Previous work in our laboratory has demonstrated that antisera to proteins found in the urine of bladder cancer patients can distinguish between urine samples from these patients and those from normal individuals when tested by a complement-fixation assay. Antisera which were reactive with individual tumor-associated ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-07-01 00:00:00
abstract：:The specific activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase was measured in lymphocytes isolated from the blood of normal subjects, from patients with chronic lymphocytic leukemia, and from tonsil tissue. The mean specific activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase in the ly...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:Genetic differences in metabolism of benzo(a)pyrene (BP) were investigated using cultured epidermal keratinocytes and dermal fibroblasts isolated from four inbred strains of mice: C3H/HeJms and C57BL/6J that are responsive; and DBA/2 and AKR/Jms that are nonresponsive in terms of inducibility of aryl hydrocarbon hydro...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-08-01 00:00:00
abstract：:Embryonal carcinoma cells localize to a specific array of target tissues including the male submaxillary gland following intracardiac injection. These target tissues or conditioned medium derived from them have been shown to stimulate the in vitro migration of embryonal carcinoma cells. Here we show that in vitro migr...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Ultrastructural studies of the effects of adriamycin on liver and cardiac cell nucleoli of the rat showed that nucleolar segregation occurred within 1 hr after an i.v. injection of a 40-mg/kg dose. Between 3 and 27 hr after this single dose, liver cell nucleoli progressively reverted to a normal ultrastructure. Nucleo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:The aim of this study was to determine whether buccal mucosa would provide an alternate source of tissue for human biomonitoring. Samples of clinically normal oral biopsies were excised, and buccal mucosa were scraped or brushed from patients while they were undergoing surgery for the excision of intra-oral squamous c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-03-15 00:00:00
abstract：:Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:The immune response against murine IgG2a immunoglobulin was studied in 42 gastrointestinal cancer patients treated with mouse monoclonal antibodies. IgM, IgA, and all 4 IgG subclasses directed against mouse immunoglobulin were studied. Thirty of 42 patients developed an anti-mouse response of IgG isotype, often associ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:The role of Janus-activated kinase (JAK) signaling in cell cycle transit and maintenance of genomic stability was determined in HL-60 myeloblastic leukemia cells. Inhibition of JAKs, all JAKs (JAK1, JAK2, JAK3, and tyrosine kinase 2), JAK2, or JAK3, caused a significant reduction in cell growth with a major G2-M arres...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0972
更新日期：2006-09-15 00:00:00
abstract：:In this study, using the carcinoembryonic antigen (CEA)-expressing C15 murine colon carcinoma system in syngeneic C57BL/6 mice, we have evaluated the efficacy of bone marrow-derived dendritic cells (DCs) pulsed with the murine anti-idiotype antibody 3H1 as a tumor vaccine. Anti-idiotype 3H1 mimics a distinct and speci...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-06-01 00:00:00
abstract：:The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in patients with VHL disease and in the majority of patients with sporadic renal cell carcinomas (RCCs). RCCs are dependent on insulin-like growth factor-1 receptor-mediated signaling for tumor growth and invasion in vivo. Reintroduction of the VHL gene prod...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:Activity increase of the cytosolic isozyme of thymidine kinase (TK) in resected specimens of lung tumor patients would be a useful marker for tumor malignancy and prognosis. In 24 resected cases of malignant lung tumors, the whole enzyme extracts of the tumorous part of the specimens showed that the activities of TK, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:Cutaneous melanomas have been found to express several immunogenic differentiation melanoma-associated antigens (MAAs) that have been suggested to play an important role in disease outcome. Adaptive host immunity to MAAs has shown some level of control on melanoma progression. To date, there has been no definitive rep...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-01-15 00:00:00
abstract：:Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the i...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-2689
更新日期：2020-05-15 00:00:00
abstract：:The localization of biliary glycoprotein (BGP) and its mRNA in normal colonic mucosa was studied by immunohistochemistry and in situ hybridization. BGP mRNA was confined to columnar epithelial cells and expressed abundantly in the superficial mature cells and at low levels in differentiating cells in the upper crypts....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-07-15 00:00:00
abstract：:Focal adhesion kinase (FAK) functions downstream of integrins and growth factor receptors to promote tumor cell motility and invasion. In colorectal cancer, FAK is activated by amidated gastrin, a protumorigenic hormone. However, it is unclear how FAK receives signals from the gastrin receptor or other G-protein-coupl...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2894
更新日期：2011-01-15 00:00:00
abstract：:Integrin β3 is critical for tumor invasion, neoangiogenesis, and inflammation, making it a promising cancer target. However, preclinical and clinical data of integrin β3 antagonists have demonstrated no benefit or worse outcomes. We hypothesized that integrin β3 could affect tumor immunity and evaluated tumors in mice...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-2663
更新日期：2016-06-15 00:00:00
