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1.
Antibodies reactive with the protein core of MUC1 mucin are present in ovarian cancer patients and healthy women 总被引:6,自引:0,他引:6
Elizabeth R. Richards Peter L. Devine Rachel J. Quin J. Darrell Fontenot Bruce G. Ward M. A. McGuckin 《Cancer immunology, immunotherapy : CII》1998,46(5):245-252
Antibodies reactive with peptide epitopes on the core protein of MUC1 epithelial mucin have been demonstrated in some patients
with adenocarcinomas. Because these epitopes can be exposed on MUC1 in the serum of healthy women, we measured concentrations
of MUC1-reactive antibodies in the serum of healthy pregnant and non-pregnant women, and in patients with benign and malignant
ovarian tumours. Antibodies were measured in an enzyme-linked immunosorbent assay utilising a synthetic peptide corresponding
to a 105-amino-acid segment of the MUC1 tandem repeat region (5.25 repeats). MUC1-reactive antibodies were always of an IgM
isotype and concentrations were highest in young healthy women and declined progressively with age (P = 0.0006) concomitantly with increasing serum MUC1 levels (P = 0.003). Regardless of age, antibody levels were lower in cancer patients than in healthy women (P<0.0001), but MUC1 levels were much higher in cancer patients (P<0.0001). Although high antibody levels were associated with greater survival in ovarian cancer (P = 0.015), multivariate regression analysis showed that this was not a significant independent prognostic indicator after
consideration of the International Federation of Gynaecology and Obstetrics (FIGO) stage, histological type, serum MUC1 levels
and age. Serial measurement of MUC1 and MUC1 antibodies during treatment in 18 patients with ovarian cancer and throughout
pregnancy in 10 women showed a negative correlation between alterations in MUC1 and MUC1 antibodies. These results show that
MUC1-peptide-reactive antibodies are present in the serum of healthy women and women with cancer and that they probably form
immune complexes with MUC1, but provide no evidence for an augmentation of the humoral immune response to MUC1 in ovarian
cancer
Received: 8 January 1998 / Accepted: 26 February 1998 相似文献
2.
Petrarca C Casalino B von Mensdorff-Pouilly S Rughetti A Rahimi H Scambia G Hilgers J Frati L Nuti M 《Cancer immunology, immunotherapy : CII》1999,47(5):272-277
The humoral immune response against a tumour-associated antigen, polymorphic epithelial mucin (PEM, MUC1) in cancer patients
was studied by isolating specific B cells primed for the antigen. Human B lymphocytes from tumour-draining lymph nodes, obtained
from 12 patients with epithelial cancers, were immunoselected with magnetic beads coated with a 60mer synthetic peptide corresponding
to three tandem repeats of the protein core of the MUC1 antigen. Short-term cultures of B cells were established utilizing
interleukin-10 (IL-10), IL-4 and monoclonal antibody anti-CD40, and were maintained for a maximum of 3␣weeks. B cell culture
supernatants contained human anti-MUC1 antibodies, as detected by enzyme-linked immunosorbent assay, in 6/12 of the patients
tested. Five of these patients, all with early-stage cancer, also had high levels of circulating anti-MUC1 IgM antibodies
in the serum. A significant correlation was found (two-tailed P = 0.041) between the presence of circulating anti-MUC1 antibodies and the ability to isolate PEM-specific B cells from tumour-draining
lymph nodes. The technique proposed provides a useful method for the analysis of natural immunity against defined tumour antigens.
Received: 30 June 1998 / Accepted: 5 October 1998 相似文献
3.
The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines 总被引:5,自引:0,他引:5
Arlen P Tsang KY Marshall JL Chen A Steinberg SM Poole D Hand PH Schlom J Hamilton JM 《Cancer immunology, immunotherapy : CII》2000,49(10):517-529
An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon γ production has been used to analyze specific T cell
responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA). Assays were performed on peripheral
blood mononuclear cells (PBMC) of HLA-A2-positive patients with CEA-expressing carcinomas, both before and after vaccination
with CEA-based vaccines, and from HLA-A2-positive healthy blood donors. The ELISPOT assay utilized aliquots of frozen PBMC,
and assays were performed after 24 h in culture with peptide to rule out any artifacts due to long-term in vitro stimulation
cycles. An internal standard was used for each assay to define reproducibility of the assay, and all samples from a given
patient (pre- and post-vaccination, with both the Flu and CEA peptides) were analyzed simultaneously. The results indicated
a trend towards healthy blood donors having higher levels of Flu-specific T cell precursors than do colon carcinoma patients,
but these results were not statistically significant (P = 0.06). On the other hand, slightly higher CEA-specific T cell responses were observed in cancer patients with CEA-expressing
carcinomas than in healthy blood donors. PBMC from two CEA-based vaccine clinical trials were analyzed for T cell responses
to the same CEA peptide and to the Flu control peptide. The first trial consisted of three monthly vaccinations of CEA peptide
(designated PPP) in adjuvant. The second trial consisted of cohorts receiving three monthly vaccinations of avipox-CEA recombinant
(designated AAA) or cohorts receiving a primary vaccination with recombinant vaccinia-CEA followed by two monthly vaccinations
with avipox-CEA (designated VAA). Few, if any, CEA-specific T cell responses were seen in the PPP vaccinations, while the
majority of patients receiving the poxvirus CEA recombinants demonstrated increases in CEA-specific T cell responses and no
increases in Flu-specific responses. CEA-specific IgG responses were also demonstrated in patients following recombinant CEA
poxvirus vaccinations. Statistical analyses of the T cell responses to the same CEA peptide demonstrated a P value of 0.028 for the recombinant poxvirus vaccines, as compared with the peptide vaccine. There were no differences seen
(P = 0.37) in Flu-specific responses after these two types of CEA vaccination. These results thus provide the first evidence
that poxvirus recombinant-based vaccines are more potent in the initiation of tumor-antigen-specific T cell responses than
vaccines employing peptide in adjuvant, when assays are conducted in an identical manner, and in defining responses to the
same peptide. These results also demonstrate for the first time that an ELISPOT assay, performed over a 24-h period and without
in vitro sensitization, can be successfully used to monitor immune responses to a tumor-associated antigen in cancer patients.
Received: 12 June 2000 / Accepted: 13 July 2000 相似文献
4.
Baritaki S Zafiropoulos A Georgopoulos E Souris S Krambovitis E 《Cancer immunology, immunotherapy : CII》2001,50(2):109-114
It has been demonstrated that IgG antibodies can be generated to self-antigen peptides as well as against viral antigens
by an antigen-specific in vitro immunization system of resting human peripheral B-lymphocytes. Using a synthetic peptide from
the consensus variable tandem-repeat region of the MUC3 mucin (TSSITTTGTTSHSTPSP) as the B cell epitope, we immunized blood
donor B-lymphocytes in vitro and tested for MUC3-specific antibodies by ELISA. After the primary activation step all antibodies
were IgM. At the end of the secondary immunization step we obtained 1.8% (21/1138) of the cultures with IgG-switched antibodies.
In a competitive inhibition ELISA using the MUC1, MUC2, MUC3, MUC4 and PIP2 peptides, only one culture (F8.1) gave satisfactory
specific inhibition. Using this antibody in fluorometric studies, it stained cells from two colon carcinoma cell lines predominantly
in the cytoplasm, whereas those from a breast cancer cell line stained predominantly the cell surface. In a preliminary immunohistological
evaluation with formalin-fixed sections, the antibody appeared to moderately stain colon sections, but not breast sections
or lymph node. This method of in vitro immunization may be a useful tool in generating IgG antibodies specific to self-antigens
and could find applications in tumour targeting and immunotherapy.
Received: 12 October 2000 / Accepted: 11 January 2001 相似文献
5.
Jin Song Xiaer Sun Lori J. Sokoll Masatoshi Maki Yuan Tian Daniel W. Chan Zhen Zhang 《Clinical proteomics》2009,5(2):125-131
Introduction Annexin A11 was previously identified as an autoantigen in 4.1–10.1% of patients with various systemic autoimmune diseases.
In this study, an enzyme-linked immunosorbent assay (ELISA) was developed to investigate the occurrence and features of anti-annexin
A11 autoantibodies in sera from patients with different types of cancer.
Methods The recombinant protein of GST fused to the N-terminal domain (1–175 residues) of human annexin A11 was expressed and used
as antigen in ELISA. A total of 246 serum specimens were analyzed, which includes sera from healthy women (77), patients with
ovarian cancer (72), breast cancer (18), colon cancer (19), pancreatic cancer (20), prostate cancer (20), and diabetes (20).
Results The overall titer of anti-annexin A11 autoantibodies in ovarian cancer patients (or primary tumors only) was found much higher
than that in healthy controls (P < 0.05). At the cut-off value designating positive reaction, anti-annexin A11 autoantibodies were detected in 12.5% (5/40)
of primary ovarian cancer patients with a significant difference from 2.6% (2/77) of the healthy controls (P < 0.05), but only in 6.25% (2/32) of recurrent tumors. ROC curve demonstrated the potential diagnostic value of anti-annexin
A11 autoantibodies in primary ovarian cancer patients with an AUC of 0.62 (0.52–0.73). Anti-annexin A11 autoantibodies were
also detected in 5.26% (1/19) of colon cancer and 10% (2/20) of diabetes patients but without significant difference from
the healthy controls.
Conclusion A convenient assay to detect anti-annexin A11 autoantibodies in patients was developed, and the experimental data are promising
but need to be expanded to address their biological/clinical relevance. 相似文献
6.
Lees CJ Apostolopoulos V Acres B Ong CS Popovski V McKenzie IF 《Cancer immunology, immunotherapy : CII》2000,48(11):644-652
MUC1 is a mucin over-expressed in breast cancer and a proposed target for immunotherapy. By immunising mice with MUC1 conjugated
to mannan (M-FP), CD8+ MHC-class-I restricted cytotoxic T lymphocytes (CTL), of high CTL precursor (CTLp) frequency (1/8000) and with significant
tumour protection, can be induced. The effect of various cytokines [interleukin-2 (IL-2), IL-4, IL-6, IL-7, interferon γ (IFNγ),
and granulocyte/macrophage-colony-stimulating factor (GM-CSF)] on the MUC1 CTL immune response was investigated (a) by measuring
the frequencies of CTLp in mice immunised with vaccinia virus constructs containing recombinant cytokines and M-FP, or (b)
by immunising cytokine- or cytokine-receptor-knockout (−/−) mice with M-FP. Vaccinia virus (VV) constructs containing recombinant
cytokines were used either individually or in combination in vivo with M-FP immunisation. M-FP immunisations combined with
VV-IL-2, VV-IL-7 and VV-GM-CSF, and combinations of VV-IFNγ + VV-IL-2, VV-IFNγ + VV-IL-4 or VV-GM-CSF + VV-IL-7 increased
CTLp frequencies up to threefold (1/17 666: M-FP + VV-GM-CSF + VV-IL-7) compared to M-FP (1/77 500) alone. By contrast, M-FP
combined with VV-IL-4 decreased the CTLp frequency threefold whereas VV-IL-6 and VV-IFNγ had no effect. Studies in cytokine-
and cytokine-receptor-gene-knockout (−/−) mice demonstrated that mice that are IL-2 −/− and IL-7 receptor −/− produce the
same CTLp response to M-FP as do control mice, whereas responses in the IL-6 −/−, IL-10 −/− and IFNγ−/− mice were marginally
improved and responses to M-FP in IL-4 −/− and tumour necrosis factor receptor 2 −/− mice were weaker. In spite of the increase
in CTLp frequency, this was not reflected in an in vivo tumour model. Tumour challenges using MUC1+ P815 cells, demonstrated that the addition of cytokines had little additive effect on the already effective tumour-regression
capabilities of M-FP alone.
Received: 24 September 1998 / Accepted: 21 September 1999 相似文献
7.
Budiu RA Mantia-Smaldone G Elishaev E Chu T Thaller J McCabe K Lenzner D Edwards RP Vlad AM 《Cancer immunology, immunotherapy : CII》2011,60(7):975-984
MUC1 (CA15-3) and MUC16 (CA125) tumor-associated antigens are upregulated in ovarian cancer and can be detected in patients’
sera by standardized tests. We postulated that increased MUC1 and MUC16 antigens augment antibody responses in platinum-resistant
ovarian cancer patients and that the frequency and intensity of these responses can be used as immune biomarkers of treatment
response and disease outcome. We measured MUC1 and MUC16 tumor expression by immunohistochemistry (IHC), assessed serum antigenic
levels and quantitated circulating antibodies by ELISA in a cohort of 28 ovarian cancer patients with platinum-resistant or
platinum-refractory ovarian cancer, and treated with intraperitoneal (IP) interleukin-2 (IL-2). MUC1 and MUC16 were overexpressed
in tumor samples and showed differential distribution profiles. Serum MUC1 (CA15-3) measurements were elevated in all patients
and significantly correlated with increased risk of death (P = 0.003). MUC1-specific IgM and IgG anitbodies were found in 92 and 50% of cases, respectively. Patients with progressive
disease had higher mean anti-MUC1 IgG than responders at both early (P = 0.025) and late (P = 0.022) time points during IP IL-2 treatment. Anti-MUC1 IgM antibodies inversely correlated with overall survival at both
early (P = 0.052) and late (P = 0.009) time points. In contrast to MUC1, neither soluble MUC16 nor MUC16-specific antibodies were significantly associated
with clinical response or overall survival in this study. Increased serum MUC1 and high anti-MUC1 antibody levels are prognostic
for poor clinical response and reduced overall survival in platinum-resistant or platinum-refractory ovarian cancer. 相似文献
8.
von Mensdorff-Pouilly S Kinarsky L Engelmann K Baldus SE Verheijen RH Hollingsworth MA Pisarev V Sherman S Hanisch FG 《Glycobiology》2005,15(8):735-746
The human epithelial cancer mucin MUC1 is able to break tolerance and to induce humoral immune responses in healthy subjects and in cancer patients. We recently showed that clusters of sequence-variant repeats are interspersed in the repeat domain of MUC1 at high frequency, which should contribute to the structural and immunological features of the mucin. Here we elucidated the potential effects exerted by sequence-variant repeats on their O-glycosylation. Evidence from in vitro glycosylation with polypeptide N-acetylgalactosaminyltransferases GalNAc-T1 and GalNAc-T2 in concert with mass spectrometric analyses of in vivo glycosylated MUC1 probes from transiently transfected HEK293 cells indicated reduced glycosylation densities of repeats with three concerted replacements: AHGVTSAPESRPAPGSTAPA. The Pro to Ala replacement in STAPA exerts not only proximal effects on the ppGalNAc-T2 preferred site at -3 and -4, but also more distant effects on the ppGalNAc-T1 preferred site at -15 (TSAPESRPAPGSTAPA). We also examined the conformational changes of MUC1 glycopeptides induced by the concerted DT to ES replacements and revealed a higher conformational flexibility of ES/P peptides compared to DT/P peptides. Differences in conformational flexibilities and in O-glycosylation densities could underlie the observed differential humoral responses in humans. We were able to show that the natural immunoglobulin G (IgG) responses to the repeat domain of MUC1 in sera from nonmalignant control subjects are preferentially directed to variant repeat clusters. In contrast, the IgG response in patients with adenocarcinoma shifted to higher frequencies of preferential DTR peptide binding. 相似文献
9.
The temperature dependence of the rate constants for the formation of oligocytidylate (oligo(C)) from the 5′-monophosphorimidazolide
of cytidine (ImpC) in the presence of Pb(II) ion catalyst has been investigated at 10–75°C. The rate constants for the formation
of oligo(C) increased in the order of the formation of 2-mer < 3-mer ≤ 4-mer; this trend resembles the trend in the cases
of the template-directed and the clay-catalyzed formations of oligonucleotides. While the rate constants of the formation
of oligo(C) increased with increasing temperature, the yield of oligo(C) decreased with increasing temperature. This is due
to the fact that the relative magnitude of the rate constants of the formation of 2-mer, 3-mer, and 4-mer to that of the hydrolysis
of ImpC decreased with increasing temperature. This is probably due to the fact that association between ImpC with the elongating
oligo(C) decreases with increasing temperature. The apparent activation energy was 61.9 ± 8.5 kJ mol−1 for the formation of 2-mer, 49.3 ± 2.9 kJ mol−1 for 3-mer, 51.8 kJ mol−1 for 4-mer, and 66.8 ± 4.5 kJ mol−1 for the hydrolysis of ImpC. The significance of the temperature dependence of the formation rate constants of the model prebiotic
formation of RNA is discussed. 相似文献
10.
A. M. Berghella Patrizia Pellegrini Tiziana Del Beato Matteo Marini Ennio Tomei Domenico Adorno Carlo Umberto Casciani 《Cancer immunology, immunotherapy : CII》1997,45(5):241-249
Current research has still not clarified the biological role of soluble interleukin(IL)-2 receptor (sIL-2R) and the significance
of its increase in the serum of colon cancer patients compared to healthy subjects. To address these questions at the immunological
level in a group of patients and healthy subjects, we determined the sIL-2R level in the serum and its release from peripheral
blood mononuclear cells (PBMC) as a function of tumour necrosis factor (TNF) α, IL-1α, IL-1β, IL-2, interferon (IFN) γ, IL-4,
IL-6 and IL-10 levels in the serum and PBMC production; and PBMC proliferative responses to IL-2, IL-4 and anti-CD3 monoclonal
antibody (CD3), variously combined. The level of sIL-2R in patients’ serum was higher than in healthy subjects and correlated
with the stage of advancement. Moreover, while in healthy subjects the serum level of sIL-2R was not significantly correlated
with other parameters, in patients it was positively related to IL-4, IL-6 and IL-10 serum levels, PBMC IL-4 production and
to the PBMC proliferative response to CD3 and CD3+IL-2; it was negatively correlated to IL-2 serum level and IL-1β PBMC release.
A negative connection between IFNγ serum level and the PBMC production of sIL-2R was also found. This suggests that the increase
of sIL-2R in the serum of patients, compared to healthy subjects, is involved in the inappropriate expansion of the T helper
(TH2) suppressive immune response, which we previously reported. The multivariate statistical method supported the above suggestions
and we also found that, in healthy subjects, the up- and down-regulation of sIL-2R in the serum within the physiological ranges
seems to have a regulating role in the relationships between TNFα, IFNγ and IL-4, IL-6, contributing to the operation of the
cytokine network between TH1 and TH2 cells. However, in patients compared to healthy subjects the increased sIL-2R serum level
seems to direct the immune response towards a suppressive type, which may be due to an alteration in the above-mentioned physiological
regulating role.
Received: 12 April 1997 / Accepted: 4 September 1997 相似文献
11.
MUC1 and cancer 总被引:25,自引:0,他引:25
Taylor-Papadimitriou J Burchell J Miles DW Dalziel M 《Biochimica et biophysica acta》1999,1455(2-3):301-313
The MUC1 membrane mucin was first identified as the molecule recognised by mouse monoclonal antibodies directed to epithelial cells, and the cancers which develop from them. Cloning the gene showed that the extracellular domain is made up of highly conserved repeats of 20 amino acids, the actual number varying between 25 and 100 depending on the allele. Each tandem repeat contains five potential glycosylation sites, and between doublets of threonines and serines lies an immunodominant region which contains the epitopes recognised by most of the mouse monoclonal antibodies. The O-glycans added to the mucin produced by the normal breast are core 2 based and can be complex, while the O-glycans added to the breast cancer mucin are mainly core 1 based. This means that some core protein epitopes in the tandem repeat which are masked in the normal mucin are exposed in the cancer associated mucin. Since novel carbohydrate epitopes are also carried on the breast cancer mucin, the molecule is antigenically distinct from the normal breast mucin. (Changes in glycosylation in other epithelial cancers have been observed but are not so well documented.) Immune responses to MUC1 have been seen in breast and ovarian cancer patients and clinical studies have been initiated to evaluate the use of antibodies to MUC1 and of immunogens based on MUC1 for immunotherapy of these patients. The role of the carbohydrates in the immune response and in other interactions with the effector cells of the immune system is of particular interest and is discussed. 相似文献
12.
Myszka A Karpinski P Slezak R Czemarmazowicz H Stembalska A Gil J Laczmanska I Bednarczyk D Szmida E Sasiadek MM 《Journal of applied genetics》2011,52(2):185-191
CHEK2 gen encodes cell cycle checkpoint kinase 2 that participates in the DNA repair pathway, cell cycle regulation and apoptosis.
Mutations in CHEK2 gene may result in kinase inactivation or reduce both catalytic activity and capability of binding other proteins. Some studies
indicate that alterations in CHEK2 gene confers increase the risk of breast cancer and some other malignancies, while the results of other studies are inconclusive.
Thus the significance of CHEK2 mutations in aetiology of breast cancer is still debatable. The aim of our study was to evaluate the relationship between
the breast/ovarian cancer and CHEK2 variants by: i) the analysis of the frequency of selected CHEK2 variants in breast and ovarian cancer patients compared to the controls; ii) evaluation of relationships between the certain CHEK2 variants and clinico-histopathological and pedigree data. The study was performed on 284 breast cancer patients, 113 ovarian
cancer patients and 287 healthy women. We revealed the presence of 430T > C, del5395 and IVS2 + 1G > A variants but not 1100delC
in individuals from both study and control groups. We did not observe significant differences between cancer patients and
controls neither in regard to the frequency nor to the type of CHEK2 variants. We discussed the potential application of CHEK2 variants in the evaluation of breast and ovarian cancer predisposition. 相似文献
13.
Mucins have been implicated in tumor-associated immunosuppression. The possibility that colon cancer mucin (CCM) may modulate
T-helper 1 (TH1) activity was evaluated by investigating its effect on the production of interleukin-2 (IL-2) by CD4+ cells, a process that requires antigen-specific and costimulatory signals. Methods: CCM was purified from human colorectal cancer cells by gel-exclusion fast-pressure liquid chromatography. Cytokine production
of purified CD4+ cells was evaluated at the protein and gene level in the presence of a phorbol ester or an anti-CD3 monoclonal antibody (mAb)
plus mAb against the CD28 costimulatory receptor to mimic two-signal activation. Results: Soluble CCM, which contains mucins MUC2 as well as MUC1, inhibited IL-2 mRNA expression and secretion of CD4+ stimulated with a phorbol ester or an anti-CD3 mAb plus anti-CD28 mAb. Pretreatment of CD4+ cells with anti-CD28 mAb abrogated the suppressive effects of CCM on IL-2 production, and flow cytometry showed decreased
binding of anti-CD28 mAb to its receptor in the presence of mucin. In addition, Ca2+ mobilization after T cell receptor cross-linking with anti-CD3 mAb was maintained in the presence of CCM. Although interferon
γ production was also diminished, CCM did not induce a general inhibition of cytokine production, nor did it decrease cell
viability. Macrophage inflammatory protein 1α production was up-regulated; the production of IL-10 and transforming growth
factor β was unchanged. Conclusions: The results indicate that CCM can alter TH1 activity and suggest that the modulation of costimulatory interactions is involved.
They provide another mechanism of immunosuppression mediated by these highly expressed tumor products.
Received: 23 March 1999 / Accepted: 3 August 1999 相似文献
14.
Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects 总被引:2,自引:0,他引:2
Qiyuan Chen Heather Jackson Peter Gibbs Ian D. Davis Joseph Trapani Jonathan Cebon 《Cancer immunology, immunotherapy : CII》1998,47(4):191-197
The spontaneous cytotoxic T cell responses to melanoma differentiation antigens and influenza matrix peptide were compared
in 20 HLA-A2+ melanoma patients and 17 healthy A2+ individuals. Cytotoxic T lymphocyte (CTL) responses were determined by mixed lymphocyte peptide culture (MLPC) involving
two stimulations of unfractionated peripheral blood lymphocytes (PBLs) with peptide in vitro. CTL responses to Melan-A 9-mer
(amino acids 27–35, AAGIGILTV) peptide were detected in 4 out of 16 normal individuals, but in none of the melanoma patients.
CTL specific for influenza matrix peptide were frequently found in both normal individuals and melanoma patients, suggesting
that generalized immuno-suppression was not responsible for this difference. No significant responses were observed in either
normal individuals or melanoma patients to Melan-A 10-mer (26–35, EAAGIGILTV), two gp100 epitopes (280–288, YLEPGPVTA; 457–466,
LLDGTATLRL) and two tyrosinase epitopes (1–9, MLLAVLYCL; 368–376, YMDGMSQV). Melan-A (27–35)-specific CTL cells generated
by normal individuals and melanoma patients recognized both synthetic peptide-pulsed T2 cells and two HLA-A2+, Melan-A+ melanoma cell lines (ME272, LAR1) in an antigen-specific, MHC class I restricted manner. T cells generated against Melan-A
9-mer were also able to recognize Melan-A 10-mer-pulsed target cells. Spontaneous CTL responses to Melan-A 9-mer from three
known responder normal individuals were further evaluated over a prolonged time course (6–11 months). All 3 subjects demonstrated
specific Melan-A 9-mer responses throughout the study period, although lytic activity fluctuated over time for a given individual.
We found the MLPC assay to be reliable and easy to perform for monitoring T cell responses, although it may still not be sufficiently
sensitive to detect low numbers of precursor T cells.
Received: 21 May 1998 / Accepted: 23 July 1998 相似文献
15.
Janardan P. Pandey Paul J. Nietert Kersti Klaamas Oleg Kurtenkov 《Cancer immunology, immunotherapy : CII》2009,58(12):2025-2029
High levels of antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in adenocarcinomas, are associated
with good prognosis in patients with breast cancer. The aim of the present investigation was to determine whether GM and KM
allotypes—genetic markers of IgG heavy chains and κ-type light chains, respectively—contribute to the magnitude of natural
antibody responsiveness to MUC1 in patients with breast cancer. A total of 153 Caucasian subjects with breast cancer were
allotyped for several GM and KM markers. These subjects were also characterized for IgG and IgM antibodies to MUC1. Anti-MUC1
IgG antibody levels in subjects who were carriers of the immunoglobulin γ2 allele GM 23 were significantly higher than in
those who were noncarriers (P = 0.003). These results could potentially divide the population into high or low responders to MUC1, which has important
implications for MUC1-based immunotherapeutic interventions in breast cancer. 相似文献
16.
Khaled M. Al-Qudah Ahmad A. Gharaibeh Maysa’a M. Al-Shyyab 《Biological trace element research》2010,136(1):40-47
The aim of this study was to determine the levels of trace minerals Zn, Cu, and Se, the effect of dermatophytosis on the level
of thiobarbituric acid reactive substances (TBARS) as an indicator of lipid peroxidation, the status of enzymatic and nonenzymatic
antioxidants, and the relationship between the mentioned trace minerals and antioxidant defense system in calves with dermatophytosis.
A total of 21 Holstein calves with clinically established diagnosis of dermatophytosis and an equal number of healthy ones
were included in this study. Results showed that 81% of mycotic isolates were Trichophyton verrucosum, while 19% were Trichophyton mentagrophytes. The level of Zn, Cu, Se, and glutathione (GSH) and the activity of the antioxidant enzymes, glutathione peroxidase (GSH-Px),
and superoxide dismutase (SOD) were significantly (P ≤ 0.05) lower. The plasma level of TBARS was significantly (P ≤ 0.05) higher in dermatophytic calves compared to healthy controls. SOD activity was fairly correlated with serum Cu and
positively correlated with serum Zn in healthy control (r = 0.68, P ≤ 0.05; r = 0.58, P ≤ 0.05) and in calves affected with dermatophytosis (r = 0.73, P ≤ 0.05; r = 0.55, P ≤ 0.05), respectively. GSH-Px activity was highly correlated with whole blood selenium (r = 0.78, P ≤ 0.05) in healthy control and dermatophytic subjects (r = 0.76, P ≤ 0.05). Our results demonstrated that in dermatophytosis, the alteration in the antioxidant enzyme activities might be secondary
to changes in their cofactor concentrations. 相似文献
17.
Zimmermann GL Krantz MJ Kane KP Longenecker BM 《Cancer immunology, immunotherapy : CII》2000,49(6):305-313
We report here the development of a mouse mammary adenocarcinoma cell line containing full-length human MUC1 cDNA that can
be more lethal than the parental cell line. The metastatic murine mammary adenocarcinoma cell line 410.4 was transfected with
cDNA coding for a 42-tandem-repeat version of human MUC1. Two cell lines were selected, one for stable, high expression in
vitro of cell-surface MUC1 (GZHi) and one for stable, low expression in vitro of cell-surface MUC1 (GZLo). Following subcutaneous
challenge of CB6F1 mice with various doses of tumor cells, GZHi tumors showed loss of MUC1 expression; negligible amounts
of serum MUC1 mucin were detected and the mice survived longer than mice challenged with GZLo or wild-type (410.4) tumor cells.
Mice challenged with GZLo tumor cells had shorter survival times than mice challenged with either GZHi or 410.4 tumor cells.
GZLo-challenged mice that showed rapidly increasing serum MUC1 mucin levels several weeks prior to death had a shorter survival
than mice without detectable rising MUC1 serum levels. Surprisingly, SCID-BEIGE mice challenged with GZLo cells also survived
for a shorter time than those challenged with either GZHi or 410.4 cells. This suggests that MUC1 mucin may also enhance the
aggressiveness of GZLo tumors by non-immune mechanisms.
Received: 30 November 1999 / Accepted: 13 March 2000 相似文献
18.
Pellegrini P Contasta I Berghella AM Gargano E Mammarella C Adorno D 《Cancer immunology, immunotherapy : CII》2000,49(7):388-394
Matrix metalloproteinases (MMP) are members of a multigene family of zinc-dependent enzymes involved in the degradation of
extracellular matrix components. Cancer research suggest that MMP and tissue inhibitors of metalloproteinases (TIMP) may be
involved in disease progression; these enzymes could therefore be used as markers in cancer prevention programmes and for
clinical monitoring. To establish whether MMP and TIMP can be used effectively as markers we determined serum levels of MMP1
and TIMP1, and studied the relationships between these enzymes and the stage of disease. The potential diagnostic and prognostic
value of serum level measurements of MMP1 and TIMP1 was evaluated by comparing them with serum levels of soluble carcinoembryonic
antigens (sCEA) and p53 antibodies. Our overall results indicate that simultaneous measurements of serum sCEA and TIMP1 in
patients with colorectal cancer could be used as prognostic and diagnostic markers for disease progression from the pre-invasive
nodal phase to the invasive phase (stages I, II to III, IV). In addition, serum levels of TIMP1 could be used as a selective
marker for metastatic disease (stage III to IV). In fact, the 95% confidence interval of the serum levels of sCEA at stage
III (18.4 ≤ sCEA ≤ 68.6 ng/ml) and TIMP1 at stage IV (1620 ≤ TIMP1 ≤ 3906 ng/ml) identified statistically significant ranges
of values (sCEA P = 0.02, TIMP1 P = 0.02), which may be useful in the monitoring of patients at these disease phases. More specifically, our data suggest that,
when the serum level of sCEA is below 18.4 ng/ml and the level of TIMP1 below 1620 ng/ml, there is a 95% probability that
the disease is in the pre-invasive nodal phase; when the serum level of sCEA falls between 18.4 ng/ml and 68.6 ng/ml and the
level of TIMP1 is below 1620 ng/ml, there is a 95% probability that the disease is in the phase when lymph node infiltration
occurs; when the level of sCEA is above 68.6 ng/ml and the level of TIMP1 is at least 1620 ng/ml, there is a 95% probability
that the disease is in the metastatic phase.
Received: 30 March 2000 / Accepted: 18 May 2000 相似文献
19.
Morikane K Tempero RM Sivinski CL Nomoto M Van Lith ML Muto T Hollingsworth MA 《Cancer immunology, immunotherapy : CII》1999,47(5):287-296
We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the
effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic
adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection.
Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously
with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice
challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from
mice that rejected Panc02-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat
peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests
that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties
and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.
Received: 25 April 1998 / Accepted: 7 October 1998 相似文献
20.
Dendritic cell-based cancer immunotherapy targeting MUC-1 总被引:3,自引:0,他引:3
Vaccination therapy using dendritic cells (DC) as antigen presenting cells (APC) has shown significant promise in laboratory
and animal studies as a potential treatment for malignant diseases. Pulsing of autologous DCs with tumor-associated antigens
(TAA) is a method often used for antigen delivery and choice of suitable antigens plays an important role in designing an
effective vaccine. We identified two HLA-A2 binding novel 9-mer peptides of the TAA MUC1, which is overexpressed on various
hematological and epithelial malignancies. Cytotoxic T cells generated after pulsing DC with these peptides were able to induce
lysis of tumor cells expressing MUC1 in an antigen-specific and HLA-restricted fashion. Within two clinical studies, we demonstrated
that vaccination of patients with advanced cancer using DCs pulsed with MUC1 derived peptides is well tolerated without serious
side effects and can induce immunological responses. Of 20 patients with metastatic renal cell carcinoma, 6 patients showed
regression of metastases with 3 objective responses (1 CR, 2 PR). Furthermore, we found that in patients responding to treatment
T cell responses for antigens not used for treatment occurred suggesting that antigen spreading in vivo might be a possible
mechanism of mediating antitumor effects. These results demonstrate that immunotherapy in patients with advanced malignancies
using autologous DCs pulsed with MUC1 derived peptides can induce immunological and clinical responses. However, further clinical
studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response
in vivo.
This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2004 (PIVAC 4)”, held in Freudenstadt-Lauterbad,
Black Forest, Germany, on 22–25 September 2004. 相似文献