Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nasopharyngeal carcinoma (NPC) is an epithelial tumor consistently associated with EBV. The histological picture is characterized by a strikingly abundant lymphocytic infiltrate. Furthermore, the epithelial tumor cells present several immunological characteristics which suggest an important role for tumor-infiltrating lymphocytes (TIL) in the biology of this tumor. The present study reports the phenotypic and functional characterization of TIL from NPC obtained after enzymatic digestion of 15 NPC biopsies. Flow cytometric analysis of TIL suspensions indicated that most TIL were mature CD3+ T lymphocytes (mean = 60%) with a variable CD4/CD8 ratio. Most TIL were TCR alpha/beta-positive (mean = 55%) and only a few TCR gamma-delta-positive cells could be identified. A small percentage (mean = 9%) displayed an activated phenotype (CD25+, HLA class II+). Using limiting dilution analysis, we found that the average frequency of proliferative T-lymphocyte precursors (PTL-P) is lower among TIL (1/40) than in autologous (1/7) or normal PBL (1/1.4). Moreover, sorting experiments have shown that this defect is significantly more pronounced in the CD8+ than in the CD4+ TIL subset. Accordingly, the TCR and the CD2-mediated antigen-independent pathways of activation were impaired. Different types of cytotoxic precursor could be detected. These included lectin-dependent cell cytotoxicity (LDCC) and NK-like or lymphokine-activated killer (LAK) activity. Interestingly, some TIL from NPC were able to lyse an NPC tumor (C15) maintained in nude mice. Thus, despite impaired activation pathways, the cytolytic potential of proliferating TIL in NPC is preserved.
 ...
PMID:Cytotoxic potential despite impaired activation pathways in T lymphocytes infiltrating nasopharyngeal carcinoma. 189 51

HLA class-I expression has been investigated by biochemical methods in 14 Burkitt lymphoma (BL) cell lines and the corresponding Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) derived from the same individuals. Selective down-regulation of one or more HLA class-I specificities was demonstrated in 9 out of 14 BL lines. The defect was restricted to a single HLA-A allele in 3 of the lines (BL29, BL72, WW-I-BL). Four lines (BL28, BL37, BL41 and Jijoye M13) showed down-regulation of both HLA-A and -C alleles, and one (BL36) failed to express one HLA-C allele. Only one BL line (WW-2-BL) had lost one HLA-A and one HLA-B allele. The allele-specific defects were mainly detected in cell lines that had maintained the phenotypic characteristics of the original tumor. Expression of B-cell activation markers and the EBV-encoded nuclear antigen (EBNA)-2 correlated with up-regulation of the Cw4 allele in the P79 subline of the BL line Jijoye. Treatment with gamma-interferon (IFN) resulted in full or partial reversion of the HLA class-I defects in some of the cases but had no significant effect in others. This was not due to a cell-line-related unresponsiveness to IFN, nor did it reflect an allele-specific mode of regulation because the same allele could respond differently in different cell lines. The data suggest that defective expression of HLA class-I antigens, which appears to be more prevalent for alleles within the HLA-A and -C loci, is a common feature of BL cell lines. Different regulatory mechanisms appear to be involved.
 ...
PMID:Aberrant expression of HLA class-I antigens in Burkitt lymphoma cells. 189 54

Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients.
 ...
PMID:Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. 190 25

Molecular characterization of HLA-class-I expression was investigated in human tumor cell lines at the protein and mRNA levels using locus-specific monoclonal antibodies (MAbs) and probes. Some cell lines exhibited a differential expression of HLA-A and HLA-B products and also showed differences in the inducibility of HLA-class-I genes by gamma-IFN. Thus, gamma-IFN stimulation induced predominantly HLA-B mRNA in the HeP-2 cell line, which showed imbalances in basal levels of HLA-A and HLA-B expression. This unequal inducibility of HLA genes may imply that locus-specific regulatory mechanisms are involved in the expression of individual HLA products. The specific mechanism controlling the differential expression of HLA subsets appears to be independent of c-myc activity. Northern blot analysis found no relationship between c-myc mRNA levels and specific mRNA for HLA-A and HLA-B antigens.
 ...
PMID:Molecular analysis of MHC-class-I alterations in human tumor cell lines. 190 50

Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been successfully generated in vitro from tumor bearing lymph nodes without any stimulation by the autologous tumor. Tumor-involved lymph node cells (LNC) were cultured in serum free medium (AIM-V) containing 1,000 U/ml of recombinant interleukin-2. The best expansion and specific cytotoxicity of CTL were achieved in 4 to 6 weeks of culture. The predominant populations in cultured LNC-derived CTL were CD2+, CD3+, CD4-, CD8+, CD56-, and HLA-DR+ T cells. These data suggested that tumor-involved LNC may provide an alternative source for the generation of tumor-specific CTL in adoptive immunotherapy.
 ...
PMID:Generation of human autologous melanoma-specific cytotoxic T cells from tumor-involved lymph nodes. 191 Jun 25

The expression of HLA antigens by a tumor may determine its progression and metastatic potential by influencing the immune response to that tumor. The upregulation of HLA antigen expression on some cell types by interferons (IFNs) may contribute to their antitumor activity. Malignant mesothelioma (MM) is a tumor that has a poor prognosis and is unaffected by conventional therapy, although immunotherapy has not been adequately assessed. In this study, we have examined the constitutive and IFN-inducible expression of class I and class II HLA antigens on MM cell lines using indirect immunofluorescence and Northern blotting. All MM cell lines constitutively expressed class I, but not class II, surface antigen, and all three class I loci (HLA-A, HLA-B, and HLA-C) were expressed. The MM cell lines were heterogeneous in their response to the IFNs. Treatment with IFN-alpha marginally increased class I surface expression, but not class II. Class I mRNA was, however, clearly increased in all cell lines after IFN-alpha treatment, suggesting that class I surface antigen was already maximally expressed. IFN-gamma increased class I mRNA expression in all but one cell line and induced DR expression on three of the cell lines. DQ-beta, but not DQ-alpha, mRNA was inducible in the same three cell lines, but DQ surface antigen was never demonstrable.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:HLA antigen expression and malignant mesothelioma. 191 Aug 7

This article reviews abnormalities in the expression of major histocompatibility antigens in colorectal neoplasia. These include the loss of HLA-A, B, C antigens and the loss of HLA-D antigen inducibility. Since these abnormalities are not seen in normal colorectal epithelium they are probably selected for during tumour progression. The crucial role of HLA-A, B, C and HLA-D molecules in the presentation of foreign antigens to the immune system suggests that their loss could directly confer a selective growth advantage to tumour cells expressing tumour specific antigens, through resistance to anti-tumour lymphocyte attack. The possible relationships between abnormalities in tumour HLA antigen expression and the presence of tumour specific antigens are discussed.
 ...
PMID:MHC antigen expression in colorectal tumours. 191 14

MHC class I and II molecules play an important role in specific interactions with cells of the immune system. Endogenous or exogenous antigens are presented to the clonotypic receptor of T cells as small peptides associated to MHC molecules. Qualitative or quantitative variation in the expression of these molecules in the surface of tumor cells could have important implications in anti-tumor immune responses. We have analysed 344 human tumors for HLA class I and II expression and found that 10-30% of tumors present a total loss of HLA ABC molecules. In addition, HLA-A or -B locus-specific losses were also detected. These alterations have been correlated with tumor aggressiveness in breast and laryngeal carcinomas. We also have observed that the expression of HLA ABC molecules in autologous metastasis did not always correspond with the expression detected in the primary tumor. In laryngeal carcinomas HLA-DR expression was associated with an excellent prognosis. We have observed in most tumors that the absence of class I molecules usually corresponds with a simultaneous loss of heavy chain and beta 2 microglobulin expression and with a low level of the mRNA specific for class I genes. Nevertheless, a variety of mechanisms are involved since in colon tumors the absence of expression is caused by beta 2 microglobulin down regulation. Also post-transcriptional mechanisms may be involved in the differential expression of HLA-A and -B locus products. There is no doubt that a more exact knowledge of the mechanisms that produce alteration in the expression of these antigens will help to manipulate MHC gene expression in human tumors and to induce a more efficient immune response.
 ...
PMID:MHC expression on human tumors--its relevance for local tumor growth and metastasis. 191 16

Previous studies in murine models have shown that in vivo or in vitro treatment of tumor cells with mutagenic triazene compounds (TZC) lead to the appearance of novel drug-mediated tumor antigens (DMTA) capable of eliciting graft resistance in syngeneic hosts. This phenomenon, defined as 'chemical xenogenization' (CX), could be of potential value for immunochemotherapy of human neoplasias. It was also shown that TZC modulate NK sensitivity of murine tumor cells. Therefore, experiments were conducted to evaluate whether susceptibility of a human lung adenocarcinoma cell line (H125) to natural cytotoxic effectors could be affected by treatment with an in vitro active TZC. The results showed that drug treatment of H125 line leads to heritable increase of susceptibility to NK and LAK cells. Moreover, increased binding between effector and drug-treated target cells was observed. Additional studies on HLA antigens showed that changes in HLA-ABC molecule expression were probably not involved in TZC-induced increase of NK/LAK susceptibility. These results suggest that TZC treatment of a human tumor could result in increased expression of membrane structures recognized by natural cytotoxic effector cells. Further studies are required to explore whether these changes are generated by mutational events correlated with TZC-induced CX of human cancer cells.
 ...
PMID:Drug-mediated increase of susceptibility of human lung cancer to NK or LAK effector cells. 191 40

Many of the tumor markers mentioned in this article may seem to be of only research or theoretic interest. However, many of those mentioned are likely to be of great clinical utility in the future. In particular, the strength of these immunohistochemical findings have been compared with standard clinical prognostic features (e.g., stage, age, B symptoms) and have been modeled to show independent prognostic relevance in both intermediate-grade and low-grade lymphomas. Beyond their predictive value, these markers have identified phenotypes that may serve as new therapeutic targets: (1) restoration of HLA loss with alpha and gamma interferons; and (2) restoration of tumor-infiltrating T-cell lymphocytes with interleukin-2. New phenotype-directed cytokine therapies seem compelling with this new knowledge. We await future prospective trials of phenotyping to further refine this new exciting prospect.
 ...
PMID:New biologic markers in non-Hodgkin's lymphomas. 193 61


<< Previous 1 2 3 4 5 6 7 8 9 10