Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have characterized the reactivity of CD8+ CTLs with ovarian and breast cancer. There is little information about the antigens and epitopes recognized by CD4+ T cells in these patients. In this study, we analyzed the ability of T cells from peripheral blood mononuclear cells of breast cancer patients to recognize HER-2/neu (HER-2) peptides. We found that 13 of 18 patients responded by proliferation to at least one of the HER-2 peptides tested. Of these peptides, one designated G89 (HER-2: 777-789) was recognized by T cells from 10 patients. Seven of nine responding patients were HLA-DR4+, suggesting that this peptide is recognized preferentially in association with HLA-DR4. Analysis of the specificity and restriction of the cytokine responses to G89 by G89-stimulated T cells revealed that these cells secreted significantly higher levels of IFN-gamma than interleukin 4 and interleukin 10, suggesting priming for a Th0-T helper 1 response. The same pattern of cytokine responses was observed to the intracellular domain of HER-2 protein, suggesting that G89-stimulated T cells recognized epitopes of the HER-2 protein in association with HLA-DR4. Because HLA-DR4 is present in 25% of humans, characterization of MHC class II-restricted epitopes inducing Th0-T helper 1 responses may provide a basis for the development of multivalent HER-2-based vaccines against breast and ovarian cancer.
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PMID:Proliferative and cytokine responses to class II HER-2/neu-associated peptides in breast cancer patients. 971 33

From September 1982 to August 1997, 767 bone marrow or peripheral blood stem cell transplants have been performed at the Health Sciences Center in Oklahoma. Five hundred and two (502) autologous transplants (AutoTX) preceded by high-dose myeloablative therapy were performed for breast cancer (BC, 36%), non-Hodgkin's lymphomas (NHL, 24%), Hodgkin's disease (HD, 10%), acute myeloid leukemia (AML, 8%), testicular cancer (TC, 4%), multiple myeloma (MM, 2%) and other malignancies (16%). Two hundred and sixty-five (265) allogeneic marrow transplants (AlloTX) (related, unrelated) were carried out in chronic myeloid leukemia (CML, 30%), AML (23%), acute lymphoid leukemia (ALL, 14%), myelodysplastic syndrome (MDS, 9%), severe aplastic anemia (SAA, 8%), and other diseases (14%). Compared between 1980s to 1990s, 100-day mortality rates have decreased from 28% to 5% for AutoTX and from 40% to 25% for AlloTX. In the AutoTX setting, major changes included the routine use of growth factors post-transplant and the switch from bone marrow to growth factor-mobilized peripheral blood as a source of stem cells over the last five years. In the AlloTX setting, improvements in recognition and control of cytomegalovirus and Candida organisms, the selective use of growth factors and screened blood products, and better selection of unrelated donors using DNA-based techniques of HLA-matching have contributed to reduce early mortality from infection and primary graft failure. The five-year survival outcomes are comparable to those reported in registry data from the International Bone Marrow Transplant Registry (IBMTR) and the National Marrow Donor Program (NMDP).
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PMID:Marrow and stem cell transplantation in Oklahoma: fifteen years of experience and results. 976 68

HLA frequencies of fifty (50) female breast cancer patients were compared with 200 age matched female controls. A total of 20 HLA-A locus, 35 HLA-B locus and 8 HLA-C locus antigens were studied. The HLA-A2, A11, Aw19 and A30; HLA-B8, B14 and HLA Cw6 were found significantly higher than the controls. The HLA-A11, HLA-Aw19 and HLA-B8 were found protective whereas, HLA-A2, HLA-B14 and HLA-Cw6 were a risk for breast cancer. The prective antigens' probable involvement through immunogenic mechanism in breast cancer is emphasized in this article.
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PMID:Human leucocytic antigens (HLA) in breast cancer. 980 7

We investigated in breast cancers the expression of the SART-1 gene encoding tumor rejection antigens. SART-1 mRNA was expressed in all of the samples tested. The SART-1(800) antigen was detectable in 20 of 50 (40%) breast cancer tissues and all breast cancer cell lines tested, but not in normal breast tissues. The SART-1(800)+ breast cancer cells transfected with HLA-A2601 or HLA-A2402 cDNA were recognized by the HLA-A26-restricted and SART-1-specific cytotoxic T lymphocytes (CTLs) or the HLA-A24-restricted and SART-1-specific CTLs, respectively. Among the 20 SART-1(800)+ tumors, 9 or 8 tumors expressed estrogen receptor or progesterone receptor, respectively. Therefore, the patients with HLA-A26 or -A24 haplotype might be appropriate candidates for specific immunotherapy with the SART-1 peptides independently or in combination with hormone therapy.
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PMID:Expression of the SART-1 tumor rejection antigen in breast cancer. 993 32

Distinction between benign reactive mesothelial cells and metastatic breast adenocarcinoma cells in effusions from patients with a known prior history of breast cancer is not the easiest task in diagnostic pathology. Here, we report the usefulness of testing the expression of class I HLA antigens (HLA A, B, C) in this respect. Cytospins were prepared from effusions of patients without the history of breast cancer (5 cases) and from effusions of patients with infiltrating ductal carcinoma (11 cases). Three effusions from cancerous patients were not malignant cytologically. The expression of HLA-A, B, C, HLA-DR and beta2-microglobulin as well as the macrophage antigen, CD14, was evaluated by immunocytochemistry. In 10 of 11 effusions the cytologically malignant cells expressed very weak or undetectable HLA-A,B,C as compared to the mesothelial cells and macrophages. The paucity of expression of HLA-A, B, C was detectable in those 3 cases where a definitive cytological diagnosis of malignancy could not be established. In contrast, mesothelial cells and macrophages from all samples were uniformly and strongly positive for both HLA-A, B, C and beta2-microglobulin. We conclude that the paucity of HLA-I antigens provides a marker helpful in distinguishing metastatic breast carcinoma cells from reactive mesothelial cells in effusions.
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PMID:Differential diagnostic significance of the paucity of HLA-I antigens on metastatic breast carcinoma cells in effusions. 1007 75

Strategies to identify tumor-associated antigens rely on the paradigm that tumor-associated peptides presented in the context of HLA-class I are recognized by the cellular immune system. Approaches to isolate tumor-specific cytotoxic T lymphocytes (CTL) from tumor-infiltrating lymphocytes are difficult because long-term growth of the CTL requires autologous tumor cells and lymphocytes (PBL) as feeder cells. In this study, a CTL line (BL.HBL-100 CTL) was generated from PBL from a normal healthy donor by stimulating with irradiated, HLA-class I partially matched breast cancer cell line HBL-100. Activated T lymphocytes generated expressed TCR alpha/beta+ with a predominant CD8+ population after 12 stimulations (98.54% CD8+ vs. 0.18% CD4+). These CTL lysed HLA-A1+, but not HLA-A1-, breast cancer cell lines. Moreover, HLA-A1+, non breast cancer cell lines were not recognized. The lytic activity of BL.HBL-100 CTL against HLA-A1+ breast cancer cell lines was blocked by monoclonal antibodies (MAbs) to HLA-class I and CD8, but not by anti-HLA-class II and CD4. Recognition of HLA-A1+ breast cancer cells by the CTL was dependent on peptides associated with HLA-class I since the lysis was inhibited by acid elution of HLA bound peptides. HBL-100 tumors were grown in severe combined immunodeficient (SCID) mice. Immunohistochemical staining of the HBL-100 tissue harvested from SCID mice demonstrated human breast cancer cells. HLA-class I molecules were affinity purified from the HBL-100 harvested from the SCID mice; class I bound peptides were eluted and separated by RP-HPLC. Pooled HPLC peptide fractions were tested for reconstituting antigenic epitopes recognized by the BL.HBL-100 CTL and found to reside within fraction 40. Our results show that a tumor reactive, HLA-class I restricted CTL was produced by stimulating normal PBL against an HLA-class I matched breast cancer cell line. We also provide evidence for a breast cancer-associated, HLA-class I bound peptide antigen(s) that reconstitutes the antigenic epitope(s) recognized by these CTL.
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PMID:Recognition of breast cancer-associated peptides by tumor-reactive, HLA-class I restricted allogeneic cytotoxic T lymphocytes. 1022 52

The number of allogeneic and autologous bone marrow transplants continues to grow worldwide. Bone marrow transplantation (BMT) has become standard therapy for many patients with leukemia, lymphoma, multiple myeloma and testicular cancer. Encouraging results of autologous BMT in treating patients with poor-risk breast cancer have led to this approach being tested in nationwide randomized trials. In order to increase availability and efficacy of BMT, other sources of hematopoietic cells are explored for transplantation, such as from HLA-matched unrelated volunteer donors, partially matched related donors, placental/umbilical cord blood and allogeneic peripheral blood. Relapse of original malignancy remains the main obstacle for the success of BMT. Recent clinical investigations have demonstrated that donor-derived peripheral blood leukocytes are effective in inducing remissions in patients with hematological malignancies who relapse after allogeneic BMT. BMT procedures are associated with significant complexity and should be carried out only in transplant units that meet adequate standards. In order to better define the role of BMT in treating cancer, more phase III clinical trials are needed. The future of BMT will depend on further improvements in its efficacy and economic constraints.
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PMID:Bone Marrow Transplantation for Cancer - An Update. 1038 82

To broaden the clinical applicability of peptide-based immunotherapy in breast cancer, there is a need to identify further tumor-associated peptide epitopes that are specific for HLA alleles, in addition to HLA-A2. The HLA-B44 haplotype is one of the most common HLA-B haplotypes, occurring in 10-20% of the population. We performed the structural characterization of HLA class I-bound self-peptides presented by a human breast cancer cell line with a HLA-A68, A32, B40, B44 haplotype, to identify potential tumor-specific antigens. Of 13 sequenced peptides, 1 peptide had the HLA-A68 peptide binding motif and 12 peptides had the HLA-B40, B44 peptide binding motif. One of the latter peptides, FEVRVCACPG, shared 100% homology to residues 270-279 of wild-type P53 protein. Our study, thus, provides direct evidence for the natural processing and presentation of p53 epitope 270-279 by HLA-B40, B44-bearing human breast tumor cells. Epitopes spanning this region of P53 may have potential use for immunotherapy in patients expressing HLA-A2 and -B44 supertypes.
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PMID:Wild-type p53 epitope naturally processed and presented by an HLA-B haplotype on human breast carcinoma cells. 1047 91

Retinoblastoma binding protein 1 (RBP-1) is a 143-kDa nuclear phosphoprotein that promotes cell growth by inhibiting the product of retinoblastoma tumour suppressor gene (pRB). We recently found that RBP-1 contains KASIFLK, a heptameric peptide (250-256) recognized by human antibodies and overexpressed by breast cancer cells. In the present study, we demonstrate that human T-cells stimulated with RBP-1 decameric peptides containing KASIFLK can kill human breast cancer cells. These decamers, GLQKASIFLK (247-256) and KASIFLKTRV (250-259), have anchor motifs for both HLA-A2 and HLA-A3. Peripheral blood lymphocytes from 41 normal donors were stimulated by these peptides in culture media containing 15 IU ml(-1) interleukin-2, 25 IU ml(-1) interleukin-7 and 500 IU ml(-1) granulocyte-macrophage colony-stimulating factor. Cytotoxic activity of the T-cells was assessed against autologous B lymphoblastoid cells pulsed with each peptide. Stimulation by GLQKASIFLK generated specific cytotoxic T lymphocyte (CTL) lines from HLA-A2, A3 donors, HLA-A2 donors and HLA-A3 donors. Stimulation with KASIFLKTRV generated specific CTL lines from HLA-A2 donors. No HLA-A2-, A3 CTL line showed specific cytotoxicity against these target cells. These CTL lines were also cytotoxic against HLA-A2 and HLA-A3 breast cancer cells but not against normal fibroblastoid cell lines, normal epidermal cell lines, or a melanoma cell line. RBP-1 peptide antigens may be of clinical significance as a potential peptide vaccine against human breast cancer.
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PMID:Cytotoxic T lymphocytes that recognize decameric peptide sequences of retinoblastoma binding protein 1 (RBP-1) associated with human breast cancer. 1049 63

Overexpression of gp185(erbB-2) has been associated with reduced survival in breast-cancer patients. Our earlier results, now confirmed in a larger cohort of patients (798), evidenced that the HLA-A2 allele may participate in the modulation of the erbB-2 tumor phenotype in vivo. In the present study, we evaluated other clinico-biopathologic parameters possibly involved in the host immune response against erbB-2. Localization of the CD3(+) T-cell infiltrate was taken into consideration in 705 primary breast tumors, and expression of HLA-class-I and HLA-A2 antigens was evaluated in a subgroup of 170 frozen primary tumors of HLA-A2-positive patients. The presence or the absence of HLA-class-I and HLA-A2 antigens in primary tumors did not correlate with erbB-2 expression. However, HLA-A2-positive tumors preferentially showed intratumoral lymphocyte localization, whereas the lesions displaying undetectable HLA-class-I expression showed peritumoral CD3(+) T-cell localization. Taking into account erbB-2 immunoreactivity, we found that the relationship between HLA-A2 expression and intratumoral CD3(+) T-lymphocyte localization is significant only in the erbB-2 negative subset, whereas the relationship between lack of HLA-class-I expression and peritumoral CD3(+) T-lymphocyte localization is significant only in the erbB-2-positive subset. These data provide novel in vivo evidence of the possible contribution of the host immune system to control of erbB-2 oncogene overexpression in breast cancer. Int. J. Cancer (Pred. Oncol.) 84:598-603, 1999.
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PMID:Host immunosurveillance contributes to the control of erbB-2 overexpression in HLA-A2-breast-cancer patients. 1056 5


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